JP2022538347A - Ophthalmic device delivery method and system - Google Patents

Abstract

The present disclosure provides ophthalmic articles. The ophthalmic article may comprise a biocompatible matrix comprising a copolymer derived from caprolactone monomer and at least one other monomer. Ophthalmic articles may also include active agents or diagnostic agents. The ophthalmic article may be configured to couple to intraocular lens (IOL) haptics. [Selection drawing] Fig. 1A

Description

cross reference
[0001] This application is based on U.S. Provisional Patent Application No. 62/867,233, filed Jun. 27, 2019, and U.S. Provisional Patent Application No. 63/012,994, filed Apr. 21, 2020. and the benefit thereof, each of which is hereby incorporated by reference in its entirety.

[0002] Cataract surgery is the second most common outpatient surgical procedure in the United States. Patients undergoing cataract surgery may receive a postoperative regimen of self-administered topical eye drops for many weeks after cataract surgery. These eye drops usually consist of antibiotics to prevent infection, and corticosteroids and/or non-steroidal anti-inflammatory drugs (NSAIDs) to prevent inflammation.

[0003] Adherence to post-operative eye drop regimens can be difficult among patients undergoing cataract surgery (eg, elderly patients). Typical post-operative prophylaxis for cataract surgery may involve complex and lengthy regimens of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotic eye drops. In addition to visual impairments, patients, particularly the elderly population, who may have physical and cognitive disabilities that limit their ability to read signs, follow instructions to physically instill eye drops into their eyes. In addition, many elderly patients live alone and cannot rely on caregiver administration of medications. Therefore, there is a need to develop a system that automatically delivers drugs to the eye to solve the problem of patient non-compliance.

[0004] Drug penetration into the eye by topical eye drops can be inefficient. It has been estimated that only 1-3% of a given eye drop actually penetrates the eye, and once inside the eye such drugs are cleared very rapidly. This can lead to a pulsatile delivery profile in which the dispensed drug does not cover a continuous area. A more efficient approach may be to release the drug inside the eye closer to the target tissue and with sustained release kinetics.

[0005] A cataract is a clouding of the lens inside the eye that interferes with visual function. Cataracts also occur as a normal part of aging and as a side effect of some drugs, systemic diseases and genetic conditions. However, cataracts can also be associated with ocular trauma, long-term diabetes, corticosteroid drugs or radiation treatments. A standard treatment for cataracts can be a surgical procedure in which the cloudy lens is removed and replaced with an artificial lens (eg, an intraocular lens) made of clear acrylic or other synthetic material.

[0006] An intraocular lens (IOL) device consists of two parts, the central optic and the haptics. The optic is the lens portion at the center of the IOL. Haptics are flexible arms that stabilize the IOL inside the lens capsule of the eye. Cataract surgery uses a foldable IOL that can be injected into the eye using a very small incision (2.2-2.8 mm). As a result, sutures to close the eye are not usually required after cataract surgery.

[0007] Although IOL-based drug delivery strategies have been previously investigated, such systems require changes to normal surgical techniques, or add additional steps to the manufacturing process, without significant modification of the IOL design. has never been successfully designed. For example, one prior IOL consisted of two dexamethasone-PLGA pellets embedded in the optic, but the implantation required a 6 mm wound and two sutures, which was accomplished with a sutureless corneal incision. It was three times the size of the current standard. Therefore, this approach is impractical for modern cataract surgery.

[0008] Prior ring-shaped drug release devices adhere to the haptics of a three-piece IOL, but because the device requires delivery through a larger corneal incision than currently used, its size and stiffness are limited. , was incompatible with standard cataract surgery techniques. Therefore, this approach was also not ideal.

[0009] Other prior approaches involve soaking the IOL in a medical solution prior to surgery, but this approach is limited by the compatibility of certain drugs with certain IOL matrix materials (e.g., acrylic lenses). water-soluble antibiotics against; corticosteroids against silicone lenses). Moreover, this approach does not exhibit controlled release; rather, it is just a diffusion limited burst release.

[0010] In another example, a system has previously been proposed in which a drug-releasing ultra-thin clear film is fabricated on the surface of an IOL without compromising the optical properties of the lens. While it is plausible that this device provides adequate drug release functionality and does not require changes to normal cataract surgical procedures, this system adds an additional step to the manufacturing process, thereby increasing the overall cost of the item. are affected. Moreover, it is not easily adaptable to IOLs of various sizes, shapes and refractive powers or materials, and doing so would require manufacturers to add this feature to each individual separately to the make and model of the IOL. may need it.

[0011] Improved ophthalmic articles, devices, methods, systems for delivering or administering active agents and/or diagnostic agents from ophthalmic devices to the eye and/or addressing at least some of the above shortcomings and kits are preferred.

[0012] Embodiments of the present disclosure provide articles, methods, devices, systems, and kits for delivery of intraocular agents (eg, active agents and/or diagnostic agents). The present disclosure provides articles, methods, systems, and kits for ocular delivery or administration of active agents and/or diagnostic agents from an ophthalmic device. The present disclosure also provides articles, methods, systems, and kits for diagnosing and/or treating ocular diseases, conditions, and/or complications.

[0013] In one aspect, the present disclosure provides an ophthalmic article. In one embodiment, an ophthalmic article comprises (a) a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer, and (b) an active or diagnostic agent, comprising an intraocular lens. (IOL) haptics. In some embodiments, the copolymer is derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the copolymer is derived from about 40 weight percent caprolactone monomer and about 60 weight percent at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the biocompatible matrix is a random, block, or gradient copolymer. In some embodiments, copolymers include random copolymers. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, the ophthalmic article has a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, the ophthalmic article has a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the ophthalmic article has a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the ophthalmic article has a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, the ophthalmic article has a modulus of elasticity of at most about 3 MPa. In some embodiments, the ophthalmic article has a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the ophthalmic article has an elongation to break of at least about 100% as measured by a tensile test. In some embodiments, the ophthalmic article has an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of the ophthalmic article is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the ophthalmic article includes an internal structure for bonding around the IOL's haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the IOL's haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the IOL's haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the IOL's haptics. In some embodiments, the ophthalmic article extends no more than about 0.32 mm beyond the haptics of the IOL when the ophthalmic article couples to the haptics of the IOL. In some embodiments, the shape of the internal structure is the same as the shape of the IOL's haptics. In some embodiments, the ophthalmic article includes an internal structure for securing around the notch area of the IOL's haptics. In some embodiments, the ophthalmic article comprises an outer diameter of at most 1.5 mm. In some embodiments, the ophthalmic article comprises an inner bore having a diameter of at most 0.7 mm. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, the ophthalmic article is configured such that the active agent or diagnostic agent is released from the biocompatible matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or released from a biocompatible matrix over a period of 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0014] In another aspect, the present disclosure provides an ophthalmic article. In one embodiment, the ophthalmic article comprises (a) a biocompatible material and (b) an active or diagnostic agent, a copolymer derived from about 40% by weight caprolactone monomers and about 60% by weight lactide monomers having equivalent elasticity, compressibility, tensile strength, shape recovery, or remoldability as another article comprising a biocompatible matrix comprising be. In some embodiments, a biocompatible material comprises a copolymer matrix. In some embodiments, the biocompatible material comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, another article comprising a biocompatible material or matrix comprises random, block, or gradient copolymers. In some embodiments, another article comprising a biocompatible material or matrix comprises a random copolymer. In some embodiments, another article comprising a biocompatible material or matrix is biodegradable. In some embodiments, another article comprises another active agent or diagnostic agent. In some embodiments, another article comprising a biocompatible matrix has a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, another article comprising a biocompatible matrix has a tensile strength of about 25 MPa to 35 MPa. In some embodiments, another article comprising a biocompatible matrix has a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, another article comprising a biocompatible matrix has a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, another article comprising a biocompatible matrix has an elastic modulus of at most about 3 MPa. In some embodiments, another article comprising a biocompatible matrix has a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, another article comprising a biocompatible matrix has an elongation at break of at least about 100% measured at about 18°C to 24°C. In some embodiments, another article comprising a biocompatible matrix has an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of the ophthalmic article is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the ophthalmic article includes an internal structure for bonding around the IOL's haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the IOL's haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the IOL's haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the IOL's haptics. In some embodiments, the ophthalmic article extends no more than about 0.32 mm beyond the haptics of the IOL when the ophthalmic article couples to the haptics of the IOL. In some embodiments, the shape of the internal structure is the same as the shape of the IOL's haptics. In some embodiments, the ophthalmic article includes an internal structure for securing around the notch area of the IOL's haptics. In some embodiments, the ophthalmic article comprises an outer diameter of at most 1.5 mm. In some embodiments, the ophthalmic article comprises an inner hole with a diameter of at most 0.7 mm. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, the ophthalmic article is configured such that the active agent or diagnostic agent is released from the biocompatible material. In some embodiments, the active agent or diagnostic agent is released from the biocompatible material over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or released from the biocompatible material over a period of 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible material by degradation of the biocompatible material. In some embodiments, the ophthalmic article or another article comprising a biocompatible matrix is sufficiently compressible to be compatible with injection by an IOL injector having an injector tip inner diameter of about 0.5 mm to 3 mm. . In some embodiments, the ophthalmic article or another article comprising a biocompatible matrix is sufficiently flexible to be compatible with injection by an IOL injector having an injector tip inner diameter of about 0.5 mm to 3 mm. be. In some embodiments, the ophthalmic article or another article comprising a biocompatible matrix is sufficiently large to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. Elastic. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0015] In one aspect, the present disclosure provides an ophthalmic system. In one embodiment, the ophthalmic delivery system comprises (a) a biocompatible matrix comprising (1) a copolymer derived from a caprolactone monomer and at least one other monomer, and (2) one or more active agents or (b) one or more intraocular lenses (IOLs) containing one or more haptics, the one or more ophthalmic articles comprising: It binds to one or more haptics of the IOL. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected with In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected to one of the In some embodiments, the copolymer is derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the copolymer is derived from about 40 weight percent caprolactone monomer and about 60 weight percent at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, the one or more ophthalmic articles include an internal structure for coupling around one or more haptics of the IOL. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the IOL's haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of one or more haptics of the IOL. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles are about Extends to 0.32 mm or less. In some embodiments, the shape of the internal structure is the same as the shape of one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the one or more ophthalmic articles comprise an inner diameter of at most 0.7 mm. In some embodiments, one or more ophthalmic articles are configured such that the active agent or diagnostic agent is released from the biocompatible matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or released from a biocompatible matrix over a period of 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0016] In another aspect, the disclosure provides a method of treating or preventing a disease. In one embodiment, the method comprises implanting an intraocular lens (IOL) for sustained intraocular drug delivery in the eye of a subject in need of treatment or prevention of disease, the IOL bound thereto comprising one or more drug release articles, wherein the one or more drug release articles comprise one or more active agents, and within seven days after implantation, the one or more drug release articles contain one or more or multiple active agents, resulting in an inflammation score of at most 1 as measured by an anterior chamber cell score using slit-lamp biomicroscopy, or by a 10-point visual analogue scale. Eliminate eye pain. In some embodiments, within 7 days after implantation, the one or more drug-releasing articles release one or more active agents such that anterior chamber biomicroscopy can be performed using slit-lamp biomicroscopy. An inflammation score of at most 1 as measured by the cell score. In some embodiments, within 7 days after implantation, one or more drug-releasing articles release one or more active agents resulting in ocular pain as measured by a 10-point visual analogue scale. disappears. In some embodiments, one or more drug-releasing articles are associated with one or more haptics of the IOL. In some embodiments, about one of the one or more drug releasing articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more drug releasing articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more drug release articles are one or more haptics of the IOL is connected with In some embodiments, about one of the one or more drug releasing articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more drug releasing articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more drug release articles are one or more haptics of the IOL is connected to one of the In some embodiments, one or more drug release articles comprise a biocompatible matrix. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more drug release articles are configured such that the active agent is released from a biocompatible matrix. In some embodiments, the active agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or 7-30 days. It is released from the biocompatible matrix over 10 days. In some embodiments, the active agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more drug release articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more drug release articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more drug release articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more drug release articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more drug release articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, one or more drug release articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, one or more drug release articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more drug release articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more drug release articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, the one or more drug release articles comprise an internal structure for binding around one or more haptics of the IOL. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the IOL's haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more drug releasing articles are about 0.32 mm or less beyond the one or more haptics when the one or more drug releasing articles bind to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more drug release articles comprise an internal structure for securing around the notch region of the one or more haptics. In some embodiments, one or more drug release articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more drug release articles are compressively coupled to the outwardly facing surface of one or more haptics. In some embodiments, one or more drug-releasing articles are associated with one or more haptics of the IOL. In some embodiments, the method comprises passing an IOL having one or more drug-releasing articles associated therewith through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm prior to implantation into the eye of a subject. Including the step of compressing. In some embodiments, compressing comprises tubularly collapsing the IOL with one or more drug releasing articles associated therewith through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0017] In another aspect, the disclosure provides a method of treating or preventing a disease. In one embodiment, the method comprises: (a) coupling one or more ophthalmic articles to one or more haptics of at least one intraocular lens (IOL), thereby releasing at least one active agent intraocularly; (b) implanting in the eye of a subject in need of treatment or prevention of a disease at least one active agent-releasing intraocular lens for sustained intraocular active agent delivery; Within 7 days after implantation, the one or more ophthalmic articles release one or more active agents resulting in inflammation as measured by an anterior chamber cell score using slit-lamp biomicroscopy. A score of at most 1 or no eye pain as measured by a 10-point visual analogue scale. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents such that the anterior chamber is examined using slit-lamp biomicroscopy. An inflammation score of at most 1 as measured by the cell score. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents resulting in ocular pain as measured by a 10-point visual analogue scale. disappears. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are associated with one or more haptics is doing. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are 1 of the one or more haptics It is connected with one. In some embodiments, one or more ophthalmic articles comprise a biocompatible matrix. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles are configured such that the active agent is released from a biocompatible matrix. In some embodiments, the active agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or 7-30 days. It is released from the biocompatible matrix over 10 days. In some embodiments, the active agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, bonding comprises indirect bonding between one or more ophthalmic articles and one or more haptics. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch region of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics. In some embodiments, the method comprises compressing at least one active agent-releasing intraocular lens through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm prior to implantation in the subject's eye. . In some embodiments, compressing comprises collapsing at least one active agent-releasing intraocular lens into a tube through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, bonding includes direct bonding between one or more ophthalmic articles and one or more haptics by chemical bonding, physical bonding, compressive force, or contractile force. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment so as not to significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0018] In another aspect, the disclosure provides a method of treating or preventing a disease. In one embodiment, the method comprises the steps of: (a) combining one or more active agents with a biocompatible matrix, thereby producing one or more ophthalmic articles; and (b) one or more binding an ophthalmic article to one or more haptics of at least one intraocular lens, thereby producing at least one active agent-releasing intraocular lens; and (c) treating or preventing a disease requiring treatment or prevention. implanting in the eye of a subject at least one active agent-releasing intraocular lens for sustained intraocular active agent delivery, wherein within seven days after implantation, the one or more ophthalmic articles comprise one or multiple active agents, resulting in an inflammation score of at most 1 as measured by an anterior chamber cell score using slit-lamp biomicroscopy, or by a 10-point visual analogue scale. Eliminate eye pain. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents such that the anterior chamber is examined using slit-lamp biomicroscopy. An inflammation score of at most 1 as measured by the cell score. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents resulting in ocular pain as measured by a 10-point visual analogue scale. disappears. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are associated with one or more haptics is doing. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are 1 of the one or more haptics It is connected with one. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the one or more active agents are intraocular pressure (IOP) lowering agents, corticosteroids, nonsteroidal anti-inflammatory agents, antibiotics, antiviral agents, antimetabolites, antifungal agents, It is an anti-fibrotic agent, or anti-angiogenic agent. In some embodiments, the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, bonding comprises indirect bonding between one or more ophthalmic articles and one or more haptics. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch region of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are configured such that the active agent is released from the biocompatible copolymer matrix. In some embodiments, the active agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or 7-30 days. It is released from the biocompatible matrix over 10 days. In some embodiments, the active agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm, and one or more The ophthalmic article is compressively bonded to the outward facing surface of the one or more haptics. In some embodiments, the method includes, prior to implanting the at least one active agent-releasing intraocular lens in the subject's eye, the at least one active agent-releasing intraocular lens is injected into an injector tip inner diameter of about 0.5 mm to 3 mm. Compressing through an IOL injector comprising: In some embodiments, compressing comprises collapsing at least one active agent-releasing intraocular lens into a tube through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, bonding includes direct bonding between one or more ophthalmic articles and one or more haptics by chemical bonding, physical bonding, compressive force, or contractile force. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0019] In another aspect, the present disclosure provides a method of preparing at least one ophthalmic article. ( b) removing the solvent from the combined mixture, thereby producing an evaporated mixture; and (c) compressing the evaporated mixture using a weighting tool, thereby producing a compacted mixture. and (d) extracting at least one ophthalmic article from the compressed mixture using a molding tool and an orifice tool. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, at least one ophthalmic article has a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, at least one ophthalmic article has a tensile strength of about 25 MPa to 35 MPa. In some embodiments, at least one ophthalmic article has a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, at least one ophthalmic article has a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, at least one ophthalmic article has a modulus of elasticity of at most about 3 MPa. In some embodiments, at least one ophthalmic article has a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, at least one ophthalmic article has an elongation to break of at least about 100% as measured by a tensile test. In some embodiments, at least one ophthalmic article has an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the at least one ophthalmic article shape is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the one or more active agents are intraocular pressure (IOP) lowering agents, corticosteroids, nonsteroidal anti-inflammatory agents, antibiotics, antiviral agents, antimetabolites, antifungal agents, It is an anti-fibrotic agent, or anti-angiogenic agent. In some embodiments, the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, at least one ophthalmic article includes an internal structure for bonding around one or more haptics of an intraocular lens. In some embodiments, at least one ophthalmic article comprises an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, at least one ophthalmic article is configured such that one or more active agents or diagnostic agents are released from a biocompatible matrix. In some embodiments, one or more active agents or diagnostic agents are released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the method comprises suspending one or more active agents or diagnostic agents in a solvent, thereby forming a suspension, prior to combining in (a). In some embodiments, the weighting tool is a steel plate. In some embodiments, the weighting tool is a heated steel plate. In some embodiments, the weighting tool is a heated steel plate lined with Teflon. In some embodiments, the weighting tool compresses the vaporized mixture into a sheet. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0020] In another aspect, the present disclosure provides a method of preparing at least one agent-releasing intraocular lens. In one embodiment, the method comprises: (a) combining one or more active agents or diagnostic agents with a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer, thereby or producing a plurality of ophthalmic articles; and (b) coupling the one or more ophthalmic articles to one or more haptics of at least one intraocular lens (IOL). In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected with In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected to one of the In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, bonding comprises indirect bonding between one or more ophthalmic articles and one or more haptics. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch region of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are configured such that one or more active agents or diagnostic agents are released from a biocompatible matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or released from a biocompatible matrix over a period of 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible copolymer matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics. In some embodiments, the method includes passing an IOL having one or more ophthalmic articles attached thereto through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm prior to implantation into the subject's eye. Including the step of compressing. In some embodiments, compressing comprises tubularly collapsing the IOL with one or more ophthalmic articles coupled thereto through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, bonding includes direct bonding between one or more ophthalmic articles and one or more haptics by chemical bonding, physical bonding, compressive force, or contractile force. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0021] In another aspect, the present disclosure provides methods of administering an active agent or diagnostic agent. In one embodiment, the method comprises: (a) bonding one or more ophthalmic articles to one or more haptics of at least one intraocular lens, thereby producing at least one agent-releasing intraocular lens; (b) compressing at least one active agent-releasing intraocular lens through an intraocular lens injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm; and (c) administering an active agent or diagnostic agent. implanting in the eye of a subject in need thereof at least one agent-releasing intraocular lens for sustained intraocular active or diagnostic agent delivery. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected with In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected to one of the In some embodiments, one or more ophthalmic articles comprise a biocompatible matrix. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles are configured such that the active agent or diagnostic agent is released from the biocompatible matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days, or released from a biocompatible matrix over a period of 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, coupling comprises indirect coupling between one or more ophthalmic articles and one or more haptics. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch region of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the one or more ophthalmic articles comprise an inner diameter of at most 0.7 mm. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics. In some embodiments, compressing comprises tubularly collapsing at least one active agent-releasing intraocular lens through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, bonding includes direct bonding between one or more ophthalmic articles and one or more haptics by chemical bonding, physical bonding, compressive force, or contractile force. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0022] In another aspect, the present disclosure provides methods of administering an active agent or diagnostic agent. In one embodiment, the method comprises: (a) compressing an intraocular lens (IOL) having one or more ophthalmic articles attached thereto through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm; producing a compressed IOL having one or more ophthalmic articles bound by and (b) administering a compressed IOL having one or more ophthalmic articles attached to the eye of a subject in need of administration of the active agent or diagnostic agent for sustained intraocular active agent or diagnostic agent delivery. and embedding for. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected with In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are one or more haptics of the IOL is connected to one of the In some embodiments, one or more ophthalmic articles comprise a biocompatible matrix. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide, or trimethylene carbonate. In some embodiments, the copolymer is a random, block, or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles are configured such that one or more active agents or diagnostic agents are released from a biocompatible matrix. In some embodiments, one or more active agents or diagnostic agents are released from the biocompatible matrix over a period of at least about 7 days. In some embodiments, one or more active agents or diagnostic agents are administered for about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, It is released from the biocompatible matrix over 7-14 days, or 7-10 days. In some embodiments, one or more active agents or diagnostic agents are released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic to recover its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of one or more ophthalmic articles is a torus, an extruded torus, a torus, or a prism with a hole in the center. In some embodiments, the prism is a circular prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory agent, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent, Or an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, one or more ophthalmic articles are indirectly coupled to one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles include an internal structure for coupling around one or more haptics of an intraocular lens. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of one or more haptics of the IOL. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of one or more haptics of the IOL. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles are about Extends to 0.32 mm or less. In some embodiments, the shape of the internal structure is the same as the shape of one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are coupled to one or more haptics of the IOL. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics of the IOL. In some embodiments, the one or more ophthalmic articles have a chemical bond, a physical bond, a compressive force, or a contractile force between the one or more ophthalmic articles and the one or more haptics. are directly connected by In some embodiments, compressing comprises tubularly collapsing the IOL with one or more ophthalmic articles coupled thereto through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0023] In another aspect, the present disclosure provides kits. In one embodiment, the kit comprises (1) a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer, and (2) one or more active or diagnostic agents. It includes a container containing one or more ophthalmic articles and instructions for use. In some embodiments, the kit further comprises another container comprising one or more intraocular lenses, each of the one or more intraocular lenses comprising one or more haptics. In some embodiments, the container further comprises one or more intraocular lenses comprising one or more haptics coupled with one or more ophthalmic articles. In some embodiments, one or more ophthalmic articles are associated with one or more haptics of one or more IOLs. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are associated with one or more haptics. ing. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are one of the one or more haptics. Combined. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide or trimethylene carbonate. In some embodiments, the copolymer is a random, block or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of the one or more ophthalmic articles is a torus, an extruded torus, a torus, a prism with a hole in the center. In some embodiments, the prism is a cylindrical prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the one or more active agents are intraocular pressure (IOP) lowering agents, corticosteroids, nonsteroidal anti-inflammatory agents, antibiotics, antiviral agents, antimetabolites, antifungal agents, It is an antifibrotic or antiangiogenic agent. In some embodiments, the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are configured such that the active agent or diagnostic agent is released from the biocompatible matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days or It is released from the biocompatible matrix over 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic so that it recovers its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted in the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0024] In another aspect, the disclosure provides a method of diagnosing a disease or condition of the eye. In one embodiment, the method comprises administering to the eye of a subject in need thereof an intraocular lens (IOL) for delivering one or more diagnostic agents to the eye of the subject, wherein the IOL is , one or more ophthalmic articles attached thereto, wherein the one or more ophthalmic articles consist of paramagnetic molecules, fluorescent compounds, magnetic molecules, radionuclides, x-ray imaging agents and contrast agents. comprising one or more diagnostic agents selected from In some embodiments, the method further comprises capturing an image in which the one or more diagnostic agents are indicative of the disease or condition. In some embodiments, the method comprises binding one or more ophthalmic articles to one or more haptics of the IOL prior to administering the IOL to which the one or more ophthalmic articles are bound. including the step of allowing In some embodiments, the method combines one or more diagnostic agents with a biocompatible copolymer matrix prior to administering an IOL to which one or more ophthalmic articles are attached, thereby Producing one or more ophthalmic articles. In some embodiments, the method removes the IOL to which the one or more ophthalmic articles are attached prior to administering the IOL to which the one or more ophthalmic articles are attached by about 0.00. Compressing through an IOL injector containing an injector tip inner diameter of 5 mm to 3 mm. In some embodiments, one or more diagnostic agents are fluorescent compounds. In some embodiments, one or more ophthalmic articles comprise a biocompatible matrix. In some embodiments, one or more ophthalmic articles are coupled to one or more haptics of the IOL. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are associated with one or more haptics of the IOL. Combined. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are of one or more haptics of the IOL. connected to one. In some embodiments, one or more ophthalmic articles comprise a biocompatible matrix. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide or trimethylene carbonate. In some embodiments, the copolymer is a random, block or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles are configured such that the diagnostic agent is released from the biocompatible matrix. In some embodiments, the diagnostic agent is released from the biocompatible matrix by degradation of the biocompatible matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic so that it recovers its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of the one or more ophthalmic articles is a torus, an extruded torus, a torus, a prism with a hole in the center. In some embodiments, the prism is a cylindrical prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the one or more ophthalmic articles include an internal structure for coupling around one or more haptics of the IOL. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the internal structure comprises a diameter of at most 0.7mm. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics. In some embodiments, one or more ophthalmic articles are coupled to one or more haptics of the IOL. In some embodiments, compressing comprises tubularly collapsing the IOL with one or more ophthalmic articles coupled thereto through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0025] In another aspect, the present disclosure provides a method of administering an active agent or diagnostic agent. In one embodiment, the method comprises the steps of: (a) combining one or more active agents or diagnostic agents with a biocompatible matrix, thereby producing one or more ophthalmic articles; or bonding a plurality of ophthalmic articles to one or more haptics of at least one intraocular lens, thereby producing at least one agent-releasing intraocular lens; (c) at least one agent-releasing eye; compressing the intraocular lens through an intraocular lens injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm; and (d) for sustained delivery of an intraocular active or diagnostic agent. Implanting at least one active agent-releasing intraocular lens in the subject's eye. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are associated with one or more haptics. ing. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are one of the one or more haptics. Combined. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. In some embodiments, the biocompatible matrix comprises a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer is lactide, glycolide or trimethylene carbonate. In some embodiments, the copolymer is a random, block or gradient copolymer. In some embodiments, the copolymer is a random copolymer. In some embodiments, the biocompatible matrix is biodegradable. In some embodiments, one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). In some embodiments, one or more ophthalmic articles have a tensile strength of about 25 MPa to 35 MPa. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry. In some embodiments, the one or more ophthalmic articles have a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. In some embodiments, one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. In some embodiments, the one or more ophthalmic articles have a modulus of elasticity between about 0.5 MPa and 3 MPa. In some embodiments, the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by tensile testing. In some embodiments, the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. In some embodiments, the shape of the one or more ophthalmic articles is a torus, an extruded torus, a torus, a prism with a hole in the center. In some embodiments, the prism is a cylindrical prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory drug, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent or It is an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil or methotrexate. In some embodiments, bonding comprises indirect bonding between one or more ophthalmic articles and one or more haptics. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm. In some embodiments, the one or more ophthalmic articles comprise an inner diameter of at most 0.7 mm. In some embodiments, one or more ophthalmic articles are configured such that the active agent or diagnostic agent is released from the biocompatible copolymer matrix. In some embodiments, one or more active agents or diagnostic agents are released from the biocompatible matrix over a period of at least about 7 days. In some embodiments, one or more active agents or diagnostic agents are administered for about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, It is released from the biocompatible matrix over 7-14 or 7-10 days. In some embodiments, one or more active agents or diagnostic agents are released from the biocompatible matrix by degradation of the biocompatible copolymer matrix. In some embodiments, the biocompatible matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic so that it recovers its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, one or more ophthalmic articles are compressively coupled to the outward facing surface of one or more haptics. In some embodiments, compressing comprises tubularly collapsing at least one active agent-releasing intraocular lens through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. In some embodiments, bonding includes direct bonding between one or more ophthalmic articles and one or more haptics by chemical bonding, physical adhesion, compression or contraction forces. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted within the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0026] In another aspect, the present disclosure provides ophthalmic drug delivery systems. In one embodiment, the ophthalmic drug delivery system is derived from (a) (1) one or more active or diagnostic agents and (2) about 40% by weight caprolactone monomers and 60% by weight lactide monomers A biocompatible copolymer matrix characterized by the following: (i) the biocompatible copolymer matrix comprises a random copolymer; (ii) the one or more ophthalmic articles has a tensile strength of about 25 megapascals (MPa) to 35 MPa; (iii) the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry; (iv) one or more ophthalmic articles. (v) the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at about 18°C to 24°C. (b) one or more intraocular lenses (IOLs) comprising one or more haptics, one or The plurality of ophthalmic articles includes an outer diameter of at most 1.5 mm, and one or more haptics for securing the one or more ophthalmic articles to one or more haptics of one or more IOLs. Configured to couple to the outward facing surface of one or more haptics of the IOL. In some embodiments, about one of the one or more ophthalmic articles is associated with one or more haptics. In some embodiments, about two of the one or more ophthalmic articles are associated with one or more haptics. In some embodiments, about 3, 4, 5, 6, 7, 8, 9 or 10 of the one or more ophthalmic articles are associated with one or more haptics. ing. In some embodiments, about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. In some embodiments, about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. In some embodiments, about 3, 4, 5, 6, 7, 8, 9, or 10 of the one or more ophthalmic articles are of one or more haptics of the IOL. connected to one. In some embodiments, the biocompatible copolymer matrix is biodegradable. In some embodiments, the shape of the one or more ophthalmic articles is a torus, an extruded torus, a torus, a prism with a hole in the center. In some embodiments, the prism is a cylindrical prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory drug, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent or It is an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil or methotrexate. In some embodiments, one or more ophthalmic articles include an internal structure for coupling around one or more haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the one or more haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the one or more haptics. In some embodiments, the one or more ophthalmic articles are about 0.32 mm or less beyond the one or more haptics when the one or more ophthalmic articles are coupled to the one or more haptics. stretched to In some embodiments, the shape of the internal structure of the one or more ophthalmic articles is the same as the shape of the one or more haptics. In some embodiments, the one or more ophthalmic articles include an internal structure for securing around the notch area of the one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an inner diameter of at most 0.7 mm. In some embodiments, one or more ophthalmic articles are configured such that the active agent or diagnostic agent is released from the biocompatible copolymer matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible copolymer matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days or It is released from the biocompatible copolymer matrix over 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible copolymer matrix by degradation of the biocompatible copolymer matrix. In some embodiments, the biocompatible copolymer matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible copolymer matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible copolymer matrix is sufficiently elastic so that it recovers its original shape after injection with an IOL injector containing an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible copolymer matrix is sufficiently elastic such that the ophthalmic article regains its shape when implanted in the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0027] In another aspect, the present disclosure provides an ophthalmic article. In one embodiment, the ophthalmic article is a biocompatible copolymer matrix derived from (a) about 40% by weight caprolactone monomer and 60% by weight lactide monomer, characterized by the following: (i) the biocompatible copolymer (ii) the ophthalmic article has a tensile strength of from about 25 megapascals (MPa) to 35 MPa; (iii) the ophthalmic article has a tensile strength of at most about (iv) the ophthalmic article has a modulus of elasticity of about 0.5 MPa to 3 MPa; (v) the ophthalmic article has a modulus of about 500% to 1500% and (b) an active or diagnostic agent, the ophthalmic article comprising an outer diameter of at most 1.5 mm, the ophthalmic article comprising It is configured to bond to the outwardly facing surface of the haptics of an intraocular lens (IOL) for fixation to the haptics of the IOL. In some embodiments, the biocompatible copolymer matrix is biodegradable. In some embodiments, the shape of the ophthalmic article is a torus, an extruded torus, a torus, a prism with a hole in the center, and may be circular, rectangular, or other shape. In some embodiments, the prism is a cylindrical prism, a rectangular prism, a prism with three or more sides, or a prism with another shape. In some embodiments, the ophthalmic article includes an internal structure for bonding around the outward facing surface of the IOL's haptics. In some embodiments, the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the IOL's haptics. In some embodiments, the perimeter of the internal structure is less than or equal to the perimeter of the IOL's haptics. In some embodiments, the maximum width of the internal structure is less than or equal to the maximum width of the IOL's haptics. In some embodiments, the ophthalmic article extends no more than about 0.32 mm beyond the haptics of the IOL when the ophthalmic article couples to the haptics of the IOL. In some embodiments, the shape of the internal structure is the same as the shape of the IOL's haptics. In some embodiments, the ophthalmic article includes an internal structure for securing around the notch area of the IOL's haptics. In some embodiments, the ophthalmic article comprises an inner bore having a diameter of at most 0.7 mm. In some embodiments, the active agent is an intraocular pressure (IOP) lowering agent, a corticosteroid, a nonsteroidal anti-inflammatory drug, an antibiotic, an antiviral agent, an antimetabolite, an antifungal agent, an antifibrotic agent or It is an angiogenesis inhibitor. In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil or methotrexate. In some embodiments, the ophthalmic article is configured such that the active agent or diagnostic agent is released from the biocompatible copolymer matrix. In some embodiments, the active agent or diagnostic agent is released from the biocompatible copolymer matrix over at least about 7 days. In some embodiments, the active agent or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days or It is released from the biocompatible copolymer matrix over 7-10 days. In some embodiments, the active agent or diagnostic agent is released from the biocompatible copolymer matrix by degradation of the biocompatible copolymer matrix. In some embodiments, the biocompatible copolymer matrix is sufficiently compressible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible copolymer matrix is sufficiently flexible to be compatible with injection by IOL injectors containing injector tip inner diameters of about 0.5 mm to 3 mm. In some embodiments, the biocompatible copolymer matrix is sufficiently elastic so that it recovers its original shape after injection with an IOL injector containing an injector tip inner diameter of about 0.5 mm to 3 mm. In some embodiments, the biocompatible matrix is sufficiently elastic such that the ophthalmic article resumes its shape when implanted in the eye. In some embodiments, the ophthalmic article is sufficiently physically stable in a physiological environment such that it does not significantly change shape within at least 7 days after implantation of the ophthalmic article in the eye of a subject. In some embodiments, the ophthalmic article comprises about 1 μg to 800 μg of one or more active agents and/or diagnostic agents.

[0028] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only illustrative embodiments of the present disclosure are shown and described. As will be realized, this disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be considered illustrative in nature and not restrictive.

[0029] In particular, the present specification is intended to supersede and/or take precedence over any such conflicting matter.
[0030] The novel features of the invention are set forth with particularity in the appended claims. Reference is made to the following detailed description and to the accompanying drawings (herein also “Figure” and “FIG.”) that set forth illustrative embodiments that utilize the principles of the present invention. A better understanding of the properties and advantages of the present invention will be obtained.

[0031] Figure IA illustrates a perspective view of an ophthalmic article, according to many embodiments. [0032] Figure IB illustrates another perspective view of an ophthalmic article, according to many embodiments. [0033] Figure 2A illustrates a plan view of an annular-shaped ophthalmic article, according to many embodiments. [0034] Figure 2B illustrates a cross-sectional view of an annular-shaped ophthalmic article, according to many embodiments. [0035] Figure 2C illustrates a plan view of a toroid-shaped ophthalmic article, according to many embodiments. [0036] Figure 2D illustrates a cross-sectional view of a toroid-shaped ophthalmic article, according to many embodiments. [0037] Figure 2E illustrates a plan view of a square-shaped ophthalmic article, according to many embodiments. [0038] Figure 2F illustrates a cross-sectional view of a square-shaped ophthalmic article, according to many embodiments. [0039] Figure 2G illustrates a plan view of an octagonal shaped ophthalmic article, according to many embodiments. [0040] Figure 2H illustrates a cross-sectional view of an octagonal shaped ophthalmic article, according to many embodiments. [0041] Figure 3A illustrates a plan view of an intraocular lens with an ophthalmic article, according to many embodiments. [0042] Figure 3B illustrates a side view of an intraocular lens (IOL) with an ophthalmic article, according to many embodiments. [0043] Figure 4A illustrates a plan view of an IOL having an ophthalmic article, according to many embodiments. [0044] Figure 4B illustrates a side view of an IOL with an ophthalmic article, according to many embodiments. [0045] Figure 5A schematically illustrates an example loading method, according to many embodiments. [0046] Figure 5B schematically illustrates an example of an embedding method, according to many embodiments. [0047] Figure 5C schematically illustrates another example of an intraocular lens having an ophthalmic article attached thereto. [0048] Figure 6 schematically illustrates examples of methods of administration, treatment, and/or diagnosis, according to many embodiments. [0049] Figure 7A illustrates an example of an ophthalmic article. [0050] Figure 7B illustrates an example of an ophthalmic article in an ophthalmic device. [0051] Figure 7C illustrates a side view of an exemplary ophthalmic article. [0052] Figure 7D illustrates a plan view of an exemplary ophthalmic article. [0053] FIG. 8A illustrates an example of an ophthalmic article located on the haptics of an IOL. [0054] Figure 8B schematically illustrates an ophthalmic article. [0055] Figure 9A illustrates a pre-stretched state of the ophthalmic article. [0056] Figure 9B illustrates the stretched state of the ophthalmic article. [0057] Figure 9C illustrates the recovery state of the ophthalmic article. [0058] Figure 10 illustrates elongation in a destructive test performed on an ophthalmic article. [0059] Figure 11 illustrates the stretched state of the ophthalmic article. [0060] FIG. 12 shows an illustrative embodiment of an ophthalmic article. [0061] FIG. 13 illustrates another illustrative embodiment of an ophthalmic article. [0062] FIG. 14A shows an exemplary appearance of an ophthalmic article and an IOL prior to in vitro IOL injection. [0063] FIG. 14B shows an exemplary appearance of an ophthalmic article and IOL after in vitro IOL injection. [0064] FIG. 15A shows an exemplary appearance of an ophthalmic article and an IOL prior to in vitro IOL injection. [0065] FIG. 15B shows an exemplary appearance of an ophthalmic article and IOL after in vitro IOL injection. [0066] FIG. 16A shows an exemplary appearance of an ophthalmic article and an IOL prior to in vitro IOL injection. [0067] FIG. 16B shows an exemplary appearance of an ophthalmic article and IOL after in vitro IOL injection. [0068] FIG. 17A shows an exemplary appearance of an ophthalmic article and an IOL prior to in vitro IOL injection. [0069] Figure 17B shows the appearance of the ophthalmic article and IOL after in vitro IOL injection. [0070] Figures 18A, 18C and 18E show the appearance of the coated IOL prior to in vitro IOL implantation. [0071] Figures 18B, 18D and 18F show the appearance of the coated IOL after in vitro IOL implantation. [0072] Figures 19A, 19C and 19E show the appearance of the coated IOL prior to in vitro IOL implantation. [0073] Figures 19B, 19D and 19F show the appearance of the coated IOL after in vitro IOL implantation. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0074] Figures 20A-20F show examples of qualitative testing of copolymers. [0075] Figures 21A-21E show examples of qualitative testing of another copolymer. [0075] Figures 21A-21E show examples of qualitative testing of another copolymer. [0075] Figures 21A-21E show examples of qualitative testing of another copolymer. [0075] Figures 21A-21E show examples of qualitative testing of another copolymer. [0075] Figures 21A-21E show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0076] Figures 22A-22F show examples of qualitative testing of another copolymer. [0077] Figures 23A-D show annulus-shaped rings made of copolymers. [0077] Figures 23A-D show annulus-shaped rings made of copolymers. [0077] Figures 23A-D show annulus-shaped rings made of copolymers. [0077] Figures 23A-D show annulus-shaped rings made of copolymers. [0078] Figure 24A shows an annulus-shaped ring comprising a copolymer. [0079] Figure 24B shows the ophthalmic article after the stretched state. [0080] FIG. 24C shows the appearance of the polymer ring and IOL prior to in vitro IOL implantation. [0081] Figure 24D shows the state of the ophthalmic article after injection. [0082] Figure 25A shows the cumulative amount of dexamethasone released from the ophthalmic article. [0083] Figure 25B shows the cumulative amount of ketorolac released from the ophthalmic article. [0084] Figure 26 shows the cumulative amount of moxifloxacin released from the ophthalmic article. [0085] Figure 27 illustrates an example of antibiotic activity of a drug (eg, moxifloxacin) released from an ophthalmic article. [0086] Figure 28A illustrates the diameter of the zone of inhibition on days 0, 1, 2, 7, and 9. [0087] Figure 28B illustrates the diameter of the zone of inhibition on days 0, 1, 2, 7, and 9. [0088] FIG. 29 shows an example of the position of an IOL in a subject's eye undergoing cataract surgery. [0089] Figures 30A-30C schematically illustrate a typical surgical implantation. [0089] Figures 30A-30C schematically illustrate a typical surgical implantation. [0089] Figures 30A-30C schematically illustrate a typical surgical implantation. [0090] FIGS. 31A-31H illustrate examples of digital planar photographs of rabbit eyes on days 1 and 7. FIG. [0091] FIG. 32 shows the mean eye examination scores at Day 0 (baseline), Day 1, Day 2, Day 4, and Day 7. [0092] Figure 33 shows the mean intraocular pressure measured at 0 (baseline), 1, 2, 4 and 7 days. [0093] Figure 34 shows ocular examination scores for groups that received implants containing vehicle or ketorolac. [0094] Figure 35 shows ocular examination scores for groups that received implants with vehicle or dexamethasone. [0095] Figures 36A-F illustrate digital planar photographs accompanying an eye examination of rabbit eyes in one group. [0096] Figures 36G-L illustrate digital planar photographs accompanying an ocular examination of rabbit eyes in another group. [0097] Figure 37A shows the mean intraocular pressure measured on days 0, 1, 3, 7, 14, 21, and 29 for the groups. [0098] Figure 37B shows the mean intraocular pressure measured on days 0, 1, 3, 7, 14, 21, and 29 for another group. [0099] Figures 38A-38D show representative images of histopathological sections of the eyes of the animals in the group. [0100] Figures 39A-39D show representative images of histopathological sections of the eyes of animals in another group. [0101] Figure 40 illustrates tissue concentrations of ketorolac in the aqueous humor. [0102] Figure 41 illustrates tissue concentrations of dexamethasone in the aqueous humor. [0103] Figure 42 illustrates area under the curve analysis for ketorolac concentration in aqueous humor. [0104] Figure 43 illustrates area under the curve analysis for dexamethasone concentrations in the aqueous humor. [0105] Figure 44 illustrates the mean gross eye examination scores for the treatment groups on days 0, 1, 3, 7, 14, 21, 30, 60 and 90. [0106] Figure 45 shows the PCO subscores at 0, 1, 3, 7, 14, 21, 30, 60 and 90 days after surgery. [0107] Figure 46 illustrates gross eye examination scores as assessed by the modified Hackett-McDonald scale. [0108] Figure 47 illustrates intraocular pressure measurements at 0, 30, 60, and 90 days after surgery. [0109] Figure 48 illustrates anterior chamber cell (ACC) scores. [0110] Figure 49 shows pain scores for subjects on days 0, 1, 7 and 28. [0111] Figures 50A-50D describe the process of loading an IOL injector cartridge with an IOL having an associated ophthalmic article. [0111] Figures 50A-50D illustrate the process of loading an IOL injector cartridge with an IOL having an associated ophthalmic article. [0111] Figures 50A-50D illustrate the process of loading an IOL injector cartridge with an IOL having an associated ophthalmic article. [0111] Figures 50A-50D illustrate the process of loading an IOL injector cartridge with an IOL having an associated ophthalmic article. [0112] Figures 51A-51D illustrate surgical implantation of an IOL having an ophthalmic article attached thereto in the eye of a human subject. [0113] Figure 52A illustrates a slit lamp photograph of a subject. [0113] Figure 52B illustrates a slit lamp photograph of a subject. [0114] Figure 53 illustrates differential scanning calorimetry of an ophthalmic article. [0115] Figure 54 illustrates storage modulus curves, loss modulus, and tan delta curves for ophthalmic articles.

[0116] While various embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided for illustrative purposes only. Numerous variations, modifications, and substitutions may occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be utilized.

[0117] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. Any reference to "or" herein is intended to include "and/or" unless stated otherwise.

[0118] As used herein, "substantially" or "substantially" means an action, characteristic, property, state, structure, item, or result of complete or nearly complete magnitude or degree. can point to For example, a substantially contained object means that the object is completely contained or nearly completely contained. The exact possible degree of deviation from absolute perfection may, in some cases, depend on the specific context. However, speaking generally of the closeness of perfection seems to have some global consequences, as if absolute perfection and total perfection were obtained. The use of "substantially" is equally applicable when used in a negative sense to refer to a complete or nearly complete absence of an action, characteristic, property, state, structure, item, or result .

[0119] As used herein, "effective amount" refers to a sufficient amount of an ingredient when included in a composition to achieve the intended compositional or physiological effect. Accordingly, a "therapeutically effective amount" refers to a substantially non-toxic but sufficient amount of an active agent to achieve a therapeutic result in treating or preventing the conditions for which the active agent is known to be effective. It is understood that various biological factors can affect the ability of a substance to perform its intended task. An "effective amount" or "therapeutically effective amount" can thus depend, in some instances, on such biological factors. In addition, although achievement of therapeutic effect may be measured by a physician or other qualified medical practitioner using assessments known in the art, individual variation and response to treatment may result in the achievement of therapeutic effect. It is recognized that it can be a subjective judgment. However, determination of an effective amount may be within the ordinary skill in the fields of pharmaceuticals and nutrition, and medicine.

[0120] As used herein, "reshaping" refers to the physical or chemical bending of the overall dimensions of an object (e.g., an ophthalmic article), e.g., the object into a desired configuration (shape). , may refer to the action of collapsing, rolling or otherwise collapsing. For that purpose, the terms "folding", "bending", "folding" and "rolling" are used to reshape the ophthalmic articles and/or ophthalmic devices of the present invention to With respect to at least one dimension, it can refer to allowing to fit a tip inner diameter of an intraocular syringe that is smaller than that of an ophthalmic article in its original shape (eg, before reshaping).

[0121] As used herein, "subject" refers to a mammal that can benefit from administration of the compositions or methods described herein. Examples of subjects include humans, and may also include other animals such as horses, pigs, cows, dogs, cats, rabbits or aquatic mammals.

[0122] Whenever the terms "at least," "greater than," or "greater than" precede the first number in a series of two or more numerical values, the terms "at least," "greater than," or "greater than" Applies to each number in the series. For example, 1, 2 or 3 or more equals 1 or more, 2 or more, or 3 or more.

[0123] Whenever the terms "at most," "not more than," "up to," "less than," or "not more than" precede the first number in a series of two or more numbers, "not more than," The terms "less than" or "less than or equal to" apply to each numerical value in the series. For example, 3, 2 or 1 or less equals 3 or less, 2 or less or 1 or less.

[0124] Cataract surgery has evolved significantly over the past 30 to 40 years. With the advent of new biomaterials (e.g., flexible acrylic polymers), the development of deformable elastic IOLs that can be folded, rolled, or otherwise deformed into a narrow profile for injection through small incisions. became possible. Advances in surgical instruments (eg, IOL syringe cartridges and syringes) have improved the efficiency of folding and rolling IOLs with greater consistency and reliability than traditional methods (eg, IOL forceps). Such innovations have made cataract surgery less invasive and shorter in duration, resulting in fewer complications, better refractive outcomes, and faster patient recovery.

[0125] When designing an ophthalmic article intended for implantation in the eye (e.g., a drug delivery device), the physical, chemical and/or biological properties of the ophthalmic article contribute to its safety profile. can influence. The ophthalmic article may be sufficiently soft and/or flexible so as not to distort, abrade, penetrate, occlude, or otherwise physically damage the internal structures of the eye. . Inert materials comprising drug delivery devices and certain degradation products thereof may be biocompatible and may not cause untoward effects in the eye. Active agents (e.g., active ingredients) and/or diagnostic agents comprising ophthalmic articles in amounts sufficient to achieve their intended function, but not exceeding levels known to cause toxicity in the eye. can exist.

[0126] Surgical techniques may be optimized to minimize the risk of possible complications and to achieve maximum benefit to the subject (eg, patient). Certain modifications to standard surgical techniques may alter the risk-benefit ratio for a subject (eg, patient). When designing an ophthalmic article (e.g. drug delivery device) to couple to an ocular device (e.g. intraocular lens), the ophthalmic device and the attached ophthalmic article can be assembled using standard surgical techniques (e.g. cataract surgery). ). Further, the utility and human factor aspects of an ophthalmic device and an ophthalmic article attached thereto can be comparable to those of the ophthalmic device alone.

[0127] The present disclosure provides articles, methods, systems and kits for delivering or administering active agents and/or diagnostic agents from an ophthalmic device to the eye. The present disclosure also provides articles, methods, systems and kits for diagnosing and/or treating diseases, conditions or complications. For example, the present disclosure provides articles, methods, devices, systems and kits for delivering active agents (eg, drugs) from an intraocular lens (IOL) to the eye. In some embodiments, the articles, systems and associated methods of the present disclosure are positioned within the anterior segment of the subject's eye (e.g., within the capsular capsule) to deliver active agents and/or diagnostic agents to the posterior segment of the subject's eye. can be delivered to Non-limiting examples of ocular regions found within the posterior segment of the eye can include at least one of vitreous humor, colloids, and retina. In addition to delivering the active agent and/or diagnostic agent to the posterior segment of the eye, the active agent and/or diagnostic agent may also be delivered to the anterior segment of the eye. The anterior segment may include at least one of the aqueous humor, the iris, and the lens capsule. Delivery can provide sustained release of the active agent and/or diagnostic agent over a period of time (eg, with sustained release kinetics). Ophthalmic articles for delivering or administering active agents and/or diagnostic agents to the eye may comprise polymeric materials (e.g., biocompatible polymeric matrices), non-polymeric materials and/or agents (e.g., active agents and/or diagnostic agents, a variety of different active agents and/or diagnostic agents, or combinations thereof). The ophthalmic articles (e.g., drug delivery devices) described herein combine with ophthalmic devices (e.g., intraocular devices) to reduce multiple injection methods or complex eye drop regimens, thereby reducing the risk of active agent and/or delivery of diagnostic agents. This allows automatic delivery of active agents to the eye and solves the problem of patient non-compliance.

[0128] In one aspect, the present disclosure provides an ophthalmic article. An ophthalmic article can include a biocompatible material (eg, a biocompatible matrix). Biocompatible materials can include polymeric materials that include one or more polymers. A polymer can be a copolymer derived from one or more monomers. In some embodiments, the polymer can be a copolymer derived from caprolactone monomer and at least one other monomer. In some embodiments, one or more ophthalmic articles can include at least one active agent and/or diagnostic agent.

[0129] In another aspect, the present disclosure provides an ophthalmic article. An ophthalmic article can include a biocompatible material (eg, a biocompatible matrix). Ophthalmic articles may also include active agents and/or diagnostic agents. The ophthalmic article may comprise elasticity, compressibility, tensile strength, shape recovery or remolding properties equivalent to another article comprising a biocompatible matrix comprising a copolymer derived from caprolactone and lactide monomers. In some embodiments, the ophthalmic article has elasticity, compressibility, tensile strength equivalent to an article comprising a biocompatible matrix comprising a copolymer derived from about 40% by weight caprolactone monomer and about 60% by weight lactide monomer. may include flexibility, shape recovery or remoldability. Ophthalmic articles can be configured to couple to ophthalmic device portions (eg, intraocular lens haptics).

[0130] In another aspect, the present disclosure provides an ophthalmic system. An ophthalmic system may include one or more ophthalmic articles. One or more ophthalmic articles may comprise a biocompatible material (eg, a polymer matrix) comprising at least a polymer. A polymer can be a copolymer. Copolymers may be derived from one or more monomers. In some embodiments, one or more monomers can be lactide, glycolide, caprolactone, ethylene glycol, trimethylene carbonate, or combinations thereof. In some embodiments, the polymer can be a copolymer derived from caprolactone monomer and at least one other monomer. In some embodiments, one or more ophthalmic articles can include at least one active agent and/or diagnostic agent. An ophthalmic system may also include one or more ophthalmic devices (eg, intraocular lenses). One or more ophthalmic devices may be coupled to one or more ophthalmic articles.

[0131] In any of its various aspects, one or more ophthalmic articles described herein are composed, sized, shaped, and shaped to maximize proximity of the ophthalmic article to the eye of a subject. Designed with a combination of them. In some embodiments, one or more ophthalmic articles may include materials. The material can be a biocompatible material (eg, a biocompatible matrix). A biocompatible matrix can be a polymeric matrix. Materials can include polymeric materials (eg, polymeric matrices) and/or non-polymeric materials. Non-polymeric materials include glass (silica), soda lime glass, alkali aluminosilicate glass, borosilicate glass, alkali-free glass, crystal glass, quartz glass, metals and metal alloys (steel, aluminum, silver, gold, tantalum, titanium, copper, nickel, platinum palladium, zinc tin, antimony, bismuth, zinc, manganese, antimony, molybdenum, vanadium), crystalline materials (diamond, sapphire, graphene), carbon fiber, fiberglass, silicon carbide, alumina, graphite, oxide Aluminum, Chromium Aluminum Oxide, Brown Fused Aluminum Oxide (ALOX), Brown Fused Aluminum Oxide Low in Titanium Dioxide (ALOX), Zirconia-Alumina, Alumina Hydrate, Ceramic Aluminum Oxide (ALOX), Green Silicon Carbide, Black Silicon Carbide, It may include boron carbide, cubic boron nitride, and diamond.

[0132] Biocompatible materials can include substances that do not lead to adverse reactions when placed in a biological environment. Biocompatible materials can be of natural or synthetic origin.
[0133] In some embodiments, polymeric materials may include biocompatible and/or biodegradable polymers. For example, polymeric materials or compositions for use in ophthalmic articles may include materials that are ocularly compatible (eg, biocompatible) so as not to cause substantial interference with ocular function or physiology. Such polymeric materials can also be biodegradable and/or bioerodible. Biodegradable polymers can erode or degrade over time (e.g., in vivo) under physiological conditions, by at least partial contact with substances found in surrounding tissue fluids, or by cellular function. It may refer to a species or multiple polymers. Release of the active agent and/or diagnostic agent can occur concurrently with or subsequent to degradation of the biodegradable polymer over time.

[0134] In some embodiments, the polymeric material is a homopolymer (e.g., a polymer comprising one type of monomer repeat unit), a copolymer (e.g., a polymer comprising two or more types of monomer repeat unit), or Polymers containing more than two different polymer units may be included. In some embodiments, a polymeric material (eg, polymeric matrix) can comprise a homogeneous mixture of polymers. For example, a homogenous mixture of polymers may not include a mixture in which one part differs from another part (eg, due to raw materials or density). In some embodiments, a polymeric material (eg, polymeric matrix) can comprise a heterogeneous mixture of polymers. In some embodiments, the polymeric material may comprise a mixture of polymers of the same type (eg, two different polylactic acid polymers) or different types (eg, polylactic acid polymer combined with polycaprolactone polymer). In some embodiments, polymeric materials may include copolymers. In other embodiments, the copolymer is one or more block copolymers (illustratively represented by PPPP-HHHH; P and H are each exemplified monomer units), alternating copolymers (illustratively represented by PHPPHPPH; P and H are each exemplified monomer units), statistical or random copolymers (illustration is represented by PHPPHPPHH; P and H are each exemplified monomer units) ), star copolymers, brush copolymers, gradient copolymers or graft copolymers. In some embodiments, a copolymer can be a random copolymer.

[0135] In some embodiments, the polymeric material is poly(L-lactide-co-caprolactone) (eg, content of L-lactide and caprolactone in various ratios), poly(D-lactide-co-caprolactone) ), poly (D, L-lactide-co-caprolactone), poly- (D-lactic acid) (PDLA), poly- (L-lactic acid) (PLLA), poly (D, L-lactic acid) (PLA), poly Caprolactone (PCL), polyvinyl alcohol (PVA), poly(ethylene glycol) (PEG), poly(glycolic acid) (PGA), poly(L-lactide-co-glycolide), poly(D-lactide-co-glycolide) , poly(D,L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-trimethylene carbonate), poly(D-lactide-co-trimethylene carbonate), poly(D,L-lactide-co -trimethylene carbonate), poly(trimethylene carbonate-co-ε-caprolactone), poly(caprolactone-co-glycolide), polyorthoesters, polyanhydrides, polyesters, polyamides, polyesteramides, polycarbonates, polyethylene, polypropylene, polygalactic acid ( polygalactic acid), polyacrylamide, polystyrene, polyurethane, silicone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyglycolic acid-polyvinyl alcohol copolymer, polycaprolactone-polyethylene glycol copolymer, collagen, croscarmellose collagen, hyaluron Acid, elastin, polyhydroxybutyrate, polyalkane anhydride, gelatin, cellulose, oxidized cellulose, polyphosphazene, poly(sebacic acid), poly(ricenolic acid), poly(fumaric acid), chitin , chitosan, polyvinylpyrrolidone (PVP), synthetic cellulose esters, polyacrylic acid, polybutyric acid; triblock copolymers (eg PLGA-PEG-PLGA, PEG-PLGA-PEG), poly(N-isopropylacrylamide), poly(ethylene oxide) -poly(propylene oxide)-poly(ethylene oxide) tri-block copolymer (PEO-PPO-PEO), polyvaleric acid, poly(valerolactone), polyhydroxyalkylcellulose; siloxanes, polysiloxy Sun; dimethylsiloxane/-methylvinylsiloxane copolymer; poly(dimethylsiloxane/-methylvinylsiloxane/-methylhydrogensiloxane) dimethylvinyl or trimethyl copolymer, polypeptide, poly(amino acid), poly(dioxanone), poly(alkylene alkylate) ), hydrophobic polyethers, polyetheresters, polyacetals, polycyanoacrylates, polyacrylates, polymethylmethacrylates, polysiloxanes, poly(oxyethylene)/poly(oxypropylene) copolymers, polyketals, polyphosphates, polyhydroxyvalerates. , polyalkylene oxalates, polyalkylene succinates, poly(maleic acid), and copolymers thereof, or oxidized, reduced, monosubstituted, disubstituted, polysubstituted derivatives or any combination thereof. It may contain derivatives. In some embodiments, the polymeric material is, for example, Abraham J. et al. Domb et al., Biodegradable Polymers in Clinical Use and Clinical Development (2011), (ISBN: 978-1-118-01580-3), which may include one or more elements described herein. is incorporated by reference in its entirety. In some embodiments, the polymeric material is a polymer (e.g., polylactic acid, polycaprolactone, poly(lactide-co-caprolactone) and/or or poly(L-lactide-co-caprolactone)). In some embodiments, the polymeric material can include polylactic acid. In other embodiments, the polymeric material may include polycaprolactone. In other embodiments, the polymeric material may include poly(lactide-co-caprolactone). In other embodiments, the polymeric material may include poly(L-lactide-co-caprolactone).

[0136] In some embodiments, the polymeric material comprises a mixture of a copolymer and another homopolymer or another copolymer. In some embodiments, the polymer may comprise a mixture of poly(lactide-co-caprolactone) (PLCL) and another homopolymer or another copolymer. In some embodiments, the polymer may comprise a mixture of poly(L-lactide-co-caprolactone) and another homopolymer or another copolymer. In some embodiments, the polymer may comprise a mixture of poly(L-lactide-co-caprolactone) and PLA. In some embodiments, the polymer may comprise a mixture of poly(L-lactide-co-caprolactone) and PGA. In some embodiments, the polymer may comprise a mixture of poly(L-lactide-co-caprolactone) and PLGA. In some embodiments, the polymer may comprise a mixture of poly(L-lactide-co-caprolactone) and PGA and/or PLGA.

[0137] In some embodiments, examples of polymeric materials are derived from and/or contain organic esters and/or organic ethers that, when degraded, result in physiologically acceptable degradation products. Including materials that contain. In some embodiments, polymeric materials may include materials derived from and/or including anhydrides, amides, esters, orthoesters, etc., alone or in combination with other monomers. The polymeric material can be addition or condensation polymers. The polymeric material can be crosslinked or non-crosslinked.

[0138] In some embodiments, in addition to carbon and hydrogen, the polymer can include at least one of oxygen and/or nitrogen. The oxygen can be present as oxy (eg hydroxy or ether), carbonyl (eg non-oxocarbonyl, carboxylic acid, carboxylic acid ester, amide). The nitrogen can be present as part of an amido, cyano or amino (including substituted amino) moiety. In some embodiments, polymers of hydroxyaliphatic carboxylic acids, polymers of hydroxyalkanoates, homopolymers or copolymers, and polysaccharides can be used in ophthalmic articles. In some embodiments, polyesters can also be used in ophthalmic articles and include polymers of D-lactic acid, L-lactic acid, racemic lactic acid (D,L-lactic acid), caproic acid, hydroxybutyric acid, glycolic acid, caprolactone, valerolactone, It can contain ratios of these polymers and copolymers, or combinations thereof.

[0139] Some properties of polymers or polymeric materials for use in embodiments of the present disclosure include biocompatibility, compatibility with active agents and/or diagnostic agents, active agents described herein and /or ease of use of the polymer in making a diagnostic agent delivery system, desirable half-life in a physiological environment, and hydrophilicity.

[0140] In some embodiments, the polymer matrix used to manufacture the ophthalmic article can be a synthetic aliphatic polyester, such as a polymer of lactic acid and/or caproic acid, which is poly-(D, L-lactide) (PLA), poly-(D-lactide), poly-(L-lactide), polycaprolactone (PCL), poly(L-lactide-co-caprolactone), poly(D-lactide-co-caprolactone ), or mixtures or copolymers thereof.

[0141] These polymers can degrade via backbone hydrolysis (bulk erosion), with the final degradation products of PLCL being lactic acid (eg, L-lactic acid) and caproic acid, which are non-toxic and is considered a natural metabolite. Lactic acid (eg L-lactic acid) and caproic acid are safely removed by conversion to carbon dioxide and water via the Krebs cycle. The ophthalmic article and/or biocompatible material can degrade homogeneously at a constant rate throughout the polymer matrix (e.g., nonenzymatic hydrolysis of its ester bonds throughout the polymer matrix in the presence of water in the surrounding tissue). degradation), thereby allowing diffusion of the active agent and/or diagnostic agent from the matrix into the surrounding environment. This is in contrast to other polymeric drug release systems that degrade through "surface erosion" with only polymer degradation occurring at the outer exposed surface.

[0142] In bulk erosion, degradation of the matrix occurs simultaneously with solubilization of oligomers in the surrounding medium throughout the matrix, and drug release occurs by diffusion, a concentration-dependent phenomenon. Surface erosion, on the other hand, originates from the front surface of the device and continues to move to the core of the device. When these types of polymers are composed of highly hydrophobic monomers, the monomers do not allow aqueous media to penetrate the core, and the oligomers usually deposit on the device itself, preventing release of the encapsulated bioactive agent. hinder further. When a certain volume of device is exposed to the environment, emission occurs in a zero-order manner. These surface eroding polymers have highly labile hydrolytic bonds and may not be suitable for sustained release in nanoscopic carriers.

[0143] In some embodiments, poly(lactide-co-caprolactone) (PLCL) can be synthesized through random ring-opening copolymerization of D,L-lactide and ε-caprolactone. Consecutive monomeric units of D,L-lactide or ε-caprolactone may be linked together by ester bonds. The ratio of lactide to caprolactone can be varied to alter the biodegradation properties of the product. By changing the ratio, the polymer degradation time can be adjusted. Drug release characteristics can be affected by biodegradation rate, molecular weight or molecular mass and crystallinity in the drug delivery system. Modification and customization of the biodegradable polymer matrix can alter the drug delivery profile.

[0144] In some embodiments, poly(L-lactide-co-caprolactone) can be synthesized through random ring-opening copolymerization of L-lactide and ε-caprolactone. Consecutive monomeric units of L-lactide or ε-caprolactone are linked together by ester bonds. The ratio of L-lactide to ε-caprolactone can be varied to alter the biodegradation properties of the product. By changing the ratio, the polymer degradation time can be adjusted. Drug release characteristics can be affected by biodegradation rate, molecular weight or molecular mass and crystallinity in the drug delivery system. Modification and customization of the biodegradable polymer matrix can alter the drug delivery profile.

[0145] Alternatively, synthesis of PLCLs of different molecular weights or molecular masses with different D,L-lactide-caprolactone ratios can be performed. For example, it is possible to synthesize poly(L-lactide-co-caprolactone) of different molecular weights or molecular masses with different L-lactide-caprolactone ratios. The polymers used to form the ophthalmic articles of the present disclosure, when combined, possess the necessary properties to provide sustained release of effective (e.g., therapeutically effective) amounts of active agents and/or diagnostic agents. have independent properties associated with them that indicate Some of the major polymer properties that control the active agent and/or diagnostic agent release rate are the molecular weight distribution or molecular mass distribution, the polymer end groups (i.e., carboxylic acid or ester) and the ratio of monomers within the copolymer, and/or the polymer It can be the ratio of polymers and/or copolymers within the matrix. This disclosure presents examples of polymer matrices that possess desirable active agent and/or diagnostic agent release properties by manipulating one or more of the aforementioned properties to develop suitable ophthalmic articles.

[0146] Some polymeric materials may be prone to enzymatic or hydrolytic instability. Water soluble polymers can be crosslinked with hydrolytically or biodegradably labile crosslinks to produce useful water insoluble polymers. Therefore, the degree of stability depends on the choice of one or more monomers, whether homopolymers or copolymers using mixtures of polymers are used, and whether the polymers contain terminal acid groups. can vary accordingly.

[0147] Another factor for controlling the biodegradation of the polymer matrix, and thus the extended release profile of the ophthalmic article, is the relative average molecular weight or molecular mass of the polymer composition used in the ophthalmic article. Varying molecular weights or molecular masses of the same or different polymer compositions can modulate the release profile (eg, extended release, non-extended release, linear release) of at least one active agent and/or diagnostic agent. In some embodiments, polymeric materials can be selected from biodegradable polymers disclosed herein that do not substantially swell in the presence of aqueous humor. For example, PLGA polymers swell when used as the matrix material for drug delivery implants, whereas PLA-based polymer blends swell less in the presence of aqueous humor.

[0148] Examples of polymers used in various embodiments of the present disclosure are 50:50, 51:49, 52:48, 53:47, 54:46, 55:45, 54:46, 53:47 , 52:48, 51:49, 60:40, 61:39, 62:38, 63:37, 64:35, 65:35, 66:34, 67:33, 68:32, 69:31, 70 : 30, 71:29, 72:28, 73:27, 74:26, 75:25, 76:24, 77:23, 78:22, 79:21, 80:20, 81:19, 82:18 , 83:17, 84:16, 85:15, 90:10 or 95:5 from about 50:50 to about 85:15 of a first monomer (eg, L-lactide) and Variations in the molar ratio with the second monomer (eg, ε-caprolactone) can be included. In some embodiments, the molar ratio of the first monomer (eg, L-lactide) to the second monomer can be any ratio except 50:50 (eg, ε-caprolactone). In some embodiments, the molar ratio of the first monomer (eg L-lactide) to the second monomer (eg ε-caprolactone) can be 60:40.

[0149] Examples of polymers used in various embodiments of the present disclosure are about 5:95, about 10:90, about 15:85, about 20:80, about 25:75, about 30:70, about 35:65, about 40:60, about 45:55, about 50:50, about 51:49, about 52:48, about 53:47, about 54:46, about 55:45, about 54:46, about 53:47, about 52:48, about 51:49, about 60:40, about 61:39, about 62:38, about 63:37, about 64:35, about 65:35, about 66:34, about 67:33, about 68:32, about 69:31, about 70:30, about 71:29, about 72:28, about 73:27, about 74:26, about 75:25, about 76:24, about 77:23, about 78:22, about 79:21, about 80:20, about 81:19, about 82:18, about 83:17, about 84:16, about 85:15, about 90:10, or Variations in the weight ratio of the first monomer (eg L-lactide) to the second monomer (eg ε-caprolactone) from about 50:50 to about 85:15 including but not limited to about 90:15 can include In some embodiments, the ratio of the first monomer (eg, L-lactide) to the second monomer can be a ratio other than 50:50. In some embodiments, the molar ratio of the first monomer (eg L-lactide) to the second monomer (eg ε-caprolactone) can be 60:40.

[0150] In one example, the polymeric material may comprise poly(lactide-co-caprolactone) having a copolymer ratio of 10:90 to 90:10, and in another case 52:48 to 90:10. In still other examples, the copolymer ratio can be from about 60:40 to about 40:60, or from about 55:45 to about 45:55. In some embodiments, the copolymer ratio can be about 60:40. In some embodiments, the copolymer ratio can be about 50:50. In some embodiments, the copolymer ratio may be a ratio other than about 50:50. In some embodiments, the copolymer ratio may be 52-78:48-22, and in another particular example, 60-90:40-10.

[0151] In one example, the polymeric material may comprise poly(L-lactide-co-caprolactone) having a copolymer ratio of 10:90 to 90:10, and in another case 52:48 to 90:10. In still other examples, the copolymer ratio can be from about 60:40 to about 40:60, or from about 55:45 to about 45:55. In some embodiments, the copolymer ratio can be about 60:40. In some embodiments, the copolymer ratio can be about 50:50. In some embodiments, the copolymer ratio may be a ratio other than about 50:50. In some embodiments, the copolymer ratio may be 52-78:48-22, and in another particular example, 60-90:40-10. Degradation rates may depend on such ratios, but additional alternative approaches may also be useful for device coating, particle encapsulation, for example.

[0152] In one example, the polymeric material may comprise poly(L-lactide-co-caprolactone) having a copolymer ratio of 10:90 to 90:10, and in another case 52:48 to 90:10. In still other examples, the copolymer ratio can be from about 60:40 to about 40:60, or from about 55:45 to about 45:55. In some embodiments, the copolymer ratio can be about 60:40. In some embodiments, the copolymer ratio can be about 50:50. In some embodiments, the copolymer ratio may be a ratio other than about 50:50. In some embodiments, the copolymer ratio may be 52-78:48-22, and in another particular example, 60-90:40-10.

[0153] In some embodiments, the polymeric material (eg, a biocompatible copolymer matrix) comprises from about 20% to about 60% by weight caprolactone monomer and from about 40% to 80% by weight of at least one other It can be derived from monomers. In some embodiments, a polymeric material (eg, a biocompatible copolymer matrix) can be derived from about 40% by weight caprolactone monomer and about 60% by weight at least one other monomer. In some embodiments, the at least one other monomer can be lactide, glycolide, caprolactone, ethylene glycol, trimethylene carbonate, or combinations thereof. In some embodiments, at least one other monomer is lactide.

[0154] In some embodiments, the polymeric material (eg, biocompatible matrix) can be derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight lactide. In some embodiments, the polymeric material (eg, biocompatible matrix) can be derived from about 40% by weight caprolactone monomer and about 60% by weight lactide.

[0155] In some embodiments, a polymeric material (eg, a biocompatible matrix) can be derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight L-lactide. . In some embodiments, a polymeric material (eg, a biocompatible matrix) can be derived from about 40% by weight caprolactone monomer and about 60% by weight L-lactide.

[0156] In some embodiments, the ophthalmic article may contain at least about 50% by weight polymeric material, and/or at least about 50% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 55% by weight polymeric material and/or at least about 45% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 60% by weight polymeric material and/or at least about 40% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 65% by weight polymeric material and/or at least about 35% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 70% by weight polymeric material and/or at least about 30% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 75% by weight polymeric material and/or at least about 25% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 80% by weight polymeric material and/or at least about 20% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 85% by weight polymeric material and/or at least about 15% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 90% by weight polymeric material and/or at least about 10% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain at least about 95% by weight polymeric material and/or at least about 5% by weight active agent and/or diagnostic agent.

[0157] In some embodiments, the ophthalmic article may contain up to about 50% by weight polymeric material and/or up to about 50% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain up to about 55% by weight polymeric material and/or up to about 45% by weight active agent and/or diagnostic agent. In some embodiments, an ophthalmic article may contain up to about 60% by weight polymeric material and/or up to about 40% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain up to about 65% by weight polymeric material and/or up to about 35% by weight active agent and/or diagnostic agent. In some embodiments, an ophthalmic article may contain up to about 70% by weight polymeric material and/or up to about 30% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain up to about 75% by weight polymeric material and/or up to about 25% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain up to about 80% by weight polymeric material and/or up to about 20% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain up to about 85% by weight polymeric material and/or up to about 15% by weight active agent and/or diagnostic agent. In some embodiments, an ophthalmic article may contain up to about 90% by weight polymeric material and/or up to about 10% by weight active agent and/or diagnostic agent. In some embodiments, an ophthalmic article may contain up to about 95% by weight polymeric material and/or up to about 5% by weight active agent and/or diagnostic agent.

[0158] In some embodiments, the ophthalmic articles contain from about 50% to about 55% by weight polymeric material, and/or from about 45% to about 50% by weight of active agents and/or diagnostic agents. can. In some embodiments, the ophthalmic article may contain from about 55% to about 60% by weight polymeric material and/or from about 40% to about 45% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 60% to about 65% by weight polymeric material and/or from about 35% to about 40% by weight active agent and/or diagnostic agent. In some embodiments, an ophthalmic article may contain from about 65% to about 70% by weight polymeric material, and/or from about 30% to about 35% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 70% to about 75% by weight polymeric material, and/or from about 25% to about 30% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 75% to about 80% by weight polymeric material, and/or from about 20% to about 25% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 80% to about 85% by weight polymeric material, and/or from about 15% to about 20% by weight active agent and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 85% to about 90% by weight polymeric material and/or from about 10% to about 15% by weight active and/or diagnostic agent. In some embodiments, the ophthalmic article may contain from about 90% to about 95% by weight polymeric material and/or from about 5% to about 10% by weight active and/or diagnostic agent.

[0159] In some embodiments, the ophthalmic article comprises at least about 50% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 40% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at least about 55% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 35% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 60% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 30% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 65% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 25% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 70% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 20% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 75% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 15% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 80% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 10% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 85% by weight polymeric material, at least about 10% by weight active agent and/or diagnostic agent, and/or at least about 5% by weight pharmaceutically acceptable. It may contain excipients.

[0160] In some embodiments, the ophthalmic article comprises at least about 50% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 30% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at least about 55% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 25% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 60% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 20% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 65% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 15% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 70% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 10% by weight pharmaceutically acceptable. It may contain excipients. In some embodiments, the ophthalmic article comprises at least about 75% by weight polymeric material, at least about 20% by weight active agent and/or diagnostic agent, and/or at least about 5% by weight pharmaceutically acceptable. It may contain excipients.

[0161] In some embodiments, the ophthalmic article comprises up to about 50% by weight polymeric material, up to about 10% by weight active agent and/or diagnostic agent, and/or up to about 40% by weight It may contain pharmaceutically acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 55% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 35% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 60% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 30% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 65% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 25% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 70% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 20% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 75% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 15% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 80% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 10% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 85% by weight polymeric material, at most about 10% by weight active agent and/or diagnostic agent, and/or at most about 5% by weight pharmaceutically It may contain acceptable excipients.

[0162] In some embodiments, the ophthalmic article comprises up to about 50% by weight polymeric material, up to about 20% by weight active agent and/or diagnostic agent, and/or up to about 30% by weight It may contain pharmaceutically acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 55% by weight polymeric material, at most about 20% by weight active agent and/or diagnostic agent, and/or at most about 25% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 60% by weight polymeric material, at most about 20% by weight active agent and/or diagnostic agent, and/or at most about 20% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 65% by weight polymeric material, at most about 20% by weight active agent and/or diagnostic agent, and/or at most about 15% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 70% by weight polymeric material, at most about 20% by weight active agent and/or diagnostic agent, and/or at most about 10% by weight pharmaceutically It may contain acceptable excipients. In some embodiments, the ophthalmic article comprises at most about 75% by weight polymeric material, at most about 20% by weight active agent and/or diagnostic agent, and/or at most about 5% by weight pharmaceutically It may contain acceptable excipients.

[0163] In some embodiments, at least the first monomer (eg, the first monomer) is about 5 wt% to about 95 wt%, or about 5 wt% to about 90 wt%, or about 5 wt% to about 85% by weight, or from about 5% to about 75% by weight, or from about 5% to about 70% by weight, or from about 5% to about 65% by weight, or from about 5% to about 60% by weight; or about 5% to about 55%, or about 5% to about 50%, or about 5% to about 45%, or about 5% to about 40%, or about 5% to about 35% by weight, or about 5% to about 30%, or about 5% to about 25%, or about 5% to about 20%, or about 5% to about 15%, or about 5% to about 10%, or about 10% to about 90%, or about 10% to about 85%, or about 10% to about 75%, or about 10% to about 70%, or from about 10% to up to about 65%, or from about 10% to up to about 60%, or from about 10% to about 55%, or from about 10% to about 50% , or about 10% to about 45%, or about 10% to about 40%, or about 10% to about 35%, or about 10% to about 30%, or about 10% It may be present in the ophthalmic article at a concentration of to about 25%, or 10% to about 20%, or about 10% to about 15% by weight.

[0164] In some embodiments, at least the second monomer (eg, the second monomer) is about 5 wt% to about 95 wt%, or about 5 wt% to about 90 wt%, or about 5 wt% to about 85% by weight, or from about 5% to about 75% by weight, or from about 5% to about 70% by weight, or from about 5% to about 65% by weight, or from about 5% to about 60% by weight; or about 5% to about 55%, or about 5% to about 50%, or about 5% to about 45%, or about 5% to about 40%, or about 5% to about 35% by weight, or about 5% to about 30%, or about 5% to about 25%, or about 5% to about 20%, or about 5% to about 15%, or about 5% to about 10%, or about 10% to about 90%, or about 10% to about 85%, or about 10% to about 75%, or about 10% to about 70 t%, or about 10% to about 65%, or about 10% to about 60%, or about 10% to about 55%, or about 10% to about 50%, or about 10% % to about 45%, or from about 10% to about 40%, or from about 10% to about 35%, or from about 10% to about 30%, or from about 10% to about 25% by weight %, or from about 10% to about 20%, or from about 10% to about 15% by weight, in the ophthalmic article.

[0165] Molecular weight (e.g., polymer molecular weight) or molecular mass can be measured by various means, such as number average molecular weight ( _Mn ) or molecular mass, weight average molecular weight ( _Mw ) or molecular mass, viscosity average molecular weight (Mv) or molecular mass. , and/or higher average molecular weights (M _z , Mz ₊₁ ) or molecular masses. Molecular weight or molecular mass can be measured by any method known in the art. By way of illustration, average molecular weight or molecular mass can be determined by end group analysis (M _n ). In another embodiment, the average molecular weight or molecular mass can be determined by boiling point elevation (boiling point elevation) or freezing point depression (freezing point depression) (M _n ). can be determined by tonometry (M _n ).In another embodiment, the average molecular weight or molecular mass can be determined by gel permeation chromatography (GPC).In another embodiment, the average molecular weight or molecular mass is (M _w ) can be determined by light scattering techniques.In another embodiment, the average molecular weight or molecular mass can be determined by sedimentation equilibrium (Mw, Mz).In another embodiment, the average molecular weight or molecular mass is It can be determined by viscometry (Mη).

[0166] In some embodiments, the active agent and/or drug release profile can be controlled by varying the molecular weight or molecular mass of the material (eg, PLCL) of the ophthalmic article. For example, PLCL-co-caprolactone) can have an average molecular weight or molecular mass from 1 kilodalton (kDa) to 200 kDa. In some embodiments, the ophthalmic article material can comprise poly(lactide-co-caprolactone) (50:50) having a number average molecular weight (M _n ) or molecular mass of about 75 kDa to about 85 kDa. In some embodiments, the ophthalmic article material can comprise poly(lactide-co-caprolactone) (60:40) having a number average molecular weight (M _n ) or molecular mass of about 75 kDa to 85 kDa. In some embodiments, the ophthalmic article material can comprise poly(lactide-co-caprolactone) (50:50) having a weight average molecular weight (M _w ) or molecular mass of about 75 kDa to about 85 kDa. In some embodiments, the ophthalmic article material may comprise poly(lactide-co-caprolactone) (60:40) having a weight average molecular weight (M _w ) or molecular mass of about 75 kDa to 85 kDa.

[0167] In some embodiments, the active agent and/or drug release profile varies with the molecular weight or molecular mass of the ophthalmic article material, which is typically poly(L-lactide-co-caprolactone). can be controlled by For example, poly(L-lactide-co-caprolactone) can have an average molecular weight or molecular mass from 1 kilodalton (kDa) to 200 kDa. In some embodiments, the ophthalmic article material can comprise poly(L-lactide-co-caprolactone) (50:50) having a number average molecular weight (M _n ) or molecular mass of about 75 kDa to about 85 kDa. . In some embodiments, the ophthalmic article material can comprise poly(L-lactide-co-caprolactone) (60:40) having a number average molecular weight (M _n ) or molecular mass of about 75 kDa to 85 kDa. In some embodiments, the ophthalmic article material can comprise poly(L-lactide-co-caprolactone) (50:50) having a weight average molecular weight (M _w ) or molecular mass of about 75 kDa to about 85 kDa. . In some embodiments, the ophthalmic article material may comprise poly(L-lactide-co-caprolactone) (60:40) having a weight average molecular weight (M _w ) or molecular mass of about 75 kDa to 85 kDa.

[0168] In some embodiments, the material of the ophthalmic article is at least about 1 kDa, at least about 2 kDa, at least about 3 kDa, at least about 4 kDa, at least about 5 kDa, at least about 6 kDa, at least about 7 kDa, at least about 8 kDa, at least about about 9 kDa, at least about 10 kDa, at least about 11 kDa, at least about 12 kDa, at least about 13 kDa, at least about 14 kDa, at least about 15 kDa, at least about 16 kDa, at least about 17 kDa, at least about 18 kDa, at least about 19 kDa, at least about 20 kDa, at least about 21 kDa , at least about 22 kDa, at least about 23 kDa, at least about 24 kDa, at least about 25 kDa, at least about 26 kDa, at least about 27 kDa, at least about 28 kDa, at least about 29 kDa, at least about 30 kDa, at least about 31 kDa, at least about 32 kDa, at least about 33 kDa, at least about about 34 kDa, at least about 35 kDa, at least about 36 kDa, at least about 37 kDa, at least about 38 kDa, at least about 39 kDa, at least about 40 kDa, at least about 41 kDa, at least about 42 kDa, at least about 43 kDa, at least about 44 kDa, at least about 45 kDa, at least about 46 kDa , at least about 47 kDa, at least about 48 kDa, at least about 49 kDa, at least about 50 kDa, at least about 51 kDa, at least about 52 kDa, at least about 53 kDa, at least about 54 kDa, at least about 55 kDa, at least about 56 kDa, at least about 57 kDa, at least about 58 kDa, at least about 59 kDa, at least about 60 kDa, at least about 65 kDa, at least about 70 kDa, at least about 75 kDa, at least about 80 kDa, at least about 85 kDa, at least about 90 kDa, at least about 95 kDa, at least about 100 kDa, at least about 110 kDa, at least about 120 kDa, at least about 130 kDa , at least about 140 kDa, at least about 150 kDa, at least about 160 kDa, at least about 170 kDa, at least about 180 kDa, at least about 190 kDa, at least about 200 kDa, at least about 250 kDa, at least about 300 kDa, at least about 350 kDa It can have an average molecular weight or average molecular mass (eg, number average molecular mass) of Da or at least about 400 kDa. In any of the above options, molecular weight or molecular mass can be determined by any of the methods described herein.

[0169] In some embodiments, the material of the ophthalmic article is up to about 1 kDa, up to about 2 kDa, up to about 3 kDa, up to about 4 kDa, up to about 5 kDa, up to about 6 kDa, up to about 7 kDa, maximum about 8 kDa, maximum about 9 kDa, maximum about 10 kDa, maximum about 11 kDa, maximum about 12 kDa, maximum about 13 kDa, maximum about 14 kDa, maximum about 15 kDa, maximum about 16 kDa, maximum about 17 kDa, maximum about 18 kDa, maximum about 19 kDa, maximum about 20 kDa, maximum about 21 kDa, maximum about 22 kDa, maximum about 23 kDa, maximum about 24 kDa, maximum about 25 kDa, maximum about 26 kDa, maximum about 27 kDa, maximum about 28 kDa, maximum about 29 kDa, maximum about 30 kDa, maximum about 31 kDa, maximum about 32 kDa, maximum about 33 kDa, maximum about 34 kDa, maximum about 35 kDa, maximum about 36 kDa, maximum about 37 kDa, maximum about 38 kDa, maximum about 39 kDa, maximum about 40 kDa, maximum about 41 kDa, maximum about 42 kDa, maximum about 43 kDa, maximum about 44 kDa, maximum about 45 kDa, maximum about 46 kDa, maximum about 47 kDa, maximum about 48 kDa, maximum about 49 kDa, maximum about 50 kDa, maximum about 51 kDa, maximum about 52 kDa, maximum about 53 kDa, maximum about 54 kDa, maximum about 55 kDa, maximum about 56 kDa, maximum about 57 kDa, maximum about 58 kDa, maximum about 59 kDa, maximum about 60 kDa, maximum about 65 kDa, maximum about 70 kDa, maximum about 75 kDa, maximum about 80 kDa, maximum about 85 kDa, maximum about 90 kDa, maximum about 95 kDa, maximum about 100 kDa, maximum about 110 kDa, maximum about 120 kDa, maximum about 130 kDa, maximum about 140 kDa, maximum about 150 kDa, maximum about 160 kDa, maximum about 170 kDa, maximum about 180 kDa, maximum about It may have an average molecular weight or average molecular mass (eg number average molecular mass) of 190 kDa, up to about 200 kDa, up to about 250 kDa, up to about 300 kDa, up to about 350 kDa or up to about 400 kDa. In any of the above options, molecular weight or molecular mass can be determined by any of the methods described herein.

[0170] In some embodiments, the material of the ophthalmic article is about 1 kDa, about 2 kDa, about 3 kDa, about 4 kDa, about 5 kDa, about 6 kDa, about 7 kDa, about 8 kDa, about 12 kDa, about 13 kDa, about 14 kDa, about 15 kDa, about 16 kDa, about 17 kDa, about 18 kDa, about 19 kDa, about 20 kDa, about 21 kDa, about 22 kDa, about 23 kDa, about 24 kDa, about 25 kDa, about 26 kDa, about 27 kDa, about 28 kDa About 45 kDa, about 46 kDa, about 47 kDa, about 48 kDa, about 49 kDa, about 50 kDa, about 51 kDa, about 52 kDa, about 53 kDa, about 54 kDa, about 55 kDa, about 56 kDa, about 57 kDa, about 58 kDa, about 59 kDa, about 60 kDa, about 65 kDa, about 70 kDa, about 75 kDa, about 80 kDa, about 85 kDa, about 90 kDa, about 95 kDa, about 100 kDa, about 110 kDa, about 120 kDa, about 130 kDa, about 140 kDa, about 150 kDa, about 160 kDa, about 170 kDa, about 180 kDa, about 190 kDa, about 200 kDa , about 250 kDa, about 300 kDa, about 350 kDa or about 400 kDa. In any of the above options, molecular weight or molecular mass can be determined by any of the methods described herein.

[0171] In some embodiments, the materials of the ophthalmic articles can have an average molecular weight or average molecular mass of from about 50 kDa to about 400 kDa. In some embodiments, the ophthalmic article material is from about 50 kDa to about 55 kDa, from about 50 kDa to about 60 kDa, from about 50 kDa to about 80 kDa, from about 50 kDa to about 100 kDa, from about 50 kDa to about 120 kDa, from about 50 kDa to about 150 kDa, about 50 kDa to about 200 kDa, about 50 kDa to about 300 kDa, about 50 kDa to about 400 kDa, about 55 kDa to about 60 kDa, about 55 kDa to about 80 kDa, about 55 kDa to about 100 kDa, about 55 kDa to about 120 kDa, about 55 kDa to about 150 kDa, about 55 kDa ~ about 200 kDa, about 55 kDa to about 300 kDa, about 55 kDa to about 400 kDa, about 60 kDa to about 80 kDa, about 60 kDa to about 100 kDa, about 60 kDa to about 120 kDa, about 60 kDa to about 150 kDa, about 60 kDa to about 200 kDa, about 60 kDa to about 300 kDa, about 60 kDa to about 400 kDa, about 80 kDa to about 100 kDa, about 80 kDa to about 120 kDa, about 80 kDa to about 150 kDa, about 80 kDa to about 200 kDa, about 80 kDa to about 300 kDa, about 80 kDa to about 400 kDa, about 100 kDa to about 120 kDa about 100 kDa to about 150 kDa, about 100 kDa to about 200 kDa, about 100 kDa to about 300 kDa, about 100 kDa to about 400 kDa, about 120 kDa to about 150 kDa, about 120 kDa to about 200 kDa, about 120 kDa to about 300 kDa, about 120 kDa to about 150 kDa, about 120 kDa to about 150 kDa It can have a number average molecular weight or average molecular mass of from to about 200 kDa, from about 150 kDa to about 300 kDa, from about 150 kDa to about 400 kDa, from about 200 kDa to about 300 kDa, from about 200 kDa to about 400 kDa, or from about 300 kDa to about 400 kDa.

[0172] In some embodiments, the ophthalmic article comprises one or more active agents and/or diagnostic agents in an effective amount (e.g., a therapeutically effective amount) or an effective amount (e.g., a therapeutically effective amount) of one or Multiple active agents and/or diagnostic agents may be included in amounts that deliver to the eye (eg, the posterior segment of the eye) through the lens capsule. The effective amount or dosage may vary depending on the particular active agent and/or diagnostic agent used in the polymeric material (eg, biodegradable polymeric matrix). Furthermore, the effective amount or dosage may vary depending on the severity of the condition or complication being treated. However, the active agent and/or diagnostic agent may be present in an amount that facilitates delivery of the active agent and/or diagnostic agent (eg, from the anterior segment (eg, from the capsular capsule) to the posterior segment of the eye).

[0173] In any of the various aspects, at least one active agent and/or diagnostic agent described herein (e.g., by the Food and Drug Administration) for use in various embodiments of the present disclosure. found in the published Orange Book), infection, inflammation (e.g., postoperative inflammation), macular edema, neovascularization, age-related macular degeneration (neovascular or dry), glaucoma, diabetic retinopathy, prematurity It can be used for the diagnosis and/or treatment or prevention of infantile retinopathy, uveitis, corneal transplant rejection, fibrosis (eg capsular fibrosis), posterior capsule opacification, retinal vein occlusion, infection and the like. For example, an ophthalmic article for delivering or administering an active agent to the eye may contain an active ingredient for treating or preventing complications associated with cataract surgery. The function of an active agent (eg, active ingredient) can be to impart pharmacological properties upon release from the ophthalmic article. An active agent can be an agent or substance that has a measurable specified or selected physiological activity when administered to a subject in a significant or effective amount. An active agent can be a therapeutic agent. A diagnostic agent can be a substance used to examine the body to detect disturbances in the body's normal function. In some cases, diagnostic agents can be pharmacological and non-pharmacological agents with functional purpose, eg, for use in detecting ocular malformations, diseases, and aspects of pathophysiology. For example, diagnostic agents may include important and effective diagnostic adjuvants that aid in visualization of ocular tissue, such as dyes such as fluorescein dyes, indocyanine green, trypan blue, dark quenchers such as cyanine dyes, azo dyes, acridines, fluorones, oxazine, phenanthridine, naphthalimide, rhodamine, benzopyrone, perylene, benzanthrone and benzoxantrone). Diagnostic agents may include paramagnetic molecules, fluorescent compounds, magnetic molecules, radionuclides, x-ray imaging agents and/or contrast agents. In some embodiments, the diagnostic agents are radiopharmaceuticals, contrast agents for use in imaging techniques, allergen extracts, activated charcoal, various test strips (e.g. cholesterol, ethanol and glucose), pregnancy tests, urea ¹³ C and May include breath testing with various stains/markers. In some embodiments, the labeling moiety is selected from the group consisting of coumarins, cyanine dyes, azo dyes, acridines, fluorones, oxazines, phenanthridines, naphthalimides, rhodamines, benzopyrones, perylenes, benzanthrones and benzoxanthrones. fluorescent dyes or dark quenchers. In certain non-limiting embodiments, the fluorescent dye is coumarin, fluorescein, cyanine 3 (Cy3), cyanine 5 (Cy5), cyanine (Cy7), Alexa dyes, bodipy derivatives, (E)-2-(4- (phenyldiazenyl)phenoxy)acetic acid, 3-(3′,3′-dimethyl-6-nitrospiro[chromene-2,2′-indolin]-1′-yl)propanoate (spiropyran), 3,5-dihydroxybenzoate and (E)-A residue of a compound selected from the group consisting of 2-(4-(phenyldiazenyl)phenoxy)acetic acid or combinations thereof.

[0174] As used herein, the phrase "radionuclide" includes any compound or chemical moiety that contains one or more radioactive isotopes. Radioisotopes are elements that emit radiation. Examples include α-, β- or γ-emitters. Radionuclides suitable for use as radioactive agents include, but are not limited to, carbon-11, fluorine-18, bromine-76 or iodine-123 and iodine-124; metal radionuclides include antimony-124, antimony -125, Arsenic-74, Barium-103, Barium-140, Beryllium-7, Bismuth-206, Bismuth-207, Cadmium-109, Cadmium-115m, Calcium-45, Cerium-139, Cerium-141, Cerium-144 , Cesium-137, Chromium-51, Cobalt-55, Cobalt-56, Cobalt-57, Cobalt-58, Cobalt-60, Cobalt-64, Copper-67, Erbium-169, Europium-152, Gallium-64, Gallium -68, gadolinium-153, gadolinium-157, gold-195, gold-199, hafnium-175, hafnium-175-181, holmium-166, indium-110, indium-111, iridium-192, iron-55, iron -59, Krypton-85, Lead-210, Manganese-54, Mercury-197, Mercury-203, Molybdenum-99, Neodymium-147, Neptunium-237, Nickel-63, Niobium-95, Osmium-185+191, Palladium-103 , platinum-195m, praseodymium-143, promethium-147, protactinium-233, radium-226, rhenium-186, rhenium-188, rubidium-86, ruthenium-103, ruthenium-106, scandium-44, scandium-6, Selenium-75, Silver-110m, Silver-111, Sodium-22, Strontium-85, Strontium-89, Strontium-90, Sulfur-35, Tantalum-182, Technetium-99m, Tellurium-125, Tellurium-132, Thallium- 204, Thorium-228, Thorium-232, Thallium-170, Tin-113, Tin-114, Tin-117m, Titanium-44, Tungsten-185, Vanadium-48, Vanadium-49, Ytterbium-169, Yttrium-86, Yttrium-88, Yttrium-90, Yttrium-91, Zinc-65 or Zirconium-95. In certain embodiments, the radionuclide is selected from, for example, 99m technetium, 201 thallium, 111 indium, 67 gallium, 90 yttrium, 177 lutetium or 123 iodine.

[0175] Many active agents are useful for a variety of ocular conditions or complications, such as infection, inflammation (e.g., postoperative inflammation), macular edema, angiogenesis, age-related macular degeneration (neovascular or dry), It is known for the treatment or prevention of glaucoma, diabetic retinopathy, retinopathy of prematurity, uveitis, corneal transplant rejection, fibrosis (eg capsular fibrosis), posterior capsule opacification, retinal vein occlusion, infections.

[0176] Areas of active agents that can be utilized for incorporation into polymeric materials include anti-inflammatory agents, anti-angiogenic agents, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), intraocular pressure (IOP) lowering agents, anti-inflammatory agents, Infectious agents, antibiotics, antimitotics, antivirals, antifungals, antimetabolites, antifibrotic agents, glaucoma agents, antiangiogenic agents, integrins, integrin antagonists, complement antagonists, cytokines, cytokine inhibition agents, antibody blocking agents, angiogenesis inhibitors, vaccines, immunomodulators, anticoagulants, antineoplastic agents, anesthetics, analgesics, adrenergic agonists or antagonists, cholinergic agonists or antagonists, enzymes, enzyme inhibitors, It may include neuroprotective agents, cytoprotective agents, regenerative agents, antisense oligonucleotides, aptamers, antibodies or combinations thereof.

[0177] Active agents can consist of proteins, peptides, lipids, carbohydrates, hormones, metals, radioactive elements and compounds, or combinations thereof.
[0178] In some embodiments, corticosteroids may include hydrocortisone, loteprednol, cortisol, cortisone, prednisolone, methylprednisolone, dexamethasone, betamethasone, triamcinolone, aldosterone, or fludrocortisone.

[0179] In some embodiments, the NSAID can include diclofenac (e.g. diclofenac sodium), flurbiprofen (e.g. flurbiprofen sodium), ketorolac (e.g. ketorolac tromethamine), bromfenac or nepafenac .

[0180] In some embodiments, the IOP-lowering agent and/or glaucoma drug is a prostaglandin analog (e.g. bimatoprost, latanoprost, travoprost or latanoprostene bunod), a rho kinase inhibitor (e.g. netarsudil) , adrenergic agonists (epinepherine or dipivefrin), beta-adrenergic antagonists (e.g. timolol, levonolol, metipranolol, carteolol or betaxolol), also known as beta-blockers, alpha 2-adrenergic agonists (e.g. apraclonidine, brimonidine or brimonidine tartrate), carbonic anhydrase inhibitors (eg brinzolamide, diclofenamide, methazolamide acetazolamide, acetazolamide or dorzolamide), pilocarpine, ecothiophate, demercarium, physostigmine, and/or isofluorophate.

[0181] In some embodiments, the anti-infective is an antibiotic, including ciprofloxacin, tobramycin, erythromycin, ofloxacin, gentamicin, fluoroquinolone antibiotics, moxifloxacin and/or gatifloxacin; antiviral agents including idoxuridine, vidarabine and/or trifluridine; and/or antifungal agents including amphotericin B, natamycin, voriconazole, fluconazole, miconazole, clotrimazole, ketoconazole, posaconazole, echinocandins, caspofungin and/or micafungin. can include

[0182] In some embodiments, the antimetabolite may comprise methotrexate, mycophenolate or azathioprine.
[0183] In some embodiments, the antifibrotic agent may comprise maitomycin C or 5-fluorouracil.

[0184] In some embodiments, the angiogenesis inhibitor is an anti-VEGF agent (eg, aflibercept, ranibizumab, bevacizumab), a PDGF-B inhibitor (eg, Fovista®), a complement antagonist (eg, eculizumab ), tyrosine kinase inhibitors (eg sunitinib, axitinib), and/or integrin antagonists (eg natalizumab and vedolizumab).

[0185] In some embodiments, the cytoprotective agent can include ebselen, sulforaphane, oltipraz, or dimethyl fumarate.
[0186] In some embodiments, neuroprotective agents may include ursodiol, memantine or acetylcysteine.

[0187] In some embodiments, the anesthetic may include lidocaine, proparacaine or bupivacaine.
[0188] In some embodiments, the active agent is dexamethasone, ketorolac, diclofenac, vancomycin, moxifloxacin, gatifloxacin, besifloxacin, travoprost, 5-fluorouracil, methotrexate, mitomycin C, prednisolone, bevacizumab (Avastin®), ranibizumab (Lucentis®), sunitinib, pegaptanib (Macugen®), timolol, latanoprost, brimonidine, nepafenac, bromfenac, triamcinolone, difluprednate, fluocinolide, It may be aflibercept or a combination thereof. In some embodiments, the active agent can be dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil or methotrexate. In some embodiments, the active agent is dexamethasone. In some embodiments, the active agent is ketorolac. In some embodiments, the active ingredient is dexamethasone.

[0189] In some embodiments, the ophthalmic article may include an inert agent (eg, a polymer). The function of inert ingredients is to impart certain physical properties such as bulk, adhesion, hardness, flexibility, conformability, erodibility, color and opacity to the ophthalmic article, as well as inert agents such as inactive ingredients). Various inactive ingredients may be used in ophthalmic articles and also approved active agents (eg, drug products) and may be biocompatible. In some embodiments, the ophthalmic article may also include pigments to aid visualization by the surgeon.

[0190] In some embodiments, ophthalmic articles may also include one or more excipients and/or disintegrants. Excipients include preservatives, permeation enhancers, plasticizers, lubricants, emulsifiers, solubilizers, suspending agents, stiffening agents, thickeners, buffers, acidifiers, alkalinizers, thickeners. Viscous agents, colorants, release modifiers, controlled release agents, opacifiers, stabilizers, gelling agents, antioxidants, dispersing agents, hydroxypropylcellulose, sodium carboxymethylcellulose, croscarmellose sodium, hyaluronic acid, and/or or may contain albumin. Excipients are for example those from Raymond C.I. Rowe et al., Handbook of Pharmaceutical Excipients (6th edition, 2009), which are incorporated herein by reference in their entireties.

[0191] The Disintegrant can be a super-disintegrant. Non-limiting examples of suitable disintegrants are crosslinked cellulose (eg croscarmellose, Ac-Di-Sol, Nymce ZSX, Primellose, SoluTab, VIVASOL), microcrystalline cellulose, alginate, crosslinked PVP (eg crospovidone, Kollidon , Polyplasdone), crosslinked starch, soy polysaccharides, calcium silicates, salts thereof, and the like.

[0192] For example, the excipient and/or disintegrant can be from 3 weight percent (wt%) to 25%, and in some cases from 3% to 20%, by weight of the ophthalmic article. More than about 25% by weight of the disintegrant can be useful for delivery times of less than about 1 week, while less than about 3% can be useful for extended delivery times of more than 6-9 months.

[0193] In some embodiments, the ophthalmic article may comprise at least or up to about 0.1% to 50% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise from about 0.5% to 50% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise from about 1.0% to 50% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 5% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 10% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 15% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 20% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise 25% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 30% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 35% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 45% to 50% by weight excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise from about 5% to 40% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise from about 5% to 35% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 5% to 30% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise from about 5% to 25% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 5% to 20% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 5% to 15% by weight of excipients and/or disintegrants. In some embodiments, an ophthalmic article may comprise about 5% to 10% by weight of excipients and/or disintegrants.

[0194] In some embodiments, an ophthalmic article can be formed, for example, by mixing a polymeric material with a loading of an active agent and/or diagnostic agent to form a matrix dispersion or solution. In some embodiments, ophthalmic articles may be formed using biodegradable matrices and/or non-biodegradable materials.

[0195] In some embodiments, non-biodegradable materials include methacrylates, acrylates and/or copolymers thereof, silicones, and/or polymers and/or copolymers of vinyl acetate, vinylpyrrolidone and/or vinyl alcohol. obtain. Methacrylates may include poly(methyl acrylate) (PMA) or poly(methyl methacrylate) (PMMA). Vinyl acetate includes vinyl acetate or ethylene vinyl acetate (EVA).

[0196] The active agent and/or diagnostic agent can be homogeneously dispersed as a solid, or can be homogeneously or partially dissolved so long as the uniformity and homogeneity is maintained. Thus, in some examples, the active agent and/or diagnostic agent can be homogeneously combined with the polymer matrix such that at least a portion (eg, the entirety) of the ophthalmic article is homogeneous or substantially homogeneous. For example, homogeneity can extend throughout an ophthalmic article such that the ophthalmic article consists essentially of a homogeneously mixed matrix and active and/or diagnostic agents and optional additives. . The loading can be selected to correspond to the desired dose during diffusion. In some cases, the loading can take into account diffusion properties such as polymeric material and active agent and/or diagnostic agent, residual active agent and/or diagnostic agent, delivery time, and the like. The matrix dispersion can then be formed into device shapes using any suitable technique. For example, matrix dispersions can be cast, sprayed and dried, extruded, die cut, and the like.

[0197] In some embodiments, ophthalmic articles (e.g., biocompatible and/or biodegradable matrices) release active agents (e.g., therapeutic agents) and/or diagnostic agents from materials (e.g., polymeric materials). It can be configured to biodegrade or bioerode to provide (eg controlled release). In some embodiments, the ophthalmic article (e.g., biocompatible and/or biodegradable matrix) comprises a polymeric material (e.g., polymeric matrix) containing an effective amount (e.g., a therapeutically effective amount) of an active agent (e.g., therapeutic agent). and/or can be configured to biodegrade or bioerode over a period of days, weeks or months to achieve release of the diagnostic agent.

[0198] In some embodiments, ophthalmic articles for delivering active agents (e.g., drug delivery) and/or diagnostic agents to the eye may include bioerodible polymers, which are sensitive to the biological environment. It can be either a natural or synthetic polymer that spontaneously degrades when placed. Mechanisms of bioerosion include ester hydrolysis, enzymatic degradation or reduction of disulfide bonds. Examples of bioerodible polymers are polylactide, polyglycolide, polycaprolactone, poly(trimethylene carbonate), chitosan, polyethylene glycol, poly-beta-aminoester, poly-L-malic acid, hyaluronic acid, peptides, nucleic acids or dextran. system polymer.

[0199] In some embodiments, articles for ocular drug delivery may be designed to release drug over a short period of time (eg, the first 24-48 hours after surgery). A "burst release" may be desirable to prevent immediate infection or inflammation after surgery. In other embodiments, articles for ocular drug delivery may be designed to release drug over an extended period of time (eg, days to weeks or even months after surgery). Such sustained release may be desirable to treat more chronic conditions such as glaucoma, posterior capsule opacification or macular edema. In some embodiments, the ophthalmic articles described herein can be targeted for relatively short duration of delivery, eg, less than 8 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 1 week to about 6 or 8 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 2 weeks to about 6 or 8 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 3 weeks to about 6 or 8 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 4 weeks to about 6 or 8 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of about 1 week to about 2 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of about 1 week to about 3 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 1 week to about 4 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of about 1 week to about 5 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 1 week to about 6 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 1 week to about 7 weeks. In some examples, the active agent and/or diagnostic agent has a delivery duration of from about 1 week to about 8 weeks.

[0200] In some embodiments, materials (eg, biocompatible matrices) and active agents (eg, drugs) and/or diagnostic agents may be selected to provide release for greater than 7 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over at least about 7 days. In some embodiments, the active agent and/or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days It is released from the biocompatible material (eg, biocompatible polymer matrix) over a period of days or 7-10 days.

[0201] In some embodiments, the active agent and/or diagnostic agent can be released from a biocompatible polymer matrix (eg, a biocompatible copolymer matrix) over a period of about 1 day to about 36 months. In some embodiments, the active agent and/or diagnostic agent has been administered for at least about 34 months, at least about 32 months, at least about 30 months, at least about 28 months, at least about 26 months, at least about 24 months, at least about 22 months. , at least about 20 months, at least about 18 months, at least about 16 months, at least about 14 months, at least about 12 months, at least about 10 months, at least about 8 months, at least about 6 months, at least about 4 months, at least about 2 months , at least about 1 month, at least about 3 weeks, at least about 2 weeks, at least about 1 week, at least about 6 days, at least about 5 days, at least about 4 days, at least about 3 days, at least about 2 days, or at least about 1 day over a period of time and can be released from a biocompatible polymer matrix (eg, a biocompatible copolymer matrix). In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over at least about 7 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over at least about 14 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over at least about 45 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over at least about 90 days.

[0202] In some embodiments, the active agent and/or diagnostic agent can be released from a biocompatible polymeric matrix (eg, a biocompatible copolymer matrix) over a period of about 1 day to about 36 months. In some embodiments, the active agent and/or diagnostic agent is administered for up to about 34 months, up to about 32 months, up to about 30 months, up to about 28 months, up to about 26 months, up to about 24 months. months, up to about 22 months, up to about 20 months, up to about 18 months, up to about 16 months, up to about 14 months, up to about 12 months, up to about 10 months, up to about 8 months, Up to about 6 months, up to about 4 months, up to about 2 months, up to about 1 month, up to about 3 weeks, up to about 2 weeks, up to about 1 week, up to about 6 days, up to It can be released from a biocompatible polymer matrix (eg, a biocompatible copolymer matrix) over a period of about 5 days, up to about 4 days, up to about 3 days, up to about 2 days, or up to about 1 day. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over a period of up to about 7 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over a period of up to about 14 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over a period of up to about 45 days. In some embodiments, the active agent and/or diagnostic agent can be released from the biocompatible polymer matrix (eg, biocompatible copolymer matrix) over a period of up to about 90 days.

[0203] In some embodiments, the active agent and/or diagnostic agent is administered for about 1 week to about 36 months, about 1 week to about 34 months, about 1 week to about 32 months, about 1 week to about 30 months. , about 1 week to about 30 months, about 1 week to about 28 months, about 1 week to about 26 months, about 1 week to about 24 months, about 1 week to about 22 months, about 1 week to about 20 months, about 1 week to about 18 months, about 1 week to about 16 months, about 1 week to about 14 months, about 1 week to about 12 months, about 1 week to about 10 months, about 1 week to about 8 months, about 1 week biocompatible polymer for about 6 months, about 1 week to about 4 months, about 1 week to about 2 months, about 1 week to about 1 month, about 1 week to about 3 weeks, or about 1 week to about 2 weeks It can be released from a matrix, such as a biocompatible copolymer matrix. In some embodiments, the active agent and/or diagnostic agent can be released from a biocompatible polymeric matrix (eg, a biocompatible copolymer matrix) over a period of about 1 day to about 7 days. In some embodiments, the active agent and/or diagnostic agent can be released from a biocompatible polymeric matrix (eg, a biocompatible copolymer matrix) over a period of about 1 day to about 14 days. In some embodiments, the active agent and/or diagnostic agent can be released from a biocompatible polymeric matrix (eg, a biocompatible copolymer matrix) over a period of about 1 day to about 45 days.

[0204] In certain instances, a therapeutically effective amount can be released over a period ranging from about 1 day to about 10 weeks. In other examples, the therapeutically effective amount can be released over a period ranging from about 1 day to about 3 weeks, about 2 weeks to about 6 weeks, or about 5 weeks to about 8 weeks. In some embodiments, the therapeutically effective amount can be released over at least about 1 day up to about 36 months.

[0205] In some embodiments, the therapeutically effective amount is at least about 34 months, at least about 32 months, at least about 30 months, at least about 28 months, at least about 26 months, at least about 24 months, at least about 22 months, at least about 20 months, at least about 18 months, at least about 16 months, at least about 14 months, at least about 12 months, at least about 10 months, at least about 8 months, at least about 6 months, at least about 4 months, at least about 2 months, for at least about 1 month, at least about 3 weeks, at least about 2 weeks, at least about 1 week, at least about 6 days, at least about 5 days, at least about 4 days, at least about 3 days, at least about 2 days, or at least about 1 day can be released. In some embodiments, the therapeutically effective amount can be released over at least about 7 days. In some embodiments, the therapeutically effective amount can be released over at least about 14 days. In some embodiments, the therapeutically effective amount can be released over at least about 45 days. In some embodiments, the therapeutically effective amount can be released over at least about 90 days.

[0206] In some embodiments, the therapeutically effective amount is up to about 34 months, up to about 32 months, up to about 30 months, up to about 28 months, up to about 26 months, up to about 24 months. , maximum about 22 months, maximum about 20 months, maximum about 18 months, maximum about 16 months, maximum about 14 months, maximum about 12 months, maximum about 10 months, maximum about 8 months, maximum But about 6 months, maximum about 4 months, maximum about 2 months, maximum about 1 month, maximum about 3 weeks, maximum about 2 weeks, maximum about 1 week, maximum about 6 days, maximum about It can be released over 5 days, up to about 4 days, up to about 3 days, up to about 2 days or up to about 1 day. In some embodiments, the therapeutically effective amount can be released over up to about 7 days. In some embodiments, the therapeutically effective amount can be released over a period of up to about 14 days. In some embodiments, the therapeutically effective amount can be released over a period of up to about 45 days. In some embodiments, the therapeutically effective amount can be released over a period of up to about 90 days.

[0207] In some embodiments, the therapeutically effective amount is about 1 week to about 36 months, about 1 week to about 34 months, about 1 week to about 32 months, about 1 week to about 30 months, about 1 week ~ about 30 months, about 1 week to about 28 months, about 1 week to about 26 months, about 1 week to about 24 months, about 1 week to about 22 months, about 1 week to about 20 months, about 1 week to about 18 months, about 1 week to about 16 months, about 1 week to about 14 months, about 1 week to about 12 months, about 1 week to about 10 months, about 1 week to about 8 months, about 1 week to about 6 months , about 1 week to about 4 months, about 1 week to about 2 months, about 1 week to about 1 month, about 1 week to about 3 weeks, or about 1 week to about 2 weeks. In some embodiments, the therapeutically effective amount can be released over about 1 to about 7 days. In some embodiments, the therapeutically effective amount can be released over about 1 day to about 14 days. In some embodiments, the therapeutically effective amount can be released over about 1 day to about 45 days. In some embodiments, the therapeutically effective amount can be released over a period of about 1 day to about 90 days.

[0208] An effective amount (eg, therapeutically effective amount) or dosage (eg, therapeutically effective dose) can range from about 1 microgram (μg) to about 10 milligrams (mg). The effective amount or dosage may depend on the active agent and/or diagnostic agent used and the severity of the condition or complication. In some embodiments, an effective amount or dose can range from about 50 μg to about 800 μg. In some embodiments, the effective amount or dose is about 50 μg to about 100 μg, about 50 μg to about 150 μg, about 50 μg to about 200 μg, about 50 μg to about 250 μg, about 50 μg to about 300 μg, about 50 μg to about 350 μg, about 50 μg to about 400 μg, about 50 μg to about 450 μg, about 50 μg to about 500 μg, about 50 μg to about 550 μg, about 50 μg to about 600 μg, about 50 μg to about 650 μg, about 50 μg to about 700 μg, about 50 μg to about 750 μg, about 50 μg to about 800 μg, about 100 μg to about 150 μg, about 100 μg to about 200 μg, about 100 μg to about 250 μg, about 100 μg to about 300 μg, about 100 μg to about 350 μg, about 100 μg to about 400 μg, about 100 μg to about 450 μg, about 100 μg to about 500 μg, about 100 μg to about 550 μg, about 100 μg to about 600 μg, about 100 μg to about 650 μg, about 100 μg to about 700 μg, about 100 μg to about 750 μg, about 100 μg to about 800 μg, about 150 μg to about 200 μg, about 150 μg to about 250 μg, about 150 μg to about 300 μg, about 150 μg to about 350 μg, about 150 μg to about 400 μg, about 150 μg to about 450 μg, about 150 μg to about 500 μg, about 150 μg to about 550 μg, about 150 μg to about 600 μg, about 150 μg to about 650 μg, about 150 μg to about 700 μg, about 150 μg to about 750 μg, about 150 μg to about 800 μg, about 200 μg to about 250 μg, about 200 μg to about 300 μg, about 200 μg to about 350 μg, about 200 μg to about 400 μg, about 200 μg to about 450 μg, about 200 μg to about 500 μg, about 200 μg to about 550 μg, about 200 μg to about 600 μg, about 200 μg to about 650 μg, about 200 μg to about 700 μg, about 200 μg to about 750 μg, about 200 μg to about 800 μg, about 250 μg to about 300 μg, about 250 μg to about 350 μg, about 250 μg to about 400 μg, about 250 μg to about 450 μg, about 250 μg to about 500 μg, about 250 μg to about 550 μg, about 250 μg to about 600 μg, about 250 μg to about 650 μg, about 250 μg to about 700 μg, about 250 μg to about 750 μg, about 250 μg to about 800 μg, about 300 μg to about 350 μg, about 300 μg to about 400 μg, about 300 μg to about 450 μg, about 300 μg to about 500 μg, about 300 μg to about 550 μg, about 300 μg to about 600 μg About 350 μg to about 600 μg, about 350 μg to about 650 μg, about 350 μg to about 700 μg, about 350 μg to about 750 μg, about 350 μg to about 800 μg, about 400 μg to about 450 μg, about 400 μg to about 500 μg, about 400 μg to about 550 μg, about 400 μg about 600 μg, about 400 μg to about 650 μg, about 400 μg to about 700 μg, about 400 μg to about 750 μg, about 400 μg to about 800 μg, about 450 μg to about 500 μg, about 450 μg to about 550 μg, about 450 μg to about 600 μg, about 450 μg to about 650 μg About 550 μg to about 600 μg, about 550 μg to about 650 μg, about 550 μg to about 700 μg, about 550 μg to about 750 μg, about 550 μg to about 800 μg, about 600 μg to about 650 μg, about 600 μg to about 700 μg, about 600 μg to about 750 μg, about 650 μg It can range from about 700 μg, from about 650 μg to about 750 μg, from about 600 μg to about 800 μg, from about 700 μg to about 750 μg, from about 700 μg to about 800 μg, or from about 750 μg to about 800 μg. In some embodiments, an effective amount or dose can range from about 50 μg to about 200 μg. In some embodiments, an effective amount or dose can range from about 50 μg to about 400 μg. In some embodiments, an effective amount or dose can range from about 50 μg to about 700 μg.

[0209] In some embodiments, the effective amount or dose is at least about 50 μg, at least about 60 μg, at least about 70 μg, at least about 80 μg, at least about 90 μg, at least about 100 μg, at least about 150 μg, at least about 200 μg, at least about about 250 μg, at least about 300 μg, at least about 350 μg, at least about 400 μg, at least about 450 μg, at least about 500 μg, at least about 600 μg, at least about 650 μg, at least about 700 μg, at least about 750 μg, at least about 800 μg, at least about 850 μg, at least about 900 μg , at least about 1 mg, at least about 2 mg, at least about 3 mg, at least about 4 mg, at least about 5 mg, at least about 6 mg, at least about 7 mg, at least about 8 mg, at least about 9 mg, or at least about 10 mg. In some embodiments, the effective amount or dose can be at least about 150 μg. In some embodiments, the effective amount or dose can be at least about 300 μg. In some embodiments, the effective amount or dose can be at least about 600 μg.

[0210] In some embodiments, the effective amount or dose is up to about 50 μg, up to about 60 μg, up to about 70 μg, up to about 80 μg, up to about 90 μg, up to about 100 μg, up to about 150 μg, up to about 200 μg, up to about 250 μg, up to about 300 μg, up to about 350 μg, up to about 400 μg, up to about 450 μg, up to about 500 μg, up to about 600 μg, up to about 650 μg, up to about 700 μg, maximum about 750 μg, maximum about 800 μg, maximum about 850 μg, maximum about 900 μg, maximum about 1 mg, maximum about 2 mg, maximum about 3 mg, maximum about 4 mg, maximum about 5 mg, maximum about It can be 6 mg, up to about 7 mg, up to about 8 mg, up to about 9 mg or up to about 10 mg. In some embodiments, the effective amount or dose can be up to about 150 μg. In some embodiments, an effective amount or dose can be up to about 300 μg. In some embodiments, an effective amount or dose can be up to about 600 μg.

[0211] In some embodiments, the effective amount or dose is about 50 μg, about 60 μg, about 70 μg, about 80 μg, about 90 μg, about 100 μg, about 150 μg, about 200 μg, about 250 μg, about 300 μg, about 350 μg, about 400 μg, about 450 μg, about 500 μg, about 600 μg, about 650 μg, about 700 μg, about 750 μg, about 800 μg, about 850 μg, about 900 μg, about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg , about 8 mg, about 9 mg, or about 10 mg. In some embodiments, the effective amount or dose can be about 150 μg. In some embodiments, the effective amount or dose can be about 300 μg. In some embodiments, the effective amount or dose can be about 600 μg.

[0212] In some examples, the ophthalmic article can release from about 1 μg to about 10 mg of active agent and/or diagnostic agent over a period of from about 1 week to about 36 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 12 weeks.

[0213] In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 6 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 8 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 10 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 12 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 14 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 16 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 18 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 20 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 22 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 24 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 26 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 28 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 30 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 32 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 34 months. In some additional examples, the ophthalmic article can release from about 1 μg to about 500 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 36 months.

[0214] In still other examples, the ophthalmic article can release from about 100 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 2 weeks to about 8 weeks. In still other examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 2 weeks to about 8 weeks. In another example, the ophthalmic article can release from about 1 μg to about 300 μg over 2-3 weeks. In another example, the ophthalmic article can release 100 μg to about 600 μg over 6-8 weeks.

[0215] In some additional examples, the ophthalmic article releases from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 6 months. obtain. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 8 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 10 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 12 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 14 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 16 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 18 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 20 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 22 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 24 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 26 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 28 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 30 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 32 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 34 months. In some additional examples, the ophthalmic article can release from about 100 μg to about 500 μg, or from about 200 μg to about 1000 μg of active agent and/or diagnostic agent over a period of from about 1 week to about 36 months.

[0216] In some examples, the ophthalmic article can deliver an average of about 0.1 μg to about 1 μg of active agent and/or diagnostic agent per day during the release period. In other examples, the ophthalmic article can deliver an average of about 1 μg to about 10 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 50 μg of active agent and/or diagnostic agent per day during the release period.

[0217] In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 100 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 150 μg of active agent and/or diagnostic agent per day during the release period. In still other examples, the ophthalmic article can deliver an average of about 10 μg to about 200 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 250 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 300 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 350 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 400 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 450 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 500 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 550 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 600 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 650 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 700 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 750 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 800 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 850 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 900 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg to about 950 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 1 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 5 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 10 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 50 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 100 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 200 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 300 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 400 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 500 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 600 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 700 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 800 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 900 μg of active agent and/or diagnostic agent per day during the release period. In yet another example, the ophthalmic article can deliver an average of about 1,000 μg of active agent and/or diagnostic agent per day during the release period.

[0218] In some embodiments, the active agent and/or diagnostic agent may be present in the ophthalmic article at a concentration of from about 5 weight percent (wt%) to about 50% by weight. In some embodiments, the active agent and/or diagnostic agent is about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 5% by weight. to about 25 wt%, about 5 wt% to about 30 wt%, about 5 wt% to about 35 wt%, about 5 wt% to about 40 wt%, about 5 wt% to about 45 wt%, about 10 wt% to about 15 wt%, about 10 wt% to about 20 wt%, about 10 wt% to about 25 wt%, about 10 wt% to about 30 wt%, about 10 wt% to about 35 wt%, about 10 wt% to about 40 wt%, about 10 wt% to about 45 wt%, about 10 wt% to about 50 wt%, about 15 wt% to about 20 wt%, about 15 wt% to about 25 wt%, about 15 wt% to about 30 wt%, about 15 wt% to about 35 wt%, about 15 wt% to about 40 wt%, about 15 wt% to about 45 wt%, about 15 wt% to about 50 wt%, about 20 wt% to about 25 wt%, about 20 wt% to about 30 wt%, about 20 wt% to about 35 wt%, about 20 wt% to about 40 wt%, about 20 wt% to about 45 wt%, about 20 wt% to about 50 wt%, about 25 wt% to about 30 wt%, about 25 wt% to about 35 wt%, about 25 wt% to about 40 wt%, about 25 wt% to about 45 wt%, about 25 wt% to about 50 wt%, about 30 wt% to about 35 wt%, about 30 wt% to about 40 wt%, about 30 wt% to about 45 wt%, about 30 wt% to about 50 wt%, about 35 wt% to about 40%, about 35% to about 45%, about 35% to about 50%, about 40% to about 45%, about 40% to about 50%, or about 45% by weight % to about 50% by weight of the ophthalmic article. In some embodiments, the active agent and/or diagnostic agent can be present in the ophthalmic article at a concentration of about 5% to about 25% by weight. In some embodiments, the active agent and/or diagnostic agent is from about 5% to about 15% by weight. % concentration in the ophthalmic article. In some embodiments, the active agent and/or diagnostic agent can be present in the ophthalmic article at a concentration of at least about 5% by weight. In some embodiments, the active agent and/or diagnostic agent can be present in the ophthalmic article at a concentration of at least about 10% by weight. In some embodiments, the active agent and/or diagnostic agent can be present in the ophthalmic article at a concentration of at least about 20% by weight.

[0219] In some embodiments, the active agent and/or diagnostic agent is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least It can be present in the ophthalmic article at a concentration of about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% by weight.

[0220] In some embodiments, the active agent and/or diagnostic agent is up to about 5%, up to about 10%, up to about 15%, up to about 20%, up to about It may be present in the ophthalmic article at a concentration of 25%, up to about 30%, up to about 35%, up to about 40%, up to about 45%, or up to about 50% by weight. In some embodiments, the active agent and/or diagnostic agent may be present in the ophthalmic article at a concentration of up to about 5% by weight. In some embodiments, the active agent and/or diagnostic agent may be present in the ophthalmic article at a concentration of up to about 10% by weight. In some embodiments, the active agent and/or diagnostic agent may be present in the ophthalmic article at a concentration of up to about 20% by weight.

[0221] In some embodiments, the active agent and/or diagnostic agent is about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about It may be present in the ophthalmic article at a concentration of 35%, about 40%, about 45% or about 50% by weight.

[0222] In some embodiments, the molecular weight, molecular mass or molecular size of the active agent and/or diagnostic agent can affect delivery of the active agent and/or diagnostic agent to the eye (e.g., the posterior segment of the eye). . Thus, in some examples, an active agent and/or diagnostic agent can have a molecular weight or molecular mass of 250,000 Daltons (Da) or less. In yet additional examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 200,000 Da or less. In yet additional examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 190,000 Da or less. In yet additional examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 180,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 170,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 160,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 150,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 140,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 130,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 120,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 110,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 100,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 90,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 80,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 70,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 60,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 50,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 40,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 30,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 20,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 10,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 5,000 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 1,000 Da or less. In yet additional examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 500 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 400 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 300 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 200 Da or less. In still other examples, the active agent and/or diagnostic agent can have a molecular weight or molecular mass of 100 Da or less.

[0223] In some embodiments, one, two or more ophthalmic articles are introduced or implanted per eye to provide an effective amount (e.g., therapeutically effective amount) and/or effective dose ( therapeutically effective doses) can be achieved. In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more ophthalmic articles can be introduced or implanted per eye. can. In some embodiments, at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ophthalmic article can be introduced or implanted per eye. In some embodiments, at least about one ophthalmic article can be introduced or implanted per eye. In some embodiments, at least about two ophthalmic articles can be introduced or implanted per eye. In some embodiments, at least about 3 ophthalmic articles can be introduced or implanted per eye. In some embodiments, at least about 4 ophthalmic articles can be introduced or implanted per eye. In some embodiments, at least about 5 ophthalmic articles can be introduced or implanted per eye.

[0224] In some embodiments, at most about one ophthalmic article can be introduced or implanted per eye. In some embodiments, up to about two ophthalmic articles can be introduced or implanted per eye. In some embodiments, up to about 3 ophthalmic articles can be introduced or implanted per eye. In some embodiments, up to about 4 ophthalmic articles can be introduced or implanted per eye. In some embodiments, up to about 5 ophthalmic articles can be introduced or implanted per eye.

[0225] In some embodiments, about one ophthalmic article can be introduced or implanted per eye. In some embodiments, about two ophthalmic articles can be introduced or implanted per eye. In some embodiments, about 3 ophthalmic articles can be introduced or implanted per eye. In some embodiments, about 4 ophthalmic articles can be introduced or implanted per eye. In some embodiments, about 5 ophthalmic articles can be introduced or implanted per eye.

[0226] In any of the various aspects, one or more ophthalmic articles described herein are designed with a size and/or shape that maximizes the proximity of the ophthalmic article to a subject's eye. there is The shape and/or size of an ophthalmic article (e.g., active agent and/or diagnostic agent homogenous delivery device) for delivering or administering an active agent and/or diagnostic agent to the eye may vary depending on the active agent and/or diagnostic agent. It can play an important role in the amount and speed of delivery. For example, the shape and/or size of the ophthalmic article (e.g., active agent and/or diagnostic agent homogenous delivery device) can be adjusted while maintaining composition parameters suitable for the desired release profile. or diagnostic homogeneous delivery device) can be designed to ensure fast and/or slow release rates of active agents and/or diagnostic agents; and large or small amounts thereof.

[0227] In some embodiments, the shape of the ophthalmic article can be a prism with an open internal structure (eg, a hole in the center). In some embodiments, the prisms can be extruded prisms. Prisms can be circular prisms, rectangular prisms, square prisms, quadrilateral prisms, pentagonal prisms, hexagonal prisms, heptagonal prisms, octagonal prisms, nine-sided prisms, decagonal prisms, decagonal prisms, dodecagonal prisms or another can be prisms of the shape of In some embodiments, a prism can be a polyhedron. In some embodiments, the ophthalmic article is a torus, extruded torus, torus, extruded square, extruded quadrilateral, extruded rectangle, extruded pentagon, extruded hexagon, extruded It can be a heptagon, an extruded octagon, an extruded decagon, an extruded decagon, an extruded dodecagon, an extruded polygon. In some embodiments, the polygon may include 3, 4, 5, 6, 7, 8, 9, or 10 sides.

[0228] In some embodiments, the shape of the ophthalmic article is disc, cylinder, nail-like plug, rod, plate, hemisphere, truncated cone with bent axis, polymer wire wrapped around ophthalmic device portion and a polymeric sheet that wraps around the ophthalmic device portion.

[0229] In some embodiments, an ophthalmic article may include an internal structure for coupling with an ophthalmic device portion. The internal structure can be pores. For example, an ophthalmic article of any shape disclosed herein may include a hole in the center for coupling with an intraocular lens. In some embodiments, the shape of the ophthalmic article and/or internal structure can be the same as the shape of the portion of the ophthalmic device (eg, intraocular device) to which the ophthalmic article is attached. For example, the shape of the ophthalmic article and/or internal structure can be identical to the shape of the haptics of the intraocular lens. In some embodiments, the shape of the ophthalmic article and/or internal structure can differ from the shape of the portion of the ocular device (eg, intraocular device) to which the ophthalmic article is coupled. For example, the shape of the ophthalmic article and/or internal structure may differ from the shape of the intraocular lens haptics.

[0230] In some embodiments, the shape of the ophthalmic article can be manipulated to prevent obstruction of the line of sight. For example, in some cases, ophthalmic articles are crescent-shaped, oval-shaped (e.g., disk-shaped, football-shaped, egg-shaped), rod-shaped, and the like.

[0231] In some embodiments, when polymeric materials (e.g., biodegradable polymeric matrices) are used in ophthalmic articles (e.g., active agent and/or diagnostic agent homogeneous delivery devices), polymeric materials (e.g., Biodegradable polymer matrices) can accommodate varying amounts of active agents and/or diagnostic agents while maintaining a desirable biodegradation profile. The amount of active agent and/or diagnostic agent that the biodegradable matrix can release (e.g., controllably release) is within a particular biodegradation profile, which is a combination of the polymer matrix and one or more It may depend on the composition of both the active agent and/or the diagnostic agent.

[0232] In some embodiments, small or large amounts of active agents and/or diagnostic agents are required to provide an effective amount (e.g., a therapeutically effective amount) to a subject to treat or diagnose a particular condition. may be The overall size of the ophthalmic article can be expanded to accommodate large amounts of active and/or diagnostic agents. Conversely, as another example, the size of an ophthalmic article can be reduced when lesser amounts of active agents and/or diagnostic agents are required.

[0233] In some embodiments, the ophthalmic article may include internal structures (eg, pores) for bonding (eg, attaching) around portions of the ophthalmic device (eg, intraocular device). For example, the ophthalmic article may include holes for bonding around the intraocular lens haptic geometry. The pores can be circular and the haptics can be circular or rectangular.

[0234] In some embodiments, the dimensions or parameters of the internal structure (e.g., pores) are less than the corresponding dimensions or parameters of the portion of the ophthalmic device (e.g., intraocular device) to which the ophthalmic article is attached. may be, be equal to, or be greater than. In some embodiments, the perimeter of the internal structure (e.g., pores) of the ophthalmic article is less than the perimeter of the portion of the ophthalmic device (e.g., intraocular device) to which the ophthalmic article is coupled. , or may be equal to In some cases, the perimeter of the pores of the ophthalmic article may be less than or equal to the perimeter of the haptics on the intraocular lens to which the ophthalmic article is coupled. For example, if the cross-sectional dimensions of the IOL (eg, Aurovue) haptics are about 1.00 mm wide by 0.32 mm, the ophthalmic article pore perimeter may be less than or equal to 2.64 mm. be. In some embodiments, the perimeter of the pores of the ophthalmic article can be about 1.57 mm. In another example, the cross-sectional dimensions of the haptics of an IOL (e.g., from a Johnson & Johnson Surgical Vision foldable acrylic IOL Tecnis 1 piece) can be approximately 0.72 x 0.46 mm wide in a rectangular shape and can fit within the pores of an ophthalmic article. may be less than or equal to 2.36 mm.

[0235] In some embodiments, the perimeter of the pores of the ophthalmic article may be from about 0.5 mm to about 6 mm. In some embodiments, the pore perimeter of the ophthalmic article is from about 0.5 mm to about 1 mm, from about 0.5 mm to about 1.5 mm, from about 0.5 mm to about 2 mm, from about 0.5 mm to about 2 mm. .5 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 3.5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 4.5 mm, about 0.5 mm to about 5 mm, about 0.5 mm. 5 mm to about 5.5 mm, about 0.5 mm to about 6 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2.5 mm, about 1 mm to about 3 mm, about 1 mm to about 3.5 mm , about 1 mm to about 4 mm, about 1 mm to about 4.5 mm, about 1 mm to about 5 mm, about 1 mm to about 5.5 mm, about 1 mm to about 6 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2 .5 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 3.5 mm, about 1.5 mm to about 4 mm, about 1.5 mm to about 4.5 mm, about 1.5 mm to about 5 mm, about 1. 5 mm to about 5.5 mm, about 1.5 mm to about 6 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2 mm to about 4.5 mm , about 2 mm to about 5 mm, about 2 mm to about 5.5 mm, about 2 mm to about 6 mm, about 2.5 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 2.5 mm to about 4 mm, about 2. 5 mm to about 4.5 mm, about 2.5 mm to about 5 mm, about 2.5 mm to about 5.5 mm, about 2.5 mm to about 6 mm, about 3 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3 mm to about 4.5 mm, about 3 mm to about 5 mm, about 3 mm to about 5.5 mm, about 3 mm to about 6 mm, about 3.5 mm to about 4 mm, about 3.5 mm to about 4.5 mm, about 3.5 mm to about 5 mm , about 3.5 mm to about 5.5 mm, about 3.5 mm to about 6 mm, about 4 mm to about 4.5 mm, about 4 mm to about 5 mm, about 4 mm to about 5.5 mm, about 4 mm to about 6 mm, about 4. 5 mm to about 5 mm, about 4.5 mm to about 5.5 mm, about 4.5 mm to about 6 mm, about 5 mm to about 5.5 mm, about 5 mm to about 6 mm, or about 5.5 mm to about 6 mm .

[0236] In some embodiments, the perimeter of the pores of the ophthalmic article is at least about 0.5 mm, at least about 1 mm, at least about 1.2 mm, at least about 1.3 mm, at least about 1.4 mm, at least about 1.5 mm, at least about 1.6 mm, at least about 1.7 mm, at least about 1.8 mm, at least about 1.9 mm, at least about 2 mm, at least about 2.1 mm, at least about 2.2 mm, at least about 2.3 mm, at least about 2.4 mm, at least about 2.5 mm, at least about 2.6 mm, at least about 2.7 mm, at least about 2.8 mm, at least about 2.9 mm, at least about 3 mm, at least about 3.2 mm, at least about 3.2 mm; 4 mm, at least about 3.6 mm, at least about 3.8 mm, at least about 4 mm, at least about 4.2 mm, at least about 4.4 mm, at least about 4.6 mm, at least about 4.8 mm, at least about 5 mm, at least about 5 mm. 2 mm, at least about 5.4 mm, at least about 5.6 mm, at least about 5.8 mm, at least about 6 mm, at least about 6.2 mm, at least about 6.4 mm, at least about 6.6 mm, at least about 6.8 mm, or at least It may be about 7 mm.

[0237] In some embodiments, the perimeter of the pores of the ophthalmic article is at most about 0.5 mm, at most about 1 mm, at most about 1.2 mm, at most about 1.3 mm, at most about 1 mm. .4 mm, maximum about 1.5 mm, maximum about 1.6 mm, maximum about 1.7 mm, maximum about 1.8 mm, maximum about 1.9 mm, maximum about 2 mm, maximum about 2.1 mm, Maximum about 2.2 mm, Maximum about 2.3 mm, Maximum about 2.4 mm, Maximum about 2.5 mm, Maximum about 2.6 mm, Maximum about 2.7 mm, Maximum about 2.8 mm, Maximum But about 2.9 mm, maximum about 3 mm, maximum about 3.2 mm, maximum about 3.4 mm, maximum about 3.6 mm, maximum about 3.8 mm, maximum about 4 mm, maximum about 4.2 mm , maximum about 4.4 mm, maximum about 4.6 mm, maximum about 4.8 mm, maximum about 5 mm, maximum about 5.2 mm, maximum about 5.4 mm, maximum about 5.6 mm, maximum It may be about 5.8 mm, up to about 6 mm, up to about 6.2 mm, up to about 6.4 mm, up to about 6.6 mm, up to about 6.8 mm, or up to about 7 mm.

[0238] In some embodiments, the maximum width of the internal structure of the ophthalmic device is less than the maximum width of the portion of the ophthalmic device (e.g., intraocular device) to which the ophthalmic article is coupled, or may be equal. For example, the maximum width of the internal structure of the ophthalmic device may be less than or equal to the maximum width of the haptics of the intraocular lens to which the ophthalmic article is coupled. The maximum haptic width for a one-piece foldable acrylic IOL may be approximately 0.7 mm to 1.0 mm, and the maximum haptic width for a 3-piece foldable IOL may be approximately 0.1 mm to 0.2 mm. There may be. In some embodiments, the diameter of the internal structure of the ophthalmic device may be less than or equal to the diameter of the portion of the ophthalmic device (eg, intraocular device) to which the ophthalmic article is coupled. For example, the diameter of the internal structure of the ophthalmic device may be less than, equal to, or greater than the diameter of the haptics of the intraocular lens to which the ophthalmic article is attached.

[0239] In some embodiments, the maximum width of any haptics of the IOLs herein may be from about 0.01 mm to about 10 mm. In some embodiments, the maximum width of the haptics of any of the IOLs herein is from about 0.01 mm to about 0.05 mm, from about 0.01 mm to about 0.1 mm, from about 0.01 mm to about 0.05 mm. 5 mm, about 0.01 mm to about 1 mm, about 0.01 mm to about 1.5 mm, about 0.01 mm to about 2 mm, about 0.01 mm to about 3 mm, about 0.01 mm to about 4 mm, about 0.01 mm to about 5 mm, about 0.01 mm to about 10 mm, about 0.05 mm to about 0.1 mm, about 0.05 mm to about 0.5 mm, about 0.05 mm to about 1 mm, about 0.05 mm to about 1.5 mm, about 0 0.05 mm to about 2 mm, about 0.05 mm to about 3 mm, about 0.05 mm to about 4 mm, about 0.05 mm to about 5 mm, about 0.05 mm to about 10 mm, about 0.1 mm to about 0.5 mm, about 0 .1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 5 mm, about 0 .1 mm to about 10 mm, about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 4 mm, about 0 .5 mm to about 5 mm, about 0.5 mm to about 10 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 3 mm, about 1 mm to about 4 mm, about 1 mm to about 5 mm, about 1 mm to about 10 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 4 mm, about 1.5 mm to about 5 mm, about 1.5 mm to about 10 mm, about 2 mm to about 3 mm, about 2 mm about 4 mm, about 2 mm to about 5 mm, about 2 mm to about 10 mm, about 3 mm to about 4 mm, about 3 mm to about 5 mm, about 3 mm to about 10 mm, about 4 mm to about 5 mm, about 4 mm to about 10 mm, or about 5 mm It may be about 10 mm.

[0240] In some embodiments, the maximum width of the haptics of any of the IOLs herein is at least about 0.01 mm, at least about 0.05 mm, at least about 0.1 mm, at least about 0.2 mm, at least about 0.3 mm, at least about 0.4 mm, at least about 0.5 mm, at least about 0.6 mm, at least about 0.7 mm, at least about 0.8 mm, at least about 0.9 mm, at least about 1 mm, at least about 1.1 mm , at least about 1.2 mm, at least about 1.3 mm, at least about 1.4 mm, at least about 1.5 mm, at least about 1.6 mm, at least about 1.7 mm, at least about 1.8 mm, at least about 1.9 mm, at least It may be about 2 mm, at least about 3 mm, at least about 4 mm, at least about 5 mm, at least about 6 mm, at least about 7 mm, at least about 8 mm, at least about 9 mm, or at least about 10. In some embodiments, the maximum width of any haptics of the IOL herein may be at least about 0.5 mm. In some embodiments, the maximum width of any haptics of the IOL herein may be at least about 0.07 mm. In some embodiments, the maximum width of any haptics of the IOL herein may be at least about 1 mm.

[0241] In some embodiments, the maximum width of any of the haptics of the IOLs herein is at most about 0.01 mm, at most about 0.05 mm, at most about 0.1 mm, at most about 0 .2 mm, at most about 0.3 mm, at most about 0.4 mm, at most about 0.5 mm, at most about 0.6 mm, at most about 0.7 mm, at most about 0.8 mm, at most about 0.2 mm. 9 mm, maximum about 1 mm, maximum about 1.1 mm, maximum about 1.2 mm, maximum about 1.3 mm, maximum about 1.4 mm, maximum about 1.5 mm, maximum about 1.6 mm, maximum But about 1.7mm, maximum about 1.8mm, maximum about 1.9mm, maximum about 2mm, maximum about 3mm, maximum about 4mm, maximum about 5mm, maximum about 6mm, maximum about 7mm, It may be up to about 8 mm, up to about 9 mm, or up to about 10. In some embodiments, the maximum width of any haptics of the IOLs herein may be at most about 1.5 mm. In some embodiments, the maximum width of any haptics of the IOL herein may be up to about 1 mm. In some embodiments, the maximum width of any haptics of the IOL herein may be at most about 0.5 mm.

[0242] In some embodiments, the diameter of the internal structure of the ophthalmic device may be between about 0.1 mm and 2.3 mm. In some embodiments, the diameter of the internal structure of the ophthalmic device is from about 0.1 mm to about 0.3 mm, from about 0.1 mm to about 0.5 mm, from about 0.1 mm to about 0.7 mm, from about 0.5 mm. 1 mm to about 0.9 mm, about 0.1 mm to about 1.1 mm, about 0.1 mm to about 1.3 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 1.7 mm, about 0. 1 mm to about 1.9 mm; about 0.1 mm to about 2.1 mm; about 0.1 mm to about 2.3 mm; about 0.3 mm to about 0.5 mm; about 0.3 mm to about 0.7 mm; 3 mm to about 0.9 mm, about 0.3 mm to about 1.1 mm, about 0.3 mm to about 1.3 mm, about 0.3 mm to about 1.5 mm, about 0.3 mm to about 1.7 mm, about 0.3 mm to about 0.9 mm. 3 mm to about 1.9 mm, about 0.3 mm to about 2.1 mm, about 0.3 mm to about 2.3 mm, about 0.5 mm to about 0.7 mm, about 0.5 mm to about 0.9 mm, about 0.9 mm 5 mm to about 1.1 mm, about 0.5 mm to about 1.3 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 1.7 mm, about 0.5 mm to about 1.9 mm, about 0.5 mm to about 1.1 mm. 5 mm to about 2.1 mm, about 0.5 mm to about 2.3 mm, about 0.7 mm to about 0.9 mm, about 0.7 mm to about 1.1 mm, about 0.7 mm to about 1.3 mm, about 0.5 mm to about 2.1 mm. 7 mm to about 1.5 mm, about 0.7 mm to about 1.7 mm, about 0.7 mm to about 1.9 mm, about 0.7 mm to about 2.1 mm, about 0.7 mm to about 2.3 mm, about 0.7 mm to about 1.5 mm 9 mm to about 1.1 mm, about 0.9 mm to about 1.3 mm, about 0.9 mm to about 1.5 mm, about 0.9 mm to about 1.7 mm, about 0.9 mm to about 1.9 mm, about 0.9 mm to about 1.9 mm 9 mm to about 2.1 mm; about 0.9 mm to about 2.3 mm; about 1.1 mm to about 1.3 mm; about 1.1 mm to about 1.5 mm; about 1.1 mm to about 1.7 mm; 1 mm to about 1.9 mm; about 1.1 mm to about 2.1 mm; about 1.1 mm to about 2.3 mm; about 1.3 mm to about 1.5 mm; about 1.3 mm to about 1.7 mm; 3 mm to about 1.9 mm; about 1.3 mm to about 2.1 mm; about 1.3 mm to about 2.3 mm; about 1.5 mm to about 1.7 mm; about 1.5 mm to about 1.9 mm; 5 mm to about 2.1 mm, about 1.5 mm to about 2.3 mm, about 1.7 mm to about 1.9 mm, about 1.7 mm to about 2.1 mm, about 1.7 mm to about 2.3 mm, about 1. It may be from 9 mm to about 2.1 mm, from about 1.9 mm to about 2.3 mm, or from about 2.1 mm to about 2.3 mm. In some embodiments, the diameter of the internal structure of the ophthalmic device may be from about 0.1 mm to about 1 mm. In some embodiments, the diameter of the internal structure of the ophthalmic device may be from about 0.1 mm to about 0.7 mm.

[0243] In some embodiments, the diameter of the internal structure of the ophthalmic device is at least about 0.1 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, at least about 1 mm, at least about 1.05 mm, at least about 1.1 mm, at least about 1.15 mm, at least about 1.2 mm, at least about 1.25 mm, at least about 1.3 mm, at least about 1.35 mm, at least about 1.4 mm, at least about 1.45 mm, at least about 1.5 mm, at least about 1.55 mm, at least about 1.6 mm, at least about 1.65 mm, at least about 1.7 mm, at least about 1.75 mm, at least about 1.8 mm, at least about 1.85 mm, at least about 1.9 mm, at least about 1.95 mm, at least about 2 mm, at least about 2.05 mm, It may be at least about 2.1 mm, at least about 2.15 mm, at least about 2.2 mm, at least about 2.25 mm, or at least about 2.3 mm. In some embodiments, the internal structure of the ophthalmic device may have a diameter of at least about 0.1 mm. In some embodiments, the internal structure of the ophthalmic device may have a diameter of at least about 0.5 mm.

[0244] In some embodiments, the diameter of the internal structure of the ophthalmic device is at most about 0.1 mm, at most about 0.2 mm, at most about 0.25 mm, at most about 0.3 mm, at most about 0.35 mm, about 0.4 mm at maximum, about 0.45 mm at maximum, about 0.5 mm at maximum, about 0.55 mm at maximum, about 0.6 mm at maximum, about 0.65 mm at maximum, at most about 0.7 mm, maximum about 0.75 mm, maximum about 0.8 mm, maximum about 0.85 mm, maximum about 0.9 mm, maximum about 0.95 mm, maximum about 1 mm, maximum about 1.05 mm , a maximum of about 1.1 mm, a maximum of about 1.15 mm, a maximum of about 1.2 mm, a maximum of about 1.25 mm, a maximum of about 1.3 mm, a maximum of about 1.35 mm, a maximum of about 1.4 mm, Maximum about 1.45 mm, Maximum about 1.5 mm, Maximum about 1.55 mm, Maximum about 1.6 mm, Maximum about 1.65 mm, Maximum about 1.7 mm, Maximum about 1.75 mm, Maximum but about 1.8 mm, maximum about 1.85 mm, maximum about 1.9 mm, maximum about 1.95 mm, maximum about 2 mm, maximum about 2.05 mm, maximum about 2.1 mm, maximum about 2 0.15 mm, up to about 2.2 mm, up to about 2.25 mm, or up to about 2.3 mm. In some embodiments, the internal structure of the ophthalmic device may have a diameter of up to about 0.5 mm. In some embodiments, the internal structure of the ophthalmic device may have a diameter of up to about 1 mm. In some embodiments, the internal structure of the ophthalmic device may have a maximum diameter of about 1.5 mm.

[0245] In some embodiments, the diameter of the internal structure of the ophthalmic device is about 0.1 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.65 mm, about 0.7 mm, about 0.75 mm, about 0.8 mm, about 0.85 mm, about 0.9 mm, about 0.95 mm, about 1 mm, about 1.05 mm, about 1.1 mm, about 1.15 mm, about 1.2 mm, about 1.25 mm, about 1.3 mm, about 1.35 mm, about 1.4 mm, about 1 .45 mm, about 1.5 mm, about 1.55 mm, about 1.6 mm, about 1.65 mm, about 1.7 mm, about 1.75 mm, about 1.8 mm, about 1.85 mm, about 1.9 mm, about 1 .95 mm, about 2 mm, about 2.05 mm, about 2.1 mm, about 2.15 mm, about 2.2 mm, about 2.25 mm, or about 2.3 mm. In some embodiments, the internal structure of the ophthalmic device may have a diameter of about 0.5 mm.

[0246] FIGS. 1A and 1B schematically illustrate examples of ophthalmic articles (eg, active agent and/or diagnostic agent delivery devices) 100 of various shapes. Ophthalmic article 100 may include internal structures (eg, pores) 110 . In some figures, the ophthalmic article 100 may be a toroidal (eg, extruded torus) shaped ophthalmic article 101 and/or a toroid shaped ophthalmic article 106 . FIG. 1A illustrates a perspective view of an ophthalmic article 101 in the shape of a torus (eg extruded torus). FIG. 1B illustrates a perspective view of a toroid-shaped ophthalmic article 106 . In some figures, the internal structure (eg, hole) 110 can be a circular hole 120 in an ophthalmic article 101 having a ring (eg, extruded ring) shape. In some figures, the internal structure (eg, hole) 110 can be a circular hole 130 in the toroidal-shaped ophthalmic article 106 .

[0247] FIGS. 2A, 2B, 2C, 2D, 2E, 2F, 2G and 2H illustrate various shapes of ophthalmic articles (eg, active agent and/or diagnostic agent delivery devices) 100. 1 schematically illustrates another view of an example (eg, plan view, cross-sectional view); Ophthalmic article 100 may include internal structures (eg, pores) 110 having inner diameters or side edges 240 . Ophthalmic article 100 may also include outer diameter or edge 230 , cross-sectional thickness 250 and/or wall thickness 260 .

[0248] FIG. 2A illustrates a plan view of an ophthalmic article 101 in the shape of a torus (eg, an extruded torus). FIG. 2B illustrates a cross-sectional view of a toroidal ophthalmic article 101 . The toroidal ophthalmic article 101 includes an internal structure 110 that is a circular aperture 120 . Internal structure 110 includes an inner diameter or side edge 240 . An inner diameter or side edge 240 can be the inner diameter 204 . The toroidal ophthalmic article 101 may also include an outer diameter or edge 230 , a cross-sectional thickness 250 and/or a wall thickness 260 . Outer diameter or edge 230 can be outer diameter 203 . Cross-sectional thickness 250 may be cross-sectional thickness 205 . Wall thickness 260 may be wall thickness 216 .

[0249] FIG. 2C illustrates a plan view of a toroid-shaped ophthalmic article 106. FIG. FIG. 2D illustrates a cross-sectional view of toroid-shaped ophthalmic article 106 . The toroid-shaped ophthalmic article 106 includes an internal structure 110 that is a circular hole 130 . Internal structure 110 includes an inner diameter or side edge 240 . An inner diameter or side edge 240 can be the inner diameter 209 . The toroid-shaped ophthalmic article 106 may also include an outer diameter or edge 230 , a cross-sectional thickness 250 and/or a wall thickness 260 . Outer diameter or edge 230 may be outer diameter 208 . Cross-sectional thickness 250 may be cross-sectional thickness 210 . Wall thickness 260 may be wall thickness 217 .

[0250] In some figures, ophthalmic article 100 may be a square-shaped (eg, extruded square-shaped) ophthalmic article 211. FIG. FIG. 2E illustrates a plan view of a square-shaped (eg, extruded square-shaped) ophthalmic article 211 . FIG. 2F illustrates a cross-sectional view of a square-shaped (eg, extruded square-shaped) ophthalmic article 211 . A square-shaped (eg, extruded square-shaped) ophthalmic article 211 can include internal structures (eg, holes) 110 that can be square holes 255 . Internal structure 110 includes an inner diameter or side edge 240 . The inner diameter or side edge 240 can be the side edge 214 . Square-shaped ophthalmic article 211 may also include outer diameter or edge 230 , cross-sectional thickness 250 and/or wall thickness 260 . The outer diameter or edge 230 can be the outer edge 213 . Cross-sectional thickness 250 may be cross-sectional thickness 215 . Wall thickness 260 may be wall thickness 218 .

[0251] In some figures, the ophthalmic article 100 may be an octagonal ophthalmic article 270. FIG. FIG. 2G illustrates a plan view of an octagonal ophthalmic article 270 . FIG. 2H illustrates a cross-sectional view of an octagonal ophthalmic article 270 . Octagonal ophthalmic article 270 may include internal structures (eg, pores) 110 , which may be octagonal pores 272 . Internal structure 110 includes an inner diameter or side edge 240 . The inner diameter or side edge 240 can be the inner diameter 274 . Octagonal ophthalmic article 270 may also include outer diameter or edge 230 , cross-sectional thickness 250 and/or wall thickness 260 . The outer diameter or edge 230 can be the outer edge 276 . Cross-sectional thickness 250 may be cross-sectional thickness 278 . Wall thickness 260 may be wall thickness 280 .

[0252] In some embodiments, inner diameter 240 (eg, inner diameter 204, inner diameter 209, inner diameter 274) or inner surface length 240 (eg, inner diameter 214) can be between about 0.05 millimeters (mm) and 6 mm.

[0253] In some embodiments, the inner diameter 240 or inner surface length 240 can be between about 0.05 mm and 6 mm. In some embodiments, the inner diameter 240 or inner surface length 240 is from about 0.05 mm to about 0.5 mm, from about 0.05 mm to about 0.1 mm, from about 0.05 mm to about 1.5 mm, from about 0.05 mm to about 0.1 mm. 0.05 mm to about 2.5 mm, about 0.05 mm to about 3 mm, about 0.05 mm to about 3.5 mm, about 0.05 mm to about 4 mm, about 0.05 mm to about 4.5 mm , about 0.05 mm to about 5 mm, about 0.05 mm to about 5.5 mm, about 0.05 mm to about 6 mm, about 0.5 mm to about 0.1 mm, about 0.5 mm to about 1.5 mm, about 0.05 mm to about 5 mm. 5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 3.5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 4.5 mm , about 0.5 mm to about 5 mm, about 0.5 mm to about 5.5 mm, about 0.5 mm to about 6 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 2.5 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 3.5 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 4.5 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 5.5 mm, about 1 mm to about 6 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 3.5 mm , about 1.5 mm to about 4 mm, about 1.5 mm to about 4.5 mm, about 1.5 mm to about 5 mm, about 1.5 mm to about 5.5 mm, about 1.5 mm to about 6 mm, about 2 mm to about 2 .5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2 mm to about 4.5 mm, about 2 mm to about 5 mm, about 2 mm to about 5.5 mm, about 2 mm to about 6 mm , about 2.5 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 2.5 mm to about 4 mm, about 2.5 mm to about 4.5 mm, about 2.5 mm to about 5 mm, about 2.5 mm to about 5.5 mm, about 2.5 mm to about 6 mm, about 3 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3 mm to about 4.5 mm, about 3 mm to about 5 mm, about 3 mm to about 5.5 mm, about 3 mm to about 6 mm, about 3.5 mm to about 4 mm, about 3.5 mm to about 4.5 mm, about 3.5 mm to about 5 mm, about 3.5 mm to about 5.5 mm, about 3.5 mm to about 6 mm, about 4 mm to about 4.5 mm, about 4 mm to about 5 mm, about 4 mm to about 5.5 mm, about 4.5 mm to about 5 mm, about 4.5 mm to about 5.5 mm, about 4.5 mm to about 6 mm, about 5 mm to about 5.5 mm, about 5 mm to about 6 mm, or about 5.5 mm to about 6 mm.

[0254] In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device is at least about 0.05 mm, at least about 0.1 mm, at least about 0.15 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.5 mm. 65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, at least about 1 mm, at least about 1.05 mm, at least about 1.1 mm, at least about 1.15 mm, at least about 1.2 mm, at least about 1.25 mm, at least about 1.3 mm, at least about 1.35 mm, at least about 1.4 mm, at least about 1.45 mm, at least about 1.5 mm 5 mm, at least about 1.55 mm, at least about 1.6 mm, at least about 1.65 mm, at least about 1.7 mm, at least about 1.75 mm, at least about 1.8 mm, at least about 1.85 mm, at least about 1.9 mm, at least about 1.95 mm, at least about 2 mm, at least about 2.05 mm, at least about 2.1 mm, at least about 2.15 mm, at least about 2.2 mm, at least about 2.25 mm, at least about 2.3 mm; 4 mm, at least about 2.5 mm, at least about 2.6 mm, at least about 2.7 mm, at least about 2.8 mm, at least about 2.9 mm, at least about 3 mm, at least about 3.5 mm, at least about 4 mm, at least about 4 mm. It can be 5 mm, at least about 5 mm, at least about 5.5 mm, or at least about 6 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be at least about 0.1 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be at least about 0.5 mm.

[0255] In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device is at most about 0.05 mm, at most about 0.1 mm, at most about 0.15 mm, at most about 0.05 mm. 2 mm, maximum about 0.25 mm, maximum about 0.3 mm, maximum about 0.35 mm, maximum about 0.4 mm, maximum about 0.45 mm, maximum about 0.5 mm, maximum about 0.55 mm , a maximum of about 0.6 mm, a maximum of about 0.65 mm, a maximum of about 0.7 mm, a maximum of about 0.75 mm, a maximum of about 0.8 mm, a maximum of about 0.85 mm, a maximum of about 0.9 mm, Maximum about 0.95 mm, Maximum about 1 mm, Maximum about 1.05 mm, Maximum about 1.1 mm, Maximum about 1.15 mm, Maximum about 1.2 mm, Maximum about 1.25 mm, Maximum about 1.3 mm, maximum about 1.35 mm, maximum about 1.4 mm, maximum about 1.45 mm, maximum about 1.5 mm, maximum about 1.55 mm, maximum about 1.6 mm, maximum about 1 .65 mm, maximum about 1.7 mm, maximum about 1.75 mm, maximum about 1.8 mm, maximum about 1.85 mm, maximum about 1.9 mm, maximum about 1.95 mm, maximum about 2 mm, Maximum about 2.05 mm, Maximum about 2.1 mm, Maximum about 2.15 mm, Maximum about 2.2 mm, Maximum about 2.25 mm, Maximum about 2.3 mm, Maximum about 2.4 mm, Maximum But about 2.5 mm, maximum about 2.6 mm, maximum about 2.7 mm, maximum about 2.8 mm, maximum about 2.9 mm, maximum about 3 mm, maximum about 3.5 mm, maximum about 4 mm , at most about 4.5 mm, at most about 5 mm, at most about 5.5 mm, or at most about 6 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be at most about 0.5 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be at most about 1 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be at most about 1.5 mm.

[0256] In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device is about 0.05 mm, about 0.1 mm, about 0.15 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.65 mm, about 0.7 mm, about 0.75 mm, about 0.8 mm, about 0.85 mm, about 0.9 mm, about 0.95 mm, about 1 mm, about 1.05 mm, about 1.1 mm, about 1.15 mm, about 1.2 mm, about 1.25 mm, about 1.5 mm 3 mm, about 1.35 mm, about 1.4 mm, about 1.45 mm, about 1.5 mm, about 1.55 mm, about 1.6 mm, about 1.65 mm, about 1.7 mm, about 1.75 mm, about 1.5 mm. 8 mm, about 1.85 mm, about 1.9 mm, about 1.95 mm, about 2 mm, about 2.05 mm, about 2.1 mm, about 2.15 mm, about 2.2 mm, about 2.25 mm, about 2.3 mm, about 2.4 mm, about 2.5 mm, about 2.6 mm, about 2.7 mm, about 2.8 mm, about 2.9 mm, about 3 mm, about 3.1 mm, about 3.2 mm, about 3.3 mm, about 3 .4 mm, about 3.5 mm, about 3.6 mm, about 3.7 mm, about 3.8 mm, about 3.9 mm, about 4 mm, about 4.1 mm, about 4.2 mm, about 4.3 mm, about 4.4 mm , about 4.5 mm, about 4.6 mm, about 4.7 mm, about 4.8 mm, about 4.9 mm, about 5 mm, about 5.1 mm, about 5.2 mm, about 5.3 mm, about 5.4 mm, about It can be 5.5 mm, about 5.6 mm, about 5.7 mm, about 5.8 mm, about 5.9 mm, or about 6 mm. In some embodiments, the inner diameter 240 or inner surface length 240 of the ophthalmic device can be about 0.5 mm.

[0257] In some embodiments, the wall thickness 260 (eg, wall thickness 216, wall thickness 217, wall thickness 218, wall thickness 280) of the ophthalmic article can be between about 0.001 mm and 3 mm. In some embodiments, the wall thickness of the ophthalmic article is about 0.001 mm to about 0.01 mm, about 0.001 mm to about 0.1 mm, about 0.001 mm to about 0.2 mm, about 0.001 mm to about 0.3 mm, about 0.001 mm to about 0.4 mm, about 0.001 mm to about 0.5 mm, about 0.001 mm to about 1 mm, about 0.001 mm to about 1.5 mm, about 0.001 mm to about 2 mm , about 0.001 mm to about 2.5 mm, about 0.001 mm to about 3 mm, about 0.01 mm to about 0.1 mm, about 0.01 mm to about 0.2 mm, about 0.01 mm to about 0.3 mm, about 0.01 mm to about 0.4 mm, about 0.01 mm to about 0.5 mm, about 0.01 mm to about 1 mm, about 0.01 mm to about 1.5 mm, about 0.01 mm to about 2 mm, about 0.01 mm to about 2.5 mm, about 0.01 mm to about 3 mm, about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.3 mm, about 0.1 mm to about 0.4 mm, about 0.1 mm to about 0 .5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 2.5 mm, about 0.1 mm to about 3 mm, about 0.5 mm. 2 mm to about 0.3 mm, about 0.2 mm to about 0.4 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 1 mm, about 0.2 mm to about 1.5 mm, about 0.2 mm to about 2 mm, about 0.2 mm to about 2.5 mm, about 0.2 mm to about 3 mm, about 0.3 mm to about 0.4 mm, about 0.3 mm to about 0.5 mm, about 0.3 mm to about 1 mm, about 0.3 mm to about 1.5 mm, about 0.3 mm to about 2 mm, about 0.3 mm to about 2.5 mm, about 0.3 mm to about 3 mm, about 0.4 mm to about 0.5 mm, about 0.4 mm to about 1 mm, about 0.4 mm to about 1.5 mm, about 0.4 mm to about 2 mm, about 0.4 mm to about 2.5 mm, about 0.4 mm to about 3 mm, about 0.5 mm to about 1 mm, about 0.4 mm to about 2.5 mm; 5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0.5 mm to about 3 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2.5 mm, about 1 mm to about 3 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 1.5 mm to about 3 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm , or from about 2.5 mm to about 3 mm. In some embodiments, the wall thickness of the ophthalmic article can be from about 0.1 mm to about 1 mm. In some embodiments, the wall thickness of the ophthalmic article can be from about 0.1 mm to about 1.5 mm.

[0258] In some embodiments, the wall thickness of the ophthalmic article is at least about 0.001 mm, at least about 0.005 mm, at least about 0.01 mm, at least about 0.02 mm, at least about 0.03 mm, at least about 0.03 mm. 0.04 mm, at least about 0.05 mm, at least about 0.06 mm, at least about 0.07 mm, at least about 0.08 mm, at least about 0.09 mm, at least about 0.1 mm, at least about 0.15 mm, at least about 0. 2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, at least about 1 mm, at least about 1.5 mm; 2 mm, at least about 1.4 mm, at least about 1.6 mm, at least about 1.8 mm, at least about 2 mm, at least about 2.2 mm, at least about 2.4 mm, at least about 2.6 mm, at least about 2.8 mm or at least about It may be 3 mm. In some embodiments, the ophthalmic article may have a wall thickness of at least about 0.1 mm. In some embodiments, the ophthalmic article may have a wall thickness of at least about 0.5 mm. In some embodiments, the ophthalmic article may have a wall thickness of at least about 1 mm.

[0259] In some embodiments, the wall thickness of the ophthalmic article is at most about 0.001 mm, at most about 0.005 mm, at most about 0.01 mm, at most about 0.02 mm, at most about 0 0.03 mm, up to about 0.04 mm, up to about 0.05 mm, up to about 0.06 mm, up to about 0.07 mm, up to about 0.08 mm, up to about 0.09 mm, up to about 0.03 mm. 1 mm, maximum about 0.15 mm, maximum about 0.2 mm, maximum about 0.25 mm, maximum about 0.3 mm, maximum about 0.35 mm, maximum about 0.4 mm, maximum about 0.45 mm , at most about 0.5 mm, at most about 0.55 mm, at most about 0.6 mm, at most about 0.65 mm, at most about 0.7 mm, at most about 0.75 mm, at most about 0.8 mm, Maximum about 0.85 mm, maximum about 0.9 mm, maximum about 0.95 mm, maximum about 1 mm, maximum about 1.2 mm, maximum about 1.4 mm, maximum about 1.6 mm, maximum about It may be 1.8 mm, up to about 2 mm, up to about 2.2 mm, up to about 2.4 mm, up to about 2.6 mm, up to about 2.8 mm, or up to about 3 mm. In some embodiments, the wall thickness of the ophthalmic article may be up to about 0.5 mm. In some embodiments, the wall thickness of the ophthalmic article may be up to about 1 mm. In some embodiments, the wall thickness of the ophthalmic article may be up to about 1.5 mm.

[0260] In some embodiments, the wall thickness of the ophthalmic article is about 0.001 mm, about 0.005 mm, about 0.01 mm, about 0.02 mm, about 0.03 mm, about 0.04 mm, about 0.04 mm. 0.05 mm, about 0.06 mm, about 0.07 mm, about 0.08 mm, about 0.09 mm, about 0.1 mm, about 0.11 mm, about 0.12 mm, about 0.13 mm, about 0.14 mm, about 0 .15 mm, about 0.16 mm, about 0.17 mm, about 0.18 mm, about 0.19 mm, about 0.2 mm, about 0.21 mm, about 0.22 mm, about 0.23 mm, about 0.24 mm, about 0 .25 mm, about 0.26 mm, about 0.27 mm, about 0.28 mm, about 0.29 mm, about 0.3 mm, about 0.31 mm, about 0.32 mm, about 0.33 mm, about 0.34 mm, about 0 .35 mm, about 0.36 mm, about 0.37 mm, about 0.38 mm, about 0.39 mm, about 0.4 mm, about 0.41 mm, about 0.42 mm, about 0.43 mm, about 0.44 mm, about 0 .45 mm, about 0.46 mm, about 0.47 mm, about 0.48 mm, about 0.49 mm, about 0.5 mm, about 0.51 mm, about 0.52 mm, about 0.53 mm, about 0.54 mm, about 0 .55 mm, about 0.56 mm, about 0.57 mm, about 0.58 mm, about 0.59 mm, about 0.6 mm, about 0.61 mm, about 0.62 mm, about 0.63 mm, about 0.64 mm, about 0 .65 mm, about 0.66 mm, about 0.67 mm, about 0.68 mm, about 0.69 mm, about 0.7 mm, about 0.71 mm, about 0.72 mm, about 0.73 mm, about 0.74 mm, about 0 .75 mm, about 0.76 mm, about 0.77 mm, about 0.78 mm, about 0.79 mm, about 0.8 mm, about 0.81 mm, about 0.82 mm, about 0.83 mm, about 0.84 mm, about 0 .85 mm, about 0.86 mm, about 0.87 mm, about 0.88 mm, about 0.89 mm, about 0.9 mm, about 0.91 mm, about 0.92 mm, about 0.93 mm, about 0.94 mm, about 0 .95 mm, about 0.96 mm, about 0.97 mm, about 0.98 mm, about 0.99 mm, about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm , about 1.6 mm, about 1.7 mm, about 1.8 mm, about 1.9 mm, about 2 mm, about 2.1 mm, about 2.2 mm, about 2.3 mm, about 2.4 mm, about 2.5 mm, about It may be 2.6 mm, about 2.7 mm, about 2.8 mm, about 2.9 mm, or about 3 mm. In some embodiments, the ophthalmic article may have a wall thickness of about 0.7 mm.

[0261] In some embodiments, the ophthalmic article comprises a portion of the ophthalmic device when the ophthalmic article is coupled (eg, adheres) to a portion of the ophthalmic device (eg, an IOL haptic). (eg, IOL haptics) to about 0.32 mm or less. In some embodiments, the ophthalmic article comprises a portion (e.g., a , IOL haptics) at most about 3 mm, 2.9 mm, 2.8 mm, 2.7 mm, 2.6 mm, 2.5 mm, 2.4 mm, 2.3 mm, 2.2 mm, 2.1 mm, 2mm, 1.9mm, 1.8mm, 1.7mm, 1.6mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1mm, 0.9mm, 0.8mm, 0.8mm It extends to 7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, 0.1 mm or less.

[0262] In some embodiments, the ophthalmic article is combined (e.g., adhered) to a portion (e.g., haptics) of an ophthalmic device (e.g., IOL) and an ophthalmic device (e.g., an IOL). at least about 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm over the portion (e.g., haptics) of the IOL) , 1mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2mm, 2.1mm, 2.2mm, 2 .3mm, 2.4mm, 2.5mm, 2.6mm, 2.7mm, 2.8mm, 2.9mm, 3mm or more.

[0263] In some embodiments, the ophthalmic article combines (e.g., adheres) a portion (e.g., haptics) of an ophthalmic device (e.g., IOL) with an ophthalmic device (e.g., IOL). about 0.1 mm, about 0.2 mm, about 0.3 mm, about 0.4 mm, about 0.5 mm, about 0.6 mm, about 0.7 mm, about 0 .8 mm, about 0.9 mm, about 1 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm, about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm , about 1.9 mm, about 2 mm, about 2.1 mm, about 2.2 mm, about 2.3 mm, about 2.4 mm, about 2.5 mm, about 2.6 mm, about 2.7 mm, about 2.8 mm, about Extends 2.9 mm or about 3 mm.

[0264] In some embodiments, the cross-sectional thickness 250 (eg, cross-sectional thickness 205, cross-sectional thickness 210, cross-sectional thickness 215, cross-sectional thickness 278) of the ophthalmic article is between about 0.05 mm and 3 mm. There may be.

[0265] In some embodiments, the cross-sectional thickness of the ophthalmic article may be from about 0.01 mm to about 4 mm. In some embodiments, the ophthalmic article has a cross-sectional thickness of about 0.01 mm to about 0.05 mm, about 0.01 mm to about 0.1 mm, about 0.01 mm to about 0.5 mm, about 0.01 mm to about 1 mm, about 0.01 mm to about 1.5 mm, about 0.01 mm to about 2 mm, about 0.01 mm to about 2.5 mm, about 0.01 mm to about 3 mm, about 0.01 mm to about 3.5 mm, about 0.01 mm to about 4 mm, about 0.05 mm to about 0.1 mm, about 0.05 mm to about 0.5 mm, about 0.05 mm to about 1 mm, about 0.05 mm to about 1.5 mm, about 0.05 mm to about 2 mm, about 0.05 mm to about 2.5 mm, about 0.05 mm to about 3 mm, about 0.05 mm to about 3.5 mm, about 0.05 mm to about 4 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 2.5 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 3.5 mm, about 0.1 mm to about 4 mm, about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0 .5 mm to about 3 mm, about 0.5 mm to about 3.5 mm, about 0.5 mm to about 4 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2.5 mm, about 1 mm to about 3 mm, about 1 mm to about 3.5 mm, about 1 mm to about 4 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 3.5 mm. 5 mm, about 1.5 mm to about 4 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2.5 mm to about 3 mm, about 2.5 mm It may be from about 3.5 mm, from about 2.5 mm to about 4 mm, from about 3 mm to about 3.5 mm, from about 3 mm to about 4 mm, or from about 3.5 mm to about 4 mm. In some embodiments, the cross-sectional thickness of the ophthalmic article may be from about 0.1 mm to about 1 mm.

[0266] In some embodiments, the cross-sectional thickness of the ophthalmic article is at least about 0.01 mm, at least about 0.05 mm, at least about 0.1 mm, at least about 0.5 mm, at least about 1 mm, at least about 1 5 mm, at least about 2 mm, at least about 2.5 mm, at least about 3 mm, at least about 3.5 mm, or at least about 4 mm. In some embodiments, the cross-sectional thickness of the ophthalmic article may be at least about 0.1 mm. In some embodiments, the cross-sectional thickness of the ophthalmic article may be at least about 0.5 mm.

[0267] In some embodiments, the cross-sectional thickness of the ophthalmic article is at most about 0.01 mm, at most about 0.05 mm, at most about 0.1 mm, at most about 0.5 mm, at most about It may be 1 mm, up to about 1.5 mm, up to about 2 mm, up to about 2.5 mm, up to about 3 mm, up to about 3.5 mm, or up to about 4 mm. In some embodiments, the cross-sectional thickness of the ophthalmic article may be at most about 1 mm. In some embodiments, the cross-sectional thickness of the ophthalmic article may be at most about 1.5 mm.

[0268] In some embodiments, outer diameter 230 (eg, outer diameter 203, outer diameter 208, outer diameter 276) or outer edge 230 (eg, outer diameter 213) is between about 0.1 millimeters (mm) and 6 mm may be In some embodiments, the outer diameter or edge of the ophthalmic article is about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 2.5 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 3.5 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 4.5 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 5.5 mm, about 1 mm to about 6 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 3.5 mm, about 1.5 mm to about 4 mm, about 1.5 mm to about 4.5 mm, about 1.5 mm to about 5 mm, about 1.5 mm to about 5.5 mm, about 1.5 mm to about 6 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2 mm to about 4.5 mm, about 2 mm to about 5 mm, about 2 mm to about 5.5 mm, about 2 mm to about 6 mm, about 2.5 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 2.5 mm to about 4 mm, about 2.5 mm to about 4.5 mm, about 2.5 mm to about 5 mm, about 2.5 mm to about 5.5 mm, about 2.5 mm to About 6 mm, about 3 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3 mm to about 4.5 mm, about 3 mm to about 5 mm, about 3 mm to about 5.5 mm, about 3 mm to about 6 mm, about 3.5 mm or more About 4 mm, about 3.5 mm to about 4.5 mm, about 3.5 mm to about 5 mm, about 3.5 mm to about 5.5 mm, about 3.5 mm to about 6 mm, about 4 mm to about 4.5 mm, about 4 mm to about 5 mm, about 4 mm to about 5.5 mm, about 4.5 mm to about 5 mm, about 4.5 mm to about 5.5 mm, about 4.5 mm to about 6 mm, about 5 mm to about 5.5 mm, about 5 mm to about 6 mm , or from about 5.5 mm to about 6 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be from about 0.1 mm to about 1.5 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be from about 0.5 mm to about 1.5 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be from about 0.5 mm to about 2 mm.

[0269] In some embodiments, the outer diameter or edge of the ophthalmic article is at least about 0.1 mm, at least about 0.15 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, at least about 1 mm, at least about 1.05 mm, at least about 1.1 mm, at least about 1.15 mm, at least about 1.2 mm, at least about 1.25 mm, at least about 1.3 mm, at least about 1.35 mm, at least about 1.4 mm, at least about 1.45 mm, at least about 1.5 mm, at least about 1.55 mm, at least about 1.6 mm, at least about 1.65 mm, at least about 1.7 mm, at least about 1.75 mm, at least about 1.8 mm, at least about 1.85 mm, at least about 1.9 mm, at least about 1.95 mm, at least about 2 mm, at least about 2.05 mm, at least about 2.1 mm, at least about 2.15 mm, at least about 2.2 mm, at least about 2.25 mm, at least about 2.3 mm, at least about 2.4 mm, at least about 2.5 mm, at least about 2.6 mm, at least about 2.7 mm, at least about 2.8 mm, at least about 2.9 mm, at least about 3 mm, at least about 3.5 mm, at least about 4 mm, at least about 4.5 mm, at least about 5 mm, at least about 5 mm. It may be 5 mm, or at least about 6 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be at least about 0.5 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be at least about 1 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be at least about 1.5 mm.

[0270] In some embodiments, the outer diameter or edge of the ophthalmic article is at most about 0.1 mm, at most about 0.15 mm, at most about 0.2 mm, at most about 0.25 mm, at most about 0.3 mm, about 0.35 mm at maximum, about 0.4 mm at maximum, about 0.45 mm at maximum, about 0.5 mm at maximum, about 0.55 mm at maximum, about 0.6 mm at maximum, at most about 0.65 mm, maximum about 0.7 mm, maximum about 0.75 mm, maximum about 0.8 mm, maximum about 0.85 mm, maximum about 0.9 mm, maximum about 0.95 mm, maximum about 1 mm , a maximum of about 1.05 mm, a maximum of about 1.1 mm, a maximum of about 1.15 mm, a maximum of about 1.2 mm, a maximum of about 1.25 mm, a maximum of about 1.3 mm, a maximum of about 1.35 mm, Maximum about 1.4 mm, Maximum about 1.45 mm, Maximum about 1.5 mm, Maximum about 1.55 mm, Maximum about 1.6 mm, Maximum about 1.65 mm, Maximum about 1.7 mm, Maximum but about 1.75 mm, maximum about 1.8 mm, maximum about 1.85 mm, maximum about 1.9 mm, maximum about 1.95 mm, maximum about 2 mm, maximum about 2.05 mm, maximum about 2 .1 mm, up to about 2.15 mm, up to about 2.2 mm, up to about 2.25 mm, up to about 2.3 mm, up to about 2.4 mm, up to about 2.5 mm, up to about 2.0 mm. 6 mm, maximum about 2.7 mm, maximum about 2.8 mm, maximum about 2.9 mm, maximum about 3 mm, maximum about 3.5 mm, maximum about 4 mm, maximum about 4.5 mm, maximum about It may be 5 mm, up to about 5.5 mm, or up to about 6 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be at most about 2 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be at most about 1 mm.

[0271] In some embodiments, the outer diameter or edge of the ophthalmic article is about 0.1 mm, about 0.15 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.65 mm, about 0.7 mm, about 0.75 mm, about 0.8 mm, about 0.85 mm, about 0.9 mm, about 0.95 mm, about 1 mm, about 1.05 mm, about 1.1 mm, about 1.15 mm, about 1.2 mm, about 1.25 mm, about 1.3 mm, about 1.35 mm, about 1 .4 mm, about 1.45 mm, about 1.5 mm, about 1.55 mm, about 1.6 mm, about 1.65 mm, about 1.7 mm, about 1.75 mm, about 1.8 mm, about 1.85 mm, about 1 .9 mm, about 1.95 mm, about 2 mm, about 2.05 mm, about 2.1 mm, about 2.15 mm, about 2.2 mm, about 2.25 mm, about 2.3 mm, about 2.4 mm, about 2.5 mm , about 2.6 mm, about 2.7 mm, about 2.8 mm, about 2.9 mm, about 3 mm, about 3.1 mm, about 3.2 mm, about 3.3 mm, about 3.4 mm, about 3.5 mm, about 3.6 mm, about 3.7 mm, about 3.8 mm, about 3.9 mm, about 4 mm, about 4.1 mm, about 4.2 mm, about 4.3 mm, about 4.4 mm, about 4.5 mm, about 4.5 mm. 6 mm, about 4.7 mm, about 4.8 mm, about 4.9 mm, about 5 mm, about 5.1 mm, about 5.2 mm, about 5.3 mm, about 5.4 mm, about 5.5 mm, about 5.6 mm, It may be about 5.7 mm, about 5.8 mm, about 5.9 mm, or about 6 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be about 1.5 mm. In some embodiments, the outer diameter or edge of the ophthalmic article may be about 1.3 mm.

[0272] In some embodiments, the shape of the ophthalmic article can also affect the release rate of the active agent and/or diagnostic agent for a homogenous delivery device. For example, in some cases, a thinner homogeneous delivery device may biodegrade more rapidly than a thicker homogeneous delivery device, resulting in a faster active agent and/or diagnostic agent release profile. Additionally, in some cases, the outer rim or other section of the ophthalmic article has a substantially zero-order release profile following the initial burst of active agent and/or diagnostic agent. It can be made thinner and/or rougher than the part. Moreover, in some instances, the overall geometry of the homogenous delivery device alone can affect the release rate of the active agent and/or diagnostic agent. For example, the exposed surface area to volume ratio can be increased to increase release rate and degradation.

[0273] In one example, it can provide efficacy for the treatment of uveitis and post-cataract surgery inflammation. For example, dexamethasone can be dispersed in a biodegradable polymer matrix. Dexamethasone dosages can vary, but generally about 100 μg to about 1000 μg can be effective. In some cases, subjects may be classified as low risk due to various factors such as age, secondary complications, pre-existing conditions, while other subjects may be classified as high risk. Low-risk patients may benefit from lower dosages of about 100 μg to about 500 μg. In contrast, high risk individuals can be administered higher dosages of about 500 μg to about 1000 μg. Ophthalmic articles can be specifically designed and tested for the various conditions and treatments disclosed herein (e.g., treatment of post-operative inflammation) and contain an active agent (e.g., a pharmaceutically active agent) at up to or about It can be delivered for 2 weeks or more. In other examples, other ophthalmic articles (e.g., biodegradable active agent delivery devices) can be designed and tested for the treatment of post-operative inflammation and uveitis, containing up to or about 4 active agents. It can be delivered for a week or more. In some cases, one, two, or more implants (e.g., ophthalmic articles and/or ophthalmic devices) are used per eye during surgery, depending on the severity of the condition (e.g., inflammation). can be administered.

[0274] In some embodiments, each eye comprises at least about 1 implant, at least about 2 implants, at least about 3 implants, at least about 4 implants, at least about 5 implants. Implants, at least about 6 implants, at least about 7 implants, at least about 8 implants, at least about 9 implants, or at least about 10 implants may be administered. In some embodiments, depending on the severity of the condition, each eye has up to about 1 implant, up to about 2 implants, up to about 3 implants, up to about 4 implants. 1 implants, up to about 5 implants, up to about 6 implants, up to about 7 implants, up to about 8 implants, up to about 9 implants or Up to about 10 implants may be administered. In some embodiments, each eye may be administered multiple implants (eg, two or more implants), the multiple implants being administered to the eye simultaneously or sequentially. good too. Multiple implants may be administered at the same location within the eye or at different locations within the eye.

[0275] In any of the various embodiments, the one or more ophthalmic articles and/or ophthalmic devices (e.g., intraocular devices) bring the ophthalmic articles and/or ophthalmic devices closest to the eye of the subject. can include materials (eg, polymeric materials) described herein that have tensile strength, glass transition temperature, modulus (eg, Young's modulus), and/or elongation at break suitable for.

[0276] An ophthalmic article, an ophthalmic article coupled with at least a portion of an ophthalmic device, and/or a biocompatible matrix as described herein can be made through a small incision (eg, about 1.8 mm to 2 mm). .5 mm) to fit within the subject's eye. The tensile strength of the material is a suitable amount such that the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix can withstand deformation after implantation. may For example, if the material is too soft and does not include adequate tensile strength, the ophthalmic article and/or ophthalmic article coupled with at least a portion of the ophthalmic device may disintegrate after implantation.

[0277] In some embodiments, the ophthalmic article, the ophthalmic article coupled with at least a portion of the ophthalmic device, and/or the biocompatible matrix can have a tensile strength of about 25 MPa to 35 MPa. can. In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix is about 25 MPa to about 26 MPa, about 25 MPa to about 27 MPa, about 25 MPa to About 28 MPa, about 25 MPa to about 29 MPa, about 25 MPa to about 30 MPa, about 25 MPa to about 31 MPa, about 25 MPa to about 32 MPa, about 25 MPa to about 33 MPa, about 25 MPa to about 34 MPa, about 25 MPa to about 35 MPa, about 26 MPa to about 27 MPa , about 26 MPa to about 28 MPa, about 26 MPa to about 29 MPa, about 26 MPa to about 30 MPa, about 26 MPa to about 31 MPa, about 26 MPa to about 32 MPa, about 26 MPa to about 33 MPa, about 26 MPa to about 34 MPa, about 26 MPa to about 35 MPa, about 27 MPa to about 28 MPa, about 27 MPa to about 29 MPa, about 27 MPa to about 30 MPa, about 27 MPa to about 31 MPa, about 27 MPa to about 32 MPa, about 27 MPa to about 33 MPa, about 27 MPa to about 34 MPa, about 27 MPa to about 35 MPa, about 28 MPa to About 29 MPa, about 28 MPa to about 30 MPa, about 28 MPa to about 31 MPa, about 28 MPa to about 32 MPa, about 28 MPa to about 33 MPa, about 28 MPa to about 34 MPa, about 28 MPa to about 35 MPa, about 29 MPa to about 30 MPa, about 29 MPa to about 31 MPa , about 29 MPa to about 32 MPa, about 29 MPa to about 33 MPa, about 29 MPa to about 34 MPa, about 29 MPa to about 35 MPa, about 30 MPa to about 31 MPa, about 30 MPa to about 32 MPa, about 30 MPa to about 33 MPa, about 30 MPa to about 34 MPa, about 30 MPa to about 35 MPa, about 31 MPa to about 32 MPa, about 31 MPa to about 33 MPa, about 31 MPa to about 34 MPa, about 31 MPa to about 35 MPa, about 32 MPa to about 33 MPa, about 32 MPa to about 34 MPa, about 32 MPa to about 35 MPa, about 33 MPa to It can have a tensile strength of about 34 MPa, about 33 MPa to about 35 MPa, or about 34 MPa to about 35 MPa.

[0278] In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix is at least about 25 MPa, at least about 26 MPa, at least about 27 MPa, It can have a tensile strength of at least about 28 MPa, at least about 29 MPa, at least about 30 MPa, at least about 31 MPa, at least about 32 MPa, at least about 33 MPa, at least about 34 MPa, or at least about 35 MPa.

[0279] In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix is at most about 25 MPa, at most about 26 MPa, at most It may have a tensile strength of about 27 MPa, up to about 28 MPa, up to about 29 MPa, up to about 30 MPa, up to about 31 MPa, up to about 32 MPa, up to about 33 MPa, up to about 34 MPa, or up to about 35 MPa. can.

[0280] In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix is about 25 MPa, about 26 MPa, about 27 MPa, about 28 MPa, It can have a tensile strength of about 29 MPa, about 30 MPa, about 31 MPa, about 32 MPa, about 33 MPa, about 34 MPa, or about 35 MPa.

[0281] In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix has a tensile strength of from about 0.5 MPa to about 50 MPa. There may be. In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix has a tensile strength of about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 0.5 MPa, about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 1 MPa, to about 0.5 MPa to about 0.5 MPa, to about 0.5 MPa to about 1 MPa. 5 MPa to about 5 MPa, about 0.5 MPa to about 10 MPa, about 0.5 MPa to about 15 MPa, about 0.5 MPa to about 20 MPa, about 0.5 MPa to about 25 MPa, about 0.5 MPa to about 30 MPa, about 0.5 MPa to About 35 MPa, about 0.5 MPa to about 40 MPa, about 0.5 MPa to about 45 MPa, about 0.5 MPa to about 50 MPa, about 1 MPa to about 5 MPa, about 1 MPa to about 10 MPa, about 1 MPa to about 15 MPa, about 1 MPa to about 20 MPa , about 1 MPa to about 25 MPa, about 1 MPa to about 30 MPa, about 1 MPa to about 35 MPa, about 1 MPa to about 40 MPa, about 1 MPa to about 45 MPa, about 1 MPa to about 50 MPa, about 5 MPa to about 10 MPa, about 5 MPa to about 15 MPa, about 5 MPa to about 20 MPa, about 5 MPa to about 25 MPa, about 5 MPa to about 30 MPa, about 5 MPa to about 35 MPa, about 5 MPa to about 40 MPa, about 5 MPa to about 45 MPa, about 5 MPa to about 50 MPa, about 10 MPa to about 15 MPa, about 10 MPa to about 20 MPa, about 10 MPa to about 25 MPa, about 10 MPa to about 30 MPa, about 10 MPa to about 35 MPa, about 10 MPa to about 40 MPa, about 10 MPa to about 45 MPa, about 10 MPa to about 50 MPa, about 15 MPa to about 20 MPa, about 15 MPa to about 25 MPa , about 15 MPa to about 30 MPa, about 15 MPa to about 35 MPa, about 15 MPa to about 40 MPa, about 15 MPa to about 45 MPa, about 15 MPa to about 50 MPa, about 20 MPa to about 25 MPa, about 20 MPa to about 30 MPa, about 20 MPa to about 35 MPa, about 20 MPa to about 40 MPa, about 20 MPa to about 45 MPa, about 20 MPa to about 50 MPa, about 25 MPa to about 30 MPa, about 25 MPa to about 35 MPa, about 25 MPa to about 40 MPa, about 25 MPa to about 45 MPa, about 25 MPa to about 50 MPa, about 30 MPa to About 35 MPa, about 30 MPa to about 40 MPa, about 30 MPa to about 45 MPa, about 30 MPa to about 50 MPa, about 35 MPa to about 40 MPa, about 35 MPa to about 45 MPa, about 35 MPa to about 50 MPa, about 40 MPa to about 45 MPa, about 40 MPa to about 50 MPa , or from about 45 MPa to about 50 MPa. In some embodiments, the ophthalmic article, the ophthalmic article associated with at least a portion of the ophthalmic device, and/or the biocompatible matrix has a tensile strength of at least about 0.5 MPa, at least about 1 MPa, at least It may be about 5 MPa, at least about 10 MPa, at least about 15 MPa, at least about 20 MPa, at least about 25 MPa, at least about 30 MPa, at least about 35 MPa, at least about 40 MPa, at least about 45 MPa, or at least about 50 MPa. In some embodiments, the ophthalmic article and/or polymeric material has a tensile strength of at most about 0.5 MPa, at most about 1 MPa, at most about 5 MPa, at most about 10 MPa, at most about 15 MPa, at most It may be about 20 MPa, up to about 25 MPa, up to about 30 MPa, up to about 35 MPa, up to about 40 MPa, up to about 45 MPa, or up to about 50 MPa. In some embodiments, tensile strength may be measured or determined by tensile testing (eg, uniaxial tensile testing, biaxial tensile testing).

[0282] The glass transition temperature is the temperature at which a polymeric material transitions from a hard, glass-like material to a soft, rubber-like material. Such parameters are such that the ophthalmic article, the ophthalmic article coupled with at least a portion of the ophthalmic device, and/or the biocompatible matrix are flexible for use at room temperature and at various operating room temperatures. important for determining whether there is An ophthalmic article should be soft when implanted in the eye, otherwise it may not expand when implanted in the eye if it is rigid. Additionally, ophthalmic articles, ophthalmic devices and/or biocompatible matrices comprising materials that may be deformable (e.g., soft and conforming to surrounding tissue) may cause harm to the eye (e.g., iris chafing or irritation). is advantageous for reducing

[0283] In some embodiments, the ophthalmic article and/or biocompatible matrix may be at least as soft as an ophthalmic device (eg, an IOL). If the ophthalmic article and/or biocompatible matrix is more rigid than the ophthalmic device, the ophthalmic article and/or biocompatible matrix cuts through or into the ophthalmic device when implanted in the eye. may produce ridges and/or marks that may affect its optical or mechanical properties.

[0284] In some embodiments, the glass transition temperature may be well below that in a room (eg, operating room) where an ophthalmic article is bonded to a portion of an ophthalmic device (eg, an IOL). In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix can have a glass transition temperature of about -50°C to 50°C as measured by differential scanning calorimetry. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry.

[0285] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is about -15°C to about -10°C, about -15°C to about -5°C, about -15°C to about 0°C, about -15°C to about 5°C, about -15°C to about 10°C, about -15°C to about 15°C, about -15°C to about 20°C, about -15°C to about 25°C, About -15°C to about 30°C, about -15°C to about 35°C, about -15°C to about 40°C, about -10°C to about -5°C, about -10°C to about 0°C, about -10°C to about 5°C, about -10°C to about 10°C, about -10°C to about 15°C, about -10°C to about 20°C, about -10°C to about 25°C, about -10°C to about 30°C, About -10°C to about 35°C, about -10°C to about 40°C, about -5°C to about 0°C, about -5°C to about 5°C, about -5°C to about 10°C, about -5°C to about 15°C, about -5°C to about 20°C, about -5°C to about 25°C, about -5°C to about 30°C, about -5°C to about 35°C, about -5°C to about 40°C, about 0°C to about 5°C, about 0°C to about 10°C, about 0°C to about 15°C, about 0°C to about 20°C, about 0°C to about 25°C, about 0°C to about 30°C, about 0°C to about 35°C, about 0°C to about 40°C, about 5°C to about 10°C, about 5°C to about 15°C, about 5°C to about 20°C, about 5°C to about 25°C, about 5°C to about 30°C, about 5°C to about 35°C, about 5°C to about 40°C, about 10°C to about 15°C, about 10°C to about 20°C, about 10°C to about 25°C, about 10°C to about 30°C , about 10° C. to about 35° C., about 10° C. to about 40° C., about 15° C. to about 20° C., about 15° C. to about 25° C., about 15° C. to about 30° C., about 15° C. to about 35° C., about 15°C to about 40°C, about 20°C to about 25°C, about 20°C to about 30°C, about 20°C to about 35°C, about 20°C to about 40°C, about 25°C to about 30°C, about 25°C C. to about 35.degree. C., about 25.degree. C. to about 40.degree. C., about 30.degree. C. to about 35.degree. Glass transition temperature may be measured by differential scanning calorimetry. In some embodiments, the glass transition temperature may be measured by differential scanning calorimetry, thermomechanical analysis and/or dynamic mechanical analysis.

[0286] In some embodiments, the ophthalmic article and/or polymeric material (eg, a biocompatible polymeric matrix) is at least or up to about -15°C, at least or up to about -10°C, at least or up to about −5° C., at least or at most about 0° C., at least or at most about 5° C., at least or at most about 10° C., at least or at most about 14° C., at least or at most about 15° C., at least or at most about 16°C, at least or at most about 18°C, at least or at most about 20°C, at least or at most about 22°C, at least or at most about 24°C, at least or at most about 25°C, at least or at most about 26°C , at least or at most about 28°C, at least or at most about 30°C, at least or at most about 32°C, at least or at most about 35°C, or at least or at most about 40°C. . Glass transition temperature may be measured by differential scanning calorimetry. In some embodiments, the glass transition temperature may be measured by differential scanning calorimetry, thermomechanical analysis and/or dynamic mechanical analysis.

[0287] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is about -15°C, about -10°C, about -5°C, about 0°C, about 5°C, about 10°C, about 14°C, about 15°C, about 16°C, about 18°C, about 20°C, about 22°C, about 24°C, about 25°C, about 26°C, about 28°C, about 30°C, about 32°C , about 35°C or about 40°C. Glass transition temperature may be measured by differential scanning calorimetry. In some embodiments, the glass transition temperature may be measured by differential scanning calorimetry, thermomechanical analysis and/or dynamic mechanical analysis.

[0288] In some embodiments, the glass transition temperature of the ophthalmic article, ophthalmic device and/or biocompatible matrix may be from about -50°C to about 50°C. In some embodiments, the glass transition temperature of the ophthalmic article and/or polymeric material is from about -50°C to about -40°C, from about -50°C to about -30°C, from about -50°C to about -20°C. , about -50°C to about -10°C, about -50°C to about 0°C, about -50°C to about 10°C, about -50°C to about 20°C, about -50°C to about 30°C, about -50°C ° C to about 40 ° C, about -50 ° C to about 50 ° C, about -40 ° C to about -30 ° C, about -40 ° C to about -20 ° C, about -40 ° C to about -10 ° C, about -40 ° C to about 0°C, about -40°C to about 10°C, about -40°C to about 20°C, about -40°C to about 30°C, about -40°C to about 40°C, about -40°C to about 50°C, about -30°C to about -20°C, about -30°C to about -10°C, about -30°C to about 0°C, about -30°C to about 10°C, about -30°C to about 20°C, about -30°C to about 30°C, about -30°C to about 40°C, about -30°C to about 50°C, about -20°C to about -10°C, about -20°C to about 0°C, about -20°C to about 10°C , about -20°C to about 20°C, about -20°C to about 30°C, about -20°C to about 40°C, about -20°C to about 50°C, about -10°C to about 0°C, about -10°C to about 10°C, about -10°C to about 20°C, about -10°C to about 30°C, about -10°C to about 40°C, about -10°C to about 50°C, about 0°C to about 10°C, about 0°C to about 20°C, about 0°C to about 30°C, about 0°C to about 40°C, about 0°C to about 50°C, about 10°C to about 20°C, about 10°C to about 30°C, about 10°C to about 40°C, about 10°C to about 50°C, about 20°C to about 30°C, about 20°C to about 40°C, about 20°C to about 50°C, about 30°C to about 40°C, about 30°C to about 50°C, or about 40°C to about 50°C. In some embodiments, the glass transition temperature of the ophthalmic article and/or polymeric material may be from about -20°C to about 24°C. In some embodiments, the ophthalmic article and/or polymeric material may have a glass transition temperature of about -20°C to about -10°C.

[0289] In some embodiments, the glass transition temperature of the ophthalmic article, ophthalmic device and/or biocompatible matrix is at least about -50°C, at least about -45°C, at least about -40°C, at least about -35°C, at least about -30°C, at least about -25°C, at least about -20°C, at least about -15°C, at least about -10°C, at least about -5°C, at least about 0°C, at least about 5°C, It may be at least about 10°C, at least about 15°C, at least about 20°C, at least about 25°C, at least about 30°C, at least about 35°C, at least about 40°C, at least about 45°C, or at least about 50°C. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix may have a glass transition temperature of at least about -20°C.

[0290] In some embodiments, the glass transition temperature of the ophthalmic article, ophthalmic device and/or biocompatible matrix is at most about -50°C, at most about -45°C, at most about -40°C. , maximum about -35°C, maximum about -30°C, maximum about -25°C, maximum about -20°C, maximum about -15°C, maximum about -10°C, maximum about -5°C, maximum about 0°C, maximum about 5°C, maximum about 10°C, maximum about 15°C, maximum about 20°C, maximum about 25°C, maximum about 30°C, maximum about 35°C, maximum It may be about 40°C, up to about 45°C or up to about 50°C. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix may have a glass transition temperature of at most about -10°C. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix may have a glass transition temperature of at most about 0°C. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix may have a glass transition temperature of at most about 25°C. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix may have a glass transition temperature of at most about 20°C. Glass transition temperature may be measured by differential scanning calorimetry. In some embodiments, the glass transition temperature may be measured by differential scanning calorimetry, thermomechanical analysis and/or dynamic mechanical analysis.

[0291] Elastic modulus or Young's modulus can be a quantity that measures the resistance of an object or substance to elastic (ie, non-sustained) deformation when stress is applied. Elastic modulus or "Young's modulus" can be a measure of the stiffness of a given material. This can be determined experimentally from the slope of the stress-strain curve generated during tensile tests performed on samples of the material. Young's modulus measurements can be made, for example, by dynamic mechanical analysis (DMA) testing.

[0292] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus from about 0.5 MPa to 3 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 3 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus from about 0.5 MPa to 10 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus from about 0.1 MPa to about 3 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus from about 0.1 MPa to about 1 MPa.

[0293] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus, and/or loss modulus from about 0.5 MPa to about 10 MPa. good too. In some embodiments, the ophthalmic article and/or polymeric material has an elastic modulus, storage modulus and/or loss modulus of about 0.5 MPa to about 1 MPa, about 0.5 MPa to about 1.5 MPa, about 0 .5 MPa to about 2 MPa, about 0.5 MPa to about 3 MPa, about 0.5 MPa to about 4 MPa, about 0.5 MPa to about 5 MPa, about 0.5 MPa to about 6 MPa, about 0.5 MPa to about 7 MPa, about 0.5 MPa to about 8 MPa, about 0.5 MPa to about 9 MPa, about 0.5 MPa to about 10 MPa, about 1 MPa to about 1.5 MPa, about 1 MPa to about 2 MPa, about 1 MPa to about 3 MPa, about 1 MPa to about 4 MPa, about 1 MPa to about 5 MPa, about 1 MPa to about 6 MPa, about 1 MPa to about 7 MPa, about 1 MPa to about 8 MPa, about 1 MPa to about 9 MPa, about 1 MPa to about 10 MPa, about 1.5 MPa to about 2 MPa, about 1.5 MPa to about 3 MPa, about 1 .5 MPa to about 4 MPa, about 1.5 MPa to about 5 MPa, about 1.5 MPa to about 6 MPa, about 1.5 MPa to about 7 MPa, about 1.5 MPa to about 8 MPa, about 1.5 MPa to about 9 MPa, about 1.5 MPa to about 10 MPa, about 2 MPa to about 3 MPa, about 2 MPa to about 4 MPa, about 2 MPa to about 5 MPa, about 2 MPa to about 6 MPa, about 2 MPa to about 7 MPa, about 2 MPa to about 8 MPa, about 2 MPa to about 9 MPa, about 2 MPa to about 10 MPa, about 3 MPa to about 4 MPa, about 3 MPa to about 5 MPa, about 3 MPa to about 6 MPa, about 3 MPa to about 7 MPa, about 3 MPa to about 8 MPa, about 3 MPa to about 9 MPa, about 3 MPa to about 10 MPa, about 4 MPa to about 5 MPa, About 4 MPa to about 6 MPa, about 4 MPa to about 7 MPa, about 4 MPa to about 8 MPa, about 4 MPa to about 9 MPa, about 4 MPa to about 10 MPa, about 5 MPa to about 6 MPa, about 5 MPa to about 7 MPa, about 5 MPa to about 8 MPa, about 5 MPa to about 9 MPa, about 5 MPa to about 10 MPa, about 6 MPa to about 7 MPa, about 6 MPa to about 8 MPa, about 6 MPa to about 9 MPa, about 6 MPa to about 10 MPa, about 7 MPa to about 8 MPa, about 7 MPa to about 9 MPa, about 7 MPa to about It may be 10 MPa, about 8 MPa to about 9 MPa, about 8 MPa to about 10 MPa, or about 9 MPa to about 10 MPa.

[0294] In some embodiments, the ophthalmic article and/or polymeric material has an elastic modulus, storage modulus, and/or loss modulus of at least about 0.5 MPa, at least about 0.6 MPa, at least about 0.5 MPa. 7 MPa, at least about 0.8 MPa, at least about 0.9 MPa, at least about 1 MPa, at least about 1.1 MPa, at least about 1.2 MPa, at least about 1.3 MPa, at least about 1.4 MPa, at least about 1.5 MPa, at least about 1.6 MPa, at least about 1.7 MPa, at least about 1.8 MPa, at least about 1.9 MPa, at least about 2 MPa, at least about 2.5 MPa, at least about 3 MPa, at least about 3.5 MPa, at least about 4 MPa, at least about 4 MPa. 5 MPa, at least about 5 MPa, at least about 5.5 MPa, at least about 6 MPa, at least about 6.5 MPa, at least about 7 MPa, at least about 7.5 MPa, at least about 8 MPa, at least about 8.5 MPa, at least about 9 MPa, at least about 9 MPa. It may be 5 MPa or at least about 10 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 0.1 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 0.5 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 1 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 1.5 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 2 MPa. In some embodiments, the ophthalmic article and/or polymeric material may have an elastic modulus, storage modulus and/or loss modulus of at least about 3 MPa.

[0295] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 0.5 MPa, at most about 0 .6 MPa, up to about 0.7 MPa, up to about 0.8 MPa, up to about 0.9 MPa, up to about 1 MPa, up to about 1.1 MPa, up to about 1.2 MPa, up to about 1.3 MPa, Maximum about 1.4 MPa, maximum about 1.5 MPa, maximum about 1.6 MPa, maximum about 1.7 MPa, maximum about 1.8 MPa, maximum about 1.9 MPa, maximum about 2 MPa, maximum about 2.5 MPa, maximum about 3 MPa, maximum about 3.5 MPa, maximum about 4 MPa, maximum about 4.5 MPa, maximum about 5 MPa, maximum about 5.5 MPa, maximum about 6 MPa, maximum about 6 MPa. 5 MPa, up to about 7 MPa, up to about 7.5 MPa, up to about 8 MPa, up to about 8.5 MPa, up to about 9 MPa, up to about 9.5 MPa, or up to about 10 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 4 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 3 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 2 MPa. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elastic modulus, storage modulus and/or loss modulus of at most about 1 MPa.

[0296] The flexibility of the material of an ophthalmic article can be important because it can include the ability of the material to stretch (eg, elongation at break). Additionally, elastic memory is an important material property because ophthalmic articles, ophthalmic devices and/or biocompatible matrices can be folded and/or unfolded in a manner that does not damage the eye of the subject. For example, if the material is too elastic, the ophthalmic article, ophthalmic device and/or biocompatible matrix may cause the intraocular injector to pop out and change its position when implanted in the eye.

[0297] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break of at least about 100% as measured by a tensile test. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break between about 100% and 2000% at 18-24°C.

[0298] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix comprises about 100% to about 200%, about 100% to about 300%, about 100% to about 400%, about 100% to about 500%, about 100% to about 600%, about 100% to about 700%, about 100% to about 800%, about 100% to about 900%, about 100% to about 1,000%, about 100% to about 1,100%, about 100% to about 1,200%, about 200% to about 300%, about 200% to about 400%, about 200% to about 500%, about 200% to about 600 %, from about 200% to about 700%, from about 200% to about 800%, from about 200% to about 900%, from about 200% to about 1,000%, from about 200% to about 1,100%, from about 200% About 1,200%, about 300% to about 400%, about 300% to about 500%, about 300% to about 600%, about 300% to about 700%, about 300% to about 800%, about 300% to about 900%, about 300% to about 1,000%, about 300% to about 1,100%, about 300% to about 1,200%, about 400% to about 500%, about 400% to about 600%, about 400% to about 700%, about 400% to about 800%, about 400% to about 900%, about 400% to about 1,000%, about 400% to about 1,100%, about 400% to about 1 , 200%, from about 500% to about 600%, from about 500% to about 700%, from about 500% to about 800%, from about 500% to about 900%, from about 500% to about 1,000%, from about 500% about 1,100%, about 500% to about 1,200%, about 600% to about 700%, about 600% to about 800%, about 600% to about 900%, about 600% to about 1,000%, About 600% to about 1,100%, about 600% to about 1,200%, about 700% to about 800%, about 700% to about 900%, about 700% to about 1,000%, about 700% or more about 1,100%, about 700% to about 1,200%, about 800% to about 900%, about 800% to about 1,000%, about 800% to about 1,100%, about 800% to about 1 , 200%, about 900% to about 1,000%, about 900% to about 1,100%, about 900% to about 1,200%, about 1,000% to about 1,100%, about 1,000 % to about 1,200%, or from about 1,100% to about 1,200%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break ranging from about 100% to about 800%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break ranging from about 500% to about 1000%. Elongation at break may be determined at 18-24°C.

[0299] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is at least about 100%, at least about 200%, at least about 300%, at least about 400%, at least about 500% , at least about 600%, at least about 700%, at least about 800%, at least about 900%, at least about 1,000%, at least about 1,100%, or at least about 1,200%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation to break of at least about 100%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation to break of at least about 500%. Elongation at break may be determined at 18-24°C.

[0300] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix comprises at most about 100%, at most about 200%, at most about 300%, at most about 400%, up to about 500%, up to about 600%, up to about 700%, up to about 800%, up to about 900%, up to about 1,000%, up to about 1,100%, or up to about 1 , with an elongation at break of 200%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break of at most about 1000%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break of at most about 1500%. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break of at most about 500%. Elongation at break may be determined at 18-24°C.

[0301] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is about 100%, about 150%, about 200%, about 250%, about 300%, about 350%, about 400%, about 450%, about 500%, about 550%, about 600%, about 650%, about 700%, about 750%, about 800%, about 850%, about 900%, about 950%, about 1 ,000%, about 1,100%, or about 1,200% elongation at break. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix has an elongation at break of about 100%. Elongation at break may be determined at 18-24°C.

[0302] In some embodiments, elongation at break may be measured or determined by pulling an object (eg, an ophthalmic article or an ophthalmic article, a biocompatible matrix) until it fractures.

[0303] In some embodiments, the ophthalmic article, ophthalmic device, and/or biocompatible matrix is at least about 30 seconds (sec), 29 sec, 28 sec, 27 sec, 26 sec, 25 sec, 24 sec, 23 sec, 22 sec. , 21 sec, 20 sec, 19 sec, 18 sec, 17 sec, 16 sec, 15 sec, 14 sec, 13 sec, 12 sec, 11 sec, 10 sec, 9 sec, 8 sec, 7 sec, 6 sec, 5 sec, 4 sec, 3 sec or less .

[0304] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix comprises at least about 3 sec, 4 sec, 5 sec, 6 sec, 7 sec, 8 sec, 9 sec, 10 sec, 11 sec, 12 sec, 13 sec, After 14 sec, 15 sec, 16 sec, 17 sec, 18 sec, 19 sec, 20 sec, 21 sec, 22 sec, 23 sec, 24 sec, 25 sec, 26 sec, 27 sec, 28 sec, 29 sec, 30 sec or more, it can return to its original shape.

[0305] In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is held for about 30 seconds (sec), about 29 sec, about 28 sec, about 27 sec, about 26 sec, about 25 sec, about 24 sec. , about 23 sec, about 22 sec, about 21 sec, about 20 sec, about 19 sec, about 18 sec, about 17 sec, about 16 sec, about 15 sec, about 14 sec, about 13 sec, about 12 sec, about 11 sec, about 10 sec, about 9 sec, about 8 sec, about It can return to its original shape in 7 sec, about 6 sec, about 5 sec, about 4 sec or about 3 sec.

[0306] In some embodiments, the ophthalmic articles, ophthalmic devices and/or biocompatible matrices are sufficiently soft, flexible, and not to cut or puncture the lens capsule when implanted. and may be compressible. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is sufficiently thin so as not to adversely affect the natural contraction of the lens capsular capsule around the ophthalmic device (e.g., IOL). It may be very soft, flexible and compressible. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix irritates the iris when direct contact occurs within the eye or when indirect contact occurs through the lens capsule. It may be sufficiently soft, flexible and compressible so as not to wear. In some embodiments, the ophthalmic article, ophthalmic device and/or biocompatible matrix is sufficiently thin so as not to shift or deflect the anterior iris to the extent that it causes angle closure and/or elevated IOP. It may be very soft, flexible and compressible.

[0307] In any of the various aspects, positioning one or more ophthalmic articles at one or more locations on an ophthalmic device (e.g., an intraocular lens) is performed by one or more target tissues. Suitable delivery of one or more active agents and/or diagnostic agents to various locations within the near eye can be provided. For example, intracapsular positioning of an ophthalmic article within the lens capsular capsule can affect delivery of active agents and/or diagnostic agents to various locations within the eye closer to one or more target tissues. The ophthalmic articles described herein can be bonded (e.g., adhered) to one or more portions of ophthalmic devices (e.g., intraocular lenses) of various sizes, shapes and refractive powers or materials. . In some embodiments, one or more portions of the ophthalmic device may be appendages of the ophthalmic device. For example, an appendage may be one or more haptics of an intraocular lens. An ophthalmic device as described herein can be a device (eg, an intraocular lens) that can be implanted inside, outside, or adjacent to a subject's eye.

[0308] In some embodiments, the ophthalmic device may be an intraocular device. In some embodiments, the ophthalmic device may be an extraocular device. In some embodiments, the ocular device comprises an intraocular lens, a capsular tension ring, a minimally invasive glaucoma surgery device, a glaucoma drainage device, a drug delivery system, an intraocular pressure sensor, a Retisart implant, a port delivery system (e.g., ranibizumab port delivery systems), scleral buckles, surgical fixation devices, prostheses, and/or devices that can be implanted inside, outside, or adjacent to the eye for therapeutic and/or diagnostic purposes. In some embodiments, the ophthalmic device is an intraocular lens (IOL). An IOL can be a lens that can be implanted in the eye to provide improved vision and can be combined with one or more of a number of surgical procedures and devices such as cataract surgery and intraocular lens injectors. . An IOL can be a lens that is implanted in a subject's eye as part of treatment for various eye conditions as described herein, such as cataracts or myopia. The most common type of IOL is the pseudophakic IOL. They are implanted after the natural lens of the opaque eye (eg, cataract) is removed during cataract surgery. Typically, an IOL replaces an existing lens, for example because the lens is opaque due to cataracts. Alternatively, the intraocular lens may be implanted in addition to the existing lens. This type of IOL, also called an intraocular contact lens or implantable contact lens, is surgically placed in the posterior chamber behind the iris of the eye and in front of the lens to correct high degrees of myopia and hyperopia. , is a small corrective lens.

[0309] An IOL can include a lens (e.g., a plastic lens) that has one or more lateral struts (e.g., plastic lateral struts) called haptics to hold the lens in position in the lens capsule within the eye. can. A haptic can include an “optics-haptics” junction, which is an area where the haptic portion of the IOL can connect to the optic portion of the IOL. In some cases, the haptics and optic-haptic junctions may be non-optical portions of the IOL. Haptics may be of any size and/or geometric shape. In some embodiments, the haptics may be straight. In some embodiments, the haptics may be curved. Intraocular lens implantation may be the most commonly performed ocular surgical procedure, and cataracts are the most common ocular disease. The procedure can be performed under local anesthesia with the patient awake throughout the procedure and usually takes less than 30 minutes in the hands of an experienced ophthalmologist. There are collapsible intraocular lenses made of acrylic or silicone that can be rolled up and inserted by means of a tube in a very small incision that does not require any sutures, but non-flexible lenses (typically PMMA (poly Methyl methacrylate)) requires a larger incision.

[0310] Figures 3A and 3B schematically illustrate an example intraocular lens (IOL) 300 having an ophthalmic article 100 for delivering active agents and/or diagnostic agents. FIG. 3A illustrates a plan view of IOL 300 with an ophthalmic article. FIG. 3B illustrates a side view of IOL 300 with an ophthalmic article. IOL 300 includes a central optic portion 301 having first haptics 302 that adhere to optic portion 301 at a first location 303 . A second haptic 304 may be adhered to the optic portion 301 at a second location 305 . IOL 300 may also include length 306 , cross-sectional length 307 , thickness 308 and optic diameter 309 . Ophthalmic article 100 for delivering active agents and/or diagnostic agents may be positioned on first haptics 302 . For example, an ophthalmic article 100 for delivering active agents and/or diagnostic agents to the eye may have an internal diameter and circumference sized to accommodate placement of the IOL 300 on the first haptics 302 . A structure 110 may be included. In some embodiments, the inner diameter or lateral edge 240 of the pores in the ophthalmic article in FIGS. may be formed to any size.

[0311] FIGS. 4A and 4B schematically illustrate an example intraocular lens (IOL) 300 having several ophthalmic articles 100. FIG. 4A and 4B illustrate an eye with a first ophthalmic article 100a, a second ophthalmic article 100b and a third ophthalmic article 100c for delivering active agents and/or diagnostic agents to the eye of a subject. An example of an inner lens (IOL) 300 is schematically illustrated. FIG. 4A illustrates a plan view of an IOL 300 having a first ophthalmic article 100a, a second ophthalmic article 100b and a third ophthalmic article 100c. FIG. 4B illustrates a side view of IOL 300 with first ophthalmic article 100a, second ophthalmic article 100b and third ophthalmic article 100c. IOL 300 includes first haptics 302 that couple with first ophthalmic article 100a and second ophthalmic article 100b. IOL 300 also includes a second haptic 304 coupled with third ophthalmic article 100c.

[0312] In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 of the one or more ophthalmic articles , 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more may be coupled to one or more portions of the ophthalmic device (eg, IOL haptics). In some embodiments, at most about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7 of the one or more ophthalmic articles , 6, 5, 4, 3, 2 or 1 may be associated with one or more portions of the ophthalmic device (eg, the IOL haptics). In some embodiments, one of the one or more ophthalmic articles may mate with one or more portions of the ophthalmic device (eg, IOL haptics). In some embodiments, two of the one or more ophthalmic articles may mate with one or more portions of the ophthalmic device (eg, IOL haptics).

[0313] In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 of one or more ophthalmic articles 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more may be associated with one of one or more portions (eg, haptics) of an ophthalmic device (eg, IOL). In some embodiments, at most about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7 of the one or more ophthalmic articles , 6, 5, 4, 3, 2 or 1 may be coupled to one of one or more portions (eg, haptics) of an ophthalmic device (eg, IOL). In some embodiments, one of the one or more ophthalmic articles may mate with one of one or more portions (eg, haptics) of an ophthalmic device (eg, IOL). In some embodiments, two of the one or more ophthalmic articles may mate with one of the one or more portions (eg, haptics) of the ophthalmic device (eg, IOL).

[0314] In some embodiments, an IOL (eg, used for cataract surgery in humans) may include a length (eg, length 306) of about 13 mm. In some embodiments, the IOL (eg, used for cataract surgery in humans) is about 10 mm to about 10.5 mm, about 10 mm to about 11 mm, about 10 mm to about 11.5 mm, about 10 mm to about 12 mm, about 10 mm to about 12.5 mm, about 10 mm to about 13 mm, about 10 mm to about 13.5 mm, about 10 mm to about 14 mm, about 10.5 mm to about 11 mm, about 10.5 mm to about 11.5 mm, about 10.5 mm to about 12 mm, about 10.5 mm to about 12.5 mm, about 10.5 mm to about 13 mm, about 10.5 mm to about 13.5 mm, about 10.5 mm to about 14 mm, about 11 mm to about 11.5 mm, about 11 mm to about 12 mm, about 11 mm to about 12.5 mm, about 11 mm to about 13 mm, about 11 mm to about 13.5 mm, about 11 mm to about 14 mm, about 11.5 mm to about 12 mm, about 11.5 mm to about 12.5 mm, about 11.5 mm to about 13 mm, about 11.5 mm to about 13.5 mm, about 11.5 mm to about 14 mm, about 12 mm to about 12.5 mm, about 12 mm to about 13 mm, about 12 mm to about 13.5 mm, about 12 mm from about 14 mm, from about 12.5 mm to about 13 mm, from about 12.5 mm to about 13.5 mm, from about 12.5 mm to about 14 mm, from about 13 mm to about 13.5 mm, from about 13 mm to about 14 mm, or from about 13.5 mm It may include a length (eg length 306) of about 14mm.

[0315] In some embodiments, the IOL (eg, used for cataract surgery in humans) is at least about 10 mm, at least about 10.5 mm, at least about 11 mm, at least about 11.5 mm, at least about 12 mm, at least about It may include a length (eg, length 306) of about 12.5 mm, at least about 13 mm, at least about 13.5 mm, or at least about 14 mm.

[0316] In some embodiments, the IOL (e.g., used for cataract surgery in humans) is at most about 10 mm, at most about 10.5 mm, at most about 11 mm, at most about 11.5 mm, at most A length (eg, length 306) of up to about 12 mm, up to about 12.5 mm, up to about 13 mm, up to about 13.5 mm, or up to about 14 mm.

[0317] In some embodiments, the IOL (e.g., used for cataract surgery in humans) is about 10 mm, about 10.5 mm, about 11 mm, about 11.5 mm, about 12 mm, about 12.5 mm, about It may include a length (eg, length 306) of 13 mm, about 13.5 mm, or about 14 mm.

[0318] In some embodiments, an IOL (eg, used for cataract surgery in humans) may include an optic diameter (eg, optic diameter 309) of about 4 mm to 7 mm.

[0319] In some embodiments, the IOL (eg, used for cataract surgery in humans) is about 4 mm to about 4.25 mm, about 4 mm to about 4.5 mm, about 4 mm to about 4.75 mm, about 4 mm to about 5 mm, about 4 mm to about 5.25 mm, about 4 mm to about 5.5 mm, about 4 mm to about 5.75 mm, about 4 mm to about 6 mm, about 4 mm to about 6.25 mm, about 4 mm to about 6.5 mm , about 4 mm to about 6.75 mm, about 4 mm to about 7 mm, about 4.25 mm to about 4.5 mm, about 4.25 mm to about 4.75 mm, about 4.25 mm to about 5 mm, about 4.25 mm to about 5 .25 mm, about 4.25 mm to about 5.5 mm, about 4.25 mm to about 5.75 mm, about 4.25 mm to about 6 mm, about 4.25 mm to about 6.25 mm, about 4.25 mm to about 6.5 mm , about 4.25 mm to about 6.75 mm, about 4.25 mm to about 7 mm, about 4.5 mm to about 4.75 mm, about 4.5 mm to about 5 mm, about 4.5 mm to about 5.25 mm; 5 mm to about 5.5 mm, about 4.5 mm to about 5.75 mm, about 4.5 mm to about 6 mm, about 4.5 mm to about 6.25 mm, about 4.5 mm to about 6.5 mm, about 4.5 mm to about 6.75 mm, about 4.5 mm to about 7 mm, about 4.75 mm to about 5 mm, about 4.75 mm to about 5.25 mm, about 4.75 mm to about 5.5 mm, about 4.75 mm to about 5.75 mm , about 4.75 mm to about 6 mm, about 4.75 mm to about 6.25 mm, about 4.75 mm to about 6.5 mm, about 4.75 mm to about 6.75 mm, about 4.75 mm to about 7 mm, about 5 mm to about 5.25 mm, about 5 mm to about 5.5 mm, about 5 mm to about 5.75 mm, about 5 mm to about 6 mm, about 5 mm to about 6.25 mm, about 5 mm to about 6.5 mm, about 5 mm to about 6.75 mm , about 5 mm to about 7 mm, about 5.25 mm to about 5.5 mm, about 5.25 mm to about 5.75 mm, about 5.25 mm to about 6 mm, about 5.25 mm to about 6.25 mm, about 5.25 mm to about 6.5 mm, about 5.25 mm to about 6.75 mm, about 5.25 mm to about 7 mm, about 5.5 mm to about 5.75 mm, about 5.5 mm to about 6 mm, about 5.5 mm to about 6.25 mm , about 5.5 mm to about 6.5 mm, about 5.5 mm to about 6.75 mm, about 5.5 mm to about 7 mm, about 5.75 mm to about 6 mm, about 5.75 mm to about 6.25 mm, about 5.5 mm to about 6.5 mm. 75 mm to about 6.5 mm, about 5.75 mm to about 6.75 mm, about 5.75 mm to about 7 mm, about 6 mm to about 6.25 mm, about 6 mm to about 6 .5 mm, about 6 mm to about 6.75 mm, about 6 mm to about 7 mm, about 6.25 mm to about 6.5 mm, about 6.25 mm to about 6.75 mm, about 6.25 mm to about 7 mm, about 6.5 mm to It may include an optic diameter (eg, optic diameter 309) of about 6.75 mm, about 6.5 mm to about 7 mm, or about 6.75 mm to about 7 mm.

[0320] In some embodiments, the IOL (e.g., used for cataract surgery in humans) is at least about 4 mm, 4.25 mm, at least about 4.5 mm, at least about 4.75 mm, at least about 5 mm, at least An optic diameter of about 5.25 mm, at least about 5.5 mm, at least about 5.75 mm, at least about 6 mm, at least about 6.25 mm, at least about 6.5 mm, at least about 6.75 mm, or at least about 7 mm (e.g., optic diameter 309 ) may be included. In some embodiments, the IOL (e.g., used for cataract surgery in humans) is up to about 4 mm, 4.25 mm, up to about 4.5 mm, up to about 4.75 mm, up to about 5 mm, up to about 5.25 mm, up to about 5.5 mm, up to about 5.75 mm, up to about 6 mm, up to about 6.25 mm, up to about 6.5 mm, up to about 6.75 mm, or up to about An optic diameter of 7 mm (eg, optic diameter 309) may be included.

[0321] In some embodiments, the IOL (e.g., used for cataract surgery in humans) is about 4 mm, 4.25 mm, about 4.5 mm, about 4.75 mm, about 5 mm, about 5.25 mm, It may include an optic diameter (eg, optic diameter 309) of about 5.5 mm, about 5.75 mm, about 6 mm, about 6.25 mm, about 6.5 mm, about 6.75 mm, or about 7 mm.

[0322] In some embodiments, the IOL haptics may include a cross-sectional length (eg, cross-sectional length 307) of about 0.1 mm to 1.0 mm.
[0323] In some embodiments, the IOL haptics are about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.3 mm, about 0.1 mm to about 0.4 mm, about 0.1 mm to about 0.5 mm, about 0.1 mm to about 0.6 mm, about 0.1 mm to about 0.7 mm, about 0.1 mm to about 0.8 mm, about 0.1 mm to about 0.9 mm, about 0.1 mm to about 1 mm, about 0.2 mm to about 0.3 mm, about 0.2 mm to about 0.4 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 0.6 mm, about 0.2 mm to about 0.5 mm 7 mm, about 0.2 mm to about 0.8 mm, about 0.2 mm to about 0.9 mm, about 0.2 mm to about 1 mm, about 0.3 mm to about 0.4 mm, about 0.3 mm to about 0.5 mm, about 0.3 mm to about 0.6 mm, about 0.3 mm to about 0.7 mm, about 0.3 mm to about 0.8 mm, about 0.3 mm to about 0.9 mm, about 0.3 mm to about 1 mm, about 0 .4 mm to about 0.5 mm, about 0.4 mm to about 0.6 mm, about 0.4 mm to about 0.7 mm, about 0.4 mm to about 0.8 mm, about 0.4 mm to about 0.9 mm, about 0 .4 mm to about 1 mm, about 0.5 mm to about 0.6 mm, about 0.5 mm to about 0.7 mm, about 0.5 mm to about 0.8 mm, about 0.5 mm to about 0.9 mm, about 0.5 mm to about 1 mm, about 0.6 mm to about 0.7 mm, about 0.6 mm to about 0.8 mm, about 0.6 mm to about 0.9 mm, about 0.6 mm to about 1 mm, about 0.7 mm to about 0.7 mm. A cross-sectional length ( For example, a cross-sectional length 307) may be included.

[0324] In some embodiments, the IOL haptics are at least about 0.1 mm, at least about 0.15 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about It may include a cross-sectional length (eg, cross-sectional length 307) of 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, or at least about 1 mm. In some embodiments, the IOL haptics are at most about 0.1 mm, at most about 0.15 mm, at most about 0.2 mm, at most about 0.25 mm, at most about 0.3 mm, at most about 0 .35 mm, at most about 0.4 mm, at most about 0.45 mm, at most about 0.5 mm, at most about 0.55 mm, at most about 0.6 mm, at most about 0.65 mm, at most about 0.5 mm. 7 mm, up to about 0.75 mm, up to about 0.8 mm, up to about 0.85 mm, up to about 0.9 mm, up to about 0.95 mm, or up to about 1 mm (e.g., cross-sectional length 307) may include

[0325] In some embodiments, the IOL haptics are about 0.1 mm, about 0.15 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.65 mm, about 0.7 mm, about 0.75 mm, about 0.8 mm, about 0.85 mm, about 0.9 mm, about It may include a cross-sectional length (eg, cross-sectional length 307) of 0.95 mm or about 1 mm.

[0326] In some embodiments, the IOL haptics may include a thickness 308 or maximum width of about 0.1 mm to 1 mm. In some embodiments, the IOL haptics are about 0.1 mm to about 0.2 mm, about 0.1 mm to about 0.3 mm, about 0.1 mm to about 0.4 mm, about 0.1 mm to about 0.5 mm , about 0.1 mm to about 0.6 mm, about 0.1 mm to about 0.7 mm, about 0.1 mm to about 0.8 mm, about 0.1 mm to about 0.9 mm, about 0.1 mm to about 1 mm, about 0.2 mm to about 0.3 mm, about 0.2 mm to about 0.4 mm, about 0.2 mm to about 0.5 mm, about 0.2 mm to about 0.6 mm, about 0.2 mm to about 0.7 mm, about 0.2 mm to about 0.8 mm, about 0.2 mm to about 0.9 mm, about 0.2 mm to about 1 mm, about 0.3 mm to about 0.4 mm, about 0.3 mm to about 0.5 mm, about 0.5 mm. 3 mm to about 0.6 mm, about 0.3 mm to about 0.7 mm, about 0.3 mm to about 0.8 mm, about 0.3 mm to about 0.9 mm, about 0.3 mm to about 1 mm, about 0.4 mm to About 0.5 mm, about 0.4 mm to about 0.6 mm, about 0.4 mm to about 0.7 mm, about 0.4 mm to about 0.8 mm, about 0.4 mm to about 0.9 mm, about 0.4 mm to about 1 mm, about 0.5 mm to about 0.6 mm, about 0.5 mm to about 0.7 mm, about 0.5 mm to about 0.8 mm, about 0.5 mm to about 0.9 mm, about 0.5 mm to about 1 mm , about 0.6 mm to about 0.7 mm, about 0.6 mm to about 0.8 mm, about 0.6 mm to about 0.9 mm, about 0.6 mm to about 1 mm, about 0.7 mm to about 0.8 mm, about 0.7 mm to about 0.9 mm, about 0.7 mm to about 1 mm, about 0.8 mm to about 0.9 mm, about 0.8 mm to about 1 mm, or about 0.9 mm to about 1 mm. good.

[0327] In some embodiments, the IOL haptics are about 0.1 mm, about 0.15 mm, about 0.2 mm, about 0.25 mm, about 0.3 mm, about 0.35 mm, about 0.4 mm, about 0.45 mm, about 0.5 mm, about 0.55 mm, about 0.6 mm, about 0.65 mm, about 0.7 mm, about 0.75 mm, about 0.8 mm, about 0.85 mm, about 0.9 mm, about It may include a thickness 308 or maximum width of 0.95 mm or about 1 mm.

[0328] In some embodiments, the IOL haptics are at least about 0.1 mm, at least about 0.15 mm, at least about 0.2 mm, at least about 0.25 mm, at least about 0.3 mm, at least about 0.35 mm, at least about 0.4 mm, at least about 0.45 mm, at least about 0.5 mm, at least about 0.55 mm, at least about 0.6 mm, at least about 0.65 mm, at least about 0.7 mm, at least about 0.75 mm, at least about It may include a thickness 308 or maximum width of 0.8 mm, at least about 0.85 mm, at least about 0.9 mm, at least about 0.95 mm, or at least about 1 mm. In some embodiments, the IOL haptics are at most about 0.1 mm, at most about 0.15 mm, at most about 0.2 mm, at most about 0.25 mm, at most about 0.3 mm, at most about 0 .35 mm, at most about 0.4 mm, at most about 0.45 mm, at most about 0.5 mm, at most about 0.55 mm, at most about 0.6 mm, at most about 0.65 mm, at most about 0.5 mm. 7 mm, at most about 0.75 mm, at most about 0.8 mm, at most about 0.85 mm, at most about 0.9 mm, at most about 0.95 mm, or at most about 1 mm. It's okay.

[0329] In some embodiments, the one or more ophthalmic articles are ophthalmic devices and ophthalmic devices having portions that are of any type, such as size, shape, and/or configuration to which the ophthalmic articles can be coupled. may be combined. The method of bonding between the ophthalmic article and the ophthalmic device may depend on the size and shape of the internal structure of the ophthalmic article. In some embodiments, the method of coupling between the ophthalmic article and the ophthalmic device may depend on the size and shape of portions of the ophthalmic device (eg, IOL haptics). In some embodiments, the one or more ophthalmic articles have haptics of any kind of size, shape, configuration, etc. and/or haptics comprising any kind of outer surface of size, shape, texture, etc. It may be combined with an intraocular lens (IOL). For example, an ophthalmic article is designed to accommodate positioning on one or more portions of an ophthalmic device (e.g., one or more haptics of an intraocular lens) as described herein be able to. In some embodiments, the ophthalmic articles have various shapes and sizes as disclosed herein to accommodate placement on an ophthalmic device (e.g., one or more haptics of an intraocular lens). It can contain sized internal structures (eg, pores).

[0330] During coupling, there may be a connection (eg, a physical connection) between an ophthalmic device (eg, one or more haptics of an intraocular lens) and one or more ophthalmic articles. In some embodiments, coupling includes indirect coupling between one or more ophthalmic articles and one or more portions of an ophthalmic device (eg, intraocular lens haptics). For example, one or more ophthalmic articles may be indirectly coupled with one or more haptics by a barrier layer. In another example, one ophthalmic article is indirectly coupled to the haptics such that the ophthalmic article can rotate or move in grooves or depressions along the haptics without detaching from the haptics. You may In some embodiments, bonding includes direct bonding between the ophthalmic article and the haptics by chemical bonding, physical adhesion, compressive and/or contractile forces.

[0331] In some embodiments, an ophthalmic article may include an internal structure that is sized to accommodate placement on a portion of an ophthalmic device. For example, the ophthalmic article may include internal structures (eg, pores) that are sized to accommodate placement around the haptics of the IOL (eg, haptics having different shapes, sizes and configurations). In some embodiments, the internal structures (eg, pores) of the ophthalmic article are precisely sized to match the cross-sectional dimensions of portions of the ophthalmic device (eg, IOL haptics). In other embodiments, the internal structures (eg, pores) of the ophthalmic article are sized small relative to the cross-sectional dimensions of the portion of the ophthalmic device (eg, the haptics of the IOL). In such cases, the elasticity of at least a portion of the ophthalmic article and/or ophthalmic device (e.g., the haptics of the IOL) is permanent without crushing any shape of at least a portion of the ophthalmic article and/or ophthalmic device. It can allow the application of an ophthalmic article onto portions of an ophthalmic device without distorting the eye. In some embodiments, the portion (e.g., haptics) of the ophthalmic device has a different perimeter (e.g., cross-sectional perimeter) than at least another region of the portion (e.g., haptics) of the ophthalmic device (e.g., IOL). It may include one or more regions. In some embodiments, the ophthalmic article can extend beyond the greatest perimeter (eg, cross-sectional perimeter) of a portion (eg, haptics) of an ophthalmic device (eg, IOL). In such cases, movement of the ophthalmic article may be limited by its position in portions (eg, haptics) of the ophthalmic device that are thinner than adjacent regions (eg, notches or valleys).

[0332] A portion of an ophthalmic device (e.g., a miniature sized ophthalmic article (e.g., internal structure of a miniature ophthalmic article) composed of a polymeric material (e.g., an elastic polymeric material). One benefit of positioning the IOL over the haptics is that the stress and/or strain induced by this placement promotes adhesion of the ophthalmic article to portions of the ocular device (e.g., the IOL haptics). . Such adhesion is advantageous for preventing displacement of the ophthalmic article from portions of the ophthalmic device (e.g., IOL haptics) during injection through narrow openings during surgery (e.g., cataract surgery). obtain. This can be an advantage over other techniques.

[0333] In some embodiments, the ophthalmic article has an interior shaped to accommodate placement around ophthalmic device portions (e.g., ophthalmic device portions having different shapes, sizes and configurations). Structures (eg, pores) may be included. For example, an ophthalmic article may include internal structures (eg, pores) shaped to accommodate placement around IOL haptics (eg, haptics having different shapes, sizes and configurations). In some embodiments, a portion of an ophthalmic device (eg, an IOL haptic) may be uniformly flat along its outer surface. In other embodiments, a portion of an ophthalmic device (eg, an IOL haptic) may include at least one depression or groove along its outer surface. The indentation or groove may include structure for receiving the circumference of the internal structure of the ophthalmic article. In other embodiments, a portion of an ophthalmic device (eg, an IOL haptic) may include at least one protrusion along its outer surface. In any of the embodiments, the ophthalmic article is sized and/or shaped such that the ophthalmic article can mate with a portion of an ophthalmic device (e.g., an IOL haptic) as described herein. may be designed to

[0334] In some embodiments, the ophthalmic article is attached to a surface (eg, an outward facing surface) of a portion of the ophthalmic device (eg, the haptics of the IOL) to secure the ophthalmic article to the portion of the ophthalmic device. It may be configured to be compressively coupled. In one example, when an elastic ophthalmic article bonds (eg, adheres) to a rigid and/or rigid portion (eg, an IOL haptic) of an ophthalmic device, the rigid and/or rigid portion reduces compression forces of the ophthalmic article. Although it may not deform in response to pressure, friction due to compressive forces may prevent movement between the ophthalmic article and hard and/or rigid portions. Friction (eg, coefficient of friction) may be a function of normal force and intrinsic properties of materials of at least portions of ophthalmic articles and ophthalmic devices. The normal force can be proportional to the extension of the ophthalmic article, eg, can be a function of the inner circumference of the ophthalmic article relative to the perimeter of the haptics around which the ophthalmic article extends.

[0335] In another example, if an elastic ring-shaped ophthalmic article is bonded (eg, adhered) to a soft haptic, the haptics will narrow in response to the compressive force of the ophthalmic article. Friction due to compressive forces can contribute to resistance to movement as well as retraction of the ophthalmic article inward into the haptic valleys.

[0336] In some embodiments, the ophthalmic article is formed by grooves, depressions, narrowings or protrusions along the surface of the portion of the ophthalmic device (e.g., the haptics of the IOL) on the surface (e.g., the haptics of the IOL). outward facing surface). For example, the ophthalmic article may include an internal structure for securing around the notch area of the IOL's haptics. In such cases, the elastic annulus ophthalmic article is applied to the notched haptic such that it initially extends to an inner circumference at least as large as the outer perimeter of the haptic distal to the notch. be able to. A resilient annulus ophthalmic article may then be advanced over the notch and allowed to contract around the narrow portion of the haptics. In this case, friction is less relevant and the sides of the notch can secure the ophthalmic article and prevent slippage of the ophthalmic article. An ophthalmic article can be hung in the notch and can move or rotate freely within the notch. Alternatively, the ophthalmic article may be hung over the notch while being restricted from movement or rotation within the notch. In another example, the ophthalmic article may be hung over the notch so that it can be compressively bonded (eg, adhered) to the surface of the haptics within the notch.

[0337] In some embodiments, coupling between an ophthalmic article and an ophthalmic device (eg, one or more haptics of an intraocular lens) is controlled by manipulation of the device prior to implantation (eg, routine manipulation). and such that wear of the device after implantation does not result in detachment of the ophthalmic article from the ophthalmic device (eg, one or more haptics of the intraocular lens). In some embodiments, the ophthalmic articles are bonded in such a way that vision is not impaired. In some embodiments, the coupling may be such that movement of the ophthalmic article relative to the ophthalmic device (eg, one or more haptics of the intraocular lens) is not possible. Alternatively, the coupling may be such that the ophthalmic article can move relative to the ophthalmic device (eg, one or more haptics of an intraocular lens).

[0338] In some embodiments, one or more ophthalmic articles may be positioned on one or more portions of an ophthalmic device (eg, one or more haptics of an IOL). In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more ophthalmic articles are one of the ophthalmic devices or may be positioned on multiple portions (eg, one or more haptics of the IOL). In some embodiments, about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 ophthalmic articles are one or more of the ophthalmic devices (eg, one or more haptics of the IOL). In some embodiments, at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ophthalmic article is one of the ophthalmic devices. It may be positioned on a portion (eg, the IOL's haptics). In some embodiments, one or more ophthalmic articles may be positioned on one portion of the ophthalmic device (eg, the IOL haptics). In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more ophthalmic articles are one ophthalmic device. may be positioned on one portion (eg, the IOL's haptics). In some embodiments, about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 ophthalmic articles are part of an ophthalmic device ( haptics of the IOL). In some embodiments, at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ophthalmic article is one of the ophthalmic devices. It may be positioned on a portion (eg, the IOL's haptics). In some embodiments, at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more ophthalmic articles are ophthalmic devices (e.g., IOL). In some embodiments, at most about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 ophthalmic articles are ophthalmic devices (e.g., IOLs) ) may be combined with In some embodiments, about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 ophthalmic articles are ophthalmic devices (e.g., IOLs) and may be combined.

[0339] In some embodiments, one or more ophthalmic articles contain greater amounts of the same active agent and/or diagnostic agent or different active agents and/or diagnostic agents from the same ophthalmic device (e.g., IOL). Delivery of any of the agents may be desirable.

[0340] Different types of ophthalmic devices can be combined with one or more ophthalmic articles described herein. For example, there are different IOL manufacturers, each promoting IOLs with different designs for various clinical conditions. One difference in IOLs is the configuration of the haptics. Some haptics are thicker and wider than others, ranging in size from approximately 0.1 to 10 mm in maximum width. In some embodiments, the maximum width of the haptics may be from about 0.1 mm to about 20 mm. In some embodiments, the maximum width of the haptics is about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 5 mm, about 0.1 mm to about 10 mm, about 0.1 mm to about 20 mm, about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 5 mm, about 0.5 mm to about 10 mm, about 0.5 mm to about 20 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 5 mm, about 1 mm to about 10 mm, about 1 mm to about 20 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 5 mm, about 1.5 mm to about 10 mm, about 1.5 mm to about 20 mm, about 2 mm to about 5 mm, about 2 mm to about 10 mm, about It may be from 2 mm to about 20 mm, from about 5 mm to about 10 mm, from about 5 mm to about 20 mm, or from about 10 mm to about 20 mm. In some embodiments, the maximum width of the haptics is at least about 0.1 mm, at least about 0.5 mm, at least about 1 mm, at least about 1.5 mm, at least about 2 mm, at least about 5 mm, at least about 10 mm, or at least about 20 mm may be In some embodiments, the maximum width of the haptics is at most about 0.1 mm, at most about 0.5 mm, at most about 1 mm, at most about 1.5 mm, at most about 2 mm, at most about 5 mm, at most about However, it may be about 10 mm or at most about 20 mm. In some embodiments, if the haptics are curved, this dimension can refer to the length of the curve.

[0341] The ophthalmic articles described herein may house one or more portions of an ophthalmic device. Portions may include different sizes, shapes and configurations (eg, notch haptics, groove haptics, haptics with one or more protrusions, rigid haptics, soft haptics) among different ophthalmic devices. In some embodiments, the ophthalmic articles described herein have different sizes, shapes and configurations (e.g., notch haptics, groove haptics, haptics with one or more protrusions, rigid haptics, soft haptics). may be accommodated. Due to the elasticity and flexibility of the materials and designs disclosed herein for ophthalmic articles, one advantage is that the ophthalmic article can be sized to fit a given ophthalmic device (e.g., an IOL). It does not need to be precisely shaped to be exact and can be used interchangeably with multiple types of ophthalmic devices (e.g., brands and models with slightly different sized haptics). The ophthalmic articles disclosed herein are ophthalmic device portions (eg, It may be designed and manufactured in assorted size ranges (eg, small, medium, large) for use with (IOLs with haptics).

[0342] It is desirable for cataract surgeons to have the flexibility to select IOLs of different sizes, shapes and powers for different clinical conditions. In various embodiments of the invention, the drug delivery article is manufactured and supplied separately from the IOL so that the physician can use it with different types of IOLs. In other embodiments, the drug delivery article and IOL are manufactured and/or supplied to the surgeon as a single product.

[0343] In one or more embodiments, the intraocular lens is selected from a range of refractive powers (eg, 5-30D in 0.5D increments). In some embodiments, the refractive power of the intraocular lens is at least about 5, at least about 5.5, at least about 6, at least about 6.5, at least about 7, at least about 7.5, at least about 8, at least about about 8.5, at least about 9, at least about 9.5, at least about 10, at least about 10.5, at least about 11, at least about 11.5, at least about 12, at least about 12.5, at least about 13, at least about 13.5, at least about 14, at least about 14.5, at least about 15, at least about 15.5, at least about 16, at least about 16.5, at least about 17, at least about 17.5, at least about 18, at least about 18.5, at least about 19, at least about 19.5, at least about 20, at least about 20.5, at least about 21, at least about 21.5, at least about 22, at least about 22.5, at least about 23, at least about 23.5, at least about 24, at least about 24.5, at least about 25, at least about 25.5, at least about 26, at least about 26.5, at least about 27, at least about 27.5, at least about 28, at least It may be about 28.5, at least about 29, at least about 29.5, or at least about 30. In some embodiments, the refractive power of the intraocular lens is at most about 5, at most about 5.5, at most about 6, at most about 6.5, at most about 7, at most about 7.5 , at most about 8, at most about 8.5, at most about 9, at most about 9.5, at most about 10, at most about 10.5, at most about 11, at most about 11.5, at most but about 12, maximum about 12.5, maximum about 13, maximum about 13.5, maximum about 14, maximum about 14.5, maximum about 15, maximum about 15.5, maximum about 16, up to about 16.5, up to about 17, up to about 17.5, up to about 18, up to about 18.5, up to about 19, up to about 19.5, up to about 20, at most about 20.5, at most about 21, at most about 21.5, at most about 22, at most about 22.5, at most about 23, at most about 23.5, at most about 24, at most about 24.5, up to about 25, up to about 25.5, up to about 26, up to about 26.5, up to about 27, up to about 27.5, up to about 28, up to about 28 .5, up to about 29, up to about 29.5, or up to about 30.

[0344] In some embodiments, the size, shape and material properties of the ophthalmic article and/or ophthalmic device are matched by an incision size (e.g., 2.2 mm) suitable for intraocular injectors and eye surgery. can assist its compressibility, flexibility and/or elasticity. In some embodiments, the material (eg, biocompatible polymer) may be sufficiently compressible and flexible to be compatible with injection by an IOL injector designed for small corneal incisions. In some embodiments, the material (eg, biocompatible copolymer matrix) is compatible with injection by an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm (eg, about 1.2 mm to 1.8 mm). , may be sufficiently compressible. In some embodiments, the material (eg, biocompatible copolymer matrix) is compatible with injection by an IOL injector comprising an injector tip inner diameter of about 0.5-3 mm (eg, about 1.2-1.8 mm). , may be sufficiently flexible. In some embodiments, the material (e.g., biocompatible polymer) may be sufficiently elastic so that it recovers its original shape after injection with an IOL injector designed for small corneal incisions. In some embodiments, the material (eg, a biocompatible copolymer matrix) retains its original shape after injection with an IOL injector comprising an injector tip inner diameter of about 0.5-3 mm (eg, about 1.2 mm-1.8 mm). It may be elastic enough to recover the

[0345] In another aspect, the present disclosure provides an ophthalmic article. In some embodiments, the ophthalmic article comprises a biocompatible copolymer matrix derived from about 40% by weight caprolactone monomers and 60% by weight lactide monomers. In some embodiments, an ophthalmic article includes an active agent and/or a diagnostic agent. In some embodiments, the ophthalmic article has the following characteristics: (i) the biocompatible copolymer matrix comprises a random copolymer; (ii) the ophthalmic article has a tensile strength of about 25 megapascals (MPa) to 35 MPa; (iii) the ophthalmic article has a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry; (iv) the ophthalmic article has a modulus of elasticity of at most about 3 MPa; (v) the ophthalmic article has an elongation at break of about 500% to 1500% at 18°C to 24°C; and (vi) the ophthalmic article comprises an outer diameter of at most 1.5 mm. including. In some embodiments, the ophthalmic article is configured to bond (eg, adhere) to the haptics of an intraocular lens (IOL).

[0346] In another aspect, the present disclosure provides ophthalmic drug delivery systems. An ophthalmic drug delivery system comprising (1) one or more therapeutic agents and (2) a biocompatible copolymer matrix derived from about 40% by weight caprolactone monomers and 60% by weight lactide monomers. Multiple ophthalmic articles may be included. In some embodiments, the one or more ophthalmic articles have the following characteristics: (i) the biocompatible copolymer matrix comprises a random copolymer; (iii) the one or more ophthalmic articles have a glass transition temperature of at most about 24° C. as measured by differential scanning calorimetry; (iv) (v) the one or more ophthalmic articles have an elongation at break of about 500% to 1500% at 18°C to 24°C; including at least one of having. Ophthalmic drug delivery systems may also include one or more intraocular lenses (IOLs) containing one or more haptics. In some embodiments, the one or more ophthalmic articles comprise an outer diameter of at most 1.5 mm and are adapted to couple (e.g., adhere) to one or more haptics of one or more IOLs. configured to

[0347] In another aspect, the present disclosure provides kits. A kit may include a container containing one or more ophthalmic articles (eg, drug delivery articles). Ophthalmic articles may include materials such as biocompatible matrices. A biocompatible matrix may comprise a copolymer derived from a first monomer (eg, a caprolactone monomer) and at least one other monomer. Ophthalmic articles may also include one or more active agents and/or diagnostic agents. In some embodiments, the kit may include instructions for use.

[0348] In another aspect, the present disclosure provides kits. A kit may include a first container containing one or more ophthalmic articles (eg, drug delivery articles). Ophthalmic articles may include materials such as biocompatible matrices. A biocompatible matrix may comprise a copolymer derived from a first monomer (eg, a caprolactone monomer) and at least one other monomer. Ophthalmic articles may also include one or more active agents and/or diagnostic agents. The kit includes one or more ophthalmic devices (e.g., intraocular lenses having one or more haptics) including one or more moieties for coupling with one or more ophthalmic articles. may also include a container of Kits may also include instructions for use.

[0349] A kit may contain one or more elements disclosed herein for any of the various aspects, in any combination. The materials in the kit may be contained in any suitable container, either in ready-to-use form or requiring combination with other materials in the kit or materials supplied by the user. good too. A kit may provide one or more tools for manipulation and one or more ophthalmic articles disclosed herein. In some embodiments, the kit may provide an applicator tool to facilitate coupling of the ophthalmic article to the ophthalmic device. A kit may provide one or more tools for manipulation and compression of an ophthalmic device to which one or more ophthalmic articles disclosed herein are coupled. In some embodiments, the one or more tools may be forceps.

[0350] Systems and/or kits may provide one or more ophthalmic device injectors (eg, intraocular lens injectors).
[0351] In some embodiments, the system and/or kit may include materials for performing cataract surgery. In some embodiments, the system and/or kit includes drapes (e.g., sterile drapes), gloves (e.g., sterile gloves), antiseptics, local anesthesia, dilating agents, knives, blades, post-operative drugs (ophthalmic (apart from the active agent and/or diagnostic agent provided in the medical article), surgical viscoelastics, sutures, gauze, tape and/or eye patch.

[0352] In some embodiments, a delivery tool may be used to implant an ophthalmic device having one or more ophthalmic articles in a subject's eye. Suitable delivery tools may include needles or needle-like applicators.

[0353] The delivery tool may be an injector or a syringe with an appropriately sized needle, or it may be an injector-like tool or a syringe-like tool with a needle-like applicator. In some embodiments, the delivery tool may have an injector tip inner diameter of about 1.2 mm to 1.7 mm.

[0354] In some embodiments, the delivery tool is about 1.2 mm to about 1.25 mm, about 1.2 mm to about 1.3 mm, about 1.2 mm to about 1.35 mm, about 1.2 mm to about 1.4 mm, about 1.2 mm to about 1.45 mm, about 1.2 mm to about 1.5 mm, about 1.2 mm to about 1.55 mm, about 1.2 mm to about 1.6 mm, about 1.2 mm to about 1.65 mm, about 1.2 mm to about 1.7 mm, about 1.25 mm to about 1.3 mm, about 1.25 mm to about 1.35 mm, about 1.25 mm to about 1.4 mm, about 1.25 mm to about 1.45 mm, about 1.25 mm to about 1.5 mm, about 1.25 mm to about 1.55 mm, about 1.25 mm to about 1.6 mm, about 1.25 mm to about 1.65 mm, about 1.25 mm to about 1.7 mm, about 1.3 mm to about 1.35 mm, about 1.3 mm to about 1.4 mm, about 1.3 mm to about 1.45 mm, about 1.3 mm to about 1.5 mm, about 1.3 mm to about 1.55 mm, about 1.3 mm to about 1.6 mm, about 1.3 mm to about 1.65 mm, about 1.3 mm to about 1.7 mm, about 1.35 mm to about 1.4 mm, about 1.35 mm to about 1.45 mm, about 1.35 mm to about 1.5 mm, about 1.35 mm to about 1.55 mm, about 1.35 mm to about 1.6 mm, about 1.35 mm to about 1.65 mm, about 1.35 mm to about 1.7 mm, about 1.4 mm to about 1.45 mm, about 1.4 mm to about 1.5 mm, about 1.4 mm to about 1.55 mm, about 1.4 mm to about 1.6 mm, about 1.4 mm to about 1.65 mm, about 1.4 mm to about 1.7 mm, about 1.45 mm to about 1.5 mm, about 1.45 mm to about 1.55 mm, about 1.45 mm to about 1.6 mm, about 1.45 mm to about 1.65 mm, about 1.45 mm to about 1.7 mm, about 1.5 mm to about 1.55 mm, about 1.5 mm to about 1.6 mm, about 1.5 mm to about 1.65 mm, about 1.5 mm to about 1.7 mm, about 1.55 mm to about 1.6 mm, about 1.55 mm to about 1.65 mm, about 1.55 mm to about 1.7 mm, about 1.6 mm to about 1.65 mm, about 1.6 mm to about It may have an injector tip inner diameter of 1.7 mm, or from about 1.65 mm to about 1.7 mm.

[0355] In some embodiments, the delivery tool is at least about 1.2 mm, at least about 1.25 mm, at least about 1.3 mm, at least about 1.35 mm, at least about 1.4 mm, at least about 1.45 mm, It may have an injector tip inner diameter of at least about 1.5 mm, at least about 1.55 mm, at least about 1.6 mm, at least about 1.65 mm, or at least about 1.7 mm. In some embodiments, the delivery tool is about 1.2 mm, about 1.25 mm, about 1.3 mm, about 1.35 mm, about 1.4 mm, about 1.45 mm, about 1.5 mm, about 1.55 mm , about 1.6 mm, about 1.65 mm, or about 1.7 mm. In some embodiments, the delivery tool is at most about 1.2 mm, at most about 1.25 mm, at most about 1.3 mm, at most about 1.35 mm, at most about 1.4 mm, at most about 1 45 mm, up to about 1.5 mm, up to about 1.55 mm, up to about 1.6 mm, up to about 1.65 mm, or up to about 1.7 mm.

[0356] In some embodiments, the delivery tool may have an injector tip inner diameter of about 0.5 mm to about 3 mm. In some embodiments, the delivery tool is about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0.5 mm to about 0.5 mm. 5 mm to about 3 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2.5 mm, about 1 mm to about 3 mm, about 1.5 mm to about 2 mm, about 1.5 mm to about 2.5 mm , about 1.5 mm to about 3 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, or about 2.5 mm to about 3 mm. In some embodiments, the delivery tool may have an injector tip inner diameter of at least about 0.5 mm, at least about 1 mm, at least about 1.5 mm, at least about 2 mm, at least about 2.5 mm, or at least about 3 mm. . In some embodiments, the delivery tool has an injector tip inner diameter of at most about 0.5 mm, at most about 1 mm, at most about 1.5 mm, at most about 2 mm, at most about 2.5 mm, or at most about 3 mm. may have In some embodiments, the delivery tool may have an injector tip inner diameter of about 1 mm to about 2 mm. In some embodiments, the delivery tool may have an injector tip inner diameter of about 1.2 mm to about 1.7 mm. In some embodiments, the delivery tool may have an injector tip inner diameter of at most about 2 mm. In some embodiments, the delivery tool may have an injector tip inner diameter of at least about 1 mm.

[0357] In some embodiments, an ophthalmic device having one or more ophthalmic articles may be loaded into a delivery tool prior to packaging. In this example, once the kit is opened, the delivery implant may be ready for use. In some embodiments, the components of the kit may be sterilized individually and combined into the kit. In some embodiments, the components of the kit may be sterilized after being combined into the kit.

Method
[0358] In another aspect, the present disclosure provides a method for preparing at least one drug-releasing ophthalmic device (eg, drug-releasing intraocular lens). In some embodiments, one or more active agents and/or diagnostic agents may be combined with a material (eg, a biocompatible matrix) to produce one or more ophthalmic articles. A biocompatible matrix may comprise a copolymer derived from a first monomer (eg, a caprolactone monomer) and at least a second monomer. One or more ophthalmic articles may then be coupled to one or more portions of the ophthalmic device (eg, intraocular lens haptics).

[0359] In another aspect, the present disclosure provides methods for treating or preventing diseases, conditions and/or complications. One or more active agents and/or diagnostic agents may be combined with a biocompatible matrix (eg, a biocompatible copolymer matrix) to produce one or more ophthalmic articles. One or more ophthalmic articles may bind to one or more portions of an ophthalmic device (e.g., intraocular lens haptics), thereby releasing at least one active agent and/or diagnostic agent. Devices (eg, active agent and/or diagnostic agent releasing intraocular lenses) may be produced. An active agent and/or diagnostic agent releasing ophthalmic device may be an ophthalmic device that is attached to an ophthalmic article containing one or more active agents and/or diagnostic agents. At least one active agent and/or diagnostic agent releasing ophthalmic device may be implanted in the eye of a subject in need thereof for sustained intraocular active agent and/or diagnostic agent delivery. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents and/or diagnostic agents, resulting in (e.g., slit lamp biomicroscopy) An inflammation score of at most 1 and/or no eye pain (as measured by the anterior chamber cell score using the method).

[0360] In another aspect, the present disclosure provides methods of treating or preventing diseases, conditions and/or complications. One or more ophthalmic articles may bind to one or more portions of an ophthalmic device (e.g., at least one intraocular lens haptic), thereby providing at least one active agent and/or diagnostic agent. Releasing ophthalmic devices (eg, active agent and/or diagnostic agent releasing intraocular lenses) may be produced. At least one active agent and/or diagnostic agent releasing ophthalmic device may be implanted in the eye of a subject in need thereof for sustained intraocular active agent and/or diagnostic agent delivery. In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents and/or diagnostic agents, resulting in (e.g., slit lamp biomicroscopy) An inflammation score of at most 1 (as measured by an anterior chamber cell score using a method) and/or no eye pain (eg, as measured by a 10-point visual analogue scale).

[0361] In another aspect, the present disclosure provides methods of treating or preventing a disease, condition or complication. In some embodiments, one or more ophthalmic articles may be implanted in the eye of a subject in need thereof for sustained intraocular drug delivery. In some embodiments, one or more ocular devices (eg, intraocular lenses) may be implanted in the eye of a subject in need thereof for sustained intraocular drug delivery. The IOL has one or more drug-releasing articles associated with it, said one or more drug-releasing articles comprising one or more active agents (e.g., therapeutic agents), within 7 days after implantation and said one or more drug-releasing articles release said one or more therapeutic agents resulting in an inflammation score (e.g., as measured by an anterior chamber cell score using slit-lamp biomicroscopy) is at most 1 and/or there is no eye pain (eg, as measured by a 10-point visual analogue scale).

[0362] In another aspect, the present disclosure provides methods of administering an active agent or diagnostic agent. One or more active agents and/or diagnostic agents may be combined with a biocompatible matrix (eg, a biocompatible copolymer matrix), thereby producing one or more ophthalmic articles. One or more ophthalmic articles may bind to one or more portions of one or more ophthalmic devices (e.g., intraocular lens haptics), thereby providing at least one active agent and/or Diagnostic agent releasing ophthalmic devices (eg, active agent and/or diagnostic agent releasing intraocular lenses) may be produced. At least one active agent and/or diagnostic agent releasing ophthalmic device may then be compressed through an ocular device injector (eg, an intraocular lens injector). In some embodiments, an ophthalmic device injector may include an injector tip inner diameter of about 0.5 mm to 3 mm (eg, about 1.2-1.7 mm). At least one active agent and/or diagnostic agent releasing ophthalmic device (e.g., active agent and/or diagnostic agent releasing intraocular lens) is then placed in the eye of a subject in need thereof with a sustained intraocular active agent and /or may be implanted for diagnostic agent delivery.

[0363] In another aspect, the present disclosure provides methods of administering active agents and/or diagnostic agents. One or more ophthalmic devices (e.g., intraocular lenses) having one or more ophthalmic articles attached thereto are compressed through an ocular device injector (intraocular injector), thereby removing one or more A compressed ophthalmic device (eg, an intraocular lens) may be produced to which the ophthalmic article is attached. An ocular device injector (eg, an intraocular device injector) may include an injector tip. The injector tip may include an inner diameter of about 1.2-1.7 mm. Compressed ophthalmic devices (e.g., intraocular lenses) having one or more ophthalmic articles attached thereto for sustained ophthalmic active and/or diagnostic agent delivery to the eye of a subject in need thereof. may be embedded in

[0364] In another aspect, the present disclosure provides methods of active agent (eg, drug) and/or diagnostic agent delivery. The method may include providing an article (eg, an ophthalmic article) for delivering active agents (eg, drugs) and/or diagnostic agents to the eye as described herein. The method may also include bonding (eg, positioning) an article (eg, an ophthalmic article) onto one or more haptics of the intraocular lens.

[0365] In another aspect, the present disclosure provides a method of diagnosing an eye disease or condition in a subject. The method includes administering one or more ophthalmic devices (e.g., intraocular lenses) to the eye of a subject in need thereof for delivery of one or more diagnostic agents to the eye of the subject. It's okay. One or more ophthalmic devices may be associated with one or more ophthalmic articles. The one or more ophthalmic articles may comprise one or more diagnostic agents selected from the group consisting of paramagnetic molecules, fluorescent compounds, magnetic molecules, radionuclides, x-ray imaging agents and contrast agents.

[0366] FIG. 6 schematically illustrates a method of administration, treatment and/or diagnosis (“method”) 600. As shown in FIG. The method includes combining one or more active agents and/or diagnostic agents with a polymeric material (e.g., a biocompatible polymeric matrix), thereby producing one or more ophthalmic articles (Method 610). . Next, the method binds one or more ophthalmic articles to one or more haptics of at least one intraocular lens, thereby producing at least one active agent and/or diagnostic agent releasing intraocular lens. (method 620). An ophthalmic article includes one or more components as provided herein. In one example, the ophthalmic article is one implementation of the ophthalmic article described above, eg, as illustrated in FIGS. 1A, 1B, 2A-2H, 3A, 3B, 4A, and/or 4B. may be in the form An intraocular lens may also include one or more components as provided herein. In another example, the intraocular lens may be an embodiment of an intraocular lens, eg, as illustrated in FIGS. 3A, 3B, 4A, and/or 4B. Referring to FIG. 6, a method includes inserting at least one active agent and/or diagnostic agent releasing intraocular lens into an intraocular lens injector (eg, an injector of about 0.5 mm to 3 mm, such as 1.2 mm to 1.7 mm). The step of compressing (method 630) through an intraocular lens injector that includes the inner diameter of the tip. The method then includes placing at least one active agent- and/or diagnostic agent-releasing intraocular lens (e.g., standard implanting (method 640) using microscopic cataract surgery techniques.

[0367] In any of the various aspects, the method can also include compressing or molding the ophthalmic device with the one or more ophthalmic articles coupled thereto prior to implanting it in the eye. To accommodate delivery by ophthalmic devices (eg, IOL injector devices) where the tip can have an inner diameter of 0.5 mm to 3 mm (eg, 1.2 to 1.7 mm), one or more ophthalmic articles are Coupling foldable ophthalmic devices disclosed herein possess sufficient elasticity to facilitate rapid deployment within the eye while retaining the size, shape and optical properties of the original device. It may be manufactured from a compressible, flexible material such as.

[0368] An ophthalmic surgeon may be able to use ophthalmic devices (eg, injector devices) having one or more ophthalmic articles attached thereto in the same manner as conventional IOLs. In some embodiments, surgery (e.g., cataract surgery) involves insertion of one or more ophthalmic devices to which one or more ophthalmic articles are attached (e.g., adhered) using an injector device. be able to. In some embodiments, the condition may be a condition resulting from or exacerbated by the implantation of an ophthalmic device. In some embodiments, the state may be the state that existed prior to embedding. In some cases, the condition may not be directly related to the condition being treated surgically. In some embodiments, one ophthalmic device may be delivered (eg, implanted) in, near, or around the subject's eye. In some embodiments, the two ophthalmic devices may be delivered (eg, implanted) in, adjacent to, or around the subject's eye. In some embodiments, 2, 3, 4, 5, 6, 7 ophthalmic devices may be delivered in, proximate to, or around the subject's eye. (may be embedded, for example). In some embodiments, the ophthalmic article is a polymeric material (e.g., biodegradable) formulated to provide sustained release of an effective amount (e.g., a therapeutically effective amount) of the active agent and/or diagnostic agent during the release period. (polyetheric copolymer matrix). When the ophthalmic article comprises a biodegradable polymer matrix, the biodegradable polymer matrix can biodegrade to provide sustained release of the active agent and/or diagnostic agent to the eye during the release period.

[0369] Prior to intraocular injection, the ocular device (to which one or more ophthalmic articles are attached) is folded or compressed (eg, into a cassette) and/or It may be loaded into an injector device (eg, intraocular lens injector) that includes an injector tip inner diameter of about 0.5 mm to 3 mm (eg, about 1.2 to 1.7 mm). In some embodiments, the compression compresses the intraocular lens to which the ophthalmic article is coupled into an injector device (eg, an IOL with an injector tip inner diameter of about 0.5 mm to 3 mm, such as about 1.2 to 1.7 mm). injector) into a tubular shape.

[0370] In some embodiments, a folding tool (eg, forceps) is used to fold an ocular device (eg, an intraocular device) in half for insertion through an incision size of about 1.5 mm to 3 mm. may In other embodiments, a folding tool (eg, forceps) may be used to roll the ophthalmic device for insertion through an incision size of approximately 1.5 mm to 3 mm.

[0371] In some embodiments, the folding tool may be used to roll the ophthalmic device for insertion through an incision size of about 0.1 mm to about 5 mm. In some embodiments, the folding tool may be used to roll the ophthalmic device for insertion through an incision size of about 1.5mm to about 2.5mm. In some embodiments, the folding tool has a thickness of about 0.1 mm to about 0.5 mm, about 0.1 mm to about 1 mm, about 0.1 mm to about 1.5 mm, about 0.1 mm to about 2 mm, about 0.1 mm to about 0.5 mm. 1 mm to about 2.5 mm, about 0.1 mm to about 3 mm, about 0.1 mm to about 3.5 mm, about 0.1 mm to about 4 mm, about 0.1 mm to about 4.5 mm, about 0.1 mm to about 5 mm , about 0.5 mm to about 1 mm, about 0.5 mm to about 1.5 mm, about 0.5 mm to about 2 mm, about 0.5 mm to about 2.5 mm, about 0.5 mm to about 3 mm, about 0.5 mm to about 3.5 mm, about 0.5 mm to about 4 mm, about 0.5 mm to about 4.5 mm, about 0.5 mm to about 5 mm, about 1 mm to about 1.5 mm, about 1 mm to about 2 mm, about 1 mm to about 2 .5 mm, from about 1 mm to about 3 mm, from about 1 mm to about 3.5 mm, from about 1 mm to about 4 mm, from about 1 mm to about 4.5 mm, from about 1 mm to about 5 mm, from about 1.5 mm to about 2 mm, from about 1.5 mm about 2.5 mm, about 1.5 mm to about 3 mm, about 1.5 mm to about 3.5 mm, about 1.5 mm to about 4 mm, about 1.5 mm to about 4.5 mm, about 1.5 mm to about 5 mm, about 2 mm to about 2.5 mm, about 2 mm to about 3 mm, about 2 mm to about 3.5 mm, about 2 mm to about 4 mm, about 2 mm to about 4.5 mm, about 2 mm to about 5 mm, about 2.5 mm to about 3 mm, about 2.5 mm to about 3.5 mm, about 2.5 mm to about 4 mm, about 2.5 mm to about 4.5 mm, about 2.5 mm to about 5 mm, about 3 mm to about 3.5 mm, about 3 mm to about 4 mm, about 3 mm to about 4.5 mm, about 3 mm to about 5 mm, about 3.5 mm to about 4 mm, about 3.5 mm to about 4.5 mm, about 3.5 mm to about 5 mm, about 4 mm to about 4.5 mm, about 4 mm to It may be used to wrap the ophthalmic device for insertion through an incision size of about 5 mm, or about 4.5 mm to about 5 mm.

[0372] In some embodiments, the folding tool is at least about 0.1 mm, at least about 0.5 mm, at least about 1 mm, at least about 1.5 mm, at least about 2 mm, at least about 2.5 mm, at least about 3 mm, It may be used to wrap the ophthalmic device for insertion through an incision size of at least about 3.5 mm, at least about 4 mm, at least about 4.5 mm, or at least about 5 mm. In some embodiments, a folding tool may be used to roll the ophthalmic device for insertion through an incision size of at least about 1.5 mm. In some embodiments, a folding tool may be used to roll the ophthalmic device for insertion through an incision size of at least about 1.8 mm.

[0373] In some embodiments, the folding tool has a thickness of at most about 0.1 mm, at most about 0.5 mm, at most about 1 mm, at most about 1.5 mm, at most about 2 mm, at most about 2.0 mm. May be used to wrap an ophthalmic device for insertion through an incision size of 5 mm, up to about 3 mm, up to about 3.5 mm, up to about 4 mm, up to about 4.5 mm, or up to about 5 mm. good. In some embodiments, the folding tool may be used to roll the ophthalmic device for insertion through an incision size of up to about 2 mm. In some embodiments, the folding tool may be used to roll the ophthalmic device for insertion through an incision size of up to about 3 mm.

[0374] In some embodiments, the method includes removing an ophthalmic device (e.g., an intraocular lens) containing an ophthalmic article into the eye by removing the ophthalmic device from an ophthalmic device injector (e.g., an intraocular injector). Including the step of introducing. For example, a method includes intraocularly (e.g., the lens of an eye) an ophthalmic device (e.g., IOL) having one or more ophthalmic articles associated therewith to deliver active agents and/or diagnostic agents to the eye of a subject. into the follicular capsule or ciliary sulcus). An ophthalmic device with one or more ophthalmic articles attached thereto may be folded, loaded, and inserted into the eye through an incision consistent with current standard of care.

[0375] In some embodiments, the ophthalmic article for active and/or diagnostic agent delivery to the eye is a standard injector device when positioned on a portion of an ocular device (e.g., an IOL haptic). It may include compressible, flexible and/or elastic polymers that do not interfere with injection of ocular devices and ophthalmic articles by the eye, nor do they interfere with deployment of the IOL within the eye after injection.

[0376] In some embodiments, the biocompatible matrix and/or ophthalmic article comprises an intraocular injector (eg, IOL It is sufficiently compressible to be compatible with injection by an injector). In some embodiments, the biocompatible matrix and/or ophthalmic article is an intraocular injector (eg, an IOL injector) comprising an injector tip inner diameter of about 0.5 mm to 3 mm (eg, about 1.2-1.7 mm). flexible enough to be compatible with injection by In some embodiments, the biocompatible matrix and/or ophthalmic article is an intraocular injector (eg, an IOL injector) comprising an injector tip inner diameter of about 0.5 mm to 3 mm (eg, about 1.2-1.7 mm). It is sufficiently elastic so that it recovers its original shape after being injected with.

[0377] FIG. 5A illustrates an example loading method ("method") 500 for loading an ophthalmic device (e.g., an intraocular device) having one or more ophthalmic articles attached thereto into an injector device. Schematically illustrated. In this example, the loading method may be an embodiment for a method for treating or preventing a disease, condition and/or complication. A loading method may also be an embodiment for a method for administering an active agent and/or a diagnostic agent. The method includes providing an ophthalmic article (method 501). An ophthalmic article includes one or more components of an ophthalmic article as disclosed herein. For example, an ophthalmic article can include a polymeric material (eg, a biocompatible copolymer matrix) and an active agent and/or diagnostic agent. In another example, the ophthalmic article is one of the ophthalmic articles described above, eg, as illustrated in FIGS. 1A, 1B, 2A-2H, 3A, 3B, 4A and/or 4B. It may be an embodiment. Referring to FIG. 5A, the method includes bonding ophthalmic article 100 onto haptics 302 of intraocular lens 300 (method 503). An intraocular lens comprises one or more components of an intraocular lens as disclosed herein. In one example, the intraocular lens may be one embodiment of the intraocular lens described above, as illustrated in FIGS. 3A, 3B, 4A, and/or 4B. Referring to FIG. 5A, the method also includes compressing intraocular lens 300 with coupled ophthalmic article 100 into cassette 507 (method 506). The method may then include loading cassette 507 containing intraocular lens 300 with associated ophthalmic article 100 into intraocular lens injector 508 (method 509).

[0378] In some examples, the method may include performing surgery (eg, cataract removal surgery) on the subject's eye. FIG. 5B schematically illustrates an example of an implantation method (“method”) 510 for implanting an intraocular lens to which an ophthalmic article is attached. In this example, the method of implantation may be an embodiment for a method for treating or preventing a disease, condition and/or complication. A method of implantation may be one embodiment for a method for administering an active agent and/or a diagnostic agent. A method of implantation may include making an incision 513 in the side of the cornea for implantation of an intraocular lens 300 with an ophthalmic article 100 attached thereto (method 511). Ophthalmic article 100 may include one or more components of ophthalmic articles as disclosed herein. For example, an ophthalmic article can include a polymeric material (eg, a biocompatible copolymer matrix) and an active or diagnostic agent. In another example, the ophthalmic article is an embodiment of the ophthalmic article described above, such as illustrated in FIGS. 1A, 1B, 2A-2H, 3A, 3B, 4A and/or 4B. may be An intraocular lens comprises one or more components of an intraocular lens as disclosed herein. In one example, the intraocular lens may be one embodiment of the intraocular lens described above, as illustrated in FIGS. 3A, 3B, 4A, and/or 4B. Referring to FIG. 5B, the method includes removing an existing lens 515 (eg, a diseased lens) from a subject's eye using a surgical instrument 520 (method 514) using a loaded intraocular lens injector 508. and implanting the intraocular lens in the subject's eye (method 516), and placing the intraocular lens 300 with the ophthalmic article 100 coupled thereto within the lens capsule (method 518). Other delivery routes for ophthalmic articles include punctal, intravitreal, subconjunctival, lens, intrascleral, fornix, anterior subtenon, suprachoroidal, posterior subtenon, subretinal, anterior and posterior chambers. can be mentioned. In some embodiments, the subject is undergoing or has undergone concurrent eye surgery. In some embodiments, the subject is undergoing or has undergone concurrent cataract surgery. FIG. 5C schematically illustrates an example of an intraocular lens 300 with an ophthalmic article 100 attached thereto, wherein the ophthalmic article does not interfere with placement of the intraocular lens in the desired position, location and orientation within the lens capsule 519 of the eye. example. The ophthalmic article can be attached to the intraocular lens by actual contact or in sufficient proximity while allowing effective diffusion of the active agent and/or diagnostic agent to the target area of the eye. The active agent and/or diagnostic agent may be released from the polymeric material (eg, biocompatible copolymer matrix) of the ophthalmic article by degradation of the polymeric material, as disclosed herein.

[0379] Over the course of release, the polymeric material (eg, biodegradable polymer matrix) can degrade while releasing the active agent and/or diagnostic agent. In some embodiments, the polymeric material biodegrades or bioerodes to provide controlled release of an effective amount (e.g., a therapeutically effective amount) of an active agent and/or diagnostic agent over a period of days, weeks, or months. can be configured to provide Upon complete release of the active agent and/or diagnostic agent, the polymer matrix is expected to disappear. In some embodiments, complete polymer matrix degradation may take longer than complete release of active agents and/or diagnostic agents. In some embodiments, polymer matrix degradation may occur at the same rate as active agent and/or diagnostic agent release.

[0380] For example, an ophthalmic article may be designed to release an effective amount of an active agent and/or diagnostic agent from a polymeric material (eg, a biocompatible copolymer matrix) from about 1 day to about 12 months. In some embodiments, the active agent and/or diagnostic agent are released from the polymeric material (eg, biocompatible copolymer matrix) over at least about 7 days. In some embodiments, the active agent and/or diagnostic agent is about 5-30 days, 5-21 days, 5-14 days, 5-10 days, 7-30 days, 7-21 days, 7-14 days Released from the polymeric material (eg, biocompatible copolymer matrix) over a period ranging from days or 7-10 days.

[0381] In some embodiments, the active agent and/or diagnostic agent may be released from the polymeric material over a period of time from about 1 day to about 365 days. In some embodiments, the active agent and/or diagnostic agent is administered from about 1 day to about 5 days, from about 1 day to about 10 days, from about 1 day to about 15 days, from about 1 day to about 20 days, from about 1 day days to about 30 days, about 1 day to about 40 days, about 1 day to about 50 days, about 1 day to about 100 days, about 1 day to about 200 days, about 1 day to about 300 days, about 1 day or more About 365 days, about 5 days to about 10 days, about 5 days to about 15 days, about 5 days to about 20 days, about 5 days to about 30 days, about 5 days to about 40 days, about 5 days to about 50 days days, about 5 days to about 100 days, about 5 days to about 200 days, about 5 days to about 300 days, about 5 days to about 365 days, about 10 days to about 15 days, about 10 days to about 20 days, About 10 days to about 30 days, about 10 days to about 40 days, about 10 days to about 50 days, about 10 days to about 100 days, about 10 days to about 200 days, about 10 days to about 300 days, about 10 days days to about 365 days, about 15 days to about 20 days, about 15 days to about 30 days, about 15 days to about 40 days, about 15 days to about 50 days, about 15 days to about 100 days, about 15 days About 200 days, about 15 days to about 300 days, about 15 days to about 365 days, about 20 days to about 30 days, about 20 days to about 40 days, about 20 days to about 50 days, about 20 days to about 100 days days, about 20 days to about 200 days, about 20 days to about 300 days, about 20 days to about 365 days, about 30 days to about 40 days, about 30 days to about 50 days, about 30 days to about 100 days, About 30 days to about 200 days, about 30 days to about 300 days, about 30 days to about 365 days, about 40 days to about 50 days, about 40 days to about 100 days, about 40 days to about 200 days, about 40 days days to about 300 days, about 40 days to about 365 days, about 50 days to about 100 days, about 50 days to about 200 days, about 50 days to about 300 days, about 50 days to about 365 days, about 100 days for a period of about 200 days, about 100 days to about 300 days, about 100 days to about 365 days, about 200 days to about 300 days, about 200 days to about 365 days, or about 300 days to about 365 days may be emitted from In some embodiments, the active agent and/or diagnostic agent is administered for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days. , at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months , at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months. In some embodiments, the active agent and/or diagnostic agent is administered for up to about 1 day, up to about 2 days, up to about 3 days, up to about 4 days, up to about 5 days, up to about 6 days. days, maximum about 7 days, maximum about 2 weeks, maximum about 3 weeks, maximum about 4 weeks, maximum about 1 month, maximum about 2 months, maximum about 3 months, maximum about 4 months, for a period of up to about 5 months, up to about 6 months, up to about 7 months, up to about 8 months, up to about 9 months, up to about 10 months, up to about 11 months, or up to about 12 months , may be released from the polymeric material.

[0382] In some examples, an effective amount (eg, a therapeutically effective amount) may be released over a period ranging from about 1 week to about 12 weeks. In other examples, an effective amount may be released over a period ranging from about 1 week to about 3 weeks, about 2 weeks to about 6 weeks, or about 5 weeks to about 8 weeks. In cases such as retinal vein/artery occlusion, diabetic retinopathy, macular edema or retinal degeneration, the duration can often range from 2 months to 12 months, in some cases from 2.5 months to 5 months. . For example, bioerodible lipid polymers and/or bioerodible caprolactone can be used as sustained release matrix materials.

[0383] In some examples, an effective amount (eg, a therapeutically effective amount) is about 1 week to about 2 weeks, about 1 week to about 3 weeks, about 1 week to about 4 weeks, about 1 week to about 5 weeks. , about 1 week to about 6 weeks, about 1 week to about 7 weeks, about 1 week to about 8 weeks, about 1 week to about 9 weeks, about 1 week to about 10 weeks, about 1 week to about 11 weeks, about 1 week to about 12 weeks, about 2 weeks to about 3 weeks, about 2 weeks to about 4 weeks, about 2 weeks to about 5 weeks, about 2 weeks to about 6 weeks, about 2 weeks to about 7 weeks, about 2 weeks ~ about 8 weeks, about 2 weeks to about 9 weeks, about 2 weeks to about 10 weeks, about 2 weeks to about 11 weeks, about 2 weeks to about 12 weeks, about 3 weeks to about 4 weeks, about 3 weeks to about 5 weeks, about 3 weeks to about 6 weeks, about 3 weeks to about 7 weeks, about 3 weeks to about 8 weeks, about 3 weeks to about 9 weeks, about 3 weeks to about 10 weeks, about 3 weeks to about 11 weeks , about 3 weeks to about 12 weeks, about 4 weeks to about 5 weeks, about 4 weeks to about 6 weeks, about 4 weeks to about 7 weeks, about 4 weeks to about 8 weeks, about 4 weeks to about 9 weeks, about 4 weeks to about 10 weeks, about 4 weeks to about 11 weeks, about 4 weeks to about 12 weeks, about 5 weeks to about 6 weeks, about 5 weeks to about 7 weeks, about 5 weeks to about 8 weeks, about 5 weeks ~ about 9 weeks, about 5 weeks to about 10 weeks, about 5 weeks to about 11 weeks, about 5 weeks to about 12 weeks, about 6 weeks to about 7 weeks, about 6 weeks to about 8 weeks, about 6 weeks to about 9 weeks, about 6 weeks to about 10 weeks, about 6 weeks to about 11 weeks, about 6 weeks to about 12 weeks, about 7 weeks to about 8 weeks, about 7 weeks to about 9 weeks, about 7 weeks to about 10 weeks , about 7 weeks to about 11 weeks, about 7 weeks to about 12 weeks, about 8 weeks to about 9 weeks, about 8 weeks to about 10 weeks, about 8 weeks to about 11 weeks, about 8 weeks to about 12 weeks, about over a range of 9 weeks to about 10 weeks, about 9 weeks to about 11 weeks, about 9 weeks to about 12 weeks, about 10 weeks to about 11 weeks, about 10 weeks to about 12 weeks, or about 11 weeks to about 12 weeks It may be released over a period of time.

[0384] In some examples, an effective amount (e.g., a therapeutically effective amount) is at least or up to about 1 week, at least or up to about 2 weeks, at least or up to about 3 weeks, at least or up to about 4 weeks. , at least or up to about 5 weeks, at least or up to about 6 weeks, at least or up to about 7 weeks, at least or up to about 8 weeks, at least or up to about 9 weeks, at least or up to about 10 weeks, at least Or it may be released over a period of up to about 11 weeks or at least or up to about 12 weeks. In some examples, an effective amount (eg, a therapeutically effective amount) is about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks. It may be released over a period of weeks, about 10 weeks, about 11 weeks or about 12 weeks.

[0385] In some examples, an effective amount (eg, a therapeutically effective amount) is about 2 months to about 3 months, about 2 months to about 4 months, about 2 months to about 5 months, about 2 months to about 6 months. , about 2 months to about 7 months, about 2 months to about 8 months, about 2 months to about 9 months, about 2 months to about 10 months, about 2 months to about 11 months, about 2 months to about 12 months, about 3 months to about 4 months, about 3 months to about 5 months, about 3 months to about 6 months, about 3 months to about 7 months, about 3 months to about 8 months, about 3 months to about 9 months, about 3 months ~ about 10 months, about 3 months to about 11 months, about 3 months to about 12 months, about 4 months to about 5 months, about 4 months to about 6 months, about 4 months to about 7 months, about 4 months to about 8 months, about 4 months to about 9 months, about 4 months to about 10 months, about 4 months to about 11 months, about 4 months to about 12 months, about 5 months to about 6 months, about 5 months to about 7 months , about 5 months to about 8 months, about 5 months to about 9 months, about 5 months to about 10 months, about 5 months to about 11 months, about 5 months to about 12 months, about 6 months to about 7 months, about 6 months to about 8 months, about 6 months to about 9 months, about 6 months to about 10 months, about 6 months to about 11 months, about 6 months to about 12 months, about 7 months to about 8 months, about 7 months ~ about 9 months, about 7 months to about 10 months, about 7 months to about 11 months, about 7 months to about 12 months, about 8 months to about 9 months, about 8 months to about 10 months, about 8 months to about 11 months, about 8 months to about 12 months, about 9 months to about 10 months, about 9 months to about 11 months, about 9 months to about 12 months, about 10 months to about 11 months, about 10 months to about 12 months , or may be released over a period of about 11 months to about 12 months.

[0386] In some examples, an effective amount (e.g., a therapeutically effective amount) is at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least It may be released over a period of about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, or at least about 12 months. at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, or at least about 11 months from.

[0387] In some examples, an effective amount (e.g., a therapeutically effective amount) is up to about 2 months, up to about 3 months, up to about 4 months, up to about 5 months, up to about 6 months, However, it may be released over a period of up to about 7 months, up to about 8 months, up to about 9 months, up to about 10 months, up to about 11 months, or up to about 12 months. at least about 2 months, at most about 3 months, at most about 4 months, at most about 5 months, at most about 6 months, at most about 7 months, at most about 8 months, at most about 9 months, at most But from about 10 months or at most about 11 months.

[0388] In some examples, an effective amount (e.g., a therapeutically effective amount) is about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months. , may be released over a period of about 10 months, about 11 months or about 12 months. From at least about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months or about 11 months.

[0389] In some examples, an effective amount (e.g., a therapeutically effective amount) is at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, or at least It may be released over a period of about 7 days. In some examples, an effective amount (e.g., a therapeutically effective amount) is up to about 1 day, up to about 2 days, up to about 3 days, up to about 4 days, up to about 5 days, up to about 6 days. may be released over a period of days or up to about 7 days.

[0390] Biodegradable systems have been used in conventional cataract surgery to provide short/limited time delivery of post-operative drugs while minimizing or eliminating the need for eye drop use by the patient. can have substantial value in The removed lens may be the eye's original natural lens or it may be a lens previously inserted into the eye as a result of a previous procedure. Once implanted, an ocular device (e.g., an intraocular device) and one or more ophthalmic articles coupled thereto may then spontaneously unfold (using a small instrument inserted into the eye). can be positioned in place and adjusted by the surgeon. In some embodiments, the ophthalmic article does not disintegrate or fracture under the stress of injection by an intraocular (eg, IOL) injector device.

[0391] Decentering or angulation of ophthalmic devices (eg, intraocular devices) within the lens capsular capsule can adversely affect the light intensity of the IOL, resulting in refractive errors and patient dissatisfaction. In some embodiments, the ophthalmic article, when positioned on a portion of the ophthalmic device (e.g., the haptics of the IOL), provides a desired position, location, and orientation of the ophthalmic device with appropriate visual outcomes. Installation cannot be hindered.

[0392] During surgery, a surgeon inserts an ocular device (e.g., an intraocular device) with an ophthalmic article attached into the eye, further maneuvers it to the correct axis and plane, and properly centers and tilts it. It may be possible to achieve the disappearance of In some embodiments, the ocular device (e.g., intraocular device) is used during the post-operative period, in which the ocular device (e.g., IOL) may contract and the lens capsule may shift in response to changes in body position. may remain in the appropriate position and orientation. In some embodiments, the ophthalmic device (eg, IOL) may remain capable of being positioned by the surgeon using various surgical techniques (eg, small-incision surgical techniques).

[0393] Procedures for implanting an ocular device (eg, an intraocular device) in a subject's eye can cause complications such as irritation and inflammation. An ocular examination can be performed using a slit lamp microscope and/or an inverse ophthalmoscope to assess the degree of inflammation and/or other complications caused by the procedure. Ocular examination may include assessing ocular surface morphology, anterior and/or posterior inflammation or capsular fibrosis. Scores are scored using a scoring system (e.g., the Hackett and Macdonald Eye Scoring System, or a modified Hackett and Macdonald Eye Scoring System with additional scoring parameters for the posterior segment) to quantify the outcome of the ocular examination. can be generated. The modified Hackett and MacDonald system is most commonly used for ocular testing in animal models of ocular disease. In human subjects, other standardized scales (eg, the Standardization of Uveitis Nomenclature Working Group developed scoring system) may be used to quantify the outcome of an ocular examination.

[0394] In some embodiments, a subject's anterior chamber cell score as measured by a scoring system (e.g., Standardization of Uveitis Nomenclature Working Group) is defined by a slit lamp beam measuring 1 x 1 mm in area: At most 1+ or 6-15 cells per area. In some embodiments, the subject's anterior chamber cell score may be from about 0 to about 2. In some embodiments, the subject's anterior chamber cell score is about 0 to about 0.5, about 0 to about 1, about 0 to about 2, about 0.5 to about 1, about 0.5 to about 2 Or it may be from about 1 to about 2. In some embodiments, the subject's anterior chamber cell score may be about 0, about 0.5, about 1, or about 2. In some embodiments, the subject's anterior chamber cell score may be at least about 0, at least about 0.5, at least about 1, or at least about 2. In some embodiments, the subject's anterior chamber cell score may be at most about 0, at most about 0.5, at most about 1, or at most about 2.

[0395] In some embodiments, the anterior chamber cell score can be characterized by having about 0 cells per area to about 30 cells per area. In some embodiments, the anterior chamber cell score is about 0 cells per area to about 1 cell per area, about 0 cells per area to about 2 cells per area, about 0 cells per area cells to about 4 cells per area, about 0 cells per area to about 6 cells per area, about 0 cells per area to about 8 cells per area, about 0 cells per area ~ 10 cells per region, ~ 0 cells per region ~ ~ 12 cells per region, ~ 0 cells per region ~ ~ 14 cells per region, ~ 0 cells per region ~ region about 16 cells per area, about 0 cells per area to about 20 cells per area, about 0 cells per area to about 30 cells per area, about 1 cell per area to about 2 cells, about 1 cell per area to about 4 cells per area, about 1 cell per area to about 6 cells per area, about 1 cell per area to about 8 cells per area cells, about 1 cell per area to about 10 cells per area, about 1 cell per area to about 12 cells per area, about 1 cell per area to about 14 cells per area , about 1 cell per region to about 16 cells per region, about 1 cell per region to about 20 cells per region, about 1 cell per region to about 30 cells per region, region about 2 cells per area to about 4 cells per area, about 2 cells per area to about 6 cells per area, about 2 cells per area to about 8 cells per area, about 2 cells to about 10 cells per area, about 2 cells per area to about 12 cells per area, about 2 cells per area to about 14 cells per area, about 2 cells per area cells to about 16 cells per area, about 2 cells per area to about 20 cells per area, about 2 cells per area to about 30 cells per area, about 4 cells per area ~6 cells per region, ~4 cells per region ~8 cells per region, ~4 cells per region ~~10 cells per region, ~4 cells per region ~region about 12 cells per area, about 4 cells per area to about 14 cells per area, about 4 cells per area to about 16 cells per area, about 4 cells per area to about 20 cells, about 4 cells per area to about 30 cells per area, about 6 cells per area to about 8 cells per area, about 6 cells per area to about 10 cells per area cells, about 6 cells per area to about 12 cells per area, about 6 cells per area to about 14 cells per area, about 6 cells per area to about 16 cells per area , about 6 cells per region to about 20 cells per region, about 6 cells per region to about 30 cells per region, about 8 cells per region to about 10 cells per region, regions about 8 cells per area to about 12 cells per area, about 8 cells per area to about 14 cells per area, about 8 cells per area to about 16 cells per area, about 8 cells to about 20 cells per area, about 8 cells per area to about 30 cells per area, about 10 cells per area to about 12 cells per area, about 10 cells per area cells to about 14 cells per area, about 10 cells per area to about 16 cells per area, about 10 cells per area to about 20 cells per area, about 10 cells per area ~ 30 cells per region, approximately 12 cells per region ~ 14 cells per region, approximately 12 cells per region ~ 16 cells per region, approximately 12 cells per region ~ region about 20 cells per area, about 12 cells per area to about 30 cells per area, about 14 cells per area to about 16 cells per area, about 14 cells per area to about 20 cells, about 14 cells per area to about 30 cells per area, about 16 cells per area to about 20 cells per area, about 16 cells per area to about 30 cells per area can be characterized by having from about 20 cells per cell or area to about 30 cells per area. In some embodiments, the anterior chamber cell score is about 0 cells per region, about 1 cell per region, about 2 cells per region, about 4 cells per region, about 6 cells per region cells, about 8 cells per area, about 10 cells per area, about 12 cells per area, about 14 cells per area, about 16 cells per area, about 20 cells per area or characterized by having about 30 cells per area. In some embodiments, the anterior chamber cell score is at least about 0 cells per area, at least about 1 cell per area, at least about 2 cells per area, at least about 4 cells per area, at least about 6 cells per region, at least about 8 cells per region, at least about 10 cells per region, at least about 12 cells per region, at least about 14 cells per region, at least about 16 cells per region cells, at least about 20 cells per area, or at least about 30 cells per area. In some embodiments, the anterior chamber cell score is at most about 0 cells per area, at most about 1 cell per area, at most about 2 cells per area, at most about 4 cells per area cells, up to about 6 cells per area, up to about 8 cells per area, up to about 10 cells per area, up to about 12 cells per area, up to about 14 cells per area cells, at most about 16 cells per area, at most about 20 cells per area or at most about 30 cells per area.

[0396] In some embodiments, the subject's anterior chamber cell score is at most 1 from 20 days to 100 days after implantation of the ocular device (eg, intraocular device). In some embodiments, the subject's anterior chamber cell score may be at most 1 from about 5 days to about 200 days after implantation of the ophthalmic device. In some embodiments, the subject's anterior chamber cell score is about 5 days to about 10 days, about 5 days to about 15 days, about 5 days to about 20 days, about 5 days after implantation of the ophthalmic device ~ about 30 days, about 5 days to about 40 days, about 5 days to about 50 days, about 5 days to about 60 days, about 5 days to about 80 days, about 5 days to about 100 days, about 5 days to about 150 days, about 5 days to about 200 days, about 10 days to about 15 days, about 10 days to about 20 days, about 10 days to about 30 days, about 10 days to about 40 days, about 10 days to about 50 days , about 10 days to about 60 days, about 10 days to about 80 days, about 10 days to about 100 days, about 10 days to about 150 days, about 10 days to about 200 days, about 15 days to about 20 days, about 15 days to about 30 days, about 15 days to about 40 days, about 15 days to about 50 days, about 15 days to about 60 days, about 15 days to about 80 days, about 15 days to about 100 days, about 15 days ~ about 150 days, about 15 days to about 200 days, about 20 days to about 30 days, about 20 days to about 40 days, about 20 days to about 50 days, about 20 days to about 60 days, about 20 days to about 80 days, about 20 days to about 100 days, about 20 days to about 150 days, about 20 days to about 200 days, about 30 days to about 40 days, about 30 days to about 50 days, about 30 days to about 60 days , about 30 days to about 80 days, about 30 days to about 100 days, about 30 days to about 150 days, about 30 days to about 200 days, about 40 days to about 50 days, about 40 days to about 60 days, about 40 days to about 80 days, about 40 days to about 100 days, about 40 days to about 150 days, about 40 days to about 200 days, about 50 days to about 60 days, about 50 days to about 80 days, about 50 days ~ about 100 days, about 50 days to about 150 days, about 50 days to about 200 days, about 60 days to about 80 days, about 60 days to about 100 days, about 60 days to about 150 days, about 60 days to about 200 days, about 80 days to about 100 days, about 80 days to about 150 days, about 80 days to about 200 days, about 100 days to about 150 days, about 100 days to about 200 days, or about 150 days to about 200 days A maximum of 1 is allowed in days. In some embodiments, the subject's anterior chamber cell score is about 5 days, about 10 days, about 15 days, about 20 days, about 30 days, about 40 days, about 50 days after implantation of the ophthalmic device , about 60 days, about 80 days, about 100 days, about 150 days or about 200 days, and may be up to 1. In some embodiments, the subject's anterior chamber cell score is at least about 5 days, at least about 10 days, at least about 15 days, at least about 20 days, at least about 30 days, at least about 40 days, at least about 50 days, at least about 60 days, at least about 80 days, at least about 100 days, at least about 150 days or at least about 200 days, and may be up to 1. In some embodiments, the subject's anterior chamber cell score is at most about 5 days, at most about 10 days, at most about 15 days, at most about 20 days, at most about 30 days, at most about 40 days, at most about 50 days, at most about 60 days, at most about 80 days, at most about 100 days, at most about 150 days or at most about 200 days, at most 1 There may be.

[0397] In some embodiments, the active agent (e.g., dexamethasone, moxifloxacin, ketorolac) concentration in the aqueous humor of a subject implanted with an ophthalmic article is at least 80 ng/mL ( For example, 2,500 ng/mL on day 3 and 2.5 ng/mL on day 14). In some embodiments, after surgery (e.g., 28 days post-surgery), the drug concentration in the aqueous humor of a subject implanted with an ophthalmic article is from about 1 ng/mL to about 2,000 ng/mL. good too. In some embodiments, after surgery, the drug concentration in the aqueous humor of a subject implanted with an ophthalmic article is from about 1 ng/mL to about 5 ng/mL, from about 1 ng/mL to about 10 ng/mL, from about 1 ng/mL to about 1 ng/mL. mL to about 15 ng/mL, about 1 ng/mL to about 20 ng/mL, about 1 ng/mL to about 40 ng/mL, about 1 ng/mL to about 80 ng/mL, about 1 ng/mL to about 100 ng/mL, about 1 ng/mL mL to about 200 ng/mL, about 1 ng/mL to about 500 ng/mL, about 1 ng/mL to about 1,000 ng/mL, about 1 ng/mL to about 2,000 ng/mL, about 5 ng/mL to about 10 ng/mL , about 5 ng/mL to about 15 ng/mL, about 5 ng/mL to about 20 ng/mL, about 5 ng/mL to about 40 ng/mL, about 5 ng/mL to about 80 ng/mL, about 5 ng/mL to about 100 ng/mL , from about 5 ng/mL to about 200 ng/mL, from about 5 ng/mL to about 500 ng/mL, from about 5 ng/mL to about 1,000 ng/mL, from about 5 ng/mL to about 2,000 ng/mL, from about 10 ng/mL about 15 ng/mL, about 10 ng/mL to about 20 ng/mL, about 10 ng/mL to about 40 ng/mL, about 10 ng/mL to about 80 ng/mL, about 10 ng/mL to about 100 ng/mL, about 10 ng/mL to about 200 ng/mL, about 10 ng/mL to about 500 ng/mL, about 10 ng/mL to about 1,000 ng/mL, about 10 ng/mL to about 2,000 ng/mL, about 15 ng/mL to about 20 ng/mL, about 15 ng/mL to about 40 ng/mL, about 15 ng/mL to about 80 ng/mL, about 15 ng/mL to about 100 ng/mL, about 15 ng/mL to about 200 ng/mL, about 15 ng/mL to about 500 ng/mL, about 15 ng/mL to about 1,000 ng/mL, about 15 ng/mL to about 2,000 ng/mL, about 20 ng/mL to about 40 ng/mL, about 20 ng/mL to about 80 ng/mL, about 20 ng/mL to about 100 ng /mL, about 20 ng/mL to about 200 ng/mL, about 20 ng/mL to about 500 ng/mL, about 20 ng/mL to about 1,000 ng/mL, about 20 ng/mL to about 2,000 ng/mL, about 40 ng/mL mL to about 80 ng/mL, about 40 ng/mL to about 100 ng/mL, about 40 ng/mL to about 200 ng/mL, about 40 ng/mL to about 500 ng/mL, about 40 ng/mL to about 1,000 ng/mL, about 40 ng/mL to about 2,000 ng/mL, about 80 ng/mL to about 100 ng/mL, about 80 ng/mL to about 200 ng/mL, about 80 ng/mL to about 500 ng/mL, about 80 ng/mL to about 1,000 ng/mL, about 80 ng/mL to about 2,000 ng/mL, about 100 ng /mL to about 200 ng/mL, about 100 ng/mL to about 500 ng/mL, about 100 ng/mL to about 1,000 ng/mL, about 100 ng/mL to about 2,000 ng/mL, about 200 ng/mL to about 500 ng/mL mL, about 200 ng/mL to about 1,000 ng/mL, about 200 ng/mL to about 2,000 ng/mL, about 500 ng/mL to about 1,000 ng/mL, about 500 ng/mL to about 2,000 ng/mL, Or it may be from about 1,000 ng/mL to about 2,000 ng/mL. In some embodiments, after surgery, the drug concentration in the aqueous humor of a subject implanted with an ophthalmic article is about 1 ng/mL, about 5 ng/mL, about 10 ng/mL, about 15 ng/mL, about 20 ng/mL. mL, about 40 ng/mL, about 80 ng/mL, about 100 ng/mL, about 200 ng/mL, about 500 ng/mL, about 1,000 ng/mL, or about 2,000 ng/mL. In some embodiments, after surgery, the drug concentration in the aqueous humor of a subject implanted with an ophthalmic article is at least about 1 ng/mL, at least about 5 ng/mL, at least about 10 ng/mL, at least about 15 ng/mL , at least about 20 ng/mL, at least about 40 ng/mL, at least about 80 ng/mL, at least about 100 ng/mL, at least about 200 ng/mL, at least about 500 ng/mL, at least about 1,000 ng/mL or at least about 2,000 ng /mL. In some embodiments, after surgery, the drug concentration in the aqueous humor of a subject implanted with an ophthalmic article is at most about 1 ng/mL, at most about 5 ng/mL, at most about 10 ng/mL, at most about 15 ng/mL, up to about 20 ng/mL, up to about 40 ng/mL, up to about 80 ng/mL, up to about 100 ng/mL, up to about 200 ng/mL, up to about 500 ng/mL, up to about It may be 1,000 ng/mL or up to about 2,000 ng/mL.

[0398] In some embodiments, drug (eg, dexamethasone, moxifloxacin, ketorolac) concentrations in plasma samples from subjects implanted with ophthalmic articles are at most 1 ng/mL. In some embodiments, drug concentrations in plasma samples from subjects implanted with ophthalmic articles may be from about 0.01 ng/mL to about 100 ng/mL. In some embodiments, drug concentrations in plasma samples from subjects implanted with ophthalmic articles are from about 0.01 ng/mL to about 0.05 ng/mL, from about 0.01 ng/m to about 0.1 ng /mL, about 0.01 ng/mL to about 0.5 ng/mL, about 0.01 ng/mL to about 1 ng/mL, about 0.01 ng/mL to about 5 ng/mL, about 0.01 ng/mL to about 10 ng /mL, about 0.01 ng/mL to about 50 ng/mL, about 0.01 ng/mL to about 100 ng/mL, about 0.05 ng/mL to about 0.1 ng/mL, about 0.05 ng/mL to about 0 .5 ng/mL, about 0.05 ng/mL to about 1 ng/mL, about 0.05 ng/mL to about 5 ng/mL, about 0.05 ng/mL to about 10 ng/mL, about 0.05 ng/mL to about 50 ng /mL, about 0.05 ng/mL to about 100 ng/mL, about 0.1 ng/mL to about 0.5 ng/mL, about 0.1 ng/mL to about 1 ng/mL, about 0.1 ng/mL to about 5 ng /mL, about 0.1 ng/mL to about 10 ng/mL, about 0.1 ng/mL to about 50 ng/mL, about 0.1 ng/mL to about 100 ng/mL, about 0.5 ng/mL to about 1 ng/mL , about 0.5 ng/mL to about 5 ng/mL, about 0.5 ng/mL to about 10 ng/mL, about 0.5 ng/mL to about 50 ng/mL, about 0.5 ng/mL to about 100 ng/mL, about 1 ng/mL to about 5 ng/mL, about 1 ng/mL to about 10 ng/mL, about 1 ng/mL to about 50 ng/mL, about 1 ng/mL to about 100 ng/mL, about 5 ng/mL to about 10 ng/mL, about 5 ng/mL to about 50 ng/mL, about 5 ng/mL to about 100 ng/mL, about 10 ng/mL to about 50 ng/mL, about 10 ng/mL to about 100 ng/mL, or about 50 ng/mL to about 100 ng/mL There may be. In some embodiments, drug concentrations in plasma samples from subjects implanted with ophthalmic articles are about 0.01 ng/mL, about 0.05 ng/mL, about 0.1 ng/mL, about 0.5 ng /mL, about 1 ng/mL, about 5 ng/mL, about 10 ng/mL, about 50 ng/mL or about 100 ng/mL. In some embodiments, the drug concentration in plasma samples from subjects implanted with ophthalmic articles is at least about 0.01 ng/mL, at least about 0.05 ng/mL, at least about 0.1 ng/mL, at least It may be about 0.5 ng/mL, at least about 1 ng/mL, at least about 5 ng/mL, at least about 10 ng/mL, at least about 50 ng/mL or at least about 100 ng/mL. In some embodiments, drug concentrations in plasma samples from subjects implanted with ophthalmic articles are at most about 0.01 ng/mL, at most about 0.05 ng/mL, at most about 0.1 ng/mL, mL, may be up to about 0.5 ng/mL, up to about 1 ng/mL, up to about 5 ng/mL, up to about 10 ng/mL, up to about 50 ng/mL, or up to about 100 ng/mL .

[0399] For safety purposes, it would be desirable to have as low a plasma drug concentration as possible in subjects implanted with ophthalmic articles. For any drug, there is a plasma concentration (eg, no observed adverse effect level (NOAEL)) below which no adverse effects are expected. A margin of safety can be estimated as the ratio between the NOAEL and the plasma concentration observed in subjects administered the ophthalmic article. When considering the pharmacokinetic properties of a drug released from an implanted ophthalmic article, the volume of distribution in the eye is significantly smaller than that for plasma, so the drug in the medium surrounding the ophthalmic article (e.g. aqueous humor) may be relatively high compared to plasma concentrations.

[0400] Histopathology of samples from subjects implanted with ophthalmic articles includes anterior segment (e.g., cornea, anterior chamber, iris, ciliary body), posterior segment (vitreous, retina, choroid, optic nerve). ) and lens regrowth histopathology.

[0401] Intraocular pressure (IOP) may range from 11 to 21 mmHg, although transient fluctuations may occur during the early postoperative period. Abnormally high IOP can be caused by, among other things, the pharmacology of active ingredients, accumulation of polymer degradation products that block outflow of aqueous humor, impingement of articles on the iris that restricts outflow of aqueous humor, or inflammatory response to ophthalmic articles. Adverse effects of the internal product may result, resulting in secondary glaucoma. The absence of abnormal IOP is an important safety indicator for ophthalmic articles.

[0402] In some embodiments, the IOP may be between about 11 mmHg and about 21 mmHg. In some embodiments, the IOP is about 11 mmHg to about 12 mmHg, about 11 mmHg to about 13 mmHg, about 11 mmHg to about 14 mmHg, about 11 mmHg to about 15 mmHg, about 11 mmHg to about 16 mmHg, about 11 mmHg to about 17 mmHg, about 11 mmHg to about 18 mmHg, about 11 mmHg to about 19 mmHg, about 11 mmHg to about 20 mmHg, about 11 mmHg to about 21 mmHg, about 12 mmHg to about 13 mmHg, about 12 mmHg to about 14 mmHg, about 12 mmHg to about 15 mmHg, about 12 mmHg to about 16 mmHg, about 12 mmHg to about 17 mmHg, about 12 mmHg to about 18 mmHg, about 12 mmHg to about 19 mmHg, about 12 mmHg to about 20 mmHg, about 12 mmHg to about 21 mmHg, about 13 mmHg to about 14 mmHg, about 13 mmHg to about 15 mmHg, about 13 mmHg to about 16 mmHg, about 13 mmHg to about 17 mmHg, about 13 mmHg to about 18 mmHg, about 13 mmHg to about 19 mmHg, about 13 mmHg to about 20 mmHg, about 13 mmHg to about 21 mmHg, about 14 mmHg to about 15 mmHg, about 14 mmHg to about 16 mmHg, about 14 mmHg to about 17 mmHg, about 14 mmHg to about 18 mmHg, about 14 mmHg to about 19 mm Hg, about 14 mm Hg to about 20 mm Hg, about 14 mm Hg to about 21 mm Hg, about 15 mm Hg to about 16 mm Hg, about 15 mm Hg to about 17 mm Hg, about 15 mm Hg to about 18 mm Hg, about 15 mm Hg to about 19 mm Hg, about 15 mm Hg to about 20 mm Hg, about 15 mm Hg to about 21 mm Hg, about 16 mmHg to about 17 mmHg, about 16 mmHg to about 18 mmHg, about 16 mmHg to about 19 mmHg, about 16 mmHg to about 20 mmHg, about 16 mmHg to about 21 mmHg, about 17 mmHg to about 18 mmHg, about 17 mmHg to about 19 mmHg, about 17 mmHg to about 20 mmHg, about 17 mmHg may be from about 21 mmHg, from about 18 mmHg to about 19 mmHg, from about 18 mmHg to about 20 mmHg, from about 18 mmHg to about 21 mmHg, from about 19 mmHg to about 20 mmHg, from about 19 mmHg to about 21 mmHg, or from about 20 mmHg to about 21 mmHg. In some embodiments, the IOP may be about 11 mmHg, about 12 mmHg, about 13 mmHg, about 14 mmHg, about 15 mmHg, about 16 mmHg, about 17 mmHg, about 18 mmHg, about 19 mmHg, about 20 mmHg, or about 21 mmHg. In some embodiments, the IOP is at least about 11 mmHg, at least about 12 mmHg, at least about 13 mmHg, at least about 14 mmHg, at least about 15 mmHg, at least about 16 mmHg, at least about 17 mmHg, at least about 18 mmHg, at least about 19 mmHg, at least about 20 mmHg, or It may be at least about 21 mmHg. In some embodiments, the IOP is up to about 11 mmHg, up to about 12 mmHg, up to about 13 mmHg, up to about 14 mmHg, up to about 15 mmHg, up to about 16 mmHg, up to about 17 mmHg, up to about 18 mmHg, It may be up to about 19 mmHg, up to about 20 mmHg or up to about 21 mmHg.

[0403] Histopathology can be an anatomical assessment of the condition of the eye after the study has been completed. Histopathology results may be interpreted within the full context of the study (including, for example, interventions and exposures experienced by the subject and all laboratory test results recorded during the study). The absence of inflammatory cells or fibrosis in the immediate vicinity of the ophthalmic article can support biocompatibility and safety when implanted in the eye. Additionally, the absence of inflammation, fibrosis, hypertrophy, atrophy and/or other pathological consequences throughout the ocular tissue further supports the safety of ophthalmic articles for intraocular use.

[0404] In some embodiments, the posterior capsule opacification (PCO) score of an eye implanted with an ophthalmic article is reduced to 100% for untreated controls (e.g., with only an ocular device such as an IOL) or topical eye drops. may be approximately 1 unit lower than subjects treated with. In some embodiments, the posterior capsule opacification (PCO) score of the eye implanted with the ophthalmic article is treated with an ophthalmic article control without active agent and/or diagnostic agent 60 days after surgery. may be approximately at least one unit lower than the target. PCO was scored on a 4-point scale (0=nothing visible, 1=mild/focal, 2=moderate/focal, 3=moderate/diffuse, 4=severe/diffuse). be done. PCO can be a natural complication of cataract surgery whereby residual lens epithelial cells within the lens capsule migrate and proliferate behind the lens capsule, forming an opaque membrane that reduces vision. An ophthalmic article that prevents or at least substantially retards this process can benefit the subject by preserving the subject's vision.

[0405] In some embodiments, the PCO score of the eye of a subject implanted with an ophthalmic article is determined by a control subject (e.g., an untreated control, a subject treated with ophthalmic drops, an active agent and/or about 0.5 Units to about 3.5 Units less than a subject treated with an ophthalmic article without a diagnostic agent). In some embodiments, the ocular PCO score of the subject implanted with the ophthalmic article is about 0.5 unit to about 1 unit, about 0.5 unit to about 1.5 unit, about 0.5 units to about 2 units, about 0.5 units to about 2.5 units, about 0.5 units to about 3 units, about 0.5 units to about 3.5 units, about 1 unit to about 1.0 unit. 5 units, about 1 unit to about 2 units, about 1 unit to about 2.5 units, about 1 unit to about 3 units, about 1 unit to about 3.5 units, about 1.5 units to about 2 units, about 1.5 units to about 2.5 units, about 1.5 units to about 3 units, about 1.5 units to about 3.5 units, about 2 units to about 2.5 units, about 2 units to about 3 units , from about 2 units to about 3.5 units, from about 2.5 units to about 3 units, from about 2.5 units to about 3.5 units, or from about 3 units to about 3.5 units lower. In some embodiments, the PCO score of the eye of the subject implanted with the ophthalmic article is about 0.5 units, about 1 unit, about 1.5 units, about 2 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 2.0 units, about 1.5 units, about 2 units. It may be 5 units lower, about 3 units lower, or about 3.5 units lower. In some embodiments, the ocular PCO score of the subject implanted with the ophthalmic article is at least about 0.5 units, at least about 1 unit, at least about 1.5 units, at least about 2 units higher than the control subject , at least about 2.5 units, at least about 3 units, or at least about 3.5 units lower. In some embodiments, the ocular PCO score of the subject implanted with the ophthalmic article is up to about 0.5 units, up to about 1 unit, up to about 1.5 units, up to about 1.5 units, up to about 2 units, up to about 2.5 units, up to about 3 units or up to about 3.5 units lower.

[0406] In some embodiments, inflammation, including iris and anterior chamber (AC) subscores on a standardized scoring scale (e.g., modified Hackett and McDonald eye scoring systems) in subjects implanted with ophthalmic articles The score is at least 1 unit lower than the inflammation score of an untreated subject, 90 days after surgery, subject treated with topical anti-inflammatory eye drops or an ophthalmic article without an active agent and/or diagnostic agent It may be 2 units lower than the subject's inflammation score.

[0407] In some embodiments, the inflammation score in a subject implanted with an ophthalmic article is measured in control subjects (e.g., untreated subjects, subjects treated with topical anti-inflammatory eye drops, active agents and/or about 0.5 to about 12.5 lower than the inflammation score of a subject treated with an ophthalmic article without a diagnostic agent). In some embodiments, the inflammation score in the subject implanted with the ophthalmic article is about 0.5 to about 1, about 0.5 to about 1.5, about 0.5 to about 1, about 0.5 to about 1.5, about 0.5 to about 2, about 0.5 to about 2.5, about 0.5 to about 3, about 0.5 to about 4, about 0.5 to about 6, about 0.5 to about 8, about 0.5 to about 10, about 0.5 to about 12, about 0.5 to about 12.5, about 1 to about 1.5, about 1 to about 2, about 1 to about 2.5, about 1 to about 3, about 1 to about 4, about 1 to about 6, about 1 to about 8, about 1 to about 10, about 1 to about 12, about 1 to about 12.5, about 1.5 to about 2, about 1.5 to about 2.5, about 1.5 to about 3, about 1.5 to about 4, about 1.5 to about 6, about 1.5 to about 8, about 1.5 to about 10, about 1.5 to about 12, about 1.5 to about 12.5, about 2 to about 2.5, about 2 to about 3, about 2 to about 4, about 2 to about 6, about 2 to about 8, about 2 to about 10 , about 2 to about 12, about 2 to about 12.5, about 2.5 to about 3, about 2.5 to about 4, about 2.5 to about 6, about 2.5 to about 8, about 2. 5 to about 10, about 2.5 to about 12, about 2.5 to about 12.5, about 3 to about 4, about 3 to about 6, about 3 to about 8, about 3 to about 10, about 3 to about 12, about 3 to about 12.5, about 4 to about 6, about 4 to about 8, about 4 to about 10, about 4 to about 12, about 4 to about 12.5, about 6 to about 8, about 6 to about 10, about 6 to about 12, about 6 to about 12.5, about 8 to about 10, about 8 to about 12, about 8 to about 12.5, about 10 to about 12, about 10 to about 12 .5, or about 12 to about 12.5 lower. In some embodiments, the inflammation score in the subject implanted with the ophthalmic article is about 0.5, about 1, about 1.5, about 2, about 2.5, about 3 greater than the inflammation score in the control subject , about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about It may be lower than 9.5, about 10, about 10.5, about 11, about 11.5, about 12 or about 12.5. In some embodiments, the inflammation score in the subject implanted with the ophthalmic article is at least about 0.5, at least about 1, at least about 1.5, at least about 2, at least about 2 greater than the inflammation score in the control subject .5, at least about 3, at least about 3.5, at least about 4, at least about 4.5, at least about 5, at least about 5.5, at least about 6, at least about 6.5, at least about 7, at least about 7 .5, at least about 8, at least about 8.5, at least about 9, at least about 9.5, at least about 10, at least about 10.5, at least about 11, at least about 11.5, at least about 12, or at least about 12 .5 may be lower. In some embodiments, the inflammation score in the subject implanted with the ophthalmic article is at most about 0.5, at most about 1, at most about 1.5, at most about 2, over the inflammation score in the control subject. , at most about 2.5, at most about 3, at most about 3.5, at most about 4, at most about 4.5, at most about 5, at most about 5.5, at most about 6, at most but about 6.5, maximum about 7, maximum about 7.5, maximum about 8, maximum about 8.5, maximum about 9, maximum about 9.5, maximum about 10, maximum about It may be lower than 10.5, up to about 11, up to about 11.5, up to about 12, or up to about 12.5.

[0408] In some cases, inflammation subscores for untreated subjects and subjects treated with topical anti-inflammatory eye drops were 4 4% higher than those treated with ophthalmic products at 90 days after surgery. twice (eg 4.5 times) and 7 times higher. These absolute and/or relative reductions in inflammation score are therapeutic potentials of an ophthalmic article for reducing the iris-anterior chamber subscore compared to topical eye drops, untreated control and/or topical anti-inflammatory eye drops. can support sexuality. The therapeutic benefits of ophthalmic articles for reducing inflammation may also indicate greater ability of ophthalmic articles to treat inflammation following cataract surgery.

[0409] In some examples, the inflammation subscore for control subjects (e.g., untreated subjects, subjects treated with topical anti-inflammatory eye drops, etc.) is (e.g., 90 days after such surgery) ophthalmic It can be from about 1 to about 20 times higher than the inflammation subscore of subjects treated with the article. In some examples, the inflammation subscore of the control subject is from about 1-fold to about 2-fold, from about 1-fold to about 3-fold, from about 1-fold to about 4-fold, than the inflammation sub-score of the subject treated with the ophthalmic article. times, about 1 to about 5 times, about 1 to about 6 times, about 1 to about 7 times, about 1 to about 8 times, about 1 to about 9 times, about 1 to about 10 times, About 1 to about 15 times, about 1 to about 20 times, about 2 to about 3 times, about 2 to about 4 times, about 2 to about 5 times, about 2 to about 6 times, about 2 about 7 times, about 2 times to about 8 times, about 2 times to about 9 times, about 2 times to about 10 times, about 2 times to about 15 times, about 2 times to about 20 times, about 3 times or more About 4 times, about 3 times to about 5 times, about 3 times to about 6 times, about 3 times to about 7 times, about 3 times to about 8 times, about 3 times to about 9 times, about 3 times to about 10 times times, about 3 times to about 15 times, about 3 times to about 20 times, about 4 times to about 5 times, about 4 times to about 6 times, about 4 times to about 7 times, about 4 times to about 8 times, About 4 times to about 9 times, about 4 times to about 10 times, about 4 times to about 15 times, about 4 times to about 20 times, about 5 times to about 6 times, about 5 times to about 7 times, about 5 times about 8 times, about 5 times to about 9 times, about 5 times to about 10 times, about 5 times to about 15 times, about 5 times to about 20 times, about 6 times to about 7 times, about 6 times or more About 8 times, about 6 times to about 9 times, about 6 times to about 10 times, about 6 times to about 15 times, about 6 times to about 20 times, about 7 times to about 8 times, about 7 times to about 9 times times, about 7 times to about 10 times, about 7 times to about 15 times, about 7 times to about 20 times, about 8 times to about 9 times, about 8 times to about 10 times, about 8 times to about 15 times, about 8-fold to about 20-fold, about 9-fold to about 10-fold, about 9-fold to about 15-fold, about 9-fold to about 20-fold, about 10-fold to about 15-fold, about 10-fold to about 20-fold, or about It may be 15 times to about 20 times higher. In some examples, the inflammation subscore of the control subject is about 1-fold, about 2-fold, about 3-fold, about 4-fold, about 5-fold, about 6-fold greater than the inflammation sub-score of the subject treated with the ophthalmic article. It may be about 7-fold, about 8-fold, about 9-fold, about 10-fold, about 15-fold or about 20-fold higher. In some examples, the control subject's inflammation subscore is at least about 1-fold, at least about 2-fold, at least about 3-fold, at least about 4-fold, at least about It may be 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 15-fold or at least about 20-fold higher. In some examples, the inflammation subscore of the control subject is at most about 1-fold, at most about 2-fold, at most about 3-fold, at most about 4-fold, than the inflammation sub-score of the subject treated with the ophthalmic article. about 5 times higher, about 6 times higher, about 7 times higher, about 8 times higher, about 9 times higher, about 10 times higher, about 15 times higher, or about 20 times higher may

[0410] In some embodiments, within 7 days after implantation, one or more ophthalmic articles release one or more active agents, resulting in (e.g., slit lamp biomicroscopy) An inflammation score of at most 1 (as measured by an anterior chamber cell score using a 10-point visual analogue scale) and/or no eye pain (eg, as measured by a 10-point visual analogue scale). In some embodiments, the anterior chamber cell score may be an average of the anterior chamber cell scores.

[0411] In some embodiments, within 7 days after implantation, one or more ophthalmic articles release one or more active agents, resulting in an inflammation score of 0-1. Inflammation scores range from about 0 to about 0.1, from about 0 to about 0.2, from about 0 to about 0.3, from about 0 to about 0.4, from about 0 to about 0.5, from about 0 to about 0.5. 6, about 0 to about 0.7, about 0 to about 0.8, about 0 to about 0.9, about 0 to about 1, about 0.1 to about 0.2, about 0.1 to about 0.7. 3, about 0.1 to about 0.4, about 0.1 to about 0.5, about 0.1 to about 0.6, about 0.1 to about 0.7, about 0.1 to about 0.5. 8, about 0.1 to about 0.9, about 0.1 to about 1, about 0.2 to about 0.3, about 0.2 to about 0.4, about 0.2 to about 0.5, about 0.2 to about 0.6, about 0.2 to about 0.7, about 0.2 to about 0.8, about 0.2 to about 0.9, about 0.2 to about 1, about 0 .3 to about 0.4, about 0.3 to about 0.5, about 0.3 to about 0.6, about 0.3 to about 0.7, about 0.3 to about 0.8, about 0 .3 to about 0.9, about 0.3 to about 1, about 0.4 to about 0.5, about 0.4 to about 0.6, about 0.4 to about 0.7, about 0.4 to about 0.8, about 0.4 to about 0.9, about 0.4 to about 1, about 0.5 to about 0.6, about 0.5 to about 0.7, about 0.5 to about 0.8, about 0.5 to about 0.9, about 0.5 to about 1, about 0.6 to about 0.7, about 0.6 to about 0.8, about 0.6 to about 0.8. 9, about 0.6 to about 1, about 0.7 to about 0.8, about 0.7 to about 0.9, about 0.7 to about 1, about 0.8 to about 0.9, about 0 0.8 to about 1, or about 0.9 to about 1.

[0412] In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents such that the inflammation score is at least about 0, at least about 0.1, at least about 0.2, at least about 0.3, at least about 0.4, at least about 0.5, at least about 0.6, at least about 0.7, at least about 0.8, at least about 0.5. 9, or at least about 1. In some embodiments, the one or more ophthalmic articles release one or more active agents within 7 days after implantation, resulting in an inflammation score of at most about 0, at most about 0 .1, at most about 0.2, at most about 0.3, at most about 0.4, at most about 0.5, at most about 0.6, at most about 0.7, at most about 0.1. 8, at most about 0.9, or at most about 1.

[0413] In some embodiments, within 7 days after implantation, the one or more ophthalmic articles release one or more active agents such that the inflammation score is about 0, about 0.0. 1, about 0.2, about 0.3, about 0.4, about 0.5, about 0.6, about 0.7, about 0.8, about 0.9, or about 1.

[0414] In some embodiments, one or more ophthalmic articles release one or more active agents resulting in a low inflammation score (eg, about 0 .4 to about 0.6). In some embodiments, one or more ophthalmic articles release one or more active agents such that about 1 day to about 2 days, about 1 day to about 3 days, about 1 day ~ about 4 days, about 1 day to about 5 days, about 1 day to about 6 days, about 1 day to about 7 days, about 1 day to about 14 days, about 1 day to about 21 days, about 1 day to about 28 days, about 2 days to about 3 days, about 2 days to about 4 days, about 2 days to about 5 days, about 2 days to about 6 days, about 2 days to about 7 days, about 2 days to about 14 days , about 2 days to about 21 days, about 2 days to about 28 days, about 3 days to about 4 days, about 3 days to about 5 days, about 3 days to about 6 days, about 3 days to about 7 days, about 3 days to about 14 days, about 3 days to about 21 days, about 3 days to about 28 days, about 4 days to about 5 days, about 4 days to about 6 days, about 4 days to about 7 days, about 4 days ~ about 14 days, about 4 days to about 21 days, about 4 days to about 28 days, about 5 days to about 6 days, about 5 days to about 7 days, about 5 days to about 14 days, about 5 days to about 21 days, about 5 days to about 28 days, about 6 days to about 7 days, about 6 days to about 14 days, about 6 days to about 21 days, about 6 days to about 28 days, about 7 days to about 14 days , about 7 days to about 21 days, about 7 days to about 28 days, about 14 days to about 21 days, about 14 days to about 28 days, or about 21 days to about 28 days to a low inflammation score. In some embodiments, one or more ophthalmic articles release one or more active agents such that about 1 day, about 2 days, about 3 days, about 4 days, about 5 days. , to a low inflammation score (eg, about 0.4 to about 0.6) within about 6 days, about 7 days, about 14 days, about 21 days, or about 28 days. In some embodiments, the one or more ophthalmic articles release one or more active agents such that at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days. , at least about 5 days, at least about 6 days, at least about 7 days, at least about 8 days, at least about 9 days, at least about 10 days, at least about 11 days, at least about 12 days, at least about 13 days, at least about 14 days , at least about 15 days, at least about 16 days, at least about 17 days, at least about 18 days, at least about 19 days, at least about 20 days, at least about 21 days, at least about 22 days, at least about 23 days, at least about 24 days , at least about 25 days, at least about 26 days, at least about 27 days, at least about 28 days, at least about 29 days, or at least about 30 days, resulting in a low inflammation score. In some embodiments, one or more ophthalmic articles release one or more active agents such that up to about 1 day, up to about 2 days, up to about 3 days, up to about But about 4 days, maximum about 5 days, maximum about 6 days, maximum about 7 days, maximum about 8 days, maximum about 9 days, maximum about 10 days, maximum about 11 days, maximum about 12 days, up to about 13 days, up to about 14 days, up to about 15 days, up to about 16 days, up to about 17 days, up to about 18 days, up to about 19 days, up to about 20 days , maximum about 21 days, maximum about 22 days, maximum about 23 days, maximum about 24 days, maximum about 25 days, maximum about 26 days, maximum about 27 days, maximum about 28 days, maximum A low inflammation score is reached within about 29 days or at most about 30 days.

[0415] Various methods may be used to manufacture ophthalmic articles. Methods can include solvent casting, phase separation, interfacial methods, molding, compression molding, injection molding, extrusion, coextrusion, hot extrusion, die cutting, hot compression and combinations thereof. In another aspect, the present disclosure provides a method for preparing at least one ophthalmic article. One or more active agents and/or diagnostic agents in a solvent may be combined with a biocompatible material (e.g., a biocompatible polymer matrix in a solvent), thereby producing a solvent-combined mixture. good. Solvent may be removed from the combined mixture to produce an evaporative mixture containing one or more active agents and/or diagnostic agents. A weighting tool may then be used to compress the vaporized mixture to produce a compressed mixture. A molding tool and/or an orifice tool may be used to extract at least one ophthalmic article from the compressed mixture.

[0416] In some embodiments, a polymeric material (e.g., a biocompatible copolymer matrix) is dispersed or dissolved in a solvent to form a dispersion, suspension, or solution and heated and shaken to form a polymer mixture. may be formed. Solvents may be selected for compatibility with the polymeric material. Temperature and agitation speed may be selected to achieve homogeneous mixing in a timely manner. For example, a polymeric material comprising a biodegradable biocompatible copolymer of caprolactone as disclosed herein can be dissolved in dichloromethane and heated to between about 50° C. and 70° C. in an orbital shaker at a speed of 300 RPM. It may be shaken at temperature for about 1 hour to 4 hours.

[0417] One or more active agents and/or diagnostic agents may be dissolved in a solvent to form a solution. When one or more agents are included in the ophthalmic article, the material may or may not be homogeneous (ie, heterogeneous). In some cases, the ophthalmic article can include multiple agents and can be homogeneous. In some cases, ophthalmic articles can include multiple agents and can be non-homogeneous. For example, one agent can be coated on the surface of an ophthalmic article. In yet another example, the ophthalmic article can be formulated to have pre-designated regions or layers containing different agents. In yet another example, the ophthalmic article can be formulated to have pre-designated regions or layers with the same agent but at different concentrations. For example, in some cases, the outer regions or layers of the ophthalmic article deliver bursts of the agent after a higher initial dose, or a prolonged lower dose over a period of days or weeks. It is possible to have higher concentrations of the agent. Further, in some cases, different regions of the ophthalmic article are adapted to biodegrade at different rates.

[0418] The polymer mixture can then be combined with a mixture of active agents and/or diagnostic agents to form a mixture of polymeric materials and active agents and/or diagnostic agents. The mixture of polymeric material and active and/or diagnostic agent can then be heated to remove the solvent to form an evaporated mixture. In a non-limiting example, the mixture may be heated to about 50° C. or about 70° C. and impregnated at a rate of about 300 RPM to complete evaporation in about 16 hours. Once the solvent has partially or completely evaporated, a weighted tool can be used to compress the evaporated mixture into a sheet. In some embodiments, the weighting tool may comprise a steel plate. In some embodiments, the weighting tool may be a heated steel plate. In some embodiments, the weighting tool may be a heated steel plate lined with Teflon. A forming tool and an orifice tool may then be used to extract at least one ophthalmic article from the compressed sheet. In some embodiments, the molding tool may comprise a forming portion having a shape and size suitable to produce an ophthalmic article of any of the geometries, sizes, and designs described herein. good. The orifice tool may include portions for creating any of the internal structures (eg, pores) described herein for ophthalmic articles. For example, a forming tool (eg, a stainless steel tube or a follicular unit extraction punch) may be used to form an ophthalmic article. Additionally, an orifice tool (eg, a stainless steel tube or pervesicular extraction punch) may be used under a microscope to create a hole in the center of the ophthalmic article. In some embodiments, the forming tool and orifice tool may be opposite sides of the same tool. In some embodiments, the forming tool and orifice tool may be different tools.

[0419] The following examples are illustrative, not limiting.
[0420] Example 1: Ophthalmic Article Overlying Intraocular Lens
[0421] Figure 7A illustrates an example of an ophthalmic article. Ophthalmic article 100 was formed like an extruded ring having internal features (eg, holes) 110 .

[0422] Figure 7B illustrates an example of an ophthalmic article on an ophthalmic device. Ophthalmic article 100 was stretched to an extended state and placed on haptics 302 of an intraocular lens (IOL) 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision).

[0423] FIG. 7C illustrates a side view of an exemplary ophthalmic article. Exemplary ophthalmic article 100 has a percentage weight (wt.%) of ketorolac tromethamine of about 12% and a percentage weight (wt. It contained poly(L-lactide-co-caprolactone). The ophthalmic article was placed on the haptics 302 of an intraocular lens (IOL) 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision). Ophthalmic article 100 was formed like an extruded ring. Outer diameter 230 of ophthalmic article 100 may be approximately 1 mm, and in this illustrative embodiment, outer diameter 230 was approximately 1.1 millimeters (mm) wide. The internal structure (e.g., central bore) 110 of ophthalmic article 100 may have an inner diameter 240 of approximately 0.6 mm, and in this illustrative embodiment, inner diameter 240 was about 0.65. . The illustrative ophthalmic article 110 can have a cross-sectional thickness 250 of about 0.5. Ophthalmic article 100 was stretched to an extended state and placed on haptics 302 of IOL 300 . Ophthalmic article 100 , in the form of a push ring, can be extended with a handpiece (eg, forceps) and placed over and around haptics 302 of IOL 300 . The inner diameter 240 of the ophthalmic article 100 was at least approximately the same as the cross-sectional length 307 of the haptics 302 . A cross-sectional length 307 of haptics 302 may be approximately 0.7 millimeters (mm) wide, and in this exemplary embodiment, cross-sectional length 307 was approximately 0.73.

[0424] FIG. 7D illustrates a plan view of an exemplary ophthalmic article. Ophthalmic article 100 contains 12% (wt%) ketorolac tromethamine and 88% (wt%) poly(L-lactide-co-caprolactone) at a ratio (eg, molar ratio) of 70:30 of L-lactide to caprolactone. included. Ophthalmic article 100 was placed on haptics 302 of an intraocular lens (IOL) 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision). Outer diameter 230 of ophthalmic article 100 may be approximately 1 mm, and in this illustrative embodiment, outer diameter 230 was approximately 1.1 millimeters (mm) wide. Ophthalmic article 100 was stretched to an extended state and placed on haptics 302 of IOL 300 . The inner diameter 240 of the ophthalmic article 100 was at least approximately the same as the cross-sectional length 307 of the haptics 302 .

[0425] Example 2: Ophthalmic Article Stretch Test
[0426] FIG. 8A illustrates an example of an ophthalmic article 100 in haptics 302 of an IOL (eg, an Aurovue IOL) 300. FIG. In this illustrative embodiment, ophthalmic article 100 comprises about 12% (wt.%) ketorolac tromethamine and about 88% (wt.%) poly(L-lactide) at a 60:40 ratio of L-lactide to caprolactone. - co-caprolactone). An illustrative ophthalmic article 100 was formed like an extruded ring. The ophthalmic article can have internal structures (eg, pores) with an outer diameter of about 1.2 mm and an inner diameter of about 0.6 mm; It has an outer diameter 230, an inner diameter of about 0.65 mm and a cross-sectional thickness 250 of 0.5 mm. The illustrative ophthalmic article 100 was tested for the elongation required to place the illustrative ophthalmic article 100 on the haptics 302 of the IOL 300 . The cross-sectional dimensions of haptics 302 at widest portion 307 may be approximately 1.00 mm by 0.3 mm, and in this illustrative example, the cross-sectional dimensions of haptics 302 at widest portion 307 are about 1.0 mm×0.3 mm. 0.00 mm x 0.32 mm.

[0427] Figure 8B schematically illustrates an ophthalmic article. The ophthalmic article can have a circumference or perimeter of about 1.5 and can extend to at least about 2.7, in this illustrative embodiment the widest portion of haptics 302 (FIG. 8A). 307, the ophthalmic article 100 should extend from a ring with a circumference of about 1.57 mm to form a rectangle with a perimeter of about 2.64 mm. . Therefore, in this illustrative embodiment, ophthalmic article 100 needs to be stretched or elongated at least about 168% in order to be placed on haptics 302 of IOL 300 (eg, Aurovue IOL) shown in FIG. 8A. there were. Equivalent calculations for foldable acrylic IOLs (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision) were performed. In an illustrative example, ophthalmic article 100 is approximately 0.7 x 0.5 mm rectangular, which can be the widest portion of a foldable acrylic IOL (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision). It may be necessary to stretch or stretch at least about 150% to accommodate the .

[0428] Example 3: Ophthalmic Article Extension Test
[0429] FIGS. 9A, 9B, and 9C schematically illustrate the results of elongation in a destructive test of the ophthalmic article 100 disclosed herein using forceps 905. FIG. In this illustrative embodiment, ophthalmic article 100 comprises about 12% (wt%) ketorolac tromethamine and about 88% (wt%) poly(L-lactide- co-caprolactone). FIG. 9A illustrates the pre-stretched state of ophthalmic article 100 . FIG. 9B illustrates the elongation of ophthalmic article 100 using forceps 905 to a pre-elongation of ophthalmic article 100 of approximately 1.8 times. FIG. 9C illustrates recovery of ophthalmic article 100 approximately four seconds after pressure from forceps 905 is released.

[0430] Example 4: Elongation in Breaking Test
[0431] As shown in Figure 10, elongation in a destructive test was performed on an ophthalmic article. In this illustrative embodiment, the article contains about 12% (wt%) ketorolac tromethamine and about 88% (wt%) poly(L-lactide-co- - caprolactone). The ophthalmic article can have internal structures (eg, pores) with an outer diameter of about 1.2 mm and an inner diameter of about 0.6 mm; It has an outer diameter 230 of 0.25 mm, an inner diameter 240 of about 0.65 mm and a cross-sectional thickness 250 of 0.5 mm. Exemplary ophthalmic article 100, in this illustrative embodiment, was applied to the tip of a standard 200 microliter (μl) micropipette 1005 and gently lifted further up using forceps until breakage occurred. The elongation in the breaking test was performed 3 times. The diameter of the ophthalmic article at break (break diameter) was recorded for each test using a microcaliper. The fracture diameter can be from about 3 mm to about 5 mm, and in this illustrative embodiment the three fracture diameters were about 3.37 mm, 3.25 mm, and 4.30 mm. The breaking diameters were 674%, 650%, and 860% wider compared to the diameter of the ophthalmic article prior to testing, indicating extensive elongation for the ophthalmic article. The stretchability of the ophthalmic article 100 described herein ensures that the ophthalmic article 100 can be stretched and applied to ophthalmic devices (eg, IOL haptics) without breaking.

[0432] Ophthalmic devices and/or ophthalmic devices, such as intraocular lenses, can exhibit sufficient strength to allow them to fold without shattering. Devices made of polymers that can break at less than 150% elongation cannot withstand the distortions that inevitably occur when rolled or folded to dimensions small enough to pass through small incisions.

[0433] Thus, the stretchability of an ophthalmic article may not only allow it to be stretched for application to an ophthalmic device (e.g., IOL), but may also allow it to be attached to an ophthalmic device (e.g., IOL). It may also be ensured that the ophthalmic article may be folded, rolled or otherwise deformed into a low profile condition for insertion into the eye using standard surgical techniques.

[0434] Example 5: Straightening of Ophthalmic Articles
[0435] A linear stretch test was performed on the ophthalmic article 100. FIG. In this illustrative embodiment, ophthalmic article 100 comprises 12% (wt%) tromethamine and 88% (wt%) poly(L-lactide-co-caprolactone) at a 60:40 ratio of L-lactide to caprolactone. included. The dimensions of the ophthalmic article 100 were the same as in illustrative Example 4. The ophthalmic article was removed using a widening forceps 1110 (e.g., 5 1/3″, 45° angled, 0.3 mm diameter tip, and 9.0 mm wide flat handle Ambler Surgical Dilator forceps). , extended linearly. The stretched length was measured using a ruler 1111, as shown in FIG. Experiments were performed in triplicate. In this illustrative example, all three samples stretched to 6 mm without breaking, which was approximately 1200% stretch compared to the diameter of the ophthalmic article prior to testing. The stretchability of the ophthalmic article 100 ensures that the ophthalmic article can be stretched and placed on an ophthalmic device (eg, an IOL haptic) without breaking. As described in this illustrative example, the ability of an ophthalmic article to stretch, bend, and deform can match the properties of the IOL in which it resides, and such properties are associated with the ophthalmic device and the ophthalmic device to which it is attached. An ophthalmic article may be allowed to be inserted into the eye through a small incision following some standard surgical technique.

[0436] Example 6: Examples of drug-loaded ophthalmic articles
[0437] FIG. 12 shows an illustrative embodiment of an ophthalmic article 100 for delivery of drugs (eg, antibiotics) to the eye. In this illustrative embodiment, ophthalmic article 100 was formed like an extruded ring having an outer diameter 230 of about 1.3 mm, an inner structure diameter 240 of about 0.5 mm, and a wall thickness of about 0.7 mm. Ophthalmic article 100 may include approximately 22% (wt%) drug (eg, moxifloxacin antibiotic) and 78% (wt%) copolymer. In this illustrative embodiment, the copolymer comprises poly(L-lactide-co-caprolactone) in a 50:50 molar ratio of L-lactide to caprolactone with a molecular weight (M _n ) of about 75-85 kDa.

[0438] Example 7: Another Example of a Drug-Loaded Ophthalmic Article
[0439] FIG. 13 illustrates another illustrative embodiment of an ophthalmic article 100. As shown in FIG. In this illustrative embodiment, ophthalmic article 100 was formed like an extruded ring having an outer diameter 230 of about 1.3 mm, an inner structural diameter 240 of about 0.5 mm, and an inner wall thickness of about 0.7 mm. . The ophthalmic article may comprise about 17% (wt%) drug and about 83% (wt%) copolymer. In this illustrative embodiment, the ophthalmic article contained approximately 16.7% (wt%) corticosteroid (eg, dexamethasone) and about 83.3% (wt%) copolymer. In this illustrative embodiment, the copolymer comprises poly(L-lactide-co-caprolactone) in a 50:50 molar ratio of L-lactide to caprolactone having a molecular weight (M _n ) of about 75-85 kDa. board.

[0440] Example 8: Examples of Ophthalmic Articles in Ophthalmic Devices
[0441] Figures 14A and 14B illustrate examples of ophthalmic articles 100 made with copolymers. The ophthalmic article 100 was formed like an extruded ring having an outer diameter 230 of about 1.3 mm, an inner structure diameter 240 of about 0.5 mm, and a wall thickness of about 0.7 mm. In this illustrative embodiment, the copolymer comprises poly(L-lactide-co-caprolactone) in a 50:50 molar ratio of L-lactide to caprolactone having a molecular weight (M _n ) of about 75-85 kDa. board. In vitro injections were performed to qualitatively test ophthalmic articles in IOLs before and after IOL injection. In vitro IOL injection was similar to the IOL injection process in cataract surgery, except that the IOL and ophthalmic device were drained into phosphate buffered saline (PBS) instead of the subject's eye. FIG. 14A shows an exemplary appearance of ophthalmic article 100 and IOL 300 prior to in vitro IOL implantation. FIG. 14B shows an exemplary appearance of ophthalmic article 100 and IOL 300 after in vitro IOL implantation. Injector designed for use with an IOL (e.g., Tecnis, Johnson & Johnson Surgical Vision) during in vitro IOL injection, ophthalmic article 100 and IOL 300 in a conventional IOL injection procedure, with a small amount of viscoelastic material. A cartridge (eg, an injector cartridge with a 1.2 mm diameter tip) was loaded. The filled cartridge was then loaded into the attached injector device. The ophthalmic article 100 and IOL 300 were then manually expelled from the injector into a small amount of PBS and left unrolled at room temperature for approximately 3 minutes. After injection, IOL 300 returned to its original size and shape, while ophthalmic article 100 assumed a different shape (FIG. 14B). Although the ophthalmic article 100 was placed in its original position on the haptics, some aspects of the ophthalmic article 100 appeared to be elongated and closer to the area closest to the main portion of the IOL 300 .

[0442] While not wishing to be bound by theory, the partially destroyed appearance of the ophthalmic article 100 after in vitro injection may be due to the mechanical stress and stress imposed on the ophthalmic article 100 during the in vitro injection process. It can be explained by the inherent material properties of ophthalmic articles. As part of the in vitro injection process, haptics 302 and 304 of IOL 300 are rounded to a narrower profile to facilitate passage through the narrow opening of the tip of the injector, thus aligning it with optic portion 301 of IOL 300. folded. Without wishing to be bound by theory, this presumably puts pressure on ophthalmic article 100 at a location where it appears to stretch and narrow. When an IOL is implanted for cataract surgery, an ophthalmic article that retains its position on the IOL to which it is attached but does not fully recover its original shape after implantation is suitable for use in cataract surgery. but not optimal.

[0443] Example 9: Another Example of an Ophthalmic Article in an Ophthalmic Device
[0444] FIGS. 15A and 15B illustrate an example of an ophthalmic article 100 in haptics 302 of an IOL 300. FIG. In this illustrative embodiment, the ophthalmic article was formed like an extruded ring of approximately 1.3 mm outer diameter, 0.5 mm hole or inner diameter and 0.7 mm thickness. The ophthalmic article is approximately 22% (wt%) moxifloxacin antibiotic and 78% (wt%) poly(L- _lactide- co-caprolactone). Ophthalmic article 100 was placed on haptics 302 of a foldable acrylic IOL 300 (eg, Aurovue by Aurolab). FIG. 15A shows an exemplary appearance of ophthalmic article 100 and IOL 300 prior to in vitro IOL implantation. FIG. 15B shows an exemplary appearance of ophthalmic article 100 and IOL 300 after in vitro IOL implantation. During in vitro IOL injection, ophthalmic article 100 and IOL 300 are placed in an injector cartridge (e.g., 1 cartridge with a tip inner diameter of 0.7 mm). The filled cartridge was then loaded into the attached injector device. Ophthalmic article 100 and IOL 300 were then manually expelled from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. After injection, ophthalmic article 100 and IOL 300 return to their original size and shape (FIG. 15B), and ophthalmic article 100 significantly distorts or collapses its original physical appearance shown in FIG. 15A. Positioned in the same position of the haptics, without.

[0445] Example 10: Examples of Ophthalmic Articles After In Vitro Injection
[0446] FIGS. 16A and 16B illustrate examples of the ophthalmic article 100 in the haptics 302 of the IOL 300. FIG. In this illustrative embodiment, ophthalmic article 100 was formed like an extruded ring with an outer diameter 230 of approximately 1.3 mm, an inner diameter 240 of about 0.5 mm, and a cross-sectional thickness 250 of about 0.7 mm. Ophthalmic article 100 comprises approximately 20% (wt%) dexamethasone antibiotic and about 80% (wt%) poly(L- _lactide- co-caprolactone). Ophthalmic article 100 was placed on haptics 302 of a foldable acrylic IOL 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision). FIG. 16A shows an exemplary appearance of ophthalmic article 100 and IOL 300 prior to in vitro IOL implantation. FIG. 16B shows an exemplary appearance of ophthalmic article 100 and IOL 300 after in vitro IOL implantation. During in vitro IOL injection, ophthalmic article 100 and IOL 300 are combined with a small amount of viscoelastic material in a conventional IOL injection procedure for use with IOL 300 (e.g., Tecnis 1-piece by Johnson & Johnson Surgical Vision). A designed injector cartridge (eg, UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision with a tip inner diameter of approximately 1.2 mm) was loaded. The filled cartridge was then loaded into the attached injector device. Ophthalmic article 100 and IOL 300 were then manually expelled from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. After injection, the ophthalmic article 100, IOL 300 returned to its original size and shape (FIG. 16A), and the ophthalmic article 100 was located in the same position on the haptics. However, the injection process resulted in partial distortion of ophthalmic article 100 as evidenced by constriction and stretching in region 1610 of the device adjacent the main portion of IOL 300 .

[0447] Example 11: Ophthalmic Articles Comprising Copolymers
[0448] FIGS. 17A and 17B illustrate an example of an ophthalmic article 100 in haptics 302 of an IOL 300. FIG. In this illustrative embodiment, ophthalmic article 100 comprises approximately 9% ( _wt . % (wt %) poly(L-lactide-co-caprolactone). In this illustrative embodiment, ophthalmic article 100 was formed like an extruded ring with an outer diameter 230 of approximately 1.3 mm, an inner diameter 240 of about 0.5 mm, and a cross-sectional thickness 250 of about 0.7 mm. FIG. 17A shows an exemplary appearance of ophthalmic article 100 and IOL 300 prior to in vitro IOL implantation. FIG. 17B shows the appearance of ophthalmic article 100 and IOL 300 after in vitro IOL implantation. During in vitro IOL injection, the ophthalmic article 100 attached to the IOL 300 is placed in the IOL 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision) with a small amount of viscoelastic material in a conventional IOL 300 injection technique. Injector cartridges designed for use) (eg, UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision, with a tip inner diameter of 1.2 mm). The filled cartridge was then loaded into the attached injector device. Ophthalmic article 100 and IOL 300 were then manually expelled from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. After injection, ophthalmic article 100 and IOL 300 return to their original pre-injection size and shape (FIG. 17A), and ophthalmic article 100 significantly distorts its original physical appearance as shown in FIG. 17A. or located at the same position of the haptics without collapsing.

[0449] Example 12: Durability of Surface Coatings for Drug Delivery on IOLs
[0450] Experiments were conducted to evaluate the durability of surface coatings on IOLs as potential vehicles for drug delivery. A surface coating was applied to a foldable acrylic IOL 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision) on the optics and entire perimeter of the haptics using a layer-by-layer coating method. The coatings consisted of 30 bilayers of chitosan and polyglutamic acid (FIGS. 18A-18B), 30 bilayers of poly(L-lysine) and polyglutamic acid (FIGS. 18C-18D) or 30 bilayers of poly(L-lysine). ) and polyacrylate glutamic acid (FIGS. 18E-18F). All of the layer coatings were impregnated with trypan blue dye as an easily visualized model drug. Figures 18A, 18C and 18E show the appearance of the coated IOL prior to in vitro IOL injection. Figures 18B, 18D and 18F show the appearance of coated IOLs after in vitro IOL injection. Injector cartridges designed for use with IOLs (e.g., Tecnis 1-piece by Johnson & Johnson Surgical Vision) during in vitro IOL injection, coated IOL 300 with a small amount of viscoelastic material in the usual IOL injection procedure. (eg, UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision, with a tip inner diameter of 1.2 mm). The filled cartridge was then loaded into the attached injector device. The coated IOL 300 was then manually expelled from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. The coating on the IOL 300 was not intact after injection. Most of the coating appeared to strip 1805 as a result of the injection process Figures 18B, 18D and 18F. These results demonstrate the lack of durability of IOL surface coatings as potential vehicles for drug delivery.

[0451] Additional experiments were performed to further assess the durability of the surface coating using a different model IOL 300 (eg, Micromed Intl. 1 piece of foldable acrylic). A surface coating was applied to the foldable acrylic IOL 300 around the optics 301 and over the haptics 302 using a layer-by-layer coating method. The coatings were 30 bilayers of FITC-chitosan and dextran sulfate (FIGS. 19A-19B), 30 bilayers of FITC-chitosan and hyaluronic acid (FIGS. 19C-19D), or 30 bilayers of FITC-chitosan and polyglutamic acid. consisted of either glutamic acid (FIGS. 19E-19F). Figures 19A, 19C and 19E show the appearance of the coated IOL prior to in vitro IOL injection. Figures 19B, 19D and 19F show the appearance of the coated IOL 300 after in vitro IOL injection. During in vitro IOL injection, the coated IOL is injected into an injector cartridge (e.g., Tecnis 1-piece by Johnson & Johnson Surgical Vision) designed for use with an IOL (e.g., Tecnis 1-piece by Johnson & Johnson Surgical Vision) with a small amount of viscoelastic material in a conventional IOL injection procedure. 1.2 mm tip inner diameter) (eg UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision). The filled cartridge was then loaded into the attached injector device. The coated IOL 300 was then manually expelled from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. The coating on the IOL 300 was not intact after injection. A large portion of the coating appeared to have come off as a result of the injection process Figures 19B, 19D and 19F. These results further indicated the lack of durability of the IOL surface coating as a potential vehicle for drug delivery.

[0452] Example 13: Copolymer Qualitative Testing
[0453] Copolymers of different compositions were tested. Figures 20A-20F show examples of qualitative testing of copolymers (eg, Bezwada CARBOMAXX TL640). The copolymer contained trimethylene carbonate (TMC) and L-lactide in a molar ratio of 60:40, respectively. A 3 mm x 3 mm rectangular piece 2001 with 0.5 mm thick copolymer was formed for qualitative testing (Fig. 20A). A rectangular piece of copolymer 2001 was then placed inside an injection device 2010 (eg UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision) (FIG. 20B). A rectangular piece of copolymer 2001 was injected through the injection device (Fig. 20C). The rectangular piece of copolymer 2001 almost completely returned to its original shape shown in FIG. 20A within 30 seconds after injection. An annulus-shaped ring 2002 was fabricated from a 0.5 mm thick sheet of the copolymer using 16G and 22G needles (Fig. 20D). A ring-shaped copolymer 2002 was then placed on the haptics 302 of an IOL 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision) (FIG. 20E). Copolymer ring 2002 was not easy to stretch and was difficult to rest on haptics 302 of IOL 300 . Copolymerization and IOLs were tested through in vitro injections. FIG. 20E shows the appearance of the copolymer ring 2002 and IOL prior to in vitro IOL 300 injection. FIG. 20F shows the appearance of copolymer ring 2002 and IOL 300 after in vitro IOL injection. During in vitro IOL injection, ring 2002 and IOL 300 are designed for use with IOL 300 (e.g., Tecnis 1-piece by Johnson & Johnson Surgical Vision) with a small amount of viscoelastic material in a conventional IOL injection procedure. Injector cartridges (eg, UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision with a tip inner diameter of 1.2 mm). The filled cartridge was then loaded into the attached injector device 2010 . The copolymer ring and IOL were then manually expelled from the injector 2010 into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. After injection, the copolymer ring 2002 shown in FIG. 20F retained its original shape prior to in vitro injection 2020 shown in FIG. 20E.

[0454] Example 14: Qualitative Testing of Another Copolymer
[0455] Figures 21A-21F show examples of qualitative testing of another copolymer (eg, Bezwada CARBOMAXX TL910). The copolymer contained trimethylene carbonate (TMC) and L-lactide in a 90:10 molar ratio, respectively. A 3 mm x 3 mm rectangular piece 2101 containing the 0.5 mm thick copolymer was compressed using forceps 2102 (Fig. 21A). Compression was removed from the rectangular piece 2101, which allowed it to recover its original shape, and the rectangular piece of copolymer 2101 did not recover its original shape after approximately 75 seconds (Fig. 21B). A rectangular piece of copolymer 2101 was then placed inside an injection device 2010 (eg, UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision) (FIG. 21C). A rectangular piece of copolymer 2101 was injected through injection device 2010 (FIG. 21D). The rectangular piece of copolymer 2101 did not recover its original shape after injection 2102. The injected piece 2102 appeared to constrict and elongate to about the same shape and proportion as the tip of the injector 2010 from which it ejected. Additional pieces of the same copolymer were cut into strips of approximately 3 mm x 12 mm x 0.5 mm and the strips were stretched longitudinally and observed to recover their shape. FIG. 21E shows the intact, unstretched strip 2110 and the stretched strip 2011 that remained stretched and never recovered its original shape.

[0456] Example 15: Qualitative Testing of Another Copolymer
[0457] Figures 22A-22F show examples of qualitative testing of another copolymer (eg, Bezwada CARBOMAXX TC910). The copolymer contained trimethylene carbonate (TMC) and caprolactone in a 90:10 molar ratio, respectively. A 2.5 mm x 2 mm x 0.5 mm thick rectangular piece 2202 of the copolymer was compressed using a pair of forceps 2203 (Figure 22A). Compression is removed from rectangular piece 2202, which allows it to regain its original shape shown in FIG. 22A after about 15 seconds. A rectangular piece of copolymer 2201 was then placed inside injection device 2010 (FIG. 22C) (eg UNFOLDER® Platinum 1 Series by Johnson & Johnson Surgical Vision). A rectangular piece of copolymer 2201 was injected through injection device 2010 (FIG. 22D). FIG. 22D shows a rectangular piece of copolymer 2201 that has recovered its original shape (eg, has nearly returned to its original shape). An annulus-shaped ring 2210 was fabricated from a 0.5 mm thick sheet of the copolymer using 16G and 22G needles (Fig. 22E). Rectangular pieces of copolymer approximately 1 cm x 1 cm x 0.5 mm thick were stretched manually. The copolymer rectangles were friable and easily crumbled 2211 (Figure 22F). It is noteworthy that this polymer exhibited elasticity and shape recovery when compressed with forceps 2203 and injected through the IOL injector system 2010 . However, it exhibited little to no elasticity under extension as shown in Figure 22F.

[0458] Example 16: Qualitative Testing of Polymers for Making Ophthalmic Articles
[0459] Figures 23A, 23B, and 23C show an annulus-shaped ring 2301 made from a copolymer (eg, Bezwada GLYCOMAX GC5545). The copolymer contained glycolic acid and caprolactone in a 55:45 molar ratio, respectively. Polymer ring 2301 exhibited the flexibility to easily stretch when an outward force was applied using forceps 905, as shown in FIG. 23B. Polymer ring 2301 also exhibited shape recovery (eg, shape memory properties) after releasing force from forceps 905 (FIG. 23C). The polymer is mixed with ketorolac, which radically alters the mechanical properties of the polymer to be brittle and wax-like 2305 (Fig. 23D), thereby making it suitable for ophthalmic devices (e.g., IOL haptics). and lacks the desired deformable elastic properties for implantation with an IOL through a small incision, eg, using standard IOL implantation techniques.

[0460] Example 17: Qualitative Testing of Another Polymer for Making Ophthalmic Articles
[0461] Figure 24A shows that the annulus-shaped ring 2401 contained 90% (wt%) copolymer (L-lactide and caprolactone in a 70:30 molar ratio) and 10% (wt%) ketorolac tromethamine. indicate. An annular ring 2401 was fabricated from a 0.5 mm thick sheet of a 90:10 mixture of copolymer and ketorolac incubated at 70° C. using 16G and 22G needles. Attempts were made to create rings at room temperature, but the copolymer-ketorolac sheets were too stiff, making the material difficult to create rings. The polymer ring 2401 was elastic to a low degree and could be forced to elongate using forceps 905 (Fig. 24A). Polymer ring 2401 regained its original shape when the extension force from forceps 905 was removed (Fig. 24B). The polymer ring 2401 was then placed on the haptics 302 of the IOL 300 (eg, Tecnis 1-piece by Johnson & Johnson Surgical Vision) with difficulty because the material is not very elastic and easy to stretch. An in vitro injection procedure was performed using a polymer ring 2401 attached to the IOL 300. FIG. 24C shows the appearance of polymer ring 2401 and IOL 300 prior to in vitro IOL implantation. During in vitro IOL injection, the polymer ring 2401 and IOL 300 are placed in a regular IOL injection procedure with a small amount of viscoelastic material for use with IOL 300 (e.g. Tecnis 1-piece by Johnson & Johnson Surgical Vision). A designed injector cartridge (eg UNFOLDER Platinum 1 Series by Johnson & Johnson Surgical Vision with a tip inner diameter of 1.2 mm) was loaded. The filled cartridge was then loaded into the attached injector device. The polymer ring 2401 and IOL 300 were then manually ejected from the injector into a small volume of phosphate buffered saline (PBS) and left unrolled for approximately 3 minutes at room temperature. After injection, IOL 300 returned to its original size and shape (Fig. 24D) and polymer ring 2401 retained its position, size and shape over haptics 302 (Fig. 24D).

[0462] Example 18: Methods of Pharmacokinetic Studies
[0463] In vitro drug release studies as well as in vivo pharmacokinetic studies were performed using the methods described herein.

[0464] Methods of drug quantification
[0465] The drug quantification methods described herein were used for the detection of dexamethasone, ketorolac and/or moxifloxacin in stability samples, rabbit plasma, rabbit aqueous humor, and/or PBS. Chromatographic separations are reversed-phase using HPLC columns (eg, Phenomenex-C18 Luna 50×2 mm 5 μm column for ketorolac and/or dexamethasone or Phenomenex-C8 Luna 50×2 mm 5 μm column for moxifloxacin). High performance liquid chromatography (RP-HPLC) was performed at 25° C. using two solvent linear gradients. The first mobile layer (A) contained 5 mM ammonium acetate, pH 2.5 with 0.1% formic acid. The second moving bed (B) contained acetonitrile. The liquid chromatography (LC) time program was adjusted as follows: from about 20% B to about 0.3 minutes (minutes), from about 20% B to about 90% B from about 0.3 minutes to about 3 minutes. Linear increase, returning to about 20% B in about 3.1 minutes and re-equilibrating to about 5.5 minutes. The flow rate was set at approximately 350 μl/min. Ketorolac and dexamethasone samples were analyzed on a mass spectrometry system (e.g. API 4000 LC/MS/MS system) equipped with an LC system (e.g. Agilent 1100 series liquid chromatograph) in positive ion electrospray ionization mode and ketorolac and/or dexamethasone was used as an internal standard (eg, reverse analyte). Similar mass spectrometric methods were used to analyze both ketorolac or dexamethasone. mass-to-charge ratio (m/z) of 256.3 m/z to 105.1 m/z for ketorolac and 393.156 m/z to 373.1 m/z or 393.156 m/z to 355.1 m/z for dexamethasone. Ion detection was performed by monitoring migration. Analytes were quantified based on the area-under-peak ratios of analytes and internal standards. Positive electrospray ionization (ESI) was performed by applying the following settings: declustering potential (DP), entrance potential (EP), collision energy (CE), and collision cell exit potential (CXP) was set to 66, 15, 25, and 8 for dexamethasone, 86, 10, 11, and 16 for dexamethasone, the ion spray voltage was set to 5,500 V with an ion source heater temperature of 300° C., source gas 1 was set to 20 psi , the source gas 2 was set at 20 psi and the curtain gas was set at 10 psi.

[0466] Moxifloxacin precursor ion detection was performed on a mass spectrometry system (e.g., API 4000 LC/MS/MS system) equipped with a chromatograph (e.g., Agilent 1100 series liquid chromatograph) in Q1 (MS) mode. went above Positive ESI was performed applying the following settings: declustering potential (DP) set to 31, entrance potential (EP) set to 10 V, ionspray voltage 5,000 V, ion source The heater temperature was set to 350° C., source gas 1 to 20 psi, source gas 2 to 20 psi, and curtain gas to 10 psi. A plasma ketorolac standard curve (1-1000 ng/mL) was generated using peak area ratios and quadratic fitting. The area under a peak or peak area count in chromatography can give a measure of the concentration of the compound it represents. Peak areas can be calculated by measuring the area under the peaks in the chromatographic plot. Peak area ratios can be used to compare the concentration of two or more compounds (eg, analytes) in a chromatographic sample. The correlation coefficient of the calibration curve was r ² =0.99. The lower limit of quantification (LLOQ) for ketorolac in rabbit plasma was determined to be 1 ng/mL. A plasma dexamethasone standard curve (1-4000 ng/mL) was generated using peak area ratios and quadratic fitting. The correlation coefficients of the calibration curves were r2>0.99. The LLOQ for ketorolac in rabbit plasma was determined to be 1 ng/mL. An aqueous ketorolac standard curve (1-4000 ng/mL) was prepared with rabbit aqueous humor diluted 5-fold in PBS (eg, Pel-Freeze rabbit aqueous humor). A standard curve was generated using peak area ratios and quadratic fitting. The correlation coefficient of the calibration curve was r2≧0.99. The LLOQ for ketorolac in rabbit plasma was determined to be 1 ng/mL.

[0467] An aqueous humor (AH) dexamethasone standard curve (1-2000 ng/mL) was prepared with rabbit aqueous humor (eg, Pel-Freeze rabbit aqueous humor) diluted 5-fold with PBS. A standard curve was generated using peak area ratios and quadratic fitting. The correlation coefficients of the calibration curves were r2>0.99. The LLOQ for ketorolac in rabbit plasma was determined to be 1 ng/mL. A moxifloxacin standard curve (100-10000 ng/mL) was prepared in PBS. LLOQ was determined as 100 ng/mL.

[0468] Plasma sample preparation
[0469] A plasma standard curve and quality control (QC) were performed. Standard concentrations ranged from 1.00 to 4000 ng/mL plasma in 50 μL aliquots transferred to deep 96-well plates for extraction. Low, medium and high level QC concentrations were prepared at concentrations of 40 ng/mL, 200 ng/mL and 1000 ng/mL in 50 μL aliquots transferred to deep well 96 well plates.

[0470] Study samples were prepared by thawing single plasma at room temperature and transferring 50.0 μL aliquots to deep-well 96-well plates for analysis. Unused samples were returned to storage at -20°C. Ketorolac standards, QC and study samples received 250 μL of 0.25 μg/mL dexamethasone in acetonitrile (Internal Standard, IS).

[0471] Dexamethasone standards, QC and study samples received 250 μL of 0.25 μg/mL ketorolac in acetonitrile (Internal Standard, IS). Samples were vortex mixed and centrifuged at approximately 3400 xg for 10 minutes. The supernatant was transferred to a new 96 deep well plate and dried using an evaporation system (eg Zymark TurboVap 96 N2 evaporation system). Samples were reconstituted with 100 μL of 95% 5 mM ammonium acetate and 0.1% formic acid and 5% acetonitrile, solubilized by vortexing and placed in the autosampler.

[0472] Preparation of Aqueous Humor Samples
[0473] Rabbit aqueous humor (eg, Pel-Freeze rabbit aqueous humor) was diluted 5-fold with PBS. Standard concentrations ranged from 1.00 to 4000 ng/mL plasma in 50 μL aliquots transferred to deep-well 96-well plates for extraction. Low, medium and high level QC concentrations were prepared at concentrations of 40 ng/ml, 200 ng/ml and 1000 ng/ml in 50 μL aliquots transferred to 96 wells of deep wells.

[0474] Study samples were prepared by thawing a single aqueous humor sample at room temperature and transferring a 50.0 μL aliquot to a deep-well 96-well plate for analysis. Unused samples were returned to storage at -20°C. Ketorolac standards, QC and study samples received 250 μL of 0.25 μg/mL dexamethasone in acetonitrile (Internal Standard, IS). Dexamethasone standards, QC and study samples received 250 μL of ketorolac at 0.25 μg/mL in acetonitrile (Internal Standard, IS).

[0475] The samples were vortex mixed and centrifuged at approximately 3400 xg for 10 minutes. The supernatant was transferred to a new 96 deep well plate and dried using an evaporation system (eg Zymark TurboVap 96 N2 evaporation system). Samples were reconstituted with 100 μL of 95% 5 mM ammonium acetate containing 0.1% formic acid and 5% acetonitrile, solubilized by vortexing and placed in the autosampler.

[0476] Example 19: In Vitro Drug Release Profiles of Ophthalmic Articles
[0477] A ring-shaped ophthalmic article was prepared comprising 9% (wt%) drug (eg, dexamethasone or ketorolac) and 91% (wt%) copolymer. The copolymer contained poly(L-lactide-co-caprolactone) in a molar ratio of L-lactide to caprolactone of about 60:40 with a molecular weight (M _n ) of about 75-85 kDa. The ophthalmic article can have an outer diameter of about 1.2 mm, an internal structure (e.g., pores) with an inner diameter of about 0.6 mm, and a cross-sectional thickness of about 0.5 mm, and in this illustrative embodiment: The ophthalmic article had approximate ring dimensions of about 1.25 mm outer diameter, about 0.5 mm inner diameter and about 0.5 mm cross-sectional thickness.

[0478] To conduct in vitro drug release studies on dexamethasone-loaded ophthalmic articles, eight ophthalmic articles with a combined mass of 4 mg were inserted into microcentrifuge tubes for drug release testing. . A drug release study was conducted over a period of 32 days using the ophthalmic articles described herein. Ophthalmic articles were placed in a phosphate buffered saline (PBS) solution at 37°C. The amount of dexamethasone present in solution was measured at predefined time points throughout the study according to the method described herein above. The cumulative amount of dexamethasone released from the ophthalmic articles is shown in Figure 25A. Dexamethasone levels were still detectable on day 32 of the study.

[0479] To conduct in vitro drug release studies on ketorolac-loaded ophthalmic articles, nine ophthalmic articles with a combined mass of 7.5 mg were inserted into microcentrifuge tubes for drug release testing. did. A drug release study was conducted over a period of 32 days using the ophthalmic articles described herein. Ophthalmic articles were placed in a phosphate buffered saline (PBS) solution at 37°C. The amount of ketorolac present in solution was measured at predefined time points throughout the study according to the methods described herein above. The cumulative amount of ketorolac released from the ophthalmic article is shown in Figure 25B. The presence of ketorolac was undetectable after 15 days.

[0480] Example 20: In Vitro Drug Release Profiles for Ophthalmic Articles Loaded with Moxifloxacin
[0481] A ring-shaped ophthalmic article was prepared comprising 9% (wt%) moxifloxacin and 91% (wt%) copolymer. The copolymer contained poly(L-lactide-co-caprolactone) in a molar ratio of L-lactide to caprolactone of about 50:50 with a molecular weight (M _n ) of about 75-85 kDa. The approximate dimensions of the ophthalmic article were 1.3 mm outer diameter, 0.5 mm inner diameter and 0.7 mm cross-sectional thickness in this illustrative embodiment. Nine ophthalmic articles with a combined mass of 7.5 mg were inserted into microcentrifuge tubes for drug release testing. A drug release study was conducted over a period of 45 days using the ophthalmic articles described herein. Ophthalmic articles were placed in a phosphate buffered saline (PBS) solution at 37°C. The amount of moxifloxacin present in solution was measured at predefined time points throughout the study according to the methods described herein above. The cumulative amount of moxifloxacin released from the ophthalmic articles is shown in FIG.

[0482] Example 21: Ophthalmic Articles Loaded with Moxifloxacin Antibiotic Activity
[0483] 9% (wt%) moxifloxacin and 91% (wt%) poly(L-lactide at a 60:40 molar ratio of L-lactide to caprolactone with a molecular weight (M _n ) of about 75-85 kDa. -co-caprolactone) was prepared. The approximate dimensions of ophthalmic article 100 were 1.3 mm outer diameter, 0.5 mm inner diameter and 0.5 mm cross-sectional thickness. FIG. 27 illustrates an example of antibiotic activity of a drug (eg, moxifloxacin) released from ophthalmic article 100. FIG. The degree of zone of inhibition marked by circle 2710 for ophthalmic article 100 may be comparable in size to the degree of zone of inhibition 2715 for positive control antibiotic disc 2705 .

[0484] To study the antibiotic activity of a drug (eg, moxifloxacin) released from the ophthalmic article 100 over time, the first ophthalmic article 100 was frozen on day 0. The second, third, and fourth ophthalmic articles were incubated for up to 9 days at 37° C. in separate tubes containing phosphate buffered saline (PBS) solution. Individual ophthalmic articles were removed from the incubation medium and frozen on days 1, 2, 7 and 9. After 9 days, frozen samples were thawed and tested for antibiotic activity using the agar dispersion method (Figure 28A). FIG. 28A illustrates the diameter of the zone of inhibition 2710 on days 0, 1, 2, 7, and 9. A graph representing the diameter of the zone of inhibition on days 0, 1, 2, 7 and 9 is shown in Figure 28B. These results demonstrate sustained antibiotic activity of the moxifloxacin-loaded ophthalmic article 100 for at least nine days.

[0485] Example 22: Intraocular IOL Location
[0486] FIG. 29 shows an example of the position of IOL 300 in a subject's eye undergoing cataract surgery. The anatomy of the eye may vary between subjects and/or may change depending on the outcome of cataract surgery. For example, the iris angle may shift after a subject's eye's natural lens is removed in cataract surgery. As the lens capsule wraps around the IOL, the position of the IOL may shift. FIG. 29 shows the IOL 300 in the subject's eye without noticeable shift.

[0487] Example 23: Materials and Methods Used in Preclinical Studies
[0488] Test Materials
[0489] A preclinical study was conducted in a rabbit model of cataract surgery. The results of these studies are discussed in Examples 24, 25, 26, and 27 herein. The materials and methods used in these studies are disclosed in Example 23 herein. Intraocular lens implants (IOLs) were obtained from intraocular lens manufacturers (eg, Tecnis 1-piece monofocal hydrophobic acrylic IOL by Johnson & Johnson Vision). IOLs were pre-bonded to ophthalmic article 100 or vehicle implants (eg, OcuRing polymer only) prior to their use in a cataract surgery model. All of the ophthalmic articles and vehicles used in the animal model of cataract surgery had an outer diameter of approximately 1.3 mm, an inner diameter of 0.5 mm and a thickness of 0.7 mm. The composition of each ophthalmic article and vehicle tested in Examples 24-27 is summarized in Table 1.

[0490]

[0491] In general, for all results obtained from an example, it is important to tie the results to what (e.g., polymer composition, amount of active agent, IOL contribution) contributed to a particular result.

[0492] On the day of implantation, all animals underwent a bilateral phacoemulsification procedure.
[0493] Test System: Animal Housing, and Environmental Conditions
[0494] Animals were identified using ear tagging and cage cards. The caging is a stainless steel cage with a slatted bottom that does not include additional bedding (e.g., 17 inches wide x 27 inches deep x 38.1 cm (15 inches) high or large). inches)). One rabbit was maintained in each cage. Environmental conditions included maintaining the temperature at 20±2° C. (68±2° F.) with 12 hours of light and 12 hours of darkness. All animals were fed Purina Hi Fiber Lab Rabbit Diet. Water (eg, Durham City Water) was provided to the animals using a bottle with a sipper tube. Water was tested for contamination at least every six months.

[0495] Animal Health, Acclimation, and Pain Control
[0496] Animals were acclimated to the study environment (eg, 1-2.5 weeks) prior to procedures (eg, dosing procedures). At the end of the acclimation period, each animal was physically examined by a laboratory animal technician for determination of suitability for study participation. Animals determined to be in good health were released for study. The Institution's Animal Care and Use Committee (IACUC) has approved the protocol described herein. At least one cage-side survey for overt signs of discomfort, such as severe blepharospasm, severe conjunctival hyperemia, epiphora, excessive rubbing on the eye, and not eating, should be conducted according to IACUC and laboratory procedures. Completed twice a day (6 hours apart). Per protocol, animals were humanely euthanized when these conditions were observed and persisted for 12 hours. None of these conditions were observed in any of the studies.

[0497] Animals were assigned to each study by animal number and uniquely identified by matching cage card number and matching ear tag number.
[0498] Embedding Procedure (Day 0)
[0499] On day 0, rabbit pupils were dilated using 1.0% tropicamide hydrochloride. Animals then receive a subcutaneous (SC) infusion of buprenorphine (eg, 0.01-0.05 mg/kg SC), followed by ketamine hydrochloride (eg, 50-80 mg/kg) and xylazine hydrochloride (5-10 mg/kg). were anesthetized with an intramuscular (IM) injection of Aseptic procedures were used for surgical procedures. All animals received a single intravenous (IV) dose of enrofloxacin (eg Baytril, 5 mg/kg) once on the day of surgery as a prophylactic antibiotic.

[0500] A sharp corneal incision (e.g., 2.5 millimeters (mm) or 2.8 mm long) is made in the superior limbus and a fornix-based conjunctival covering is performed to maintain homeostasis, if necessary, lightly. Obtained at the margins by cauterization. A corneal scleral incision was then made using a crescent blade, or common equivalent, to enter the anterior chamber (eg, with a 2.8 mm keratome). After instillation of epinephrine (eg, 1:10,000) in balanced salt solution (BSS), the anterior chamber was then inflated (eg, with viscoelastic 1.8% hyaluronic acid).

[0501] A capsulorhexis forceps was used to create a continuous curvilinear capsulotomy (CCC) right in the center with a diameter of approximately 5.5 mm. After BSS hydrodissection, a phacoemulsification handpiece (eg Alcon Constellation system) was inserted into the posterior chamber to remove the lens nucleus and cortical material. One milliliter (mL) of epinephrine 1:1,000 (1 mg/mL) and 0.5 mL of heparin (10,000 USP units/mL) were added to each 500 mL of wash solution to promote pupil dilation and control inflammation. . Intracapsular techniques were used in conjunction with phacoemulsification to occur (eg, completely) within the lens capsule. The residual cortex was then removed using a handpiece (eg, using an irrigation/aspiration (I/A) handpiece). Viscoelasticity was used to enlarge the lens capsule (eg, up to about 2.7 or up to about 2.8 mm).

[0502] Pre- and post-operative pain medications were prescribed after veterinary approval. After surgery, animals received 1 drop of Neopolygram in each eye and a second dose of buprenorphine (eg, 0.01-0.05 mg/kg SC) the afternoon after surgery. Rabbit body weights were collected after acclimatization, prior to surgery, and prior to necropsy. During acclimatization and during the studies described in Examples 2, 3 and 4, animals were evaluated for mortality and morbidity and general health, with particular attention to the eyes.

[0503] Eye Examination and Irritation Score
[0504] Ophthalmic examination (OE) was performed using a slit lamp microscope and indirect ophthalmoscope to serve as a baseline at predetermined time points in each study described elsewhere herein. , ocular surface morphology and anterior and posterior ocular segmental inflammation were evaluated in all animals prior to the implantation procedure. For the posterior segment, inflammation was graded using a modified Hackett and McDonald eye scoring system with additional scoring parameters. The extent of capsular fibrosis was also assessed at predetermined time points in each study described elsewhere herein by slit-lamp retrophotography. The posterior capsule opacification (PCO) score was calculated according to a scoring system (e.g., none or 0, mild/focal or 1, moderate/focal or 2, moderate/dispersed or 3, severe/dispersed or Each animal was evaluated using a PCO scoring system of 0-4, including 4). A topical mydriatic was given after an anterior segment examination to facilitate fundus examination. Animals were not sedated for examination.

[0505] Tonometry
[0506] Intraocular pressure (IOP) was measured in all animals after OE with a probe (e.g., with a Tonovet probe) at predetermined time points in each study described elsewhere herein. Binocular measurements were taken. IOP measurements were made with animals maintained in a standing position. Using the Tonovet probe, the tip of the probe was oriented in gentle contact with the central cornea. Multiple consecutive measurements (eg, 6 consecutive measurements) were taken and the mean IOP shown on the display was recorded. Multiple independent measurements (eg, triplicate) were obtained and recorded for both eyes at predetermined time points in each study described elsewhere herein.

[0507] Aqueous humor recovery
[0508] Animals were given buprenorphine (eg, 0.01-0.05 mg/kg SC once daily) at predetermined time points in each study described elsewhere herein. Prior to aqueous humor (AH) collection, animals were sedated (e.g., with 50 mg/kg ketamine and 10 mg/kg xylazine intramuscular (IM)) and eyes were sterilized (e.g., topical 5% betadine solution). followed by irrigation with sterile eye wash and administration of 1 drop of 0.5% proparacaine HCL). Approximately 100 microliters (μL) of AH were collected from both eyes (eg, at approximately the 12 o'clock position using a 30 gauge needle). After AH collection, samples were weighed, flash frozen and stored at −80° C., and animals were allowed to recover normally from anesthesia.

[0509] Blood collection
[0510] After AH collection, plasma was collected at pre-determined time points in each study described elsewhere herein (e.g., at least 0.5 mL of whole blood into a K2EDTA tube from a vein around the ear). subtracted). After collection, the collected blood was gently mixed (eg, by inverting the tube 5-8 times). Blood samples were stored on wet ice until plasma processing. Samples were centrifuged in a swinging-bucket refrigerated centrifuge (eg at 2000 g for 10 minutes at 4° C.). After blood collection (eg, within 20 minutes), clarified plasma was stored (eg, clarified plasma was transferred to pre-labeled polypropylene tubes, flash frozen, and stored frozen at -80°C).

[0511] Eye Histopathology Examination
[0512] In some cases, after surgery (eg, within at least about 28 days), animals were euthanized, eg, with an overdose of sodium pentobarbital, and confirmed dead by auscultation. Both eyes were immediately enucleated and fixed (eg, in Davidson's solution for 24 hours followed by alcohol). Tissue specimens were stored (eg, at −80° C.) for histopathological examination of the eye. In other cases, after surgery (e.g., within at least about 30 days), animals are sedated with one or more drugs (e.g., 50/10 mg/kg ketamine/xylazine IM), e.g., sodium They were euthanized by an overdose of pentobarbital and confirmed dead by auscultation. Immediately after euthanasia, all eyes were enucleated and fixed (eg, overnight in Davidson's solution at room temperature). The next day, eyes were washed (eg, in 70% ethanol) and stored (eg, 70% ethanol) until paraffin embedding. Selected central eye segments, including the optic nerve, were stained (eg, with hematoxylin and eosin) and examined using a light microscope.

[0513] Example 24. One Week Efficacy and Tolerability
[0514] Efficacy and tolerability of ophthalmic article (e.g., OcuRing-D dexamethasone) implants after phacoemulsification with intraocular lens (IOL) implants were evaluated over 7 days after surgery for cataract surgery. was evaluated in a rabbit model of An ophthalmic article (e.g., OcuRing) is a substantially small, bioerodible ring that can be attached to an IOL (e.g., to the IOL's haptics) and, for example, during a post-operative period, a predetermined dosage (e.g., , dexamethasone 300 μg or 600 μg) can provide sustained release of drug. Phacoemulsification is a modern method of cataract surgery in which an intraocular lens is emulsified with an ultrasonic handpiece and aspirated from the eye. The aspirated fluid is replaced with a balanced salt solution wash to maintain the anterior chamber.

[0515] Rabbits are the preferred species for evaluating the safety of intraocular devices and have been evaluated by the United States Food and Drug Administration (US FDA), the American National Standards Institute (ANSI), and the International Organization for Standardization/European Committee for Standardization (ISO). /CEN) has all the performance guidelines for conducting studies utilizing the rabbit model.

[0516] Phacoemulsification was performed bilaterally. Corneal incisions in animals undergoing surgery were closed with a continuous suture pattern of 9-0 nylon. Surgery was followed by implantation of either a control IOL or an IOL with an ophthalmic article (eg, OcuRing-D). Control IOLs were either IOLs without an attached ophthalmic article or vehicle implant. Vehicle implants included an IOL with an attached ophthalmic article (eg, polymer ring only) without drug. Videos were recorded through a surgical microscope for each implantation procedure. Still pictures from a typical surgical video are shown in Figures 30A-30C. 30A shows the injector cartridge tip 3001 expanded from the corneal incision to the anterior chamber with an ophthalmic article attached to the leading haptics of the IOL 300, rolled together and compressed into the tip of the injector cartridge 3001. In FIG. In FIG. 30B, ophthalmic article 100 and IOL 300 are shown protruding from injector tip 3001 into the anterior chamber. Note that the exposed portion of IOL 300 begins to spread out, while the portion of IOL remaining within the injector tip remains rolled up. In FIG. 30B, ophthalmic article 100 and IOL 300 are shown fully expanded within the lens capsule of the eye. The tip of instrument 3002 is visible and used by the surgeon to rotate and center IOL 300 in its correct position.

[0517] Experimental design
[0518] A total of eight male New Zealand White adult rabbits aged 6.5 months were randomized into two groups. Four rabbits were assigned to each group. The first group received vehicle implants and an IOL in their left eye (OS) and dexamethasone (300 μg) and an IOL-loaded ophthalmic article (e.g., OcuRing-D) in their right eye (OD). received. A second group received an IOL without an ophthalmic article in their left eye (OS) and dexamethasone 600 μg and an IOL-loaded ophthalmic article (e.g., OcuRing-D) in their right eye (OD). received. Two rabbits were maintained as reserves. Animals were acclimated to the study environment for a minimum of 2 weeks prior to dosing or implantation and evaluated over a period of 1 week after dosing or implantation.

[0519] Mortality and morbidity were observed twice daily with cage-side observations, with special attention to both eyes. Intraocular pressure (IOP) and complete ocular examination (OE) include ocular surface morphology and ocular inflammation at predetermined time points. Predetermined time points included day 0 (baseline), days 1, 2, 4, and 7. Animals were euthanized 7 days after surgery. Animal weights were collected on Day 0 prior to surgery and prior to necropsy. An illustrative study design is summarized in Table 2. Details of the animals, housing, and environmental conditions as well as the animal's diet and water are shown in Table 3.

[0520]

[0521]

[0522] Results
[0523] Surgical implantation of IOLs with and without ophthalmic article implants (eg, OcuRing) was performed without complications. Ease of injector loading, insertion into the eye, deployment and positioning within the capsular capsule is comparable between IOLs with and without ophthalmic article implants (e.g., OcuRing) Met. No tilting or dispersion was observed for intraocular implants and IOLs with ophthalmic article implants (eg, OcuRing). All surviving animals remained healthy throughout the study, including normal activity, feeding, urination, and defecation. Animals weighed 3.0±0.23 kg before surgery and 3.0±0.23 kg at necropsy. Individual animals maintained their weight or gained small amounts over the course of the study.

[0524] Posterior capsule opacification scoring showed higher scores in eyes that received higher doses of dexamethasone (OD of second group: dexamethasone 600 μg) IOLs. No clouding of the lens was observed, indicating a lack of calcification during the duration of the study. Dexamethasone and whole IOL implant-loaded ophthalmic articles were well tolerated in rabbits.

[0525] At predetermined time points described herein, OE was performed on all animals and stimulation scores were collected. Figures 31A-31H illustrate examples of digital planar photographs of rabbit eyes on days 1 and 7. Figures 31A, 31C, 31E, 31G are representative photographs on day 1 and Figures 31B, 31D, 31F, 31H are representative photographs on day 7. A representative image of IOL 300 is shown in FIG. 31F and IOL 300 was implanted in all animals as described herein above. Vehicle implants 3110 and dexamethasone implants 3120 all appeared intact and were correctly positioned on day one. By day 7, the shape of some of the vehicle implants 3130 and dexamethasone implants 3140 changed, but they remained in the correct position on the IOL. Without wishing to be bound by theory, implanted devices can change shape under physiological conditions, and the extent to which this occurs for a given formula was not predictable. In this example, without wishing to be bound by theory, the drug and/or polymer compositions of the devices presented in this example are smaller than some of the compositions of other devices presented in subsequent examples. It can be concluded that in vivo shape retention can be demonstrated. FIG. 31G illustrates two ophthalmic devices 3120a and 3120b loaded with a drug (eg, dexamethasone).

[0526] Figure 32 shows the mean total OE scores on Day 0 (baseline), Day 1, Day 2, Day 4, and Day 7. Error bars represent standard error of the mean. Open squares connected by dashed curve 3210 represent OE scores for left eyes with vehicle controls in animals in the first group. Solid black squares connected by dashed-dotted line 3220 represent OE scores for right eyes of animals in the first group that had ophthalmic articles loaded with 300 μg dexamethasone. OE scores for the left eye of animals in the second group with only IOLs are represented by open circles connected by dash-dotted line 3230 . Solid black circles connected by solid black line 3240 represent OE scores for right eyes of animals in the second group that had ophthalmic articles loaded with 600 μg dexamethasone. OE scores showed slight inflammation across all groups for the first 2 days post-implantation, with OE scores for both IOL 3220 loaded with dexamethasone 300 μg and IOL 3240 loaded with dexamethasone 600 μg compared to fellow controls 3210 and 3230. was significantly lower at all time points examined. A fellow eye control 3210 received a vehicle implant (eg, an IOL without an ophthalmic article and drug). Fellow eye control 3230 received the IOL only. OS (fellow eye control) of animals treated with dexamethasone implant 3240 600 μg had lower inflammation scores than fellow eyes of animals treated with dexamethasone 3220 300 μg at all time points after cataract surgery. . Total OE scores for dexamethasone-loaded implants were on average lower than control IOLs throughout the duration of the study, with a peak inflammatory response at 2 days post-implantation. In general, the IOL was well tolerated with moderate post-implantation inflammation that began to resolve 2 days after surgery.

[0527] Intraocular pressure (IOP) was measured in all animals at predetermined time points. FIG. 33 shows mean IOP measured on days 0 (baseline), 1, 2, 4 and 7. Error bars represent standard error of the mean. Unfilled squares with dotted line 3310 for OS receiving vehicle implants (companion eye control) and dash-dotted line for ophthalmic article loaded with 300 μg dexamethasone and OD eyes receiving IOL (300 μg dexamethasone). Solid squares with 3320 are used to indicate IOP for animals in the first group. IOP in those left eyes (OS) that received IOL only (companion control), represented by open circles and dash-dot line 3330, for animals in the second group, ophthalmic article loaded with 600 μg dexamethasone. The IOP in those right eyes (OD) that received the IOL together is represented by solid circles and solid line 3340 . In general, IOP followed a similar pattern to changes in OE score, which increased on the first day after implantation and decreased by the second day. All eyes were within normal IOP range by the end of the study. These findings provide preliminary support for the safety of dexamethasone-loaded and vehicle devices for use in cataract surgery.

[0528] Example 25. Four Week Efficacy and Tolerability
[0529] The efficacy and tolerability of post-phacoemulsification ophthalmic article (e.g., OcuRing-D dexamethasone or OcuRing-K ketorolac) implants with intraocular lens (IOL) implants was evaluated 30 days after surgery. have been evaluated in a rabbit model of cataract surgery over a period of time. An ophthalmic article (e.g., OcuRing) is a substantially small, bioerodible ring that can be attached to an IOL (e.g., to the IOL's haptics), e.g. For example, dexamethasone 300 μg or 600 μg or ketorolac 150 μg or 300 μg) can provide sustained release of drug. Phacoemulsification is a modern method of cataract surgery in which an intraocular lens is emulsified with an ultrasonic handpiece and aspirated from the eye. The aspirated fluid is replaced with a balanced salt solution wash to maintain the anterior chamber.

[0530] Phacoemulsification was performed bilaterally. Corneal incisions in animals undergoing surgery were closed with a continuous suture pattern of 9-0 nylon. Surgery was followed by implantation of either control IOLs or IOLs with ophthalmic articles (eg, OcuRing-D or OcuRing-K). Control IOLs were either IOLs without an attached ophthalmic article or vehicle implant. Vehicle implants included an IOL with an attached ophthalmic article (eg, polymer ring only) without drug.

[0531] Experimental design
[0532] A total of eight male New Zealand White adult rabbits aged 6.0 months were randomized into two groups. Four rabbits were assigned to each group. The first group received vehicle implants and an IOL (eg, an IOL with OcuRing polymer only) in their left eye and ketorolac 150 μg and an IOL implant (eg, OcuRing-K) in their right eye (OD). received an ophthalmic article loaded with an IOL having a A second group received vehicle implants and an IOL (eg, an IOL with OcuRing polymer only) in their left eye and dexamethasone 150 μg and an IOL implant (eg, OcuRing-D) in their right eye (OD). received an ophthalmic article loaded with an IOL having a Two rabbits were maintained as reserves. Animals were acclimated to the study environment for a minimum of 2 weeks prior to dosing or implantation and evaluated over a period of 4 weeks post-surgery.

[0533] Complete OE and photographs and intraocular pressure measurements were performed on all animals at 0 (baseline), 1, 3, 7, 14, 21 and 30 days after surgery. All animals were euthanized 30 days after surgery and both eyes were enucleated for ocular histology as described herein. The study design is outlined in Table 4. Details of the animals, housing, and environmental conditions and the animal's diet and water are shown in Tables 5 and 6, respectively.

[0534]

[0535]

[0536]

[0537] Results
[0538] Surgical implantation of IOLs with and without ophthalmic article implants (eg, OcuRing) was performed without complications. When implanted in the eye, there was no evidence of tilting or dispersion for the IOLs with ophthalmic article implants (eg, OcuRing). All surviving animals remained healthy throughout the study, including normal activity, feeding, urination, and defecation. Animals weighed 2.9±0.14 kg before surgery and 3.3±0.29 kg at necropsy. Individual animals maintained their weight or gained small amounts over the four weeks of the study.

[0539] To assess postoperative inflammation, OE was performed in all animals on days 0 (baseline), 1, 3, 7, 14, 21, and 29. Mean total OE scores with corresponding standard errors of the mean (error bars) for the first group that received vehicle or ketorolac-containing implants are shown in FIG. The mean total OE scores with corresponding standard error of the mean (error bars) for the second group are shown in FIG. The total score of the ocular examination for eyes receiving an ophthalmic article with dexamethasone or ketorolac, if the inflammation score in the control IOL group decreased to the level observed in eyes receiving an ophthalmic article with ketorolac or dexamethasone , on average lower than eyes receiving vehicle implants by day 14. A peak inflammatory response was observed on day 3 after surgery for vehicle controls, while peak inflammation was observed on day 1 for eyes receiving ophthalmic articles with ketorolac or dexamethasone.

[0540] Illustrative examples of digital planar photographs associated with OE of rabbit eyes in Groups 1 (Figure 36) and 2 (Figure 37) for days 3, 14 and 29 post-surgery. show. Each row represents three digital planar photographs of the same eye in a rabbit. Representative images of the left eye of rabbits in the first group that received vehicle implants and IOLs are shown for days 3 (FIG. 36A), 14 (FIG. 36B) and 29 (FIG. 36C). rice field. First group receiving ketorolac (eg, OcuRing-K) 150 μg and IOL-loaded ophthalmic article on days 3 (FIG. 36D), 14 (FIG. 36E) and 29 (FIG. 36F) Shown are representative images of the right eye of a rabbit in . Representative images of the left eye of rabbits in the second group with vehicle implants and IOLs at days 3 (FIG. 36G), 14 (FIG. 36H) and 29 (FIG. 36I) are shown. . A second group that received 150 μg dexamethasone (eg, OcuRing-D) and an IOL-loaded ophthalmic article on days 3 (FIG. 36J), 14 (FIG. 36K) and 29 (FIG. 36L). Shown are representative images of the right eye of a rabbit in . Photographs of vehicle-treated eyes in the first and second groups on day 3 appear to show more inflammation than eyes treated with ketorolac or dexamethasone. By day 14, the eyes of all animals appear to have less inflammation present, but this finding continues through day 29. These findings are consistent with trends observed with OE scores (Figures 34 and 35). The absence of significant inflammation observed in eyes implanted with either vehicle or drug-loaded implants by day 29 demonstrates the potential safety and efficacy of the device material for use in human cataract surgery. Supports biocompatibility.

[0541] Intraocular pressure (IOP) was measured at predetermined time points in all animals. Mean IOP measured on days 0 (baseline), 1, 3, 7, 14, 21, and 29 for the first group that received vehicle or ketorolac-containing implants is shown in FIG. Mean IOP measured on days 0 (baseline), 1, 3, 7, 14, 21, and 29 for the second group that received implants containing dexamethasone are shown in Figure 37B. Error bars represent standard error of the mean. The IOP of the left eye of animals in the first group with vehicle implants is represented using open circles and the second group with vehicle implants is represented using triangles with dashed lines. . The IOP of the right eye of animals in the first and second groups with ophthalmic article implants is indicated using filled circles and triangles with solid lines, respectively. IOP scores increased on the first day after surgery and then decreased by day 3 for both eyes of animals in both groups. From Day 3 to Day 29, IOP measurements for all groups remained within the normal range. These findings provide preliminary support for the safety of dexamethasone-loaded and vehicle devices for use in cataract surgery.

[0542] Euthanasia and tissue collection were performed satisfactorily as described herein above. Representative images of histopathological sections of the eyes of animals in the first group (FIGS. 38A-38D) and the second group (FIGS. 39A-39D). Representative of the left eye (OS) of animals receiving vehicle control (companion control) for the iris and ciliary body (FIGS. 38A and 39A), and for the vitreous and retina (FIGS. 38B and 39B). A histopathological examination portion is shown. Representative of the right eye (OD) of an animal receiving an ophthalmic article implant, for the iris and ciliary body (FIGS. 38C and 39C), and for the vitreous and retina (FIGS. 38D and 39D). A histopathological examination portion is shown. From the slides examined, fellow eye controls in the first group that received vehicle implants had moderate cellular infiltrates ( Figure 38A) and consistently had mild to moderate cells in the main part of the vitreous (Figure 38B). Eyes in the first group that received an ophthalmic article (eg, OcuRing-K) loaded with 150 μg of ketorolac implants had substantially little anterior and posterior inflammation, mostly both There was no inflammation or was accompanied by mild inflammation (Figures 38C and 38D). Left eyes in animals in the second group that received vehicle controls had mild to moderate cellular infiltrates (Figures 39A and 39B). The right eyes of animals in the second group that received an ophthalmic article loaded with dexamethasone (eg, OcuRing-D) 150 μg had no or very mild inflammation (FIGS. 39C and 39D); The lowest inflammation was observed among the four groups in this study.

[0543] Conclusion
[0544] A study was conducted in comparison to an ophthalmic article without a drug (e.g., OcuRing), referred to herein as a vehicle implant, attached to an IOL inserted into the eye of a rabbit model of cataract surgery. , evaluated the potential efficacy and tolerability of drug-loaded ophthalmic articles, either ketorolac (eg, OcuRing-K) or dexamethasone (eg, or OcuRing-D). IOLs and ophthalmic article implants (eg OcuRing/IOL) were successful in all animals. Ocular examination showed slight inflammation that peaked on Day 1 for groups receiving either ketorolac (eg, OcuRing-K) or dexamethasone (eg, or OcuRing-D)-loaded ophthalmic articles. , inflammation was higher and peaked later (eg, day 3) for eyes with vehicle controls. OE scores for eyes with ophthalmic articles loaded with either ketorolac or dexamethasone were higher than OE scores for vehicle-treated eyes with ketorolac (eg, OcuRing-K) or dexamethasone (eg, or OcuRing-D). was significantly lower at all time points through day 7 compared to eyes with vehicle controls, after decreasing to a range of levels including eyes receiving an ophthalmic article loaded with either In addition, by histopathological examination, significantly low or even present in eyes receiving either ketorolac (eg, OcuRing-K) or dexamethasone (eg, or OcuRing-D)-loaded ophthalmic articles. revealed no inflammation and edema.

[0545] Example 26. Pharmacokinetics
[0546] One or more drugs (eg, , dexamethasone, or ketorolac) was evaluated over 28 days after surgery. An ophthalmic article (e.g., OcuRing) is a substantially small, bioerodible ring that can be attached to an IOL (e.g., to the haptics of the IOL) and is administered at a predetermined dosage (e.g., For example, dexamethasone 300 μg or 600 μg or ketorolac 150 μg or 300 μg) can provide sustained release of drug. Phacoemulsification is a modern method of cataract surgery in which the internal lens of the eye is emulsified with an ultrasonic handpiece and aspirated from the eye. The aspirated fluid is replaced with a balanced salt solution wash to maintain the anterior chamber.

[0547] Phacoemulsification was performed bilaterally in all animals. Corneal incisions in animals undergoing surgery were closed with a continuous suture pattern of 9-0 nylon. Surgery was followed by implantation of either an IOL with a dexamethasone (eg, OcuRing-D dexamethasone)-loaded ophthalmic article or an IOL with a ketorolac (eg, OcuRing-K ketorolac)-loaded ophthalmic article. . A total of eight male New Zealand White adult rabbits aged 6.5 months were randomized into two groups. Four rabbits were assigned to each group. The first group received ophthalmic articles and IOL implants loaded with ketorolac 150 μg in both eyes (OU). A second group received ophthalmic articles and IOL implants loaded with dexamethasone 150μ in both eyes (OU). Two rabbits were maintained as reserves. Animals were acclimated to the study environment for a minimum of 1 week prior to surgery and evaluated over a period of 4 weeks post-surgery.

[0548] Complete OE and photographs and AH collections were performed on all animals on days 0 (baseline), 1, 3, 7, 14, 21 and 28 post-surgery. For PK analysis, IOLs were externally implanted on day 28. All animals were euthanized 28 days after surgery and final AH collection. The right eye of the animal was enucleated, flash frozen in liquid nitrogen, and stored at -80°C for PK tissue analysis. The study design is outlined in Table 7. Details of the animals, housing, and environmental conditions as well as the animal's diet and water are shown in Table 8.

[0549]

[0550]

[0551] Results
[0552] Surgical implantation of IOLs with ophthalmic article implants (eg, OcuRing K or OcuRing D) was performed without complications. When implanted in the eye, there was no evidence of tilting or drifting for the IOLs with ophthalmic article implants (eg, OcuRing). All surviving animals remained healthy throughout the study, including normal activity, feeding, urination, and defecation. Animals weighed 2.8±0.12 kg before surgery and 3.1±0.14 kg at necropsy. Individual animals maintained their weight or gained small amounts over the course of the four weeks of the study.

[0553] Pharmacokinetic Analysis
[0554] Aqueous humor and plasma were collected at predetermined time points specified herein above. Concentrations of ketorolac and dexamethasone in plasma and aqueous humor were measured according to the methods described above. All plasma test levels in all of the study rabbits were below the limit of quantitation (BLQ ), plasma ketorolac was <1 ng/mL below the lower limit of quantitation (LLOQ), and plasma dexamethasone was <1 ng/mL below the LLOQ). Mean tissue concentrations of drug in aqueous humor are shown in FIG. 40 for ketorolac and in FIG. 41 for dexamethasone. Error bars represent standard error of the mean (SEM). In the first group, ketorolac test article levels ranged from 2,500 ng/mL on day 3 to 2.5 ng/mL on day 14 and were detectable in all samples on days 3-14. rice field. On days 22 and 28, all samples were below the limit of quantitation (LLOQ<1 ng/mL). In the second group, dexamethasone levels were below the limit of quantitation (LLOQ<1 ng/mL) at all time points post-surgery, except for one aqueous humor sample on day 22 from the left eye of rabbit #5317. It was detectable and ranged from 350 ng/mL on day 3 to 80 ng/mL on day 28.

[0555] Shown are area under the curve (AUC) analyzes for ketorolac (Figure 42) and dexamethasone (Figure 43) concentrations in the aqueous humor (AH). AUC curves provide an estimate of the cumulative release of drug within the eye over time. This in vivo release profile for ketorolac and/or dexamethasone resembles the general trend observed in vitro described hereinabove, with a sustained release of about 2 weeks for ketorolac and at least 4 weeks for dexamethasone. It is worth noting that Moreover, measurements of ketorolac and/or dexamethasone in the eye for at least 2 weeks are consistent with the persistence of the observed reduction in inflammation compared to vehicle shown in FIGS.

[0556] Conclusion
[0557] The pharmacokinetics of 150 μg ketorolac (eg, OcuRing-K) or 150 μg dexamethasone (eg, OcuRing-D)-loaded ophthalmic articles attached to IOLs implanted after cataract surgery in a rabbit model were evaluated. Phacoemulsification was performed bilaterally in two groups of animals. The first group received an ophthalmic article loaded with ketorolac μg attached to an IOL and the second group received an ophthalmic article loaded with dexamethasone 150 μg attached to an IOL.

[0558] Quantitation of ketorolac and dexamethasone in aqueous humor and plasma samples collected throughout the study showed that ketorolac in aqueous humor was detectable through day 14, while dexamethasone in aqueous humor was detectable at all time points examined through day 28. was found to be detectable in Plasma levels in either study were below the limit of quantification at all time points examined. Ocular examination showed slight inflammation peaking at day 22 in the first group with ketorolac treatment and day 14 in the second group with dexamethasone treatment. OE scores in the second group with the ophthalmic article with dexamethasone (eg, OcuRing-D) were consistently on average lower than the first group with Posterior capsule opacification scoring showed little or no difference between the first and second groups during the study described herein. No lens opacification was observed, indicating a lack of calcification during the duration of the study described herein. Drug levels released from ophthalmic article (eg, OcuRing-D or OcuRing-K) implants persisted in the aqueous humor for at least two weeks and were well tolerated in rabbits in both groups.

[0559] Example 27: Comparison of Ophthalmic Articles in a Topical Drug 90 Day Study
[0560] After cataract surgery, general treatment may include the use of topical anti-inflammatory drugs such as 0.1% dexamethasone eye drops. As noted herein above, non-adherence is a common drawback of such treatments (eg, eye drops). An ophthalmic article with time-release capability that can be implanted with an intraocular lens (IOL) during cataract surgery can eliminate non-adherence concerns. In a 90-day long-term study, the efficacy of ophthalmic articles disclosed herein was compared to a common topical drug (eg, 0.1 dexamethasone eye drops) in a rabbit model of cataract surgery. Four treatment groups were included in the study. Rabbits were randomly assigned to treatment groups. All rabbits underwent cataract surgery and IOL implantation. The first treatment group received an ophthalmic article (eg, OcuRing) in the IOL but no drug, and the first group represented the vehicle control group. A second treatment group received an ophthalmic article (eg, OcuRing) loaded with 150 μg of dexamethasone in the IOL. A third treatment group received the IOL only and a third group represented the IOL only control group. A fourth treatment group received tapered 0.1% dexamethasone eye drops over a period of 4 weeks. The study design is outlined in Table 9.

[0561]

[0562] Ocular examinations (OE) were performed in all rabbits at the predetermined time points described herein. The mean total OE scores for each treatment group on days 0, 1, 3, 7, 14, 21, 30, 60 and 90 are shown in FIG. Error bars represent standard error of the mean. The dash-dotted open circle 4401 represents the first treatment group or vehicle control group. A solid black filled square 4402 connected by a solid black line represents a second treatment group that received a dexamethasone-loaded ophthalmic article and an IOL. An empty downward pointing triangle 4403 connected by a dotted line represents the third treatment group or IOL only control group. A black solid upward-pointing triangle 4404 connected by a dash-dotted line represents the fourth treatment group that received 0.1% dexamethasone eye drops.

[0563] Posterior capsule opacification (PCO) was quantified using a modified Hackett and McDonald eye scoring system, reported as a PCO subscore. FIG. 45 shows post-surgery 0, 1, 3, 7, 14, 21, 30, 30, 30, 30, 30, 30, 30, 30, 30, 30, 4404 for first group 4401, second treatment group 4402, third group 4403, and fourth treatment group 4404. PCO subscores at 60 and 90 days are shown. PCO scores for all groups increased over the 90-day period. The second group, which received dexamethasone-loaded ophthalmic articles and IOLs, showed significantly lower PCO subscores compared to the other groups. Gompertz nonlinear regression was performed for all four groups. Analysis suggested that PCO growth rate was lowest for Group 2, followed by Groups 4, 3 and 1, respectively. The results of the Gompertz analysis are outlined in Table 10.

[0564]

[0565] The total OE score, assessed by the modified Hackett-McDonald scale, shown in Figure 46, provided an aggregated index of ocular inflammation and other abnormalities across all ocular tissues. Without wishing to be bound by theory, when individual subscores, such as PCO, become very high compared to other tissue scores, it identifies even smaller changes in these individual scores over time. can pose difficulties for Iris and anterior chamber (AC) inflammation subscores were combined and analyzed to better assess specific changes in inflammation within the anterior segment of the eye over the course of the 90-day study. The average combined iris-AC subscores through 90 days post-surgery are shown in FIG. show. Error bars represent standard error of the mean. A second group 4402 that received a dexamethasone-loaded ophthalmic article and an IOL had significantly lower combined iris/ AC subscores are indicated.

[0566] Intraocular pressure (IOP) was measured in all rabbits at days 0, 30, 60, and 90 (Figure 47). The dash-dotted open circle 4401 represents the first treatment group or vehicle control group. A solid black filled square 4402 connected by a solid black line represents a second treatment group that received a dexamethasone-loaded ophthalmic article and an IOL. An empty downward pointing triangle 4403 connected by a dotted line represents the third treatment group or IOL only control group. A black solid upward-pointing triangle 4404 connected by a dash-dotted line represents the fourth treatment group that received 0.1% dexamethasone eye drops. IOP levels were similar between all treatment groups.

[0567] Example 28: 28 Day Clinical Study
[0568] The efficacy and safety of the ophthalmic articles described herein (eg, OcuRing) were evaluated in an open-label, single-dose, 4-week long clinical study. In this study, five subjects received an ophthalmic article attached to an intraocular lens (IOL) after cataract surgery. The ophthalmic article (e.g., OcuRingK ketorolac) used in this study is a substantially small, bioerodible ring attached to an IOL (e.g., to the IOL's haptics) that provides 14 days post-surgical ketorolac ) resulted in a sustained release of Efficacy assessments of ophthalmic products (eg, OcuRing) included visual acuity, eye examination, and patient-reported symptoms. Safety evaluations of ophthalmic products (eg, OcuRing) include measuring intraocular pressure, corneal thickness, and recording the frequency of emergent adverse events of treatment.

[0569] Cataract surgery is one of the most common outpatient surgical procedures in the world. A cataract is a clouding of the lens that affects vision and is removed when the condition worsens to the point that it interferes with daily activities. The most common cataract extraction is via phacoemulsification followed by intraocular lens (IOL) implantation. Phacoemulsification may consist of making an incision on the side of the cornea and delivering ultrasound waves to break up the lens to allow removal by aspiration. The lens can then be replaced with an IOL. The most common side effects can be inflammation (pain, redness, and swelling) which, if left uncontrolled, can include pain, photophobia, visual impairment, corneal edema, cystoid macular edema, post-adhesion, uveal Can lead to inflammation and glaucoma. Pseudophakic cystoid macular edema (CME) is the most common cause of visual impairment after cataract surgery and is more common in subjects with increased postoperative inflammation. Other risks include retinal detachment, infection and hemorrhage.

[0570] Post-operative inflammation from cataract surgery is typically treated with topical corticosteroids, nonsteroidal anti-inflammatory drug (NDAID) eye drops, or a combination thereof. Corticosteroid eye drops are associated with increased risk of intraocular pressure (IOP) and impaired corneal healing and increased risk of corneal infection. NSAID eye drops cause pain, which can lead to poor drug tolerance. NSAID eye drops also impair corneal healing and carry the risk of corneal ulceration and perforation. Compliance with topical eye drops can be a common problem, especially for patients undergoing cataract surgery. This study was designed to evaluate the safety, biocompatibility and preliminary efficacy of an implanted ophthalmic article disclosed herein (eg, OcuRing-K) in patients undergoing cataract surgery.・It was an in-human clinical trial.

[0571] The purpose of the studies described herein were (i) preliminary results of implanted ophthalmic articles disclosed herein (e.g., OcuRing-K ketorolac) in patients undergoing cataract surgery. (ii) evaluating the utility of ophthalmic articles disclosed herein (e.g., OcuRing-K Ketorolac) in human cataract surgery; showing application of an ophthalmic article disclosed herein (e.g., OcuRing-K ketorolac) to an IOL that does not require modification; (iii) an ophthalmic article disclosed herein to an IOL (e.g., and (iv) ophthalmic articles disclosed herein (e.g., OcuRing-K ketorolac ) does not adversely affect the iris or lens capsularis or migrate to the anterior chamber.

Clinical study design
[0572] The study disclosed herein was designed as a single-arm, open-label study evaluation of the preliminary safety and efficacy of ophthalmic articles (e.g., OcuRing-K) in human subjects undergoing cataract surgery. did.

[0573] It is common practice for patients undergoing cataract surgery to receive both NSAIDs and steroid eye drops for the management of postoperative inflammation, but via ophthalmic products (eg, OcuRing-K). Inclusion of a topical steroid in addition to the drug (e.g., ketorolac) delivered to the eye of the subject may influence the outcome of the study or mask possible adverse events associated with the device and its polymeric components. I had concerns. Therefore, all patients received an ophthalmic product (eg, OcuRing-K) as monotherapy, and the protocol allowed the use of steroid eye drops as salvage therapy in events of uncontrolled inflammation. The subject's first eye to receive the ophthalmic article and IOL is referred to herein as the "study eye." The control second eye that did not receive the ophthalmic article and the IOL is referred to herein as the "companion eye."

[0574] Post-operative examinations were scheduled on days 1, 7 and 28 after surgery, as is customary after cataract surgery. Safety assessments were performed, including visual acuity, intraocular pressure and treatment emergent adverse events. Safety results are presented with descriptive statistics as described herein.

[0575] Anterior chamber cell (ACC) and post-operative pain scores were used as measures of efficacy for post-operative inflammation after cataract surgery. Data were collected for all patients at baseline (day 0) and days 1, 7, and 28 after surgery. As this was a single-arm study, statistical comparisons between groups were not possible.

[0576] Slit-lamp photographs and refraction data are also collected to assess the position of the ophthalmic article (eg, OcuRing-K) and IOL within the eye and to assess the location of the ophthalmic article (eg, OcuRing-K) on the IOL. ) affected the position or tilt of the IOL, or included adverse effects on the iris and adjacent tissues.

[0577] Efficacy endpoints were selected based on a registry study design from existing products approved for the treatment of post-operative inflammation after cataract surgery. Anterior chamber cell (ACC) scores were assessed using standardization of the Uveitis Nomenclature (SUN) scale. Pain scores were assessed using a 10-point visual analogue scale.

[0578]
A summary of the study design is presented in Table 11.
[0579]

[0580] Target
[0581] Subjects were screened within one month prior to scheduling cataract surgery. Subject eligibility was assessed based on medical and ophthalmic history, including the diagnostic tests described herein. Qualified subjects provided written informed consent to participate in the study.

[0582] Subjects described herein as patients were observed for 4 weeks after cataract surgery and monitored for safety and efficacy on days 1, 7 and 28 after surgery. A standard ophthalmologic examination procedure was performed on the subjects to assess any response to treatment. Evaluation included grading and scoring according to established rating scales described herein below. Curative therapy consisting of corticosteroid eye drops was available for all patients.

[0583] As there is no prior human data available for the ophthalmic articles disclosed herein, the sample size could not be estimated. A sample size of 5 participants was selected based on clinical and practical considerations. Descriptive statistics were used to tabulate and summarize study results.

[0584] Inclusion/Exclusion Criteria:
[0585] Inclusion Criteria
[0586] The criteria for admitting a subject to the clinical trial disclosed herein are subjects to undergo unilateral cataract extraction and monofocal intraocular lens (IOL) implantation, male or female ages 18-85 years and subjects willing and able to comply with protocol requirements. All subjects underwent a consent process and signed an approved informed consent form.

[0587] Exclusion Criteria Subjects must meet the following criteria: severe/major corneal pathology that could preclude study completion; any extraocular/intraocular inflammation in the study eye at the screening visit. (Blepharitis allowed if only mild and concomitant conjunctivitis and no lid erythema/edema) or ongoing, unresolved uveitis; ophthalmic surgery; scheduled surgery in a fellow eye within the study period; any medical history or clinical research study that may make the subject suitable for the study; anterior chamber inflammation measured by slit lamp examination at baseline; Any topical ophthalmic medication used in any eye, other than tear substitutes for dry eye, for at least 2 weeks prior to the line visit; current or within the past 5 years, successfully treated squamous cell or basal skin Has a history of malignancy other than cell carcinoma or successfully treated in situ cervical cancer; received oral corticosteroids within the past 14 days prior to the first visit or topical corticosteroids less than 48 hours prior to the first visit prescribed non-steroidal anti-inflammatory drugs (NSAIDs) or immunosuppressants whose dose is stable for 6 weeks and no change in medication is expected for the duration of the study; within the past 6 months prior to the first visit. of study eyes had received intravitreal or semi-tenone corticosteroid treatment; in study eyes, intraocular pressure (IOP) ≥25 mmHg at baseline, history of glaucoma, or requiring ocular antihypertensive medication known steroid intraocular pressure responders in any eye; and/or participation in another investigational device or drug study within 3 months prior to the study, they were excluded from the study. .

[0588] Treatment Taken
[0589] An ophthalmic article (eg, OcuRing-K) was attached to the IOL and administered to the subject during cataract surgery. All five subjects received a single-piece foldable hydrophobic acrylic IOL (eg, Alcon AcrySof IQ Monofocal IOL) commonly used in cataract surgery. An ophthalmic article (eg, OcuRing-K) was attached to the haptics of an intraocular lens (IOL) for implantation during cataract surgery. An ophthalmic article (eg, OcuRing) delivered a therapeutic dose (eg, a dose of 150 μg) ketorolac into the subject's eye for approximately 14 days after cataract surgery.

[0590] The ophthalmic articles described herein (eg, OcuRing-K) are made of soft, flexible materials that ensure standard cataract surgical techniques, and do not require specialized devices for implantation in the eye. and not. An ophthalmic article (eg, OcuRing-K) can be made from a biocompatible, biodegradable polymer that allows sustained release of ketorolac over a period of at least 14-21 days. The ophthalmic article used in this clinical study (eg, OcuRing-K) contained 12% ketorolac tromethamine and 88% poly(L-lactide-co-caprolactone) at a 60:40 ratio of L-lactide to caprolactone. contained. An ophthalmic article can be formed like an extruded ring of approximately 1.2 mm outer diameter, 0.6 mm hole or internal structure diameter and 0.5 mm cross-sectional thickness. In an illustrative embodiment, the ophthalmic articles used in this study were shaped like extruded rings with an outer diameter of approximately 1.25 mm, a hole or inner diameter of 0.65 mm and a cross-sectional thickness of 0.5 mm.

[0591] Ophthalmic articles (eg, OcuRing-K) were provided as single-use, sterile packages labeled with protocol number, name and address, manufacturing lot number, and instructions for use and storage. The drug delivery device (eg OcuRing-K) was refrigerated at about 2-8°C. On the day of surgery, drugs may be stored at room temperature (20-22° C.) for up to 3 hours, ready for use in the operating room.

[0592] Ketorolac is a non-steroidal anti-inflammatory (NSAID) medication with a long history of use in cataract surgery. Ketorolac is the active ingredient in several commercially available eye drop products (eg, Acular eye drops by Allergan, Omidria eye wash solution by Omeros Corporation). In addition, existing evidence suggests that ketorolac has the potential to reduce pain and inflammation after cataract surgery and to treat cystoid macular edema (CME) associated with cataract surgery. The selected dose of 150 μg ketorolac was based on a pre-nonclinical (eg, pre-clinical) study of the formulation in an animal model of cataract surgery (eg, a rabbit model of cataract surgery) disclosed herein.

[0593] An investigational ophthalmic article (eg, OcuRing-K) was designed to be administered intraoperatively with an IOL in cataract surgery. In the studies disclosed herein, an ophthalmic article (eg, OcuRing-K) was attached to the IOL just prior to implantation and they were implanted together inside the lens capsule of the subject's eye. Prior and concurrent therapy were not allowed in the studies disclosed herein. Due to the nature of the application of ophthalmic articles (eg, implanted in the eye) as opposed to other methods such as eye drops, subject non-compliance with eye drop use was not a concern in this study.

[0594] All of the diagnostic tests and procedures that accompany this study may generally be used in clinical practice and generally do not represent any risks present in standard of care for cataract surgery.
[0595] Benefits for Patients
[0596] The known safety and tolerability risks and compliance issues that can be associated with corticosteroid and NSAID eye drops are well known, as described herein. Elimination of the administration of topical anti-inflammatory eye drops from the postoperative treatment regimen may represent a clear efficacy and safety advantage for the patient. Furthermore, the potential for intraocular ketorolac treatment to reduce the risk of pseudophakic CME may be of further benefit, especially in high-risk patients with a history of diabetes and other chronic ocular inflammatory conditions.

[0597] Demographic Information and Other Baseline Characteristics
[0598] Due to the relatively small sample size (n=5), the age of the subjects did not follow the normal distribution. All subjects were of Spanish ethnicity and the study was conducted on site in Mexico.

[0599] Of the five subjects enrolled, three were females aged 77, 85 and 87 years with typical age-associated cataracts. A first female subject had nonexudative age-associated macular degeneration with geographic atrophy, a condition that can limit vision after cataract surgery. A second female subject has already been diagnosed with probable glaucoma with a collapse of her optic nerve. This condition also has the potential to limit vision after cataract surgery. Two other subjects, both men in their 40s, had juvenile cataracts. One of the male subjects had a history of diabetes, a known risk factor for juvenile cataracts. Other male subjects had a history of smoking and alcoholism, which also increased the risk of juvenile cataracts. A summary of subject demographics is provided in Table 12.

[0600]

[0601] A summary of all assessments and procedures performed at each study visit is provided in Table 13.
[0602]

[0603] The first visit included procedures performed within 30 days prior to surgery. Procedures include: obtaining informed consent; collecting demographic information; medical/ophthalmic history; assessing inclusion/exclusion criteria; blood chemistry), electrocardiogram (ECG) testing, vital signs, height, weight, measurement of best corrected visual acuity (BCVA), measurement of intraocular pressure, slit lamp examination, fundus examination, and/or for example and/or vision including assessment of ocular pain using a clinical analogue scale.

[0604] Laboratory tests include white blood cell (WBC) count, hemoglobin, hematocrit, platelet count, and/or red blood cell (RBC) with differentiation (neutrophils, lymphocytes, eosinophils, monocytes, basophils) Hematology including count; albumin, alkaline phosphatase (AP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), calcium, chloride, bicarbonate, creatinine, glucose, potassium serum chemistry profiles, including sodium, total bilirubin, and total protein; and/or female fertility, including urine pregnancy tests. If positive, serum βHCG was obtained to confirm the results. Any subject confirmed to be pregnant was excluded from the study.

[0605] A second visit was performed on the day of cataract surgery, and included an evaluation of adverse events, review of concomitant medications, measurement of cataract surgery vital signs, implantation of an ophthalmic article (e.g., Ocuring-K), and/or included surgical videos during surgery.

[0606] Visits 3 and 4 were performed on days 1 and 7 (± 1) after cataract surgery and included adverse event assessment, concurrent medication review, vital sign measurements, highest It included assessment of corrected visual acuity (BCVA), measurement of intraocular pressure, slit lamp examination, fundus examination, eg, visual analog scales for eye pain.

[0607] A fourth visit was performed 28 days (± 2) after cataract surgery, and included an evaluation of adverse events, a review of concurrent medications, measurement of vital signs, best corrected visual acuity (BCVA), intraocular pressure. measurement, slit lamp examination, fundus examination, assessment of eye pain using e.g. visual analogue scales, corneal topography using imaging devices (e.g. Pentacam), anterior partial optical coherence tomography (oct), and/or included slit lamp photographs.

[0608] Vital signs were measured after resting for at least 5 minutes, sitting systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), and/or core temperature. contained.

[0609] An adverse event (AE) is defined as any undesired event during his/her participation in this study, whether or not related to ophthalmic article and IOL implantation, in conjunction with drug use. , can be physical, psychological, or behavioral effects experienced by a subject. The occurrence of AEs was determined by subjects' non-directive questioning at each visit. AEs can be subjective or objective symptoms voluntarily reported by a subject and/or observed by an investigator or medical staff. AEs may also be changes in clinically relevant laboratory abnormalities assessed by investigators or medical staff and medical intervention initiated. The signs, symptoms, and/or laboratory abnormalities of the disease that existed prior to the use of the ophthalmic article either reappear after the subject recovers from the preexisting condition or, in the investigator's opinion, They cannot be considered post-treatment AEs unless their intensity or frequency can represent a clinically significant exacerbation. AEs were collected from the time the subject signed the informed consent form until study completion (eg, days 28-30 post-surgery). AEs reported prior to surgery/medication were captured and considered untreated emergency AEs. This included any laboratory AEs arising from laboratory tests performed during the first visit.

[0610] The severity of the AE is classified as mild, easily tolerated with awareness of signs or symptoms, and moderate, unpleasant enough to cause interference with normal activities, and/or Or serious and/or life-threatening classification was assessed based on criteria such as inability to work or perform normal activities, inability to live a normal life. Treatment emergent adverse events (TEAEs) were defined as AEs that occurred after the first dose of ophthalmic article, IOL, and/or drug during the study. Serious adverse events (SAEs) were defined as outcomes of the following: death, including death that could not be related to ophthalmic device implantation; life-threatening experience; patient hospitalization required or prolonged; , may include planned hospitalization, including elective treatment not associated with research and outpatient-based treatment, for phenomena that do not result in hospitalization; exceptions; prolonged or significant disability/incapacity; Any AE is defined as and/or a serious medical event that may not result in death, including immediate life-threatening consequences, or one that does not require hospitalization, based on medical judgment and that puts the patient at risk. It was considered an SAE if it was obtained and might require intervention to prevent one of the outcomes described herein above.

Efficacy analysis
[0611] Mean anterior chamber cell (ACC) and pain scores for all study visits are summarized in Table 14.

[0612]

[0613] Average anterior chamber cell (ACC) scores are shown in FIG. Post-operative inflammation was quantified by counting the number of cells in the anterior chamber within a 1×1 mm slit beam viewed through a slit-lamp biomicroscope, and the criteria for the uveitis nomenclature (SUN) scale shown in Table 15. was rated with Mean ACC scores on days 1 and 7 were 0.6 and 0.4 by the SUN scale, which is very slight inflammation. By day 28, no ACC was observed. All subjects were pain free at all post-operative visits.

[0614]

[0615] Figure 49 shows the pain scores for all subjects at 0 (baseline), 1, 7 and 28 days.
[0616] Conclusion
[0617] There were no treatment emergent adverse events related to study drug. All reported adverse events were expected based on the subject's ophthalmic history and receipt for cataract surgery. All adverse events were of mild grade and there were no serious adverse events (SAEs).

[0618] Observation during surgery
[0619] Cataract surgery was performed in all subjects without complications. Surgical videos were recorded for all subjects. An ophthalmic article (eg, OcuRing-K) was attached to the IOL and inserted using standard surgical techniques. In all cases, the IOL was located inside the lens capsule, and evidence that the presence of an ophthalmic article (e.g., OcuRing-K) affected the user's (e.g., surgeon's) ability to position the IOL. There was no.

[0620] Figures 50A-50D show an attached ophthalmic article 100 (e.g., The loading of an IOL 300 (eg Alcon AcrySof IQ Monofocal IOL SN60WF) with OcuRing-K) is described. Haptics 302 of IOL 300 with attached ophthalmic article 100 were captured with forceps 5005 (Fig. 50A) and then inserted behind injector cartridge 5003 (Fig. 50B). Plunger 5003 of injector 5001 advances IOL 300 with attached ophthalmic article 100 halfway through the injector cartridge, where IOL 300 and attached ophthalmic article 100 are folded inward toward the center of the eye. The IOL 300 appears partially curled with the leading haptics 302 of the IOL 300 (FIG. 50C). Further advancing the IOL 300 and attached ophthalmic article 100, they appear to be more fully curled with both IOL haptics folded inwards within the curled configuration of the IOL of the eye (FIG. 50D).

[0621] FIG. 51 illustrates surgical implantation of an IOL and attached ophthalmic article inside the eye of a human subject. The tip of the IOL injector cartridge 5101 is first inserted into the anterior chamber through a corneal incision (Fig. 51A). The injector tip 5101 is then advanced further through the pupil 5110 into the anterior opening of the capsular bag and the injector plunger 5003 is slowly advanced to deliver the IOL 300 and attached ophthalmic article to the capsular bag (FIG. 51B). After the IOL and attached ophthalmic article are fully delivered to the capsular bag, the plunger tip of the injector is used to position the IOL in the desired location and orientation (FIG. 51C). FIG. 51D shows the appearance of a correctly positioned IOL inside the capsular bag. Due to the constriction of the pupil, the ophthalmic article is not visible in this image, but by confirming its original shape and position on the IOL haptics, the surgeon still had visibility of the ophthalmic article during surgery. Please note that

[0622] Visual acuity, intraocular pressure and corneal thickness were used as safety measures after cataract surgery. The results of safety measures are shown in Tables 16, 17 and 18. All subjects experienced improvement in visual acuity from day 0 (baseline) to day 28. Some subjects experienced greater improvement in visual acuity than others. For example, subjects #4 and #5 reached 20/20 visual acuity by day 28.

[0623] Subjects #2 and #3 showed suboptimal visual acuity recovery. This may be explained by pre-existing ocular conditions not associated with cataracts that limited their vision. Subject #2 was diagnosed with suspected glaucoma based on her optic nerve depression. and Subject #3 had a prior diagnosis of geographic atrophy confirmed by optical coherence tomography (OCT). Suboptimal visual acuity recovery in these subjects may be explained by these pre-existing conditions.

[0624] Table 16 shows the results for changes in visual acuity from day 0 (baseline) to day 28. Visual acuity was measured using the LogMAR chart and quantified by the Snellen score.

[0625]

[0626] Table 17 shows the intraocular pressure (IOP) measurements for each subject on Days 0, 1, 7 and 28. All subjects maintained normal IOP for 28 days after surgery. A transient increase in IOP was observed on day 1, which may be common immediately following cataract surgery, with IOP measurements returning to baseline levels by day 7.

[0627]

[0628] Table 18 shows the corneal thickness measurements for each subject 28 days after surgery. Corneal thickness measurements are a common indicator of corneal health. Corneal endothelium damage from cataract surgery can be evidenced by an increase in corneal thickness. Corneal thickness measurements obtained on day 28 were normal for all subjects (Table 18).

[0629]

[0630] Slit lamp examinations were performed at all post-operative visits to assess the position of the ophthalmic article (eg, OcuRing-K) and IOL within each subject's study eye. Representative slit lamp photographs on day 28 are shown for the subjects (Figures 52A and 52B). The portion of ophthalmic article 100 attached to IOL 300 is visible at the pupillary edge of the eye located at gaze. The retroillumination study eye showed centralization of the IOL with no evidence of tilt (FIG. 52A) and no defect in iris illumination, indicating that the ophthalmic article (eg, OcuRing-K) is adequately iris and avoid contact, suggesting that it did not cause iris thinning. This is further supported by an image obtained with the eye in inferior temporal gaze (FIG. 52B), which shows the ophthalmic article (eg, OcuRing-K) 100 within the lens capsule, posterior to the iris. These findings were consistent for all subjects studied at all postoperative time points.

[0631] Ultrasound biomicroscopy (UBM) scans were obtained in 4 of 5 subjects at study completion. All UBM scans showed that the IOL was correctly centered on the visual axis with no significant tilt and no evidence of impingement of the ophthalmic article or IOL on the iris or other intraocular tissues. FIG. 29 is a typical UBM image showing ophthalmic article 100 positioned at the IOL haptics proximal to the optic portion of IOL 301 .

[0632] No safety issues were identified with ophthalmic articles (eg, OcuRing-K). All treatment emergent adverse events (TEAEs) were mild grade and expected for cataract surgery. An ophthalmic article (eg, OcuRing-K) and IOL device were correctly positioned in the study eye of all subjects.

[0633] Conclusion
[0634] The studies described herein provide preliminary evidence of the safety and efficacy of an implanted ophthalmic article (eg, OcuRing-K) in subjects for the treatment of post-operative inflammation in cataract surgery. Brought. All surgeries were performed using standard surgical techniques without complications. The physical presence of the ophthalmic article (eg, OcuRing-K) on the IOL did not affect the IOL insertion procedure or cause adverse effects in the eye after cataract surgery. Postoperative inflammatory response, as measured by anterior chamber cell score, was minimal for all subjects and resolved completely by day 28. All subjects were pain free throughout the postoperative period. No topical anti-inflammatory drugs (eg NSAIDs) were used and ophthalmic products (eg OcuRing-K) were administered as monotherapy.

[0635] There were no drug-related side effects observed, which is consistent with the known safety profile of other ophthalmic ketorolac formulations. The safety of ophthalmic articles (eg, OcuRing-K) was assessed by assessing possible side effects related to the physical properties of the device and/or its polymeric components. No side effects related to ophthalmic products (eg, OcuRing-K) were observed. Slit lamp examination showed that the ophthalmic article (eg, OcuRing-K) did not physically affect the IOL position and/or contact the iris in the subject's study eye. Furthermore, ketorolac had no evidence of "rebound" inflammation after being fully evaluated by day 14, an observation that supports the long-term efficacy of ophthalmic articles (e.g., OcuRing-K) and its polymeric components in human subjects. It can support biocompatibility.

[0636] Example 29: Glass transition temperature
[0637] Differential scanning calorimetry (DSC) was performed to determine the glass transition temperature of a disc-shaped polymer sample of approximately 23 mm diameter and 10 mm thickness, with a mass of approximately 4 g. Disk-shaped polymer samples contained poly(L-lactide-co-caprolactone) in a ratio of 60:40 with molecular weights of approximately 75-85 kDa. Experiments were performed using a TA Q2000 differential scanning calorimeter (DSC) heated at a rate of 10°C/min over a temperature range of -80 to 150°C. A DSC curve is shown in FIG. The glass transition temperature of the polymer can range from about -20°C to about 50°C, and in this embodiment the polymer had a glass transition temperature of about -16.94°C.

[0638] Example 30: Dynamic Mechanical Analysis Testing:
[0639] A dynamic mechanical analysis (DMA) study was performed to determine the mechanical properties of a disk-shaped polymer sample, approximately 23 mm in diameter and 10 mm in thickness, weighing approximately 4 g, which is approximately It contained a 60:40 ratio of poly(L-lactide-co-caprolactone) with a molecular weight (M _n ) of 85 kDa. Experiments were performed using a Q800 dynamic mechanical analyzer (DMA) manufactured by TA Instruments at 25° C. with a strain amplitude of 10 micrometers (μm) and a frequency range of 1 Hz to 200 Hz. DMA curves, including storage modulus curve 5401, loss modulus curve 5402, and tan delta curve 5403, are shown in FIG.

[0640]

[0641] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided for purposes of illustration only. It is not intended that the invention be limited by the specific examples provided within the specification. While the present invention has been described with reference to the foregoing specification, the descriptions and illustrations of the embodiments herein are not meant to be taken in a limiting sense. Numerous variations, modifications, and substitutions may occur to those skilled in the art without departing from the invention. Furthermore, it will be understood that all aspects of the present invention are not limited to the specific depictions, arrangements or relative proportions set forth herein which are dependent on various conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the invention. Accordingly, the invention is also intended to cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims (71)

a. a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer;
b. An ophthalmic article comprising an active agent or diagnostic agent, the ophthalmic article configured to bind to haptics of an intraocular lens (IOL). The ophthalmic article of claim 1, wherein said copolymer is derived from about 20% to about 60% by weight of said caprolactone monomer and about 40% to 80% by weight of said at least one other monomer. 3. The ophthalmic article of claim 1 or 2, wherein said copolymer is derived from about 40% by weight of said caprolactone monomer and about 60% by weight of said at least one other monomer. An ophthalmic article according to any one of the preceding claims, wherein the at least one other monomer is lactide, glycolide, or trimethylene carbonate. An ophthalmic article according to any one of the preceding claims, wherein the copolymer comprises a random copolymer. An ophthalmic article according to any one of the preceding claims, wherein the active agent is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. a. a biocompatible material;
b. an ophthalmic article comprising an active agent or diagnostic agent, the elasticity equivalent to another article comprising a biocompatible matrix comprising a copolymer derived from about 40% by weight caprolactone monomers and about 60% by weight lactide monomers; An ophthalmic article that is compressible, tensile strength, shape recoverable, or remoldable and configured to bond to the haptics of an intraocular lens (IOL). 8. The ophthalmic article of claim 7, wherein said another article comprising said biocompatible matrix has a tensile strength of at least about 0.5 megapascals (MPa). 9. The ophthalmic article of claim 7 or 8, wherein said another article comprising said biocompatible matrix has a glass transition temperature of at most about 24[deg.]C as measured by differential scanning calorimetry. An ophthalmic article according to any one of the preceding claims, wherein said another article comprising said biocompatible matrix has a glass transition temperature of about -20°C to 24°C as measured by differential scanning calorimetry. . 4. An ophthalmic article according to any one of the preceding claims, wherein said another article comprising said biocompatible matrix has a modulus of elasticity of at most about 3 MPa. An ophthalmic article according to any one of the preceding claims, wherein said another article comprising said biocompatible matrix has a modulus of elasticity between about 0.5 MPa and 3 MPa. An ophthalmic article according to any one of the preceding claims, wherein said another article comprising said biocompatible matrix has an elongation to break of at least about 100% measured at about 18°C to 24°C. An ophthalmic article according to any one of the preceding claims, wherein said another article comprising said biocompatible matrix has an elongation at break of about 500% to 1500% at about 18°C to 24°C. 10. An ophthalmic article according to any one of the preceding claims, comprising an internal structure for coupling around the haptics of the IOL. 16. The ophthalmic article of Claim 15, wherein the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the haptics of the IOL. a. (1) a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer; and (2) one or more ophthalmic articles comprising one or more active or diagnostic agents;
b. and one or more intraocular lenses (IOLs) containing one or more haptics, wherein the one or more ophthalmic articles are the one or more lenses of the IOLs. An ophthalmic delivery system coupled to haptics. 18. The ophthalmic delivery system of Claim 17, wherein about one of the one or more ophthalmic articles is associated with the one or more haptics of the IOL. 19. The ophthalmic delivery system of claim 17 or 18, wherein about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. 6. The copolymer of any one of the preceding claims, wherein the copolymer is derived from about 20% to about 60% by weight of the caprolactone monomer and about 40% to 80% by weight of the at least one other monomer. Ophthalmic delivery system. 4. The ophthalmic delivery system of any one of the preceding claims, wherein the copolymer is derived from about 40% by weight of the caprolactone monomer and about 60% by weight of the at least one other monomer. 10. The ophthalmic delivery system of any one of the preceding claims, wherein the at least one other monomer is lactide, glycolide, or trimethylene carbonate. 5. The ophthalmic delivery system of any one of the preceding claims, wherein the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. 10. The ophthalmic delivery system of any one of the preceding claims, wherein the one or more ophthalmic articles comprise an internal structure for coupling around the one or more haptics of the IOL. 25. The ophthalmic delivery system of claim 24, wherein the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics of the IOL. 1. A method of treating or preventing a disease comprising implanting an intraocular lens (IOL) for sustained intraocular drug delivery in the eye of a subject in need thereof, wherein the IOL is attached thereto. comprising one or more drug release articles, said one or more drug release articles comprising one or more active agents, and within 7 days after implantation, said one or more drug release articles comprising said Releases one or more active agents resulting in an inflammation score of at most 1 as measured by an anterior chamber cell score using slit-lamp biomicroscopy or by a 10-point visual analogue scale. how to get rid of eye pain. Within 7 days after implantation, the one or more drug-releasing articles released the one or more active agents as measured by an anterior chamber cell score using slit-lamp biomicroscopy. 27. The method of claim 26, wherein the inflammation score is at most 1. 10. Within 7 days after implantation, said one or more drug-releasing articles release said one or more active agents, resulting in a loss of eye pain as measured by a 10-point visual analogue scale. The method according to 26 or 27. 4. The method of any one of the preceding claims, wherein the one or more drug-releasing articles are associated with one or more haptics of the IOL. 30. The method of claim 29, wherein one of the one or more drug releasing articles is associated with one of the one or more haptics of the IOL. 30. The method of claim 29, wherein two of the one or more drug releasing articles are associated with one of the one or more haptics of the IOL. 4. The method of any one of the preceding claims, wherein the one or more drug release articles comprise a biocompatible matrix. 33. The method of claim 32, wherein the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight at least one other monomer. . The method of any one of the preceding claims, wherein said one or more drug release articles comprises between about 1 μg and 800 μg of said one or more active agents. 4. The method of any one of the preceding claims, wherein the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. 10. The method of any one of the preceding claims, wherein the subject is undergoing or has undergone concurrent ophthalmic surgery. 10. The method of any one of the preceding claims, wherein the subject is undergoing or has undergone concurrent cataract surgery. A method of preparing at least one active agent-releasing intraocular lens comprising:
(a) combining one or more active or diagnostic agents with a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer, thereby producing one or more ophthalmic articles; and
(b) coupling said one or more ophthalmic articles to one or more haptics of at least one intraocular lens (IOL). 39. The method of claim 38, wherein about one of the one or more ophthalmic articles is associated with one of the one or more haptics of the IOL. 40. The method of claim 38 or 39, wherein about two of the one or more ophthalmic articles are associated with one of the one or more haptics of the IOL. Any one of the preceding claims, wherein the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. The method described in section. 10. The method of any one of the preceding claims, wherein the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by a tensile test. 4. The method of any one of the preceding claims, wherein the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. 10. The method of any one of the preceding claims, wherein said coupling comprises an indirect coupling between said one or more ophthalmic articles and said one or more haptics. 4. The method of any one of the preceding claims, wherein the one or more ophthalmic articles comprise an internal structure for coupling around the one or more haptics. 46. The method of claim 45, wherein the perimeter or maximum width of the internal structure is less than or equal to the perimeter or maximum width of the one or more haptics. A method of administering an active or diagnostic agent comprising:
(a) compressing an intraocular lens (IOL) to which one or more ophthalmic articles are attached through an IOL injector comprising an injector tip inner diameter of about 0.5 mm to 3 mm, thereby compressing one or more ophthalmic producing a compressed IOL to which the articles are attached, wherein the one or more ophthalmic articles comprise one or more active agents or diagnostic agents;
(b) administering said compressed IOL having one or more ophthalmic articles associated with it to the eye of a subject in need of administration of the active agent or diagnostic agent for sustained intraocular active or diagnostic agent delivery; and embedding in the method. 48. The method of claim 47, wherein the one or more ophthalmic articles comprise a biocompatible matrix. 49. The method of claim 48, wherein the biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight at least one other monomer. . 50. The method of claim 48 or 49, wherein the biocompatible matrix is sufficiently compressible to be compatible with injection by an IOL injector containing an injector tip inner diameter of about 0.5mm to 3mm. 51. The method of any one of claims 48-50, wherein the one or more ophthalmic articles have a tensile strength of at least about 0.5 megapascals (MPa). 10. The method of any one of the preceding claims, wherein the one or more ophthalmic articles have a glass transition temperature of at most about 24[deg.]C as measured by differential scanning calorimetry. 3. The method of any one of the preceding claims, wherein the one or more ophthalmic articles have a modulus of elasticity of at most about 3 MPa. 10. The method of any one of the preceding claims, wherein the one or more ophthalmic articles have an elongation to break of at least about 100% as measured by a tensile test. 12. The method of any preceding claim, wherein said compressing comprises tubularly collapsing said IOL with said one or more ophthalmic articles coupled thereto through said IOL injector including said injector tip inner diameter of about 0.5 mm to 3 mm. A method according to any one of paragraphs. (1) a biocompatible matrix comprising a copolymer derived from a caprolactone monomer and at least one other monomer; and (2) one or more ophthalmic articles comprising one or more active or diagnostic agents. a container;
Kit including instructions for use. 57. The kit of claim 56, further comprising another container containing one or more intraocular lenses, each of said one or more intraocular lenses containing one or more haptics. 57. The kit of claim 56, wherein the container further comprises one or more intraocular lenses comprising one or more haptics associated with the one or more ophthalmic articles. 59. The kit of Claims 57 or 58, wherein one of said one or more ophthalmic articles is associated with said one or more haptics. 59. The kit of claim 57 or 58, wherein two of said one or more ophthalmic articles are associated with said one or more haptics. 6. The copolymer of any one of the preceding claims, wherein the copolymer is derived from about 20% to about 60% by weight of the caprolactone monomer and about 40% to 80% by weight of the at least one other monomer. kit. 4. The kit of any one of the preceding claims, wherein the one or more active agents is dexamethasone, ketorolac, diclofenac, moxifloxacin, travoprost, 5-fluorouracil, or methotrexate. 9. A kit according to any one of the preceding claims, further comprising one or more intraocular device injectors. A method of diagnosing an ocular disease or condition comprising administering to the eye of a subject in need thereof an intraocular lens (IOL) for delivering one or more diagnostic agents to the eye of the subject. wherein the IOL comprises one or more ophthalmic articles attached thereto, said one or more ophthalmic articles comprising a paramagnetic molecule, a fluorescent compound, a magnetic molecule, a radionuclide, an x-ray imaging agent, and a contrast agent. 65. The method of claim 64, further comprising capturing an image containing said one or more diagnostic agents indicative of said disease or condition. binding said one or more ophthalmic articles to one or more haptics of said IOL prior to administering said IOL having one or more ophthalmic articles bound thereto. 64 or 65. Prior to administering the IOL to which the one or more ophthalmic articles are attached, one or more diagnostic agents are combined with a biocompatible matrix to thereby bind the one or more ophthalmic articles. 9. A method according to any one of the preceding claims, comprising the step of generating. Prior to administering the IOL to which the one or more ophthalmic articles are attached, the IOL to which the one or more ophthalmic articles are attached is injected with an injector tip of about 0.5-3 mm. 10. The method of any one of the preceding claims, comprising compressing through an IOL injector that includes an inner diameter. 4. The method of any one of the preceding claims, wherein said one or more diagnostic agents is a fluorescent compound. 4. The method of any one of the preceding claims, wherein the one or more ophthalmic articles comprise a biocompatible copolymer matrix. 71. The method of claim 70, wherein said biocompatible matrix comprises a copolymer derived from about 20% to about 60% by weight caprolactone monomer and about 40% to 80% by weight of at least one other monomer. .

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