JP2020058915A - Intraocular delivery system and method - Google Patents

Abstract

To provide a suitable intraocular delivery system and method.SOLUTION: Described here are a system and a method for accessing Schlemm's canal and for delivering an ocular device, tool, or fluid composition therein. The ocular device may maintain the patency of Schlemm's canal without substantially interfering with transmural fluid flow across the canal. The fluid composition may be a viscoelastic fluid that is delivered into the canal to facilitate drainage of aqueous humor by disrupting the canal and surrounding trabecular capillary tissues. Some systems described here may be configured to cut or tear the trabecular meshwork with the body of an elongate member located within Schlemm's canal. Other tools for disrupting these tissues and minimally invasive methods for treating medical conditions associated with elevated intraocular pressure, including glaucoma, are also described.SELECTED DRAWING: Figure 25B

Description

  Described herein are systems and methods for accessing Schlemm's canal in the eye and delivering an ophthalmic device, instrument, or fluid composition therein. The ophthalmic device may maintain Schlemm's canal patency without significantly interfering with transmural, transluminal, circumferential, or longitudinal aqueous humor fluid flow across the canal. The resulting device can be used to disrupt the trabecular meshwork. The fluid composition may be a viscoelastic fluid that is delivered into the canal or aqueous humor collector channel to expand the canal, disrupt the wall of the proximal capillary network and the adjacent Schlemm's canal, and Facilitates drainage of aqueous humor by increasing aqueous humor permeability through / or trabecular tubule or transmural outflow tracts. Also described are minimally invasive methods for treating medical conditions associated with elevated intraocular pressure, including glaucoma.

  Glaucoma is a potentially blinding disease affecting more than 60 million people worldwide, or about 1-2% of the population. Glaucoma is typically characterized by elevated intraocular pressure. The increased pressure in the eye can cause irreversible damage to the optic nerve, which can lead to loss of vision and progress to blindness if left untreated. The consistent reduction of intraocular pressure can delay or stop the progressive loss of vision associated with glaucoma.

  Increased intraocular pressure is generally caused by suboptimal outflow or drainage of fluid (aqueous humor) from the eye. Aqueous humor or fluid is a clear, colorless fluid that is continuously replenished in the eye. After being produced by the ciliary body, aqueous humor eventually leaves the eye primarily through the trabecular meshwork. The trabecular meshwork is a circle around the eye at the anterior chamber angle or drainage angle, formed at the intersection between the peripheral iris or iris root, the anterior sclera or scleral cape, and the peripheral cornea. It extends in the circumferential direction. The trabecular meshwork flows outward into Schlemm's canal, which is a narrow circumferential passage that generally surrounds the outer boundary of the trabecular meshwork. An aqueous humor vein or collector channel that receives drained fluid is located around Schlemm's canal and extends radially from Schlemm's canal. A net drainage or outflow of aqueous humor results in decreased outflow capacity, reduced outflow through the canal of the trabecular meshwork and Schlemm's drainage device, increased episcleral venous pressure, and possibly increased aqueous humor production. Can be reduced as a result of Flow out of the eye may be limited by trabecular meshwork and / or obstruction or stenosis in Schlemm's canal and its collector channel.

  Glaucoma, pre-stage glaucoma, and ocular hypertension are currently by reducing intraocular pressure using one or more modalities, including medication, open surgery, laser surgery, cryosurgery, and other forms of surgery. Can be treated. Generally, medication and drug therapy are the first stage of therapy. If drug therapy is not effective enough, more invasive surgical treatments may be used. For example, standard incision procedures to reduce intraocular pressure are trabeculectomy or filtration surgery. This procedure involves creating a new drainage for the aqueous humor. Instead of natural drainage through the trabecular meshwork, a new drainage channel is created by removing a portion of the sclera and trabecular meshwork at the drainage angle. This creates an opening or passage between the anterior chamber and the subconjunctival space that is drained by the conjunctival blood vessels and lymphatics. The new opening can be coated with sclera and / or conjunctiva to create a new reservoir called a bleb, into which aqueous humor can drain. However, traditional trabeculectomy procedures carry both short-term and long-term risks. These risks include occlusion of the opening created by scarring or surgery through other mechanisms, hypotonia or abnormally low intraocular pressure, bleeding in the anterior chamber, intraocular infection or endophthalmitis. , Shallow anterior chamber angle, macular hypotonia, choroidal effusion, suprachoroidal hemorrhage, and others.

  One alternative is to implant a device in Schlemm's canal that either maintains the patency of the canal or assists in the anterior chamber to canal flow of aqueous humor. A variety of stents, shunts, catheters, and procedures have been devised for this purpose, and the ab-externo (from outside the eye) method is used to deliver the implant or catheter to Schlemm's canal. This placement method is invasive and typically long-term, requiring the creation of a tissue flap and a deep incision to access the canal. In addition, finding and accessing Schlemm's canal with this external dissection technique is common to many surgeons because the diameter of Schlemm's canal is small, eg, about 50-250 microns in cross-sectional diameter, and can be even smaller when crushed. Very difficult for One such procedure, ab externo angioplasty, involves creating a deep scleral incision and valve, locating Schlemm's canal, peeling off the roof, and catheterizing the entire 360 degrees of the canal from the outside of the eye, viscoelastic. It involves using material, circumferential tension sutures, or both to help maintain the patency of the canal. This procedure is extremely difficult and can take as long as 45 minutes to 2 hours. Although the long-term safety and efficacy of angioplasty is promising, the procedure remains surgically challenging and invasive.

  Another alternative is Viscocanalostomy, which involves injecting a viscoelastic solution into Schlemm's canal to dilate the canal and associated collector channels. Expansion of the canal and collector channels in this manner generally facilitates drainage of aqueous humor from the anterior chamber through the trabecular meshwork and Schlemm's canal and out of the natural trabecular tubule outflow tract. Biscocanalostomy is similar to tubeplasty (both invasive and ab externo), except that Biscocanalostomy does not involve suturing and does not restore all 360 degrees of the outflow facility. Some of the benefits of Biscocanarostomy are that it can avoid sudden drops in intraocular pressure, anterior chamber bleeding, hypotony, and flattening of the anterior chamber. The risk of cataract formation and infection can also be minimized due to reduced intraocular manipulation and complete ocular wall penetration, anterior chamber opening and superficial, and the absence of iridectomy. A further advantage of biscocanarostomy is that this procedure avoids the need for external filtration and its associated short-term and long-term risks in the majority of eyes by restoring a physiological outflow tract. Is. This makes the success of this procedure partially unrelated to conjunctival or episcleral scarring, which is the major cause of failure in traditional trabeculectomy procedures. Moreover, the absence of elevated filtration blebs avoids associated eye discomfort and potentially serious eye infections, and the procedure can be performed in any quarter of the outflow tract. .

  However, current Viscocanarostomy and angioplasty techniques allow access to Schlemm's canal by making a deep incision in the sclera, creating a scleral flap, and peeling the roof of Schlemm's canal. It is still highly invasive as it needs to be created. In their current form, both of these procedures are "ab externo" procedures. “Ab externo” generally means “from the outside”, which is inherently more invasive given the location of Schlemm's canal and the amount of tissue disruption required to access Schlemm's canal from the outside. Is. On the other hand, "ab-interno" means "from the inside" and is relatively invasive due to the reduced amount of tissue disruption required to access Schlemm's canal from the inside. It is a low technique. As a result, the Abinterno approach to Schlemm's canal provides the surgeon with easier access to the canal, while at the same time reducing the risk to the patient's eye and reducing patient morbidity. All of these lead to improved patient recovery and rehabilitation. The Biscokanarostomy and angioplasty procedures also remain difficult for the surgeon due to the difficulty of finding and accessing Schlemm's canal from the outside using deep dissection techniques due to the small diameter of Schlemm's canal. Is high. Yet a further drawback is that, at most, Viscocanalostomy extends Schlemm's canal, which is a 360-degree annulus-shaped outflow-like structure, to 60 degrees. The greater the canal expansion, the more total aqueous humor outflow can be restored.

  Therefore, it would be beneficial to have a system that uses the abinterno approach to provide easy and atraumatic access to Schlemm's canal for the delivery of intraocular devices, instruments, and compositions. It would also be useful to have a system for rapid delivery of devices, devices, and compositions to Schlemm's canal to reduce the time required for the procedure and the risk of infection without sacrificing the safety and accuracy of the delivery procedure. Ah Also, as a cataract and glaucoma surgery can both be accomplished during the same round of surgery using the exact same corneal or scleral incision, the device, instrument, and It would be useful to have a system for delivering fluid compositions to Schlemm's canal. Such incisions are relatively small, allowing for less invasive surgery and faster patient recovery. This technique allows access to Schlemm's canal from inside the eye through the trabecular meshwork and is called "abinterno". Using this system, in a minimally invasive ab-intern manner, the neighboring capillary network and the wall of the adjacent Schlemm's canal, also known as the inner wall of the Schlemm's canal, are effectively disrupted to patency the Schlemm's canal. Methods of delivering intraocular devices, devices, and compositions that maintain sex, increase outflow, reduce resistance to outflow, or effectively dilate the canal and / or its collector channels are also desirable. Will.

  Systems and methods for easy and reliable access to Schlemm's canal with minimal or reduced trauma, and systems and methods for delivering intraocular devices (eg, implants) therein are provided. Described in the specification. Other systems and methods may include no implants and / or treatments to improve flow through the trabecular tubule outflow system, which consists of trabecular meshwork, proximal tubule tissue, Schlemm's canal, and collector channels. Reliance on delivery and removal of an infusion (cutting) device and / or delivery of fluid composition to Schlemm's canal. When implanting an intraocular device, the intraocular device can maintain Schlemm's canal patency without significantly interfering with transmural fluid flow across the canal. Transmural flow or transmural aqueous flow begins at the outer wall of Schlemm's canal, continues from the anterior chamber through the trabecular meshwork to the lumen of Schlemm's canal, and along it along the lumen of Schlemm's canal. Flow, and is defined as the flow of aqueous humor that eventually enters the aqueous humor collector channel. When the fluid composition is delivered to the canal, the fluid composition to be delivered to the canal, for example, a viscoelastic fluid, expands the canal, making the trabecular meshwork and the inner wall of Schlemm's canal more permeable to aqueous humor. The collector channel can also be expanded to facilitate drainage of aqueous humor. When delivering a therapeutic device, the device expands the canal, expands the collector channel, disrupts or pulls the trabecular meshwork, disrupts or pulls the proximal tubule tissue, and tears the trabecular meshwork or the proximal tubule tissue. The drainage of aqueous humor may be facilitated by cutting or cutting, or by completely removing the trabecular meshwork or nearby tubule tissue. Any or all of these actions may reduce resistance to outflow, increase aqueous outflow and drainage, and reduce intraocular pressure.

  One of the beneficial features of the system may be a cannula configured with a distal bend that defines a radius of curvature, where the radius of curvature is distal to the cannula. Directly engages the bevel at the tip. However, in some variations, the system may include a straight cannula. The particular configuration of the handle of the system may also be useful. The handle can be sized and shaped for easy manipulation with one hand. Further, the handle can be designed for general purpose operation. "Universal" means that the handle is for both right and left hand use, for access to any quadrant of the eye, and for the cannula or elongate member in a clockwise fashion or Means being ergonomically configured for use in advancing Schlemm's canal in a counterclockwise fashion. Such a configuration can be easily activated in a first orientation (eg, for delivering implants, instruments, and / or fluids in a clockwise fashion) and easily activated in a second inverted orientation (eg, A drive assembly may be included to deliver implants, instruments, and / or fluids in a counterclockwise fashion. Such a configuration may allow the drive assembly to be activated with either the left or right hand, and may also allow the drive assembly to be used with either the left or right eye. . Alternatively, in some variations, the cannula itself may be rotated the required degree (eg, 180 degrees) to provide ambidextrous usability in either clockwise or counterclockwise forward direction.

  The intraocular delivery system described herein generally includes a dual-purpose handle having a grip portion and a housing having an inner end and a distal end. The cannula typically connects to and extends from the distal end of the housing. The cannula may include a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between the ends. The cannula may also be configured to include a body, a beveled distal tip, and a lumen extending from the proximal end through the distal tip. The bevel may directly engage the distal end of the curved portion of the cannula (ie, the bevel may directly engage the radius of curvature). The system may also generally include a drive assembly substantially contained within the housing that includes a gear that converts rotational movement into linear movement.

  If the intraocular device is to be implanted in Schlemm's canal, the system may further include a slidable positioning element having a proximal end and a distal end coaxially disposed within the lumen of the cannula. The distal end of the slidable locator element may comprise an engagement mechanism for intracanalally determining the position of the intraocular device, including manipulating the device. Exemplary engagement mechanisms that can be used include hooks, jaws, fasteners, forceps, or complementary mating elements for releasable attachment of intraocular devices.

  The system is configured to include a fluid assembly in the handle and an elongated member having a lumen coaxially disposed within the lumen of the cannula when the fluid composition is delivered to Schlemm's canal. Can be done. The fluid composition may be delivered through the distal end of the lumen of the elongate member or through openings spaced along the axial length of the elongate member. In addition, the fluid assembly may be coupled to a fill component configured to transfer the fluid composition to a reservoir at least partially defined by the assembly. Some variations of the system may have the fluid composition pre-filled in the reservoir. Exemplary fluid compositions include, but are not limited to, saline, pharmaceutical compounds, and viscoelastic fluids. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, or salts, derivatives or mixtures thereof. It may be beneficial to use sodium hyaluronate as a viscoelastic fluid. Some systems may be configured to deliver a therapeutic (cutting) device to Schlemm's canal without the delivery of implants or fluids. In these variations, the handle may or may not include a fluid reservoir, and the device may have various configurations for disrupting tissue. The exemplary system may include an elongate member with an atraumatic distal tip, the atraumatic distal tip configured to be advanced through Schlemm's canal, when the system is removed from the eye. The body of the elongate member is configured to tear or cut the trabecular meshwork.

  Methods for implanting an intraocular device within Schlemm's canal are also described. Using the intraocular delivery system disclosed herein, the method generally comprises the steps of creating an incision in the eye wall that provides access to the anterior chamber of the eye, the cannula of the system, and the incision. Through a portion of the anterior chamber and advanced into the trabecular meshwork to puncture the trabecular meshwork, cannula access Schlemm's canal, and implant the device within the canal. The cannula will typically comprise a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between these ends. A body; a distal tip having a bevel that directly engages the distal end of the curved portion of the cannula; and a lumen extending from the proximal end through the distal tip. A positioning element slidable within the lumen of the cannula may be used during the step of implanting the device within the canal. The device may be implanted to reduce intraocular pressure or to treat medical conditions such as glaucoma, pre-stage glaucoma, or ocular hypertension.

  Further described is a method for delivering a fluid composition to Schlemm's canal. Using the intraocular delivery system disclosed herein, the method generally comprises the steps of creating an incision in the wall of the eye that provides access to the anterior chamber of the eye, the cannula of the system passing through the incision. Delivering a fluid composition to Schlemm's canal using an elongate member having a step of advancing into the trabecular meshwork, cannulating Schlemm's canal, and a lumen and slidable within the lumen of the cannula. Including the step of performing. The cannula will typically comprise a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between these ends. A body; a distal tip having a bevel that directly engages the distal end of the curved portion of the cannula; and a lumen extending from the proximal end through the distal tip. The fluid composition may be delivered to Schlemm's canal through the distal end of the elongated member or through openings spaced along the axial length of the elongated member. Fluids such as saline and viscoelastic solutions can be delivered to the canal to expand the canal and collector channels and / or disrupt the inner wall of the proximal capillary network or Schlemm's canal to enhance aqueous humor permeability, It may reduce resistance to water outflow or increase aqueous outflow. Examples of viscoelastic solutions are solutions containing hyaluronic acid, chondroitin sulphate, cellulose, and their derivatives and mixtures. As mentioned above, it may be beneficial to use sodium hyaluronate as a viscoelastic solution. Also, a drug for treating glaucoma, a steroid, an anti-angiogenesis (for example, an anti-vascular endothelial growth factor (anti-VEGF) antibody and derivative), an anti-inflammatory drug, or an anti-fibrotic drug may be combined with a viscoelastic solution. Good. These drugs may also be delivered alone without a viscoelastic solution if desired.

  When delivering a fluid composition, the delivering step pressurizes the reservoir in an amount sufficient that retracting at least a portion of the gear (or reversing gear movement) forces the fluid composition through the lumen of the elongate member. As such, activating the drive assembly may be included. The fluid composition may be delivered to dilate Schlemm's canal. Fluid compositions may also be delivered to reduce intraocular pressure or to treat medical conditions such as glaucoma.

  The systems, devices, and methods described herein also use varying degrees of force to trabecular tubule tissue, eg, trabecular meshwork, proximal tubule tissue, Schlemm's wall of Schlemm's canal, in Schlemm's canal. The septum, obstruction or stenosis, and collector channels may be disrupted to improve drainage of aqueous humor, thereby reducing intraocular pressure and treating ocular conditions. The disruption force can deliver a disruption volume of viscoelastic fluid that can expand the canal and collector channels and pull trabecular meshwork in a non-implantable manner, such as delivering one or more disruption components at the distal end. It may be generated by advancing a disruption device, which may or may not be included above, such as a cannula, conduit, catheter, dilation probe, balloon, etc., or both. Depending on factors such as the type or severity of the condition being treated, disruption forces can partially cut, tear, pull, expand, destroy, or completely disrupt trabecular meshwork and / or nearby tubule tissue. May be generated and / or removed and may be adjusted by varying the volume of viscoelastic fluid delivered or by changing the instrument configuration, as discussed further below. .

  The viscoelastic fluid or aqueous humor may be delivered using an integrated system controlled by a single operator with one hand. Advancement of the disruption instrument may also be provided by an integrated system controlled by a single operator with one hand. "Integral" refers to a system for advancing an elongate member through at least a portion of Schlemm's canal, and in some cases, delivering a viscoelastic fluid, device, or implant into Schlemm's canal. Means to use. “Single operator control” means that all features of the system, such as cannula and elongate member and instrument advancement and storage, intraocular device delivery, fluid delivery, etc., can be performed by a single user. Means This may be separate from or independent of the forceps for advancing the delivery catheter into Schlemm's canal and / or the delivery catheter, and may be assisted by the assistant (singular) while the surgeon holds the delivery catheter during the procedure. In contrast to other systems that use a device containing a viscoelastic fluid, where multiple (or multiple) need to be attached to the delivery catheter. After delivery of the disrupted volume of fluid or device, an implant, eg, a helical support or skeleton, is advanced into the Schlemm's canal to maintain its patency, or energy is delivered to the Schlemm's canal and / or surroundings. The structure of the trabecular tubule tissue of may be modified.

  A single operator, one-handed control system for delivering fluid includes a cannula; an elongate member having a lumen, slidably disposed within the cannula and advanceable distally from the cannula; and a cannula. And a portion of the handle defines a fluid reservoir, the handle being operable with one hand to deliver fluid from the reservoir through the lumen of the elongate member.

  Alternatively, the system for delivering the viscoelastic fluid is a cannula; an elongate member having a lumen, slidably disposed within the cannula and advanceable distally from the cannula; a handle coupled to the cannula. And a linear gear moveable to advance fluid from the fluid reservoir through the lumen of the elongate member, a handle, a portion of which defines the fluid reservoir.

  A system for delivering a viscoelastic fluid also includes a dual-purpose handle having a proximal end and a distal end; a cannula extending from the distal end having a proximal portion and a distal portion; And a housing having an inner surface and upper and lower surfaces; and a wheeled drive assembly extending beyond the upper and lower surfaces of the housing. Such a system with a dual-purpose handle is for example a wheeled drive assembly comprising a rotating cannula that can rotate from left to right and a single wheel (rotary component) configured to slide an elongated member. It may further include a solid. Instead of wheels, buttons, slides, foot pedals, or electric mechanisms can also be configured to slide the elongate members.

  In all variations of the viscoelastic fluid delivery system, the elongate member may comprise a lumen, about 25 microns to about 1000 microns, about 25 microns to about 500 microns, about 50 microns to about 500 microns, about 150 microns. It may have an outer diameter ranging from about 500 microns, about 200 microns to about 500 microns, about 300 microns to about 500 microns, about 200 microns to about 250 microns, or about 180 microns to about 300 microns. In some examples, it may be beneficial for the elongate member to have an outer diameter of about 240 microns. The elongate member may also have a plurality of openings spaced along its axial length, or have a distal end with a cutout configured as a half tube.

  In addition to disrupting Schlemm's canal and surrounding trabecular tubule tissue using a disruption volume of viscoelastic fluid, the outer diameter of the elongated member may be sized to disrupt these tissues. For example, an elongate member having an outer diameter in the range of about 200 microns to about 500 microns can be beneficial for tissue disruption. In addition, the distal portion of the elongate member may include a disruption component, such as a tissue disruption notch, hook, barb, balloon, or combinations thereof. However, the system may include both features, i.e. deliver a disrupted volume of viscoelastic fluid and need not also have an elongated member sized for disruption. An elongate member configured for disruption of Schlemm's canal and surrounding tissue may be used alone to reduce intraocular pressure without delivering fluid. Such elongate members may or may not have a lumen. In some variations, the elongate member can be configured such that the body of the elongate member cuts or tears the trabecular meshwork when the system is removed from the eye. The elongate member may also be configured to include a balloon or be inflatable or expandable to a size that disrupts tissue as it advances.

  The handle of the viscoelastic fluid delivery system described herein can include a drive assembly that can cause delivery of fluid from the reservoir through the lumen of the elongate member. The drive assembly may be a wheeled drive assembly that includes one rotary component or multiple rotary components. The reservoir may be pre-filled with the viscoelastic fluid. Exemplary viscoelastic fluids can include hyaluronic acid, chondroitin sulfate, cellulose, polymers, or salts, derivatives, or mixtures thereof. It may be beneficial to use sodium hyaluronate as a viscoelastic fluid.

  In some examples, a system for introducing a fluid composition described herein into Schlemm's canal may include a housing, a cannula, a flexible elongate member, a reservoir, and a drive assembly. The cannula may be attached to the distal end of the housing and may include a distal tip. The flexible elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The reservoir may comprise a fluid composition and the reservoir may be in fluid communication with the lumen of the flexible elongate member. The drive assembly may be configured to move the flexible elongate member from the extended position to the stored position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible elongate member. In some variations, the system may further include a lock configured to resist movement of the reservoir relative to the housing. In some examples, the system can be configured to prevent movement of the flexible elongate member toward the extended position after the flexible elongate member has been stored at a certain cumulative distance. In some of these examples, the constant cumulative distance may be about 40 mm.

  In some examples, the drive assembly may include a linear gear. Translation of the linear gear in the first direction may cause the flexible elongate member to move toward the storage configuration and deliver the fluid composition from the reservoir through the lumen of the elongate member. In some of these examples, translation of the linear gear in the second direction may cause the flexible elongate member to move toward the extended configuration. The volume of fluid composition delivered from the reservoir may correspond to the distance of travel of the flexible polymeric elongate member toward the extended configuration. In some variations, the drive assembly may further comprise a rotary component, rotation of which may cause translation of the linear gear. In some examples, the volume of fluid composition delivered from the reservoir may correspond to the translational distance of the linear gear in the first direction.

  Also described herein is a device for introducing a fluid composition into Schlemm's canal. The device may include a housing, a reservoir, a flexible polymeric elongate member, and a drive assembly. The reservoir may hold the fluid composition and may be located within the housing. The flexible polymeric elongate member may include a lumen in fluid communication with the reservoir. The drive assembly delivers a volume of fluid composition from the reservoir to Schlemm's canal via the lumen of the flexible polymer elongate member and the flexible polymer elongate member relative to the housing. It may be configured to translate at a distance. The volume of fluid composition delivered may be constant for the distance translated by the flexible elongate member. In some variations, the drive assembly may comprise rotating wheels, where the volume of fluid composition delivered and the distance translated by the flexible polymeric elongate member are relative to the amount of wheel rotation. Can be constant.

  Non-implantation methods for treating ocular conditions include advancing an elongate member filled with a volume of viscoelastic fluid into Schlemm's canal and sufficient viscoelastic to dissect trabecular tubule tissue. Delivering to the Schlemm's canal in volume to reduce intraocular pressure. However, non-implantation methods for treating ocular conditions need not necessarily include delivery of viscoelastic fluids. In these examples, the method may include advancing the elongate member into Schlemm's canal, wherein the elongate member has a diameter of about 200 to about 500 microns, and advancing, storing, the elongate member into Schlemm's canal. Alternatively, the ablation severes the trabecular tubule tissue sufficiently to reduce intraocular pressure. In some examples, the method can include removing the system from the eye, and then cutting or tearing the trabecular meshwork with the body of the elongate member.

  Another method for treating an ocular condition may be a single operator's one-handed method for introducing viscoelastic fluid into Schlemm's canal, where an elongate member filled with a volume of viscoelastic fluid is placed in Schlemm's canal. And advancing the viscoelastic fluid into Schlemm's canal, delivering the volume of viscoelastic fluid is accomplished by a one-handed system used by a single operator.

  When delivering a viscoelastic fluid by the methods described herein, the disruption volume can be about 2 μl (microliter) to about 16 μl (microliter), or about 2 μl to about 8 μl. In some variations of the method, the volume of fluid capable of disrupting trabecular tubule tissue is about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 9 μl. 10 μl, about 11 μl, about 12 μl, 13 μl, about 14 μl, about 15 μl, or about 16 μl. In certain instances, it may be beneficial to deliver a volume of about 4 μl of viscoelastic fluid. In yet a further variation, the volume of fluid delivered is in the range of about 1 μl per 360 degrees canal to about 50 μl per 360 degrees canal. In yet a further variation, the volume of fluid delivered is in the range of about 0.5 μl per 360 degrees canal to about 500 μl per 360 degrees canal. The viscoelastic fluid may be used to withdraw a slender member from the Schlemm's canal while advancing the slender member of a system controlled by a single operator from Schlemm's canal, clockwise, counterclockwise, or both. In between, it may be delivered. The volume of viscoelastic fluid delivered may be constant with respect to the distance the elongate member travels, and the viscoelastic fluid may be as far as Schlemm's canal as the elongate member advances around the canal. , May be delivered. As mentioned above, viscoelastic fluid may be delivered to disrupt Schlemm's canal and surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid may expand Schlemm's canal, increase the porosity of the trabecular meshwork, pull the trabecular meshwork, form tiny tears or perforations in nearby tubule tissue, remove the septum from Schlemm's canal, The disruption may be caused by expanding the collector channel, or a combination thereof. Initiation of an ophthalmic procedure so that a single operator can operate the system using one hand (eg, advance and retract the elongate member or any associated instrument) and deliver fluid to the trabecular tubule tissue. Sometimes the elongated member may be filled with a viscoelastic fluid.

  The method includes the elongate member surrounding a 360 degree arc of Schlemm's canal, a 180 degree arc of Schlemm's canal, a 90 degree arc of Schlemm's canal, or another degree of arc (eg, a 5 degree arc to a 360 degree arc). (Around an arc). Advancement may occur from a single access point in Schlemm's canal or from multiple access points in the canal. The disclosed methods can also be used to treat various conditions including, but not limited to, glaucoma, pre-stage glaucoma, and ocular hypertension.

  Also disclosed is a method for abnotinotravectomy and goniotomy using the systems and steps disclosed herein, which advances a cannula at least partially through the anterior chamber of the eye, Entry into Schlemm's canal at a single access point using a cannula and disrupting Schlemm's canal and surrounding trabecular tubule tissue to provide a sufficient volume of viscoelastic fluid to reduce intraocular pressure; Delivering through the lumen of an elongate member slidable within and extendable from the cannula. Another method that may be useful in treating an eye condition is to enter Schlemm's canal using an elongate member that is extendable from a single operator-controlled handle that includes a fluid reservoir; Delivering a volume of viscoelastic fluid from the fluid reservoir through the lumen of the elongate member by increasing the pressure in the reservoir, the volume of the delivered viscoelastic fluid comprising: It is sufficient to disrupt the structure of the tissue and reduce intraocular pressure. Other methods for ab innotravectomy and goniotomy can include cutting, tearing, and / or removing the trabecular meshwork without delivering viscoelastic fluid. Such methods may use elongate members configured to mechanically tear or cut and remove the trabecular meshwork. In some methods, the elongate member is configured to mechanically tear or cut the trabecular meshwork when the delivery system is removed from the eye after advancing the elongate member into Schlemm's canal. Alternatively, the elongate member may comprise a larger diameter, cutting feature, and / or instrument along or at the distal portion of the elongate member. For example, if the trabecular meshwork is cut and removed, the conduit may pull the resected tissue back into the cannula during storage.

  A method for treating an ocular condition described herein can include advancing an elongate member into Schlemm's canal and retracting the elongate member. The elongate member may comprise a lumen having a distal opening at the distal tip of the elongate member, the storing of the elongate member simultaneously delivering the fluid composition from the distal opening of the lumen. including. In some variations, storing the elongate member and delivering the fluid composition may both be triggered by rotation of the wheels. In some examples, the elongate member may be advanced a first length about Schlemm's canal and the fluid composition may be delivered about the same about Schlemm's canal at a first length. In some of the methods described herein, the elongate member may be advanced about the Schlemm's canal about 180 degrees in a first direction. Some of these methods include advancing the elongate member 180 degrees about Schlemm's canal in a second direction and retracting the elongate member while simultaneously allowing the fluid composition to exit the lumen at the distal opening. It may further include delivering.

  In some variations, a device comprising a reservoir, a plunger having a lumen and a proximal end, and a flexible elongate member having a lumen is used to deliver a fluid composition to Schlemm's canal. The method described herein for the reservoir to be in fluid communication with the lumen of the flexible elongate member through the lumen of the plunger, the proximal end of the plunger being slidably positioned within the reservoir, Moving the proximal end of the plunger proximally within the reservoir from the extended position to a depressed position within the reservoir, thereby causing the plunger to displace the fluid composition from the reservoir. The displaced fluid composition may move through the lumen of the plunger and into the lumen of the flexible elongate member.

  In another variation, a drive comprising a housing and a first wheel having a portion extending from a first side of the housing and a second wheel having a portion extending from a second side of the housing. The present specification for treating an ocular condition using a delivery system comprising a mechanism, a cannula extending from a distal end of a housing, and a slidable elongate member slidably positioned within the cannula. Can be slidable by cannulating the trabecular meshwork of the eye and proximally displacing a portion of a first wheel extending from a first side of the housing. Extending an elongate member distally from a retracted position within the cannula such that it advances about Schlemm's canal in a first direction; and a first member extending from a first side of the housing. Sliding slender part that moves a part of the wheel distally It may include a storing back proximally into storage position. In some variations, moving the portion of the first wheel extending from the first side of the housing distally can also deliver the fluid composition to Schlemm's canal. In some examples, the method moves proximally a portion of a second wheel extending from a second side of the housing to cause the slidable elongate member to move in a second direction. Extending distally from a retracted position within the cannula to advance about the Schlemm's canal and moving a portion of a second wheel extending from a second side of the housing distally. And retracting the slidable elongate member proximally back to the stowed position for stowage. In some examples, distally moving a portion of a second wheel extending from the second side of the housing may also deliver the fluid composition to Schlemm's canal.

  A device comprising a cannula, a flexible instrument slidable within the cannula between a retracted position and an extended position within the cannula, and a drive assembly is used to disrupt the trabecular meshwork of the eye. Methods include: advancing a cannula into the anterior chamber through a corneal or scleral incision, cannulating the trabecular meshwork of the eye, extending a flexible device from a retracted position to an extended position. And retracting the cannula from the anterior chamber without retracting the flexible device. The drive assembly may be configured to advance the flexible instrument a first maximum distance without retracting and limit cumulative cumulative advancement of the flexible instrument to a maximum total distance. . In some variations, the first maximum distance may be 15 mm to 25 mm and the maximum total distance may be 35 mm to 45 mm.

  In some variations, the trabecular of the eye using a device that includes a cannula and a body and a flexible instrument slidable within the cannula between a retracted position and an extended position within the cannula. Methods for severing the omentum include advancing the cannula into the anterior chamber through a corneal or scleral incision, piercing the trabecular meshwork of the eye with the distal tip of the cannula, and placing the flexible device from the retracted position. It may include extending to the extended position and progressively tearing the trabecular meshwork by the body of the flexible instrument from the proximal end of the body to the distal end of the body.

  The kits described herein may include a first device and a second device. The first device may include a housing, a cannula, a flexible polymeric elongate member, a reservoir, and a drive assembly. The cannula may be attached to the distal end of the housing and may include a distal tip. The flexible polymeric elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The reservoir may comprise the fluid composition and the reservoir may be in fluid communication with the lumen of the flexible polymeric elongate member. The drive assembly may be configured to move the flexible polymer elongate member from the extended position to the stored position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible polymer elongate member. .

  The second device may also include a housing, a cannula, a flexible polymer elongate member, and a drive assembly. The cannula may be attached to the distal end of the housing and may include a distal tip. The flexible polymer elongate member may include a lumen and a distal end. The distal end may be slidable within the cannula between a retracted position and an extended position, the distal end being within the cannula in the retracted position and distal of the cannula in the extended position. It can be distal to the tip. The drive assembly may be configured to move the flexible polymer elongate member from the extended position to the retracted position. The second device may not have a reservoir.

  In some variations, the kits described herein may include a device and tray. The device may include a housing, a cannula, and a flexible polymeric elongate member. The cannula may be attached to the distal end of the housing and may include a distal tip. The flexible polymeric elongate member may include a lumen and a distal end, which may be slidable within the cannula between a retracted position and an extended position. The distal end may be within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position. The tray may be configured to removably receive the device. The tray may include a first set of pinch points and a second set of pinch points, and the cannula may not contact the tray when the device is in the tray.

  In some examples, the device may further comprise a drive assembly, which may be configured to advance the flexible polymeric elongate member a first maximum distance without retracting. The device may be configured to limit the cumulative advancement of the flexible polymer elongate member to a maximum total distance. In some of these examples, the first maximum distance may be 15 mm to 25 mm and the maximum total distance may be 35 mm to 45 mm.

  Described herein are methods of making a cannula for accessing Schlemm's canal. The method can include creating a bevel at the distal tip of the cannula, sharpening the cannula, and smoothing a portion of the cannula. The distal tip of the cannula may include an inner peripheral edge and an outer peripheral edge, and the cannula may include a lumen therethrough. The bevel may traverse the lumen and by creating the bevel the proximal and distal ends of the distal tip may be created. Sharpening the cannula can include sharpening the distal end of the distal tip of the cannula to create a sharp piercing tip. Smoothing a portion of the cannula may include smoothing a portion of the inner or outer peripheral edge. In some variations, the cannula may comprise a subcutaneous tube made of stainless steel, nitinol, or titanium.

  In some variations, sharpening the distal end of the distal tip can include sharpening a portion of the outer surface and / or a portion of the outer periphery of the cannula. In some variations, the pointed piercing tip can be configured to pierce the trabecular meshwork of the eye. In some examples, the pointed piercing tip may comprise two beveled surfaces. In some of these examples, the angle between the two ramps may be 50-100 degrees.

  In some examples, smoothing the inner peripheral edge or a portion of the outer peripheral edge can include smoothing the inner peripheral edge at the proximal end of the distal tip. In some variations, smoothing a portion of the inner or outer peripheral edge can include smoothing the outer peripheral edge at the proximal end of the distal tip. In some examples, smoothing a portion of the inner or outer perimeter may include smoothing both the inner and outer perimeters at the proximal end of the distal tip. In some variations, smoothing a portion of the inner or outer edge may include smoothing the inner edge at the proximal end of the distal tip. In some examples, smoothing the inner peripheral edge or a portion of the outer peripheral edge can include smoothing the entire inner peripheral edge and the outer peripheral edge at the proximal end of the distal tip. In some of these variations or examples, smoothing may include abrasively ejecting the soda medium.

  In some variations, the manufacturing method may further include applying a protective cover to the sharpened piercing tip prior to the smoothing step. In these variations, the pointed piercing tip may comprise a bevel, which may be covered by a protective cover.

  In some examples, the manufacturing method may further include polishing the distal tip. In some of these examples, polishing may include electropolishing. In some variations, the method can further include passivating the cannula. In some of these variations, passivation can remove iron oxide from the cannula. In addition, in some of these variations, passivation may include acid passivation. In some examples, the method can further include roughening at least a portion of the cannula that is proximal to the distal tip. In some of these examples, roughening may include abrading the soda medium.

  In a variation of the manufacturing method described herein, the method may further include cutting the cannula to a length of 50 mm to 70 mm. In some of these variations, cutting the cannula may include cutting the cannula to a length of 60 mm.

  In some examples, the manufacturing method can further include bending the distal portion of the cannula along the longitudinal axis of the cannula. In some of these examples, bending the distal portion of the cannula can include bending the distal portion to an angle of 100 degrees to 125 degrees. In some of these examples, bending the distal portion of the cannula can include bending the distal portion to an angle of 118 degrees.

In some variations, a method of manufacturing a cannula for accessing Schlemm's canal includes cutting the cannula to a working length, roughening the outer surface of the cannula, and creating a bevel at the distal tip of the cannula. Sharpening the distal end of the distal tip, applying a protective cover, smoothing a portion of the cannula, bending the cannula, electropolishing the cannula, and passivating the cannula. May be included. In some variations, the cannula may comprise a proximal portion, a central portion, a distal portion and a lumen therethrough, the distal portion may comprise a distal tip. In some examples, hardening the outer surface of the cannula may include roughening the outer surface of the central portion of the cannula. In some variations, the distal tip of the cannula may include an inner peripheral edge and an outer peripheral edge, and the cannula may include a lumen therethrough. In some examples, the bevel may traverse the lumen and creating the bevel may create the proximal and distal ends of the distal tip. In some variations, sharpening the distal end of the distal tip may further sharpen the distal end of the distal tip, creating a sharp piercing tip. In some examples, applying the protective cover may include applying the protective cover to a sharp piercing tip, and smoothing a portion of the cannula may result in a portion of the inner or outer peripheral edge. It may include smoothing. In some variations, bending the cannula can include bending the distal portion of the cannula along the longitudinal axis of the cannula, and electropolishing the cannula electropolishing the distal tip. May be included. In some examples, passivating the cannula may include passivating the cannula with an acid.
The present invention provides the following, for example.
(Item 1)
A system for introducing a fluid composition into Schlemm's canal, comprising:
Housing,
A cannula attached to the distal end of the housing and comprising a distal tip;
A flexible elongate member having a lumen and a distal end, the distal end slidable within the cannula between a retracted position and an extended position, the distal end comprising: A flexible elongate member within the cannula in the retracted position and distal to the distal tip of the cannula in the extended position;
A reservoir containing a fluid composition, the reservoir being in fluid communication with the lumen of the flexible elongate member;
Configured to move the flexible elongate member from the extended position to the stored position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible elongate member. A drive assembly, the system comprising:
(Item 2)
The system of claim 1, further comprising a lock configured to resist movement of the reservoir relative to the housing.
(Item 3)
The drive assembly comprises a linear gear, translation of the linear gear in a first direction causes the flexible elongate member to move toward the storage configuration and the fluid composition from the reservoir to the flexible configuration. The system of item 1 delivering through the lumen of a flexible elongate member.
(Item 4)
The system of paragraph 3, wherein translation of the linear gear in a second direction moves the flexible polymer elongate member toward the extended configuration.
(Item 5)
The system of claim 3, wherein the drive assembly further comprises a rotary component, wherein rotation of the rotary component causes translation of the linear gear.
(Item 6)
The system of paragraph 3, wherein the volume of fluid composition delivered from the reservoir corresponds to the distance of translation of the linear gear in the first direction.
(Item 7)
The system of claim 4, wherein the volume of fluid composition delivered from the reservoir corresponds to the distance of travel of the flexible elongate member toward the extended configuration.
(Item 8)
Item 1. The device is configured to prevent movement of the flexible polymeric elongate member toward the extended position after the flexible elongate member has been stored at a cumulative distance. The system described in.
(Item 9)
The system of claim 8 wherein the constant cumulative distance is about 40 mm.
(Item 10)
A system for introducing a fluid composition into Schlemm's canal, comprising:
Housing,
A reservoir for holding the fluid composition located within the housing;
A flexible polymeric elongate member having a lumen in fluid communication with the reservoir and a volume of fluid composition from the reservoir to Schlemm's canal via the lumen of the flexible polymeric elongate member. And a drive assembly configured to translate the flexible polymer elongate member at a distance relative to the housing.
The system wherein the volume of fluid composition delivered is constant with respect to the distance translated by the flexible polymeric elongate member.
(Item 11)
The drive assembly comprises a rotatable wheel, the volume of fluid composition delivered and the distance translated by the flexible polymeric elongate member being constant with respect to the amount of rotation of the wheel. Item 10. The system according to Item 10.
(Item 12)
A method for treating an eye condition comprising:
Advancing an elongate member into Schlemm's canal, the elongate member comprising a lumen having a distal opening at a distal tip of the elongate member;
Storing the elongate member while simultaneously delivering a fluid composition from the distal opening of the lumen.
(Item 13)
13. The method of item 12, wherein both storage of the elongate member and delivery of the fluid composition are triggered by wheel rotation.
(Item 14)
13. The method of item 12, wherein the elongate member is advanced about the Schlemm's canal for a first length and the fluid composition is delivered about the Schlemm's canal for the same first length.
(Item 15)
13. The method of item 12, wherein the elongate member advances about 180 degrees around Schlemm's canal in a first direction.
(Item 16)
Advancing the elongate member about 180 degrees around Schlemm's canal in a second direction;
16. The method of item 15, further comprising retracting the elongate member while simultaneously delivering a fluid composition from the distal opening of the lumen.
(Item 17)
A method for delivering a fluid composition to Schlemm's canal using a device comprising a reservoir, a plunger having a lumen and a proximal end, and a flexible elongate member having a lumen. , The reservoir is in fluid communication with the lumen of the flexible elongate member via the lumen of the plunger, the proximal end of the plunger being slidably positioned within the reservoir. ,
Moving the proximal end of the plunger proximally within the reservoir from an extended position to a depressed position within the reservoir such that the plunger displaces the fluid composition from the reservoir. Including that,
The method wherein the displaced fluid composition moves through the lumen of the plunger and into the lumen of the flexible elongate member.
(Item 18)
A drive mechanism comprising a housing and a first wheel having a portion extending from a first side of the housing and a second wheel having a portion extending from a second side of the housing; A method for treating an ocular condition using a delivery system comprising a cannula extending from the distal end of the housing and a slidable elongate member slidably positioned within the cannula. And
Puncturing the trabecular meshwork of the eye with the cannula,
The portion of the first wheel extending from the first side of the housing is moved proximally to move the slidable elongate member around the Schlemm's canal in a first direction. Extending distally from a retracted position within the cannula to advance;
The portion of the first wheel extending from the first side of the housing is moved distally to retract the slidable elongate member proximally back to the retracted position for storage. Comprising:
(Item 19)
19. The method of item 18, wherein moving the portion of the first wheel extending from the first side of the housing distally also delivers a fluid composition to Schlemm's canal.
(Item 20)
Moving the portion of the second wheel extending from the second side of the housing proximally causes the slidable elongate member to move in a second direction about the Schlemm's canal. Extending distally from the stored position within the cannula to advance;
Moving the portion of the second wheel extending from the second side of the housing distally to retract the slidable elongate member proximally back to the retracted position for storage. 19. The method of item 18, further comprising:
(Item 21)
21. The method of item 20, wherein moving distally the portion of the second wheel extending from the second side of the housing also delivers a fluid composition to Schlemm's canal.
(Item 22)
A trabecular meshwork of the eye using a device comprising a cannula and a flexible instrument slidable within the cannula between a retracted position and an extended position within the cannula and a drive assembly. Is a method for dividing
Advancing the cannula into the anterior chamber through a corneal or scleral incision;
Puncturing the trabecular meshwork of the eye with the cannula,
Extending the flexible device from the stored position to the extended position;
Retracting the cannula from the anterior chamber without retracting the flexible device;
The drive assembly is configured to advance the flexible instrument a first maximum distance without retracting and limit the cumulative advancement of the flexible instrument to a maximum total distance. The method as described above.
(Item 23)
23. The method according to item 22, wherein the first maximum distance is 15 mm to 25 mm and the maximum total distance is 35 mm to 45 mm.
(Item 24)
A trabecular meshwork of the eye using a device comprising a cannula and a torso and a flexible instrument slidable within the cannula between a retracted position and an extended position within the cannula. Is a method for dividing
Advancing the cannula into the anterior chamber through a corneal or scleral incision;
Puncturing the trabecular meshwork of the eye with the distal tip of the cannula;
Extending the flexible device from the stored position to the extended position;
Progressively tearing the trabecular meshwork by the body of the flexible instrument from a proximal end of the body to a distal end of the body.
(Item 25)
A kit,
The first device,
Housing,
A cannula attached to the distal end of the housing and comprising a distal tip;
A flexible polymer elongate member having a lumen and a distal end, the distal end being slidable within the cannula between a retracted position and an extended position, the distal end being A flexible polymer elongate member within the cannula in the retracted position and distal of the distal tip of the cannula in the extended position;
A reservoir containing a fluid composition, the reservoir being in fluid communication with the lumen of the flexible polymeric elongate member;
Configured to move the flexible polymeric elongate member from the extended position to the stored position while simultaneously delivering the fluid composition from the reservoir through the lumen of the flexible polymeric elongate member. A first device comprising: a drive assembly,
A second device,
Housing,
A cannula attached to the distal end of the housing and comprising a distal tip;
A flexible polymer elongate member having a lumen and a distal end, the distal end being slidable within the cannula between a retracted position and an extended position, the distal end being A flexible elongate member within the cannula in the retracted position and distal of the distal tip of the cannula in the extended position;
A second assembly comprising a drive assembly configured to move the flexible polymer elongate member from the extended position to the retracted position;
The kit, wherein the second device comprises no reservoir.
(Item 26)
A kit,
A flexible polymeric elongate member having a housing, a cannula attached to the distal end of the housing and having a distal tip, and a lumen and a distal end, the distal end extending from a retracted position with a retracted position. Slidable within the cannula with respect to an exit position, the distal end within the cannula in the retracted position and distal of the distal tip of the cannula in the extended position. A device comprising a flexible polymer elongate member,
A tray configured to removably receive the device, the tray comprising a first set of pinch points and a second set of pinch points, the device being in the tray. The kit, wherein the cannula does not contact the tray at one time.
(Item 27)
The device further comprises a drive assembly, the drive assembly configured to advance the flexible polymer elongate member at a first maximum distance without retracting and the flexible polymer elongate member. 27. The kit of item 26, configured to limit cumulative advancement of the member to a maximum total distance.
(Item 28)
28. The method of item 27, wherein the first maximum distance is 15 mm to 25 mm and the maximum total distance is 35 mm to 45 mm.
(Item 29)
A method of manufacturing a cannula for accessing Schlemm's canal, comprising:
Creating a bevel at the distal tip of the cannula, the distal tip comprising an inner peripheral edge and an outer peripheral edge, the cannula comprising a lumen therethrough, the bevel comprising: Creating a bevel that traverses a cavity and creates the bevel, creating a proximal end and a distal end of the distal tip;
Creating a sharp piercing tip by sharpening the distal end of the distal tip,
Smoothing a part of the inner peripheral edge or the outer peripheral edge.
(Item 30)
30. The method of item 29, wherein sharpening the distal end of the distal tip comprises sharpening a portion of the outer surface of the cannula and / or a portion of the outer peripheral edge.
(Item 31)
30. The method of item 29, wherein the sharpened piercing tip is configured to pierce the trabecular meshwork of the eye.
(Item 32)
30. The method of item 29, wherein the sharpened piercing tip comprises two beveled surfaces.
(Item 33)
Item 30. The method according to item 29, wherein the angle between the two inclined surfaces is 50 to 100 degrees.
(Item 34)
30. The method of item 29, wherein smoothing a portion of the inner or outer edge comprises smoothing the inner edge at the proximal end of the distal tip.
(Item 35)
30. The method of item 29, wherein smoothing a portion of the inner or outer peripheral edge comprises smoothing the outer peripheral edge at the proximal end of the distal tip.
(Item 36)
30. The method of item 29, wherein smoothing a portion of the inner or outer edge comprises smoothing both the inner and outer edges at the proximal end of the distal tip.
(Item 37)
30. The method of item 29, wherein smoothing a portion of the inner or outer edge comprises smoothing the inner edge at the distal end of the distal tip.
(Item 38)
30. The smoothing of the inner peripheral edge or a portion of the outer peripheral edge comprises smoothing the entire inner peripheral edge and smoothing the outer peripheral edge at the proximal end of the distal tip. Method.
(Item 39)
39. The method of item 38, wherein the smoothing comprises abrading the soda media.
(Item 40)
30. The method of item 29, wherein the smoothing comprises abrading the soda media.
(Item 41)
30. The method of item 29, further comprising applying a protective cover to the sharpened piercing tip prior to the smoothing step.
(Item 42)
42. The method of item 41, wherein the sharpened piercing tip comprises a bevel, the bevel being covered by the protective cover.
(Item 43)
30. The method of item 29, further comprising polishing the distal tip.
(Item 44)
44. The method of item 43, wherein polishing comprises electropolishing.
(Item 45)
30. The method of item 29, further comprising passivating the cannula.
(Item 46)
46. The method of item 45, wherein passivation removes iron oxide from the cannula.
(Item 47)
46. The method of item 45, wherein the passivation comprises acid passivation.
(Item 48)
30. The method of item 29, further comprising roughening at least a portion of the cannula proximal to the distal tip.
(Item 49)
49. The method of item 48, wherein the roughening comprises abrasively ejecting the soda medium.
(Item 50)
30. The method of item 29, further comprising cutting the cannula to a length of 50 mm to 70 mm.
(Item 51)
51. The method of item 50, wherein cutting the cannula comprises cutting the cannula to a length of 60 mm.
(Item 52)
30. The method of item 29, further comprising bending the distal portion of the cannula along a longitudinal axis of the cannula.
(Item 53)
53. The method of item 52, wherein bending the distal portion of the cannula comprises bending the distal portion at an angle of 100-125 degrees.
(Item 54)
54. The method of item 53, wherein bending the distal portion of the cannula comprises bending the distal portion at an angle of 118 degrees.
(Item 55)
30. The method of item 29, wherein the cannula comprises a subcutaneous tube made of stainless steel, nitinol, or titanium.
(Item 56)
A method of manufacturing a cannula for accessing Schlemm's canal, comprising:
Cutting the cannula to a working length, the cannula comprising a proximal portion, a central portion, a distal portion and a lumen therethrough, the distal portion comprising a distal tip. Disconnecting,
Roughening the outer surface of the central portion of the cannula;
Creating a bevel at the distal tip of the cannula, the distal tip comprising an inner peripheral edge and an outer peripheral edge, the cannula comprising a lumen therethrough, the bevel comprising: Creating a bevel that traverses a cavity and creates the bevel, creating a proximal end and a distal end of the distal tip;
Sharpening the distal end of the distal tip to further sharpen the distal end of the distal tip, creating a sharp piercing tip.
Applying a protective cover to the pointed puncture tip,
Smoothing a part of the inner peripheral edge or the outer peripheral edge,
Bending the distal portion of the cannula along a longitudinal axis of the cannula;
Electropolishing the distal tip,
Passivating the cannula with an acid.

FIG. 3 shows a stylized cross-sectional view of some of the structures involved in the flow of aqueous humor out of the eye. FIG. 6 shows a perspective view of an exemplary delivery system for implanting an intraocular device. FIG. 6 shows a side view of an exemplary cannula of the delivery system. FIG. 6 shows a perspective view of an exemplary drive assembly. 4A shows the drive assembly in the handle of the system in a first orientation and FIG. 4B shows the handle in a second inverted orientation. FIG. 6 shows a perspective view of an exemplary drive assembly. 4A shows the drive assembly in the handle of the system in a first orientation and FIG. 4B shows the handle in a second inverted orientation. FIG. 6 shows a perspective view of an exemplary engagement mechanism for delivery of an exemplary ocular implant. FIG. 6 shows a perspective view of an exemplary engagement mechanism for delivery of an exemplary ocular implant. FIG. 6A shows a perspective view of an engagement mechanism for delivery of an exemplary ocular implant according to one variation. FIG. 6 shows a perspective view of an engagement mechanism for delivery of an exemplary ocular implant according to another variation. FIG. 6 shows a perspective view of an engagement mechanism for delivery of an exemplary ocular implant according to another variation. FIG. 6 shows a perspective view of an engagement mechanism for delivery of an exemplary ocular implant according to yet a further variation. FIG. 6 shows a perspective view of an engagement mechanism for delivery of an exemplary ocular implant according to yet a further variation. FIG. 6A shows a perspective view of another exemplary engagement mechanism for delivery of an exemplary ocular implant. 1 illustrates an exemplary delivery system for delivering a fluid composition to Schlemm's canal. FIG. 10A is a perspective view of the present system. FIG. 10B is a partial cross-sectional view of the present system. 1 illustrates an exemplary delivery system for delivering a fluid composition to Schlemm's canal. FIG. 10A is a perspective view of the present system. FIG. 10B is a partial cross-sectional view of the present system. 6 illustrates an exemplary method of delivering a fluid composition from the delivery system. 6 illustrates an exemplary method of delivering a fluid composition from the delivery system. 6 illustrates an exemplary method of delivering a fluid composition from the delivery system. 3 illustrates an exemplary slidable elongate member for delivering a fluid composition. FIG. 6 shows a side or perspective view of a slidable elongate member according to another variation. FIG. 6 shows a side or perspective view of a slidable elongate member according to another variation. FIG. 6 shows a side or perspective view of a slidable elongate member according to another variation. 1 is a stylized depiction of the Abinterno method for accessing Schlemm's canal with a cannula of an exemplary delivery system. 6 shows an exemplary cannula according to another variation. 8 is a stylized depiction of the abinterno method of accessing Schlemm's canal from a single point and delivering viscoelastic fluid while advancing the fluid delivery elongate member along the 360 ° arc of the canal. A stylized depiction of the Abinterno method for accessing the Schlemm's canal from a single point and delivering viscoelastic fluid while advancing the fluid delivery elongate member both clockwise and counterclockwise along the canal's 180 degree arc. is there. 6 illustrates an exemplary Abinterno method of cutting or tearing the trabecular meshwork. 6 illustrates an exemplary Abinterno method of cutting or tearing the trabecular meshwork. 6 illustrates an exemplary Abinterno method of cutting or tearing the trabecular meshwork. 3 is a flow chart illustrating an exemplary manufacturing method for a cannula that may be used with the devices, systems, and methods described herein. FIG. 7 is a perspective view of a modification of the distal tip of the cannula. FIG. 6 is a perspective view and a front view of a modification of the distal tip of the cannula, respectively. FIG. 6 is a perspective view and a front view of a modification of the distal tip of the cannula, respectively. FIG. 6 shows a perspective view of an exemplary drive assembly of the delivery system. FIG. 22C shows a perspective view of the delivery system with the slidable elongate member extending. FIG. 22D shows a perspective view of the delivery system without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary drive assembly of the delivery system. FIG. 22C shows a perspective view of the delivery system with the slidable elongate member extending. FIG. 22D shows a perspective view of the delivery system without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary drive assembly of the delivery system. FIG. 22C shows a perspective view of the delivery system with the slidable elongate member extending. FIG. 22D shows a perspective view of the delivery system without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary drive assembly of the delivery system. FIG. 22C shows a perspective view of the delivery system with the slidable elongate member extending. FIG. 22D shows a perspective view of the delivery system without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of an exemplary delivery system for delivering a fluid. 23B shows a cutaway view of the delivery system of FIG. 23A. 23C-23D show perspective views of the delivery system of FIG. 23A without a housing. Figure 23E shows a close-up cutaway view of the proximal end of the delivery system of Figure 23A. 23F shows a perspective view of the delivery system of FIG. 23A without the top of the housing with the slidable elongate member extending. FIG. 6 shows a perspective view of another exemplary delivery system for delivering a fluid. 25A shows a perspective view of an exemplary delivery system with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cut-away views, respectively, of the lock rotated to allow filling of the reservoir. 25A shows a perspective view of an exemplary delivery system with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cut-away views, respectively, of the lock rotated to allow filling of the reservoir. 25A shows a perspective view of an exemplary delivery system with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cut-away views, respectively, of the lock rotated to allow filling of the reservoir. 25A shows a perspective view of an exemplary delivery system with the lock removed (FIG. 25A) and inserted into the handle (25B). Figures 25C-25D show perspective and cut-away views, respectively, of the lock rotated to allow filling of the reservoir. 26A shows a perspective view with the delivery system (FIG. 26A) and a perspective view with the delivery system and a filling device (FIG. 26B) of an exemplary tray for the delivery system. FIG. 26C shows an exploded view of an exemplary packaged kit. 26A shows a perspective view with the delivery system (FIG. 26A) and a perspective view with the delivery system and a filling device (FIG. 26B) of an exemplary tray for the delivery system. FIG. 26C shows an exploded view of an exemplary packaged kit. 26A shows a perspective view with the delivery system (FIG. 26A) and a perspective view with the delivery system and a filling device (FIG. 26B) of an exemplary tray for the delivery system. FIG. 26C shows an exploded view of an exemplary packaged kit. 1 illustrates an exemplary kit comprising multiple delivery systems. 1 illustrates an exemplary kit comprising multiple delivery systems. 3 is a flow chart illustrating an exemplary method for delivering fluid to Schlemm's canal. 28B-D show the delivery of fluid when the slidable elongate member is retracted as part of the method of FIG. 28A. 3 is a flow chart illustrating an exemplary method for delivering fluid to Schlemm's canal. 28B-D show the delivery of fluid when the slidable elongate member is retracted as part of the method of FIG. 28A. 3 is a flow chart illustrating an exemplary method for delivering fluid to Schlemm's canal. 28B-D show the delivery of fluid when the slidable elongate member is retracted as part of the method of FIG. 28A. 3 is a flow chart illustrating an exemplary method for delivering fluid to Schlemm's canal. 28B-D show the delivery of fluid when the slidable elongate member is retracted as part of the method of FIG. 28A. 4 is a flow chart illustrating an exemplary method for disrupting a trabecular meshwork. 29B-D show the dissection of the trabecular meshwork as part of the method of FIG. 29A. 4 is a flow chart illustrating an exemplary method for disrupting a trabecular meshwork. 29B-D show the dissection of the trabecular meshwork as part of the method of FIG. 29A. 4 is a flow chart illustrating an exemplary method for disrupting a trabecular meshwork. 29B-D show the dissection of the trabecular meshwork as part of the method of FIG. 29A. 4 is a flow chart illustrating an exemplary method for disrupting a trabecular meshwork. 29B-D show the dissection of the trabecular meshwork as part of the method of FIG. 29A.

  Systems and methods for treating ocular conditions by accessing the Schlemm's canal and delivering an intraocular device, instrument, and / or fluid composition therein to reduce intraocular pressure are provided. Described in the specification. For disrupting trabecular tubule tissue, including fluid, and certain components of the system, such as slidable elongate members, including trabecular meshwork, proximal tubule tissue, Schlemm's canal, and collector channels. Can provide power. As used herein, the term "dissociate" refers to the delivery of a volume of fluid or system component that modifies tissue in a manner that improves flow through the trabecular tubule outflow tract. Examples of tissue disruption include Schlemm's canal dilation, collector channel dilation, increased trabecular meshwork porosity, trabecular meshwork tension, formation of microscopic tears or perforations in nearby tubule tissue, septum separation from Schlemm's canal. But not limited to, cutting, tearing, or removing trabecular tubule tissue, or combinations thereof.

  In order to better understand the systems and methods described herein, it may be useful to describe some of the basic ocular structures. FIG. 1 is a stylized depiction of a normal human eye. The anterior chamber (100) is shown attached to its anterior surface by the cornea (102). The cornea (102) connects at its periphery to the sclera (104), which is the hard fibrous tissue forming the white protective shell of the eye. The trabecular meshwork (106) is located on the outer circumference of the anterior chamber (100). The trabecular meshwork (106) extends 360 degrees circumferentially around the anterior chamber (100). Schlemm's canal (108) is located on the outer peripheral surface of trabecular meshwork (106). Schlemm's canal (108) extends 360 degrees circumferentially around trabecular meshwork (106). The anterior chamber angle (112) is present at the apex formed between the iris (110), trabecular meshwork (106), and sclera (104).

  The system is generally configured for one-handed operation and control by a single operator and includes one or more features useful for easy access to Schlemm's canal with minimal trauma. Once access to the canal is obtained, the system may deliver the intraocular device, instrument, and / or fluid composition. In some variations, the system advances an instrument that disrupts Schlemm's canal and surrounding tissue without delivery of an intraocular device or fluid composition. For example, the device may be an elongated member having an outer diameter sized to divide the canal and surrounding tissue and slidable within a cannula used to access the canal. It is movable and can be extended from the cannula. The body of the elongate member may, in some instances, be configured to cut or tear the trabecular meshwork when removing the system from the eye while the elongate member is in Schlemm's canal, and / or Alternatively, the distal end of the elongate member may be provided with a cutting component to aid in the cutting of trabecular tubule tissue.

  When the device is implanted in the canal, the device will generally be configured to maintain the patency of Schlemm's canal without significantly interfering with transmural fluid flow across the canal. This may restore, enable, or enhance normal physiological outflow of the aqueous humor through the trabecular tubule tissue. Delivering intraocular implants, such as those disclosed in US Pat. No. 7,909,789, and those disclosed in US Pat. No. 8,529,622, each incorporated herein by reference in its entirety. Good. In some variations, the implants in US Pat. No. 7,909,789 and US Pat. No. 8,529,622 show transmural or longitudinal fluid flow across or along the canal. A support having at least one fenestration that completely traverses the central nucleus of Schlemm's canal without significantly interfering with. The intraocular device may also disrupt the proximal trabecular meshwork, or the adjacent inner wall of Schlemm's canal. The intraocular device may also be coated with a drug useful in the treatment of ocular hypertension, glaucoma or pre-stage glaucoma, infections, or scarring, angiogenesis, fibrosis, or post-operative inflammation. The intraocular device may also be formed to be solid, semi-solid, or bioabsorbable.

  The system can also be used to deliver fluid compositions such as saline or viscoelastic fluids. Saline may be used for irrigation. Viscoelastic fluids may also be used in the absinterno type Viscocanarostomy or angioplasty procedures to disrupt the canal and surrounding tissue.

I. Systems / Devices The systems described herein can generally be single operator, one-hand controlled devices that include a dual-purpose handle having a grip portion and a housing having an inner end and a distal end. The cannula typically connects to and extends from the distal end of the housing. The cannula may include a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between the ends. In other variations, the cannula may be straight and may not have a distal bend. The cannula may also be configured to include a body, a beveled distal tip, and a lumen extending from the proximal end through the distal tip. The bevel may directly engage the distal end of the curved portion of the cannula (ie, the bevel may directly engage the radius of curvature). The system may also include a drive assembly that is partially housed within a housing that generally includes a gear that converts rotational movement into linear movement. If the intraocular device is to be implanted in Schlemm's canal, the system may further include a slidable positioning element having a proximal end and a distal end coaxially disposed within the lumen of the cannula. The system may also be configured to include a slidable elongate member having a lumen coaxially disposed within the lumen of the cannula. The system may also be configured to include a fluid assembly in the handle if the fluid composition is to be delivered to Schlemm's canal. Fluid compositions such as saline, viscoelastic fluids including viscoelastic solutions, air, and gases may be delivered using the system. Suitable markings, tints, or indicators may be included on any part of the system to identify the location or location of the distal end of the cannula, positioning element, engagement mechanism, intraocular device, or slidable elongate member. You may help. In some examples, the systems described herein include abinterno travecrotomy, ab intelino transluminal trabectomy, transparent corneal travectomy, transparent corneal transluminal trabectomy, ab intelno tube formation. Surgery and / or clear keratoplasty and may be used to deliver the fluid composition to the anterior or posterior segment of the eye.

  An exemplary intraocular delivery system is shown in FIG. In this view, the delivery system (200) includes a universal handle (202) having a grip portion (204) and a housing (206). The housing has a proximal end (208) and a distal end (210). A cannula (212) connects to and extends from the housing distal end (210). The drive assembly (214) is substantially contained within a housing (206) that initiates movement of a positioning element (not shown). A port (216) is provided on the distal end (210) of the housing for removable connection to a source of irrigation fluid.

  The delivery system described herein may be completely disposable in some variations. In other variations, a portion of the delivery system may be reusable (eg, a material that does not contact the patient, such as a handle), while a portion of the delivery system may be disposable (eg, a cannula). And materials that contact the patient, such as elongated members). In yet other variations, the delivery system described herein may be fully reusable.

Universal Handle The intraocular delivery system described herein can include a universal handle that can be used with one hand. For example, the handle may be configured for left or right hand use, left or right eye use, or clockwise or counterclockwise use. That is, the handle has the ability to use the present delivery system to determine which hand to use, which eye to perform the procedure on, or in which direction around the canal, an intraocular device, instrument, or fluid. It can be configured to be independent of whether the composition is delivered. For example, the delivery system may be used to deliver an intraocular device, an elongate member, and / or a fluid composition in the eye in a clockwise direction, after which the handle is simply inverted to a second orientation. (Or in another variation, by rotating the cannula itself 180 degrees) may be used to deliver the intraocular device, the elongate member, and / or the fluid composition in a counterclockwise direction. However, in other variations, the delivery system described herein is configured for use in a particular configuration (eg, one side up, clockwise only, counterclockwise only, etc.). Please understand that it is good. The handle generally includes a grip portion and a housing. The gripping portion is raised, recessed, or grooved or textured in certain areas to improve the grip of the handle by the user or to improve user comfort. obtain. The housing can include an inner portion and a distal end. The inner portion of the housing may house the drive assembly and the positioning element (both described further below). In some variations, the distal end of the housing includes a fluid port that can provide fluid for irrigation of the surgical field or for purging air from the system.

  The universal handle may be made from any suitable material including, but not limited to, fluoropolymers; thermoplastic materials such as polyetheretherketone, polyethylene, polyethylene terephthalate, polyurethane, nylon, and the like; and silicones. . In some variations, the housing or part thereof may be made of a transparent material. Suitable transparent materials are typically polymers such as acrylic copolymers, acrylonitrile butadiene styrene (ABS), polycarbonate, polystyrene, polyvinyl chloride (PVC), polyethylene terephthalate glycol (PETG), and styrene acrylonitrile ( SAN). Acrylic copolymers that may be particularly useful include, but are not limited to, polymethylmethacrylate (PMMA) copolymers and styrenemethylmethacrylate (SMMA) copolymers (eg, Zylar 631® acrylic copolymer). In variations where the universal handle is reusable, the handle may be made from a sterilizable (eg, autoclaved) material such as a refractory metal (eg, stainless steel, aluminum, titanium).

  The length of the universal handle can generally be from about 1 inch (2.5 cm) to about 20 inches (50.8 cm). In some variations, the length of the universal handle can be about 4 inches (10.2 cm) to 10 inches (25.4 cm). In some variations, the length of the universal handle is about 7 inches (17.8 cm).

Cannula The cannula of an intraocular delivery system typically connects to and extends from the housing distal end and is generally easy and traumatic to Schlemm's canal using a minimally invasive abinterno technique. Is configured to provide access that is minimal. The cannula may be fixedly attached to the distal end of the housing or, in other variations, may be rotatably attached to the distal end of the housing. In variants of the delivery system where the handle is reusable and the cannula is disposable, the cannula may be removably attached to the distal end of the housing. Some variations of the cannula may include a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between these ends. . However, it should be appreciated that in other variations, the cannula may be straight and may not include a distal bend. The cannula may also be configured to include a body, a distal tip having a bevel and a pointed piercing tip, and a lumen extending from the proximal end through the distal tip. If the cannula comprises a distal curved portion, the bevel may directly engage the distal end of the curved portion of the cannula (ie, the bevel may directly engage the radius of curvature). In some variations, the pointed piercing tip may include one or more beveled surfaces, which is described in more detail below.

  The cannula may be made of any suitable material that is sufficiently rigid to allow it to be advanced through the eye wall and the anterior chamber. For example, the cannula may be formed of a metal such as stainless steel, nickel, titanium, aluminum, or alloys thereof (eg, Nitinol metal alloys), polymers, or composites. Exemplary polymers include, but are not limited to, polycarbonate, polyetheretherketone (PEEK), polyethylene, polypropylene, polyimide, polyamide, polysulfone, polyetherblockamide (PEBAX), and fluoropolymers. In some examples, it may be advantageous to coat the cannula with a lubricious polymer to reduce friction between the eye tissue and the cannula during the procedure. Lubricating polymers are well known in the art and include polyvinyl alcohol, polyethylene glycol, polyvinylpyrrolidone, fluorinated polymers (including polytetrafluoroethylene (including PTFE or Teflon®)), and poly. Examples include, but are not limited to, ethylene oxide. In variants in which the cannula is reusable, the cannula may be made from sterilizable (eg, by autoclaving) materials such as refractory metals (eg, stainless steel, aluminum, titanium).

  The cannula generally has an outer diameter that is sized to gain access to the lumen of Schlemm's canal while at the same time minimizing obstruction of the surgeon's field of view. Thus, the outer diameter can range from about 50 microns to about 1000 microns. In some variations, the outer diameter can range from about 150 microns to about 800 microns. The cannula also has an inner diameter, which can range from about 50 microns to about 400 microns. The cannula may also be formed to have any suitable cross-sectional profile, such as circular, oval, triangular, square, rectangular, etc.

  The cannula may be configured to include multiple parts or pieces. A bevel at the distal tip of the cannula that directly engages the barrel, a distal curved portion having proximal and distal ends, a radius of curvature defined between the ends, and a distal portion of the curved portion of the cannula. A cannula having may be particularly useful for accessing the lumen of Schlemm's canal. Here, the body (straight portion of the cannula) may have a length in the range of about 5 mm to about 50 mm, about 10 mm to about 30 mm, or about 14 mm to about 20 mm. In some variations, the fuselage may have a length of about 18 mm. The distal curved portion of the cannula may have a uniform cross-sectional shape, or it may taper closer to the distal end to facilitate entry into Schlemm's canal. The radius of curvature of the distal curved portion can be adapted to facilitate tangential entry and entry into Schlemm's canal with precision and minimal trauma, in the range of about 1 mm to about 10 mm, or about 2 mm to about 5 mm. Can be. In one variation, the radius of curvature is about 2.5 mm. The cannula also has a suitable angular span to facilitate entry into Schlemm's canal, and can range from about 70 degrees to about 170 degrees, or about 100 degrees to about 150 degrees. In one variation, the angular span is about 120 degrees.

  The size, shape, geometry, etc. of the bevel at the distal end of the curved portion of the cannula can be beneficial in allowing easy and minimally traumatic access to Schlemm's canal. In this regard, it may be particularly useful to have a bevel that directly engages the radius of curvature of the distal end of the cannula, as described in more detail below.

  In other variations, the cannula may include a short straight segment that connects to the distal end of the distal curved portion of the cannula (eg, at the end of the radius of curvature). Here, the bevel engages a straight segment rather than a radius of curvature. The length of the linear segment can range from about 0.5 mm to about 5 mm. In some variations, the length of the linear segment ranges from about 0.5 mm to about 3 mm, or about 0.5 mm to about 1 mm. The length of the linear segment may also be less than about 0.5 mm, for example about 0.1 mm, about 0.2 mm, about 0.3 mm, or about 0.4 mm. In the variant where the bevel directly engages the distal end of the curved portion of the cannula (ie the bevel directly engages the radius of curvature), the cannula lacks a straight segment (the straight segment has zero length). ).

  It can also be useful for any intraocular device to have a short pointed bevel to minimize the distance that must be traveled during implantation in the canal. Exemplary bevel angles can be about 10 degrees to about 90 degrees. In some examples, the bevel angle can range from about 10 degrees to about 50 degrees. In one variant, the bevel angle is about 35 degrees, while in another variant, the bevel is about 25 degrees. The bevel can also be oriented in any suitable direction. For example, the bevel can be oriented such that it opens towards the surgeon or flips open away from the surgeon or in any plane therebetween.

  As described in more detail below, in some further variations, the cannula is configured to include one pointed section and another rounded (eg, deburred) section. . Such a dual surface configuration of the cannula provides easier access to the canal by piercing the mesh while at the same time retracting the elongate member into the cannula to avoid cutting and breaking of the elongate member due to storage forces. It may be advantageous as it may also provide a gentle, dispersed force to the elongate member therein. For example, as shown in FIG. 15, the distal end (1500) of the cannula may have a sharp piercing tip (1502) and a smooth edge (1504), which are part of the opening (1506). And an slidable member (not shown) slidable through this opening (1506) may be advanced and stored. As will be described in more detail with reference to FIGS. 19, 20A-20B, and 21, the pointed tip (1502) may be formed by combining a plurality of bevels, with a smooth edge (1504). , May be created by smoothing or deburring the inner and / or outer edges of the distal tip. In addition, in some embodiments, the inner and / or outer surface of the elongate member adjacent the opening (1506) may also be smoothed. The method of making the cannula is described in more detail below.

  The cannula of an exemplary delivery system is shown in more detail in FIG. Here, the cannula (300) comprises a proximal end (302), a distal curved portion (304), a torso (314), and a distal tip (306). Distal curved portion (304) has a proximal end (308) and a distal end (310) and a radius of curvature (R) defined between these ends (308, 310). The distal curved portion (304) also has an inner radius (320) defined by the surface of the cannula closest to the center of the radius of curvature (R) and an outer radius (322) defined by the surface of the cannula further away from the center. ) Has. The bevel (312) at the distal tip (306) directly engages the distal end (310) of the curved portion of the cannula. In other words, the bevel (312) may abut the distal end (310) of the curved portion of the cannula. As mentioned above, this distal curved portion (304) and bevel (312) configuration may be beneficial or advantageous to allow easy, atraumatic, controlled access to Schlemm's canal. The bevel angle may also be important. In general, short bevels can be beneficial. The bevel (312) may comprise an angle (A) of about 5 degrees to about 85 degrees. In some variations, the angle (A) is about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 85 degrees. obtain. In some variations, angle (A) can be about 23 degrees to about 27 degrees. In the variant shown in FIG. 3, the bevel angle (A) is about 25 degrees.

  FIG. 20 shows a perspective view of the distal tip (2002) of cannula (2000) with bevel (2014). The distal tip (2002) may be angledly cut or sharpened to create a bevel (2014). As shown, the beveled distal tip (2002) comprises a proximal end (2008), a distal end (2010), and an elongated opening (2012) having an oval rather than a circular shape. Distal tip (2002) may comprise an oval-shaped lumenal opening, where the top of the oval-shaped opening is beveled closer to the proximal portion of the cannula than the bottom of the oval-shaped opening. . The inner and outer peripheral edges (2004, 2006) are also shown in FIG.

  21A and 21B show perspective and front views, respectively, of a variation of the distal tip (2100) of a cannula with a bevel (2102) and a pointed piercing tip (2114). As shown there, the distal tip (2100) also comprises a proximal end (2108), a distal end (2110), inner and outer perimeter edges (2104, 2106), and a lumen opening (2112). The sharpened piercing tip (2114) may comprise two beveled surfaces (2116) that merge to form a sharpened tip. The beveled surface (2116) can have any suitable angle that results in a sharp piercing tip (2114). For example, in some examples, the ramped surface (2116) may be about 20, 25, 30, 35, 40, 45, or 50 degrees, about 25 to about 50 degrees, or about 37.5 to about 42.5 degrees. May have an angle (B) with respect to the longitudinal axis of the distal tip (2100). In some examples, angle (B) may be about 40 degrees. Thus, in some examples, the angle between the two sloping surfaces (2116) may be between about 50 and about 100 degrees, and in some examples, the angle between the two sloping surfaces (2116) is It may be about 80 degrees. Although the distal tip (2100) is shown with two beveled surfaces, it should be understood that a distal tip having a single beveled surface could also be used.

Elongate Member The delivery system described herein may comprise a slidable elongate member coaxially disposed within the lumen of the cannula. The elongated members used with the systems described herein may be of various configurations, which may or may not include a lumen. The elongate member may or may not be configured to deliver a fluid composition.

  The elongate member may be coaxially disposed and slidable within the lumen of the cannula of the delivery system described herein. When the elongate member is in the retracted position with respect to the cannula, the distal end of the elongate member may be located within (ie, proximal to) the distal tip of the cannula. When the elongate member is in the extended position relative to the cannula, the distal end of the elongate member may be located outside (ie, distal) of the distal tip of the cannula. The length of extension of the elongate member beyond the distal tip of the cannula may be traversed by the elongate member (eg, to disrupt Schlemm's canal and / or surrounding trabecular tubule tissue and / or deliver a fluid composition. To correspond to the distance around Schlemm's canal. In variations where the delivery system is configured to deliver a fluid composition, the length traversed by the elongate member may correspond to the perimeter of Schlemm's canal to which the fluid composition is delivered. In variations where the delivery system is configured to tear or cut the trabecular meshwork, the length traversed by the elongate member may correspond to the length of the trabecular meshwork being cut or torn. In some variations, this length can be from about 1 mm to about 50 mm. In some of these variations, the length is about 10 mm to about 40 mm, about 15 mm to about 25 mm, about 16 mm to about 20 mm, about 18 mm to about 20 mm, about 19 mm to about 20 mm, about 18 mm to about 22 mm, about. It can be 20 mm, about 30 mm to about 50 mm, about 35 mm to about 45 mm, about 38 mm to about 40 mm, about 39 mm to about 40 mm, or about 40 mm. The elongate member may be moved between an extended position and a retracted position using the drive assembly of the present delivery system, as described in more detail below.

  The elongate member is advanced through the cannula into a portion of Schlemm's canal to disrupt trabecular tubule tissue, stent, and / or tension the canal and / or deliver a fluid composition. May be sized (eg, 0 to 360 degrees of canal). The elongate member is made of any suitable material that provides the desired flexibility and extrudability for introduction through the eye wall, access to Schlemm's canal, and / or orientation through other eye tissue structures. Can be made. For example, the elongate member may be a polymer (eg, nylon, polypropylene); a polymer reinforced with wire, braid, or coil; a composite of polymer and metal; or stainless steel, titanium, a shape memory alloy (eg, nitinol), or Metals such as these alloys may be included. In variations where the elongate member is reusable, the elongate member may be made from a sterilizable (eg, by autoclaving) material such as a refractory metal (eg, stainless steel, aluminum, titanium). The elongate member may be straight with sufficient flexibility and extrudability to orient the annular Schlemm's canal, or it may more easily encircle the Schlemm's canal partially or in its entirety. As such, a radius of curvature of about 2-10 mm or a radius of curvature of about 6 mm (ie, the approximate radius of Schlemm's canal in an adult human) may be preformed. In some variations, the elongate member can be configured to be advanced over or along the guidewire.

  In some variations, it may be desirable for the elongated member to have one or more features to improve visualization of the elongated member. For example, the elongated member may be colored (eg, red, orange, yellow, green, blue, purple, etc.). Additionally or alternatively, the visualization may use illuminated labels, fiber optics, side illuminated fiber optics, luminescence, fluorescence, or the like to improve visualization. For example, an optical fiber may travel along the body of the elongate member to deliver light to the distal tip of the elongate member, as it is advanced or retracted around Schlemm's canal. Visualization of the tip may be improved.

  In some variations, the elongate member can be sized to have an outer diameter sufficient to disrupt Schlemm's canal and surrounding trabecular tubule tissue. The outer diameter is about 25 microns to about 1000 microns, about 25 microns to about 500 microns, about 50 microns to about 500 microns, about 150 microns to about 500 microns, about 200 microns to about 500 microns, about 300 microns to about 500. It may range from microns, about 200 microns to about 250 microns, about 150 microns to about 200 microns, or about 180 microns to about 300 microns. In some examples, it may be beneficial for the elongate member to have an outer diameter of about 240 microns.

  In some variations, the distal end of the elongate member is a blunt bevel, an atraumatic tip, an enlarged atraumatic tip, or the like, to assist in advancing the elongate member through Schlemm's canal. Can be configured. In some of these variations, the distal end may comprise an atraumatic tip shaped like a blunted umbrella. In other variations, the distal portion of the elongate member optionally includes fracturing components, such as notches, hooks, barbs, roughened surfaces, or combinations thereof, of Schlemm's canal or proximal trabecular meshwork. The neighboring trabecular portion can be divided. One or more projections emanating from the elongated member may further disrupt Schlemm's canal or the proximal trabecular portion of the proximal trabecular meshwork to increase permeability of aqueous humor through the trabecular meshwork to Schlemm's canal. In some examples, the elongate member may also deliver energy to trabecular tubule tissue (eg, ultrasonic energy, radio frequency energy (eg, for electrocautery, electrical ablation), electromagnetic radiation, light energy). (Eg, via optical fiber)).

  In some examples, the elongate member may comprise filaments (eg, filaments including nylon, polypropylene, metal, or the like). For example, the elongate member may comprise a nylon monofilament. An exemplary range of filament size can range from about 50 microns to about 300 microns. The filament may be configured to advance through all or part of Schlemm's canal. In some examples, the body of filaments can be configured to cut or tear the trabecular meshwork when removing the cannula from the eye. In other examples, the filaments may be configured to disrupt trabecular tubule tissue during advancement into or storage from Schlemm's canal. In yet another example, the filaments can be configured to remain in the canal to deliver tension continuously to the omentum and maintain patency of the canal.

  In some variations, the elongate member may comprise a lumen. For example, in one variation, the elongate member may comprise a microcatheter (eg, nylon microcatheter). In some of the examples in which the elongate member comprises a lumen, the elongate member can be configured to deliver a fluid composition. The fluid composition may travel through the lumen of the elongate member and may be delivered through an opening in the lumen. For example, as shown in FIG. 12, the elongate member (1200) may be a flexible tube having a lumen in fluid communication with the opening at the distal tip (1202). In some variations, the distal end of the elongate member can be configured or modified to assist in delivering the fluid composition to Schlemm's canal. For example, the distal end of the elongate member may comprise a cut configured as a half tube. In addition to, or as an alternative to, the openings at the distal tip, the elongate member may optionally include a plurality of openings through its wall that are spaced along the axial length of the elongate member. Good. In this variation, the fluid composition may be delivered from the reservoir through an opening in the elongate member to Schlemm's canal. This lateral fluid (eg, viscoelastic fluid) drainage may, in some instances, enhance disruption of outflowing tissue and enhance the permeability of aqueous humor. It is understood that the openings can be of any suitable number, size, and shape and can be spaced along the axial length of the elongate member (including the distal tip) in any suitable manner. I want to be done.

Drive Assembly The delivery system generally includes a drive assembly. The driver assembly of the delivery system is generally configured to move the intraocular device, the elongate member, and / or the fluid composition into Schlemm's canal. The drive assembly may also, in some variations, be configured to position the intraocular device within the canal, including advancing the device to the canal and retracting the device from the canal. The drive assembly may be at least partially housed within the housing and may include any suitable component or combination of components capable of providing a handle with universal functionality.

  The drive assembly may translate external input (eg, user thumb or finger movement) into movement of one or more components of the delivery system. More specifically, the drive assembly may extend the slidable elongate member distally from the cannula and / or may cause the slidable elongate member to be stored proximally in the cannula. Good. The drive assembly may also optionally deliver the fluid composition from the reservoir through the elongate member and / or cannula.

  Two or more of these effects (ie, extending the slidable elongate member, retracting the slidable elongate member, and / or delivering the fluid composition) can be activated using the same activation mechanism. Good. This may allow one-handed use of the delivery system. For example, if the activation mechanism comprises a rotatable element (such as one or more wheels as in the variants described herein), rotating the rotatable element in the first direction is slidable. The extension of the elongate member may be caused and rotating the rotatable element in the second direction may cause storage of the slidable elongate member. If the delivery system is configured to deliver the fluid composition, rotating the rotatable element (eg, in the second direction) may also cause delivery of the fluid composition. Delivery of the fluid composition may occur concurrently with movement (eg, storage) of the slidable elongate member. In some of these examples, the fluid composition may be delivered to a portion of Schlemm's canal in which a slidable elongate member is advanced, i.e., the fluid composition is It can be delivered at the same Schlemm's canal angle and length as the extension. When the fluid composition occurs simultaneously with the storage of the elongated member, the fluid composition may replace it when the slidable elongated member is stored, and in place in Schlemm's canal and Schlemm's canal. And / or the collector channel may be expanded. Further, the amount of fluid delivered is related to the amount of movement of the elongate member, which means that a certain, predetermined constant volume of fluid composition will result in a certain amount of movement of the elongate member (eg, storage distance). , And for a certain amount of rotation of the rotatable element, can be delivered through the elongated member (eg, delivered from the distal end of the elongated member).

  In some variations, the drive mechanism may be configured to allow only one use of the delivery system, which means that the drive mechanism may, for example, after a predetermined amount of extension and / or storage. That is, re-extension of the slidable elongated member can be prevented. Exemplary mechanisms that may translate external input into movement of one or more components of the delivery system are described in more detail below.

  In some variations, the drive assembly includes components that convert rotational movement into linear movement. For example, the drive assembly may include a linear gear and a pair of pinion gear mechanisms. The linear gear may have teeth on its surface that engage corresponding teeth on the pinion gear. Each of the pinion gear mechanisms may also be coupled to rotary components (eg, wheels). Such a connection includes a pin that can be screwed through a central opening in the rotary component and pinion gear, and the rotary component and pinion gear, where rotation of the rotary component causes the pinion gear to rotate, and vice versa. It may also be achieved with a nut that locks in some fashion. The wheel may be attached to the pinion gear, for example, by one of the following methods; 1) the wheel and pinion gear are molded as one piece using plastic injection molding techniques; 2) the wheel is pinion. Slide on gear and fix with glue; or 3) slide wheel on pinion gear and mechanically fix by fasteners or "press fit", where wheel is pushed on pinion gear , Friction holds them fixed. In all of the situations mentioned, the wheels and pinion gears can rotate coaxially, in the same direction and at the same angular velocity. In some variations, each pinion gear mechanism couples at least two rotatable components. In other variations, the drive assembly may be configured to include a single rotary component, multiple rotary components, or no rotary components. The wheels may have markings or colorings to indicate the degree of forward movement or the direction of forward movement.

  One variation of a drive assembly useful for inclusion in a universal handle comprises a linear gear, a pair of pinion gear mechanisms, and two rotary components associated with each pinion gear (a total of four rotary components). In another variation, the drive assembly includes a linear gear and a single pinion gear mechanism with two associated wheels. In a variation with a pair of pinion gear mechanisms, the pinion gear mechanism and associated wheels may be located on opposite sides of the linear gear. The pinion gear and the linear gear contact each other, which means that the teeth of the pinion gear can directly engage the corresponding teeth on the linear gear and the wheels on one side of the linear gear can contact the wheels on the opposite side of the linear gear. That's what it means. At least a portion of the wheels on either side of the linear gear may extend outside the housing. In this variation, the drive assembly can be operated with one hand when in the first configuration and then with the same or the other hand when inverted to the second configuration. Such a flexible performance drive assembly is easy to use by right-handed and left-handed surgeons, and the cannula is oriented in a first direction during a first part of the procedure and a second direction during the procedure. May be used in a procedure in which the handle is inverted during the procedure so as to face a second direction in the section. In a further variation, the drive assembly may include one rotatable component on one side of the handle and a "universal" feature of the handle provided by the cannula, which cannula instead of inverting the handle. Can rotate on its own.

  In the variation shown in FIG. 4A, the delivery system (400) includes a drive assembly (402) having a linear gear (eg, rack) (404) and a pair of pinion gear mechanisms (406). Both the linear gear and the pinion gear mechanism have teeth that engage one another to convert rotational movement (of the pinion gear mechanism (406)) into linear movement (of the linear gear (404)). Each of the pinion gear mechanisms (406) couples to two rotary components, which are shown as wheels (408) in the figure, for a total of four rotary components. The wheels (408) extend outside the housing (414) of the delivery system (400) so that they are rotated by one or more of the surgeon's fingers and correspondingly move the pinion gear mechanism (406). The rotation may advance or retract the linear gear (404). The wheels (408) are coaxial with the pinion gear mechanism (406) and rotate in harmony with the pinion gear mechanism. Movement of the linear gear (404) advances or retracts a positioning element (410) that is coaxially disposed and slidable within the cannula (412). FIG. 4B shows the system of FIG. 4A in a second inverted orientation. In the orientation of FIG. 4A, the cannula is oriented with the curvature pointing clockwise, while in the orientation of FIG. 4B the cannula is oriented with the curvature pointing counterclockwise. The wheels (408) extend on both sides outside the housing (414) to allow the delivery system (400) to be used in any orientation, in any hand, and in any eye of the patient. Can be. That is, the orientation of FIG. 4B may be used with the same or opposite hand as the orientation of FIG. If so, clockwise cannulation) is desired.

  Another variation of the drive assembly is shown in two different perspective views in Figures 22A-22B. As shown therein, the drive assembly (2202) may include a linear gear (eg, a rack) (2204) and a pair of pinion gear mechanisms (2206). Both the linear gear and the pinion gear mechanism have teeth that engage one another to convert rotational movement (of the pinion gear mechanism) into linear movement (of the linear gear). More specifically, the linear gear (2204) may include teeth on both the first side (2220) and the second side (2222), the teeth on the first side being the first pinion gear. The mechanism engages and the teeth on the second side engage the second pinion gear mechanism. Each of the pinion gear mechanisms (2206) couples to two rotary components, which are shown as wheels (2208) in the figure, for a total of four rotary components. The wheels (2208) are coaxial with the pinion gear mechanism (2206) and rotate in harmony with the pinion gear mechanism. The drive assembly may include one or more features to stabilize the pinion gear mechanism or otherwise keep them in place. For example, the drive assembly (2202) may include a wheel spacer (2216) configured to seat between the axles (2218) of the pinion gear mechanism. Translation of the linear gear (2204) may occur due to rotation of one or more wheels (2208).

  As shown in FIGS. 22C and 23A-23B, the wheels (2208) may extend outside the delivery system housing (2334), which causes the wheels to be rotated by the surgeon and correspondingly the pinion. Rotating the gear mechanism (2206) may advance or retract the linear gear (2204). The cannula (2344) may be slidable within the linear gear (2204) such that the cannula and wheels are fixed relative to each other and to the housing (2334), while the linear gear (2204) is relative to the housing. Will be translated. Linear movement of the linear gear (2204) may be produced by rotational movement of either of the two pinion gear mechanisms (2206), which rotational movement may also be generated by any of the wheels (2208) extending from the housing (2334). Is generated by the rotation of the delivery system (2300) so that the first or second side faces up, and thus the cannula (2344) faces in the first or second direction. Can be easily operated using one hand at.

  In other variations, one or both pinion gear mechanisms may be able to disengage from the linear gear by biasing their position off-axis from the linear gear. This action decouples the teeth of the pinion gear from the teeth of the linear gear to prevent movement of the linear gear. Rotation may also be prevented by locking the pinion gear mechanism to engage intersecting pins or features that prevent rotation of the wheels.

  A further modification of the drive assembly may not use the conversion of rotary motion into linear motion. For example, a slide on the handle (eg, a finger slide) that is fixed or removably coupled to a gear (eg, a linear gear as described above) within the handle's housing. Here, the drive assembly may be configured such that advancement or storage of the slide causes advancement or storage of the intraocular device and / or elongate member, and / or delivery of the fluid composition to Schlemm's canal. In yet a further variation, a pushable or pinchable button may be used in place of the slide, or a foot pedal may be used to deliver the intraocular device, instrument, and / or fluid composition. ..

Extending and Retracting the Elongate Member In some variations, the proximal end of the elongate member may be secured to a portion of the drive assembly (eg, the linear gear (2204)) while the distal end. May be coaxially slidable within the lumen of the cannula. If the elongate member does not have a lumen (eg, is a filament), the elongate member may be attached to the drive assembly by crimping, in some examples. If the elongate member comprises a lumen, the elongate member may, in some instances, be secured (eg, by an adhesive) to the drive assembly to prevent the lumen of the elongate member from being occluded. The cannula may also be fixedly attached to the housing. In a variation of the delivery system where the handle is reusable and the cannula and elongate member are disposable, the disposable assembly with the elongate member pre-assembled within the cannula may be a threaded fastener or snap-in feature. It may be attached to the reusable handle by any suitable mechanism.

  As a portion of the drive assembly moves proximally or distally within the housing, this may cause a corresponding movement of the elongate member relative to the cannula. That is, movement of a portion of the drive assembly toward the cannula (i.e., toward the distal end of the housing) may cause the elongate member to move from the retracted position to the extended position. Away from the cannula (eg, towards the proximal end of the housing) may move the elongate member from the extended position to the retracted position. An example of the elongated member in the extended position is shown in Figures 22C-22D. The linear gear (2204) is in the distal position, as shown in the pictorial illustration in FIG. 22D with the top of the housing (2334) removed. As such, the elongate member (2346) extends from the cannula (2344).

Reservoir The system generally includes a reservoir when the fluid composition is to be delivered to Schlemm's canal. The reservoir may contain a variety of fluid compositions for delivery. Exemplary fluid compositions include saline and viscoelastic fluids. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, derivatives or mixtures thereof, or solutions thereof. In one variation, the viscoelastic fluid comprises sodium hyaluronate. In another variation, the viscoelastic composition may further include a drug. For example, the viscoelastic composition is suitable for treating glaucoma, reducing or lowering intraocular pressure, reducing inflammation, and / or preventing infection, fibrosis, scarring, blood clots, thrombus formation, hemorrhage, or angiogenesis. It may contain a drug. Antimetabolite drug, vasoconstrictor drug, anti-VEGF drug, steroid, heparin, anti-inflammatory drug, nonsteroidal anti-inflammatory drug (NSAID), other anticoagulant drug, fibrinolytic compound, biological drug, and gene therapy drug Drugs such as can also be delivered in combination with the viscoelastic composition. Examples of glaucoma drugs include prostaglandins, beta blockers, miotics, alpha adrenergic agonists, or carbonic anhydrase inhibitors. Anti-inflammatory drugs such as NSAIDs, corticosteroids, or other steroids may be used. For example, steroids such as prednisolone, prednisone, cortisone, cortisol, triamcinolone, or shorter acting steroids may be used. Examples of antimetabolite drugs include 5-fluorouracil or mitomycin C. Examples of drugs or antibodies that prevent angiogenesis include bevacizumab, ranibizumab, and others. In yet another variation, the system delivers only the drug without the viscoelastic composition. Saline solution may also be the fluid used. In yet another variation, the system can be configured to deliver gases such as, but not limited to, air, inflatable gases (eg, SF6, C3F8), etc.

  In some variations, the reservoir may be at least partially defined by the fluid assembly and housing, and the linear gear within the handle. The fluid assembly may be made of any suitable material described above for the cannula and housing. The volume of fluid contained in the reservoir (microliters) can range from about 2 μl to about 1000 μl, or from about 2 μl to about 500 μl. In some variations, the reservoir volume may range from about 50 μl to about 100 μl.

  The fluid composition may be pre-filled into the reservoir so that the fluid may be delivered by a single device and a single user, or prior to use of the system, for example at the beginning of an ophthalmic procedure. May be filled. Again, forceps or other advancement instrument for advancing the fluid delivery catheter into Schlemm's canal, and / or separate or independent of the delivery catheter or catheter advancement instrument, during the procedure, one of the surgeons' Using a device containing a viscoelastic fluid that needs to be connected to the delivery catheter or catheter advancement device while it is being held by the hand, for example by an assistant or by the hand of a surgeon In contrast to the system. For example, a fill component may be provided in the fluid assembly for transfer of the fluid composition to the reservoir. The filling component may have any suitable configuration that provides reversible immobilization to the system, such as a fluid container, eg, syringe, cartridge, and filling of a reservoir of fluid composition. The filling component may be a luer fit or may include a one way valve.

  An exemplary delivery system with a reservoir is shown in Figures 23A-23F. The delivery system (2300) shown with housing (2334) (FIGS. 23A, 23B, and 23E), without housing (2334) (FIGS. 23C and 23D), and partially without housing (2334) (FIG. 23F) includes: A fluid assembly (2316) is provided that includes a reservoir (2302). In an exemplary method, the fluid composition can be loaded into the reservoir (2302) through the proximal opening (2328) and via the proximal seal (2318). As best shown in FIG. 23E, the distal end of reservoir (2302) may be formed by a plunger (2338) (discussed in more detail below) and a distal seal (2354).

  A proximal seal (2318) is located at the proximal end of the reservoir (2302) and is spring loaded against an o-ring or gasket (2330) to close and seal the reservoir. It may be a mechanical sealing part including (2324). The filling device (2326) (eg, nozzle) is used to squeeze the ball bearing (2324) to move the ball bearing (2324) proximally toward the open position to open the seal. Good. The reservoir may be filled with the fluid composition while the proximal seal (2318) is open. After filling with the fluid composition, the filling device (2326) can be removed to return the ball bearing (2324) to its closed position. The close-up cross-sectional view in Figure 23E shows the proximal opening (2328) and ball bearings (2324). The O-ring or gasket (2330) and the ball bearing (2324) allow the force from the spring to push the ball bearing into the gasket, forming a seal between the ball bearing and the gasket in the closed position. Sit between (2332). The filling device (2326) is configured to fit into the proximal opening (2328) and squeeze the ball bearing (2324). The force oriented distally to the ball bearing (2324) moves it distally to an open position, compressing the spring (2332) and opening the ball bearing to the gasket (2330). Through which the fluid composition can flow. When the filling device (2326) is removed from the proximal opening (2328), the spring (2332) pushes the ball bearing (2324) proximally to return it to the closed position.

  It should be appreciated that in other variations, the reservoir may include other types of seals to allow filling of the fluid composition into the reservoir. For example, FIG. 24 shows an alternative variation of the delivery system (2400) where the seal comprises a membrane (eg, a silicone membrane). As shown, the fluid composition can be loaded into the reservoir (after movement of the optional lock (2404)) by piercing the membrane with a needle (2402) (eg, a 25 gauge needle). In yet another variation, the delivery system described herein can be configured to receive a prefilled cartridge that comprises a fluid composition. For example, the handle and fluid assembly may be configured such that the filled cartridge can be inserted into the fluid assembly.

  To fill the reservoir, it may be desirable to secure the fluid assembly in place at least temporarily to allow the application of distal force to the seal. In some variations, the delivery system may include a lock configured to hold the fluid assembly in place while injecting the fluid composition into the reservoir. However, it should be appreciated that in other variations, the delivery system may not include a lock. In the variant with a lock, the lock is removable from the delivery system (otherwise releases the fluid assembly) to allow the fluid assembly to translate relative to the housing after filling the reservoir. It may be desirable. As described in more detail herein, translation of the fluid assembly may allow extension of the slidable elongate member and / or injection of the fluid composition during a procedure.

  In variants of the delivery system with a lock, the lock may optionally further act as a cap to protect the distal opening to the reservoir. In these variations, the lock has a first configuration in which it holds the reservoir in place and covers the proximal opening to the reservoir, and which holds the reservoir in place. A second configuration that allows access to the proximal opening to the reservoir, thereby allowing the reservoir to be filled with the fluid composition. In some examples, the lock may alternate from the first position to the second position.

  25A-25D illustrate an exemplary lock (2502). As shown therein, the lock (2502) may comprise a pin (2508) configured to fit into an opening (2504) in the handle (2506) of the delivery system (2500). In the first configuration, as shown in FIG. 25B, the lock (2502) may be inserted into the opening (2504) in the handle and may cover the proximal opening (2510). Lock (2502) may comprise a protrusion (2518) configured to mate with proximal opening (2510) to stabilize the lock in the first configuration. In the second configuration, as shown in FIGS. 25C-25D, the lock (2502) may remain inserted in the opening (2504) but pivot within the opening (2510). Exposing the may allow filling of the reservoir (2512). When the pin (2508) is inserted into the opening (2504), the pin may limit movement of the reservoir (2512) relative to the housing. This allows the filling device (2514) to apply a force through the proximal opening (2510) to allow the reservoir to proximally seal the reservoir (2512) without sliding distally within the handle (2506). It may be possible to open the stop (2516). Restricting movement of the reservoir (2512) relative to the handle (2506) may prevent movement of the reservoir or other internal components of the delivery system prior to use (eg, during shipping). Once the reservoir (2512) is filled, the lock (2502) may be removed from the opening (2504), as shown in FIG. 25A, at which point the reservoir (2512) is no longer locked by the housing. You may no longer be restricted from moving.

Delivery of Fluid Compositions The delivery systems described herein can be configured to deliver fluids to Schlemm's canal. The fluid may be delivered in a volume that provides sufficient force to disrupt Schlemm's canal and surrounding trabecular tubule tissue. Exemplary disruption volumes are about 1 μl, about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl, about 11 μl, about 12 μl, about 13 μl, about 14 μl, about. It may be 15 μl, about 16 μl, about 17 μl, about 18 μl, about 19 μl, or about 20 μl. In some variations, the disrupted volume of fluid may range from about 1 μl to about 50 μl, or from about 20 μl to about 50 μl.

  As mentioned above, the elongate member may be coaxially disposed within the lumen of the cannula. In a variation of the delivery system configured to deliver the fluid composition, the elongate member may comprise a lumen. The lumen of the elongate member may be operably coupled to a reservoir for delivering the fluid composition to Schlemm's canal. The elongate member generally has a proximal end, a distal end, and a wall, the wall having a wall defining a lumen extending therethrough. However, in some examples, the delivery system lacks the elongated member conduit and the fluid composition is delivered only through the cannula. In another example, two elongate members may be used, each of which advances simultaneously through the canal both clockwise and counterclockwise to more rapidly cannulate Schlemm's canal. Deliver a therapeutic agent.

  When delivering a fluid composition using the delivery system, the fluid composition may be pre-filled in the reservoir of the system, or may be loaded prior to use of the system. An exemplary delivery system for delivering a fluid composition to Schlemm's canal is shown in FIGS. 10A and 10B. Referring to FIG. 10A, the delivery system (1000) includes a universal handle (1002) having a grip portion (1004) and a housing (1006). The housing (1006) has a proximal end (1008) and a distal end (1010). A cannula (1012) connects to and extends from the housing distal end (1010). The drive assembly (1014) is substantially contained within a housing (1006) that initiates movement of a slidable elongate member (not shown). The cannula (1012) and drive assembly (1014) have the same configuration as shown and described in FIGS. 3 and 4A-4B for the present system adapted for implantation of an intraocular device and will not be detailed here. ..

  The delivery system (1000) also includes a filling component (1018) configured to allow transfer of the fluid composition from an external source to the reservoir (1020) defined by the fluid assembly and the linear gear. Included within the handle (1002) has a fluid assembly (1016) (shown in FIG. 10B). A slidable elongate member (1022) is coaxially disposed within the lumen of the cannula in fluid communication with the reservoir. As mentioned above, for implant-based or instrument-based systems that do not deliver fluids, the system may not include a reservoir.

  In the exemplary method, the fluid composition may be transferred to the reservoir (1102) of the system (1100) by filling through the filling component (1104), as illustrated by FIGS. As shown in the drawing, the reservoir (1102) is defined by the fluid assembly (1106) and the linear gear (1108). The linear gear (1108) has a proximal end (1110) and a distal end (1112), and a lumen (1114) extending from the proximal end (1110) to the distal end (1112). The lumen (1114) is in fluid communication with the lumen (not shown) of the slidable elongate member (1118). To deploy the fluid composition from the reservoir (1102), the linear gear (1108) is retracted in the direction of the arrow (FIG. 11B) so that the reservoir (1102) is under pressure. Retraction can be accomplished by rotation of the pinion gear mechanism (1120). Once a sufficient amount of pressure has been created in the reservoir (1102), the fluid composition contained therein is injected through the lumen of the linear gear (1114) and the elongate member (1118) into Schlemm's canal. ..

  Here, any fluid to be delivered flows through distal end (1202) to Schlemm's canal. In other variations, the slidable elongate member (1300) can be configured to include a plurality of openings spaced along its axial length. The openings may have any suitable shape, for example slots (1302) (FIG. 13A) or circles (1304) (FIG. 13B). The fluid composition delivered using the elongate member shown in FIGS. 13A and 13B may exit the elongate member partially through the opening and partially through the distal end of the elongate member. The distal end of the elongate member may also be configured as a half tube (1306) (FIG. 13C).

  Some variations of the fluid assembly include a locking mechanism to prevent movement of the assembly within the handle, for example when the linear gear is advanced or retracted. The locking mechanism may also include a ratchet pawl, a combination of ratchet pawls, or any other suitable mechanism that may be locked to prevent movement of the fluid assembly and unlocked to allow movement of the fluid assembly. Good.

  23A-23F, another exemplary delivery system (2300) for delivering the fluid composition shown therein to Schlemm's canal is shown extending from a housing (2334) and a distal end of the housing. A cannula (2344) may be included. Drive assembly (2202) (discussed above with respect to FIGS. 22A-22D) is located within housing (2334), as fluid assembly (2316) may be (as described in more detail above). Good. As mentioned above, the drive assembly (2202) may include a linear gear (2204) and a pair of pinion gear mechanisms (2206) coupled to the wheels (2208). The delivery system (2300) may include a slidable elongate member (2336). The proximal end of the elongate member may be secured to the linear gear (2204), while the distal end of the elongate member may be slidably coaxially disposed within the lumen of the cannula (2334). The reservoir (2302) of the fluid assembly (2316) may be in fluid communication with the lumen of the elongate member. For example, a plunger (2338) with a lumen places the reservoir (2302) in fluid communication with the lumen of the elongate member. The proximal end (2350) of the plunger (2338) may be slidably positioned within the reservoir (2302) and the distal end (2352) of the plunger may be linear gear (2204) of the drive assembly (2202). It may be fixedly attached to.

  The fluid assembly (2316) and drive assembly (2202) may be connected by a linkage (2348), as best shown in FIG. 23D. (The delivery system (2300) is shown without the linkage assembly in FIG. 23A to better show the other components.) The linkage (2348) includes a fluid assembly (2316) and a drive assembly (2202). May be configured to move in unison and may allow limited movement of the fluid assembly and the drive assembly relative to each other. In some variations, the linkage (2348) may allow the fluid assembly (2316) to move closer, but not far from the drive assembly (2202). For example, the proximal end (2340) of the linkage (2348) may be fixedly attached to the fluid assembly (2316), as best shown in FIG. 23D. The distal end (2342) of the linkage (2348) may be attached to the linear gear (2204) of the drive assembly (2202) by a one-way ratchet. The distal end (2342) may be able to move distally along a track in the linear gear (2204), but the teeth in the track are proximal to the distal end (2342) along the track. Can resist the movement of. As such, the fluid assembly (2316) causes the linear assembly (2204) to move closer together (by shortening the portion of the linkage (2348) between the fluid assembly and the linear gear). The fluid assembly may not be able to move proximally away from the linear gear, although it may be able to move distally towards. It should be appreciated that in other variations, the linkage may be fixedly attached to the linear gear and slidably attached to the fluid assembly.

  As such, the linear gear (2204) and fluid assembly (2316) may be movable relative to each other and may be movable within the housing (2334). Movement of the linear gear (2204) and the fluid assembly (2316) relative to each other and relative to the housing (2334) may cause one or more effects, which include extension and storage of the slidable elongate members, and And / or delivery of the fluid composition. More specifically, the proximal end (2350) of the plunger (2338) is slidably positioned within the reservoir (2302) and the distal end (2352) of the plunger is fixedly attached to the linear gear (2204). As such, movement of the reservoir closer to the linear gear may cause proximal movement of the plunger within the reservoir. This increases the length of the plunger (2338) located within the reservoir (2302). The portion of the plunger (2338) within the reservoir (2302) may displace the fluid within the reservoir. The displaced fluid may travel distally through the lumen of the plunger (2338) and through the lumen (2336) of the elongate member and may be delivered from a distal opening in the lumen of the elongate member.

  Additionally, as described above, movement of linear gear (2204) relative to housing (2334) may cause slidable elongate member (2336) to extend or retract. The linear gear (2204) may be movable between the proximal and distal portions by rotation of the wheel (2208), while the wheel (2208) remains fixed relative to the housing (2334). . The proximal end of the elongate member is secured to the linear gear (2204) and the distal end of the elongate member may be slidable within the lumen of the cannula (2344) so that the drive assembly (2202) is proximal. When in the position, the elongate member can correspondingly be in the retracted position relative to the cannula (2344). The distal end of the elongate member may be located within the cannula (2344) (eg, proximal to the distal tip of the cannula) when the elongate member is in the retracted position. When the drive assembly (2202) is in the distal portion, the elongate member may correspondingly be in an extended position relative to the cannula (2344). When the elongate member (2336) is in the extended position, the distal end of the elongate member may extend from the cannula (eg, distal to the distal tip of the cannula).

  The relative movement of the drive assembly (2202), the fluid assembly (2316), and the housing (2334) thus causes the slidable elongate member (2336) to extend within the Schlemm's canal and causes the elongate member within the Schlemm's canal. It can be used to deliver fluid at the same time it is stored in. The delivery system (2300) may begin in a configuration in which the fluid assembly (2316) and the linear gear (2204) are separated over the length of the linkage (2348), the fluid assembly being proximal to the housing (2334). The end-located, slidable elongate member is in a retracted position within the cannula (2344). This configuration is shown in Figures 23A-23D. Wheels (2208) may rotate in a first direction to advance linear gear (2204) distally within housing (2334). The linkage (2348) moves the fluid assembly (2316) equidistantly distally within the housing to maintain separation between the fluid assembly and the linear gear (2204). As the linear gear (2204) advances, the elongate member (2336) can move from the stowed position to the extended position. This allows the elongate member (2336) to move through Schlemm's canal. This configuration is shown in Figure 23F, which shows the delivery system (2300) without the top of the housing (2334) to show the linear gear (2204) in the distal position. As can be seen there, the elongate member (2336) is in an extended position relative to the cannula (2344) and the fluid assembly (2316) is also in a distal position within the housing (2334).

  Wheels (2208) may then rotate in a second direction to retract linear gear (2204) proximally within housing (2334). This allows the slidable elongate member (2336) to move from the extended position to the stowed position. However, the fluid assembly (2316) may not correspondingly move proximally within the housing (2334). The housing (2334) may include inner teeth (2446) near the fluid assembly (2316) configured to engage outer teeth on the fluid assembly. These teeth may allow the fluid assembly (2316) to move distally within the housing (2334) but not proximally within the housing. As such, when the linear gear (2204) is stored in the housing (2334), the fluid assembly (2316) may remain fixed relative to the housing. The linear gear (2204) and fluid assembly (2316) thus move closer together, and the linkage (2348) moves distally along a trajectory in the linear gear (2204) to accommodate this movement. . As linear gear (2204) and fluid assembly (2316) move closer together, plunger (2338) may displace fluid within reservoir (2302), as described in more detail above. Fluid may then travel through the lumen of the plunger (2338) and be delivered through the lumen of the elongate member (2336).

  In this manner, fluid can be delivered from the elongate member at the same time as the elongate member is stored. The fluid may replace the elongate member when the elongate member is retracted, so that the fluid can be delivered to the angle and length of Schlemm's canal that is the same as the angle and length to which the elongate member has been advanced. . A constant and predetermined volume of fluid may be delivered to a given amount of storage of the elongate member due to displacement of the fluid in the reservoir by the plunger, the elongate member storage and fluid composition Delivery may be accomplished by a single user movement (wheel (2208) rotation). In some examples, full containment of the elongate member may result in delivery of about 2 μl to about 9 μl of fluid. In some of these examples, full containment of the elongate member may result in the delivery of about 4.5 μl of fluid. The delivery system (2300) may produce incremental audible and / or tactile clicks when the elongate member (2336) is retracted. These clicks may be due, for example, to ratcheting of the distal end (2342) of the linkage (2348), which is distal to the linear gear (2204). Each click may correspond to a constant and predetermined volume of fluid, in some cases about 0.5 μl.

  In some variations, the delivery system may be configured to allow for a constant cumulative amount of extension and / or storage of the slidable elongate member. The constant cumulative amount of extension / retraction may correspond to, for example, the entire circumference of Schlemm's canal, two full circumferences of Schlemm's canal, or any desired distance. An exemplary constant cumulative amount can be from about 39 mm to about 41 mm, about 38 mm to about 40 mm, about 35 mm to about 45 mm, about 78 mm to about 82 mm, about 76 mm to about 80 mm, or about 70 mm to about 90 mm, It is not limited to these. Additionally or alternatively, the delivery system may be configured to allow for a constant cumulative delivery of fluid (eg, in some variations about 9 μl of fluid). For example, in the delivery system (2300), as described above, the fluid assembly (2316) may move distally within the housing (2334), but not proximally within the housing. The assembly can move towards the linear gear (2204) but not away from the linear gear (2204). Thus, each extension of the slidable elongate member may move the linear gear (2204) and fluid assembly (2316) distally, while each retracting elongate member causes the linear gear to move proximally. While moving, the fluid assembly may remain fixed. The delivery system (2300) may include a stop (eg, a protrusion on the inner wall of the housing) that may prevent the fluid assembly (2316) from moving beyond a certain point distally. When the fluid assembly (2316) reaches its most distal portion, either the fluid assembly or the linear gear (2204) may not move distally or proximally and the wheels (2208) may not rotate further. is there. The distance between the initial position of the fluid assembly (2316) and its final re-distal position determines a constant cumulative amount of extension / retraction of the slidable elongate member and a constant cumulative delivery of fluid. You can However, it should be appreciated that other variations of the delivery system may not have a limited cumulative amount of elongate member extension and / or storage. This means that some delivery systems may be able to be repeatedly extended and stored without certain restrictions.

  It should be appreciated that the delivery system (2300) may advance and retract the slidable elongate member multiple times as long as the total cumulative amount is below the limit. Indeed, in some variations, the maximum amount that the elongate member can advance without being retracted can be less than its total progressive amount. For example, the elongate member may be advanced a first time about half way around Schlemm's canal in the first direction (ie, 180 degrees, or about 19 mm to about 20 mm), which stores the elongate member. It can be the maximum amount that can be advanced without. The elongate member may then be fully retracted (while the fluid may be delivered). After this first extension, the fluid assembly (2316) may have traveled half its maximum distance and its distance to the linear gear (2204) is approximately half of all possible reductions. May be decreased by. The delivery system (2300) may then rotate about the handle and the elongate member may advance a second time about half way around Schlemm's canal in a second direction. The elongate member may then be retracted (while the fluid may be delivered). Upon completion of the second extension, the fluid assembly (2316) may be located in its most distal position and its distance to the linear gear (2204) may be its minimum. At this point, the elongate member may not be advanced any further, no further fluid may be delivered, and the wheel may not rotate any further.

Devices Not Configured to Deliver Fluids It should be understood that not all delivery systems described herein are configured to deliver fluid compositions. A device that is not configured to deliver a fluid composition may operate similar to a delivery system that is configured to deliver the fluid composition, but the storage or advancement of the elongate member is performed simultaneously with the fluid composition. May not cause delivery. In some examples, the delivery system may be the same one configured to deliver the fluid composition, but may not be filled with the fluid composition. In other examples, the elongate member of the delivery system that is not configured to deliver the fluid composition need not include a lumen. Similarly, a delivery system that is not configured to deliver a fluid composition need not include a reservoir or plunger. Instead of a reservoir, the delivery system may include a solid surrogate component that has a similar profile to the fluid assembly. The surrogate component may be connected to the linear gear of the delivery system via a linkage that may or may not be integral with the surrogate component. This allows many of the components to be compatible between a delivery system configured to deliver a fluid composition and a delivery system not configured to deliver a fluid composition. Can be simplified. Thus, a system that is not configured to deliver a fluid, such as a delivery system that is configured to deliver a fluid, will have a fixed cumulative amount of delivery as described in more detail herein. And / or may or may not be configured to allow storage.

  Some delivery systems that are not configured to deliver a fluid composition may be configured such that the elongate members disrupt the trabecular meshwork. In some variations, the elongate member may be configured such that advancement and / or storage of the elongate member may disrupt the trabecular meshwork during advancement or storage. One or more features for facilitating may be provided, for example a splitting component at the distal end of the elongate member such as barbs, hooks, balloons, or the like. In other variations, the elongated member may be configured such that the body of the elongated member is configured to cut or tear the trabecular meshwork. For example, the delivery system may be configured such that the elongate member exits the cannula and advances around Schlemm's canal, and if the cannula is subsequently removed from the eye without retracting the elongate member, the elongate member is The fuselage may cut or tear the trabecular meshwork when the cannula is removed. The body of the elongate member is "unzipped" on the mesh to elongate from the first position of the trabecular meshwork near the cannula tip (ie, at the proximal end of the elongate member) and then around the trabecular meshwork. It may be configured to cut or tear towards the distal end of the member. The elongate member may be configured to apply a dividing force to cut or tear the mesh at one mesh position at a time, and subsequently around Schlemm's canal, wherein the dividing force Do not simultaneously cut or tear the net across the trabecular meshwork to be cut or torn.

Implantation of Intraocular Devices The cannulas of the systems described herein may also deliver various surgical instruments by the Abinterno method. For example, to access the Schlemm's canal and then create a hole, partial thickness cut, or perforation in an unobtrusive position or along the trabecular meshwork or the entire inner wall of the Schlemm's canal, a catheter, wire, Probes and other instruments can also be used with Abinterno. The surgeon also advances the instrument across the entire canal and through the outer wall of the collector channel to access the sclera and subconjunctival space (again, all by the Abinterno technique), with aqueous humor drained into it. Create an incision that creates a scleral space (lake) that can flow into the scleral vein or subconjunctival space, or reside in the scleral space or subconjunctival space and into the anterior chamber or Schlemm's canal And deliver the drained intraocular device by abinterno.

  When using the delivery system to implant an intraocular device, the cannula may include a slidable positioning element coaxially disposed within the lumen of the cannula. The slidable locating element generally includes an engagement mechanism for manipulation, eg, releasable engagement, advancement, and / or storage of an intraocular device. An exemplary engagement mechanism is shown in Figures 5-9.

  In FIG. 5A, the engagement mechanism (500) comprises a first jaw (502) and a second jaw (504). In these closed configurations (shown in FIG. 5A), the jaws (502, 504) are constrained within the cannula (512) and comprise an intraocular device (support) (508) and at least one fenestration (510) ( 506) is retained. As the jaws (502, 504) advance out of the cannula (512), they assume their open configuration, as shown in FIG. 5B, as the jaws are no longer constrained. Opening the jaws (502, 504) releases the intraocular device (506) from the engagement mechanism (500). At least one tine (514) may be provided in the first jaw (502) to help secure the fenestrated intraocular device when the jaw is in its closed configuration, at least 1 One aperture (516) may be provided in the second jaw (504). In Figure 6, a variation of the engagement mechanism (600) is shown, where the first jaw (602) and the second jaw (604) assist in grasping the fenestrated intraocular device (610). Therefore, it includes both the tines (606) and the apertures (608).

  7A-7B, a further exemplary engagement mechanism is shown. In FIG. 7A, the engagement mechanism (700) comprises complementary mating elements. Specifically, the engagement mechanism (700) includes a notch (702) that is a female element, which is shown as a complementary male element (704) shown as a hook-like protrusion on the intraocular device (706). ) Is configured to join. Here, the notch (702) may be manufactured at the end of the hypotube (708) (which may serve as a locator element). Instead of the notch (702), the female element of the engagement mechanism (710) may have an opening (712), as shown in Figure 7b, which is on the intraocular device (706). Mates with male element (704). In FIG. 7B, the locator element (714) may be manufactured from a metal wire or rod and the opening (712) is created by laser machining or other processes known in the art.

  In other variations, the engagement mechanism can be configured as shown in FIGS. 8A and 8B. In these figures, the engagement mechanism (800) comprises an annular portion (802). This particular engagement mechanism may be beneficial for use with an intraocular device (804) that includes a fastener (806) with arms or knobs (808) having a closed configuration and a deployed configuration. Similar to the variations shown in FIGS. 5A and 5B, the knob (808) is constrained within the cannula (810) in a closed configuration prior to advancement from the cannula (810). In these constrained configurations, the knob (808) engages the annular portion (802) of the engagement mechanism (800) to prevent release of the intraocular device (804) from the system. When the annular portion (802) of the engagement mechanism (800) is advanced sufficiently that the knob (808) is no longer constrained by the cannula (810), the knob (808) is moved into its position, as shown in FIG. 8B. The deployed configuration releases intraocular device (804) from annular portion (802) into Schlemm's canal.

  Another exemplary engagement mechanism (900) comprising a coiled portion (902) and a hook (904) is shown in FIG. When an intraocular device (906) having at least one fenestration (908) (eg, a proximal fenestration) is implemented, the hook (904) may releasably engage the fenestration (908). . The intraocular device (906) is a separate component () that can be advanced on the coil (902) or advanced over the coil (902) to push the device (906) out of the hook (904). Can be disengaged from the hook (not shown). It may be advantageous to use the hook (904) when storage of the intraocular device (906) is desired.

  The intraocular delivery system may further include a slidable positioning element coaxially disposed within the lumen of the cannula for controlled implementation of the intraocular device in Schlemm's canal. The locator element generally comprises a proximal end, a distal end, and an engagement feature at the distal end. The intraocular device generally releasably couples to the engagement mechanism. The locator element may be advanced to deploy the intraocular device within the cannula into Schlemm's canal, or may be retracted to position and / or reposition the intraocular device or from an engagement mechanism of the intraocular device. May help disengage the.

  Some variations of the engagement mechanism include a proximal coiled portion and a distal hook. If an implant having at least one fenestration (eg, a proximal fenestration) is implemented, the hook can releasably engage the fenestration. Intraocular devices are shaped to disengage by the application of gentle force on the coil, or by another component that can be advanced over the coil to push the device out of the hook, or passively as it exits the cannula. The memory material may be used to disengage from the hook. It may be advantageous to use the hook when storage of the intraocular device is desired. The surgeon may simply move the delivery system and engagement mechanism so that they disengage from any fenestrations or notches on the implant.

  In another variation, the engagement mechanism includes opposing jaws. Here, the engagement mechanism may include a first jaw and a second jaw, the jaws having a closed configuration and an open configuration. The jaws may be used to grasp and manipulate the intraocular device to releasably couple the intraocular device to the positioning element. The jaws may be formed by splitting or bifurcating the distal end of the wire, for example by laser cutting. The gripping force of the jaw may be obtained by constraining the jaw within the cannula. The intraocular device may be released as the jaws are advanced and deployed from the cannula. The jaws may also be pivotally connected. In yet another variation, the first jaw may include at least one tine and the second jaw includes at least one aperture for receiving the tine when the jaw is in the closed configuration. But it's okay.

  In a further variation, the engagement mechanism comprises an annular portion. This variation of the engagement mechanism will typically be used with an intraocular device that includes a spring-like fastener at its proximal end that has a collapsed configuration and an expanded configuration. The fasteners are generally manufactured in the deployed position. Thus, when the device with the fastener is disposed within the cannula, the first and second arms or tabs of the fastener are folded around the annular portion of the engagement mechanism. As the pinned portion of the device exits the cannula, the arms or tabs may deploy to release the intraocular device from the annular portion.

  Yet another variation of the engagement mechanism involves male and female mating. For example, the engagement mechanism may comprise a notch configured to mate with a complementary mating element (eg, tab) on the intraocular device. The notch (female component) may be formed in the hypotube, or may be made by creating a fenestration through the distal end of a positioning element made of solid wire or element, the knob Alternatively, the hook (male component) may be formed as part of the intraocular device and inserted into a fenestration or notch in the positioning element. With this configuration, the intraocular device is positioned as it is advanced from the cannula, either by manipulation of the surgeon, or by the configuration of positioning elements that passively disengage it from the intraocular device, or both. Can be released from the element.

II. Kits The delivery system described herein may be placed in a specialized package. The package may be designed to protect the system, in particular to protect the cannula. It may be desirable for the package to prevent contact between the distal tip of the cannula and any other object or surface. To do so, the package may include one or more elements configured to secure the delivery system to the packaging at one or more locations proximal to the distal tip of the cannula. It may be desirable to secure the delivery system at at least two locations proximal to the distal tip of the cannula to limit the ability of the delivery system to pivot relative to the packaging.

  In one exemplary variation, the packaging has a recess having a shape that generally corresponds to the shape of the delivery system, and one or more corresponding ones that are configured to secure the delivery system proximal to the cannula. And a tray including the pinch points of. FIG. 26A shows an exemplary tray (2604) for the delivery system (2600). The tray (2604) may include a recess (2606) configured to receive the delivery system (2600). The tray (2604) is configured to secure the delivery system (2600) within the recess (2606), a first distal pinch point (2608) and a second distal pinch point (2610), And a first proximal pinch point (2612) and a second proximal pinch point (2614). When the delivery system (2600) is secured within the tray (2604), the delivery system cannula (2602) may be suspended so that the cannula does not contact the tray, and the pinch point is the cannula (2602). May limit pivoting of the delivery system (2600) in such a way that the) may come into contact with the tray. The pinch points may also be configured to secure the delivery system (2600) securely in the tray (2604) while allowing the user to remove the delivery system from the tray in a controlled manner. In variations in which the kits described herein include additional components, the packaging can be designed to retain these additional components. For example, FIG. 26B shows an exemplary tray (2626) with a recess (2628) configured to hold a filling device (2624) and a delivery system (2620). As shown in FIG. 26C, the tray (2640) may be configured to be sealed (eg, heat sealed) by a lid (2642) and placed in a box (2644). The box (2644) may optionally further contain instructions for use (2646). A label (2648) may optionally be affixed to the lid (2642) and / or the box (2644).

  It should be appreciated that the packaging may have other configurations that protect the distal tip of the cannula. For example, in another variation, the packaging may comprise a rigid planar sheet to which the delivery system may be attached in an orientation such that the cannula does not contact the planar sheet. The delivery system may be attached at two or more points along the housing to prevent movement of the delivery system with respect to the flat sheet (eg, by lace or other material wrapped around the housing). It may be desirable to protect the cannula on at least two sides. For example, a portion of the flat sheet proximate the cannula may be bent around the cannula to protect the cannula on at least two sides, or a second rigid flat sheet may be provided on the opposite side of the first flat sheet. May be attached to the delivery system at.

  Some kits described herein may include multiple delivery systems. For example, the kit may include two delivery systems. In some variations, the kit may comprise two of the same systems such that, for example, the first delivery system may be used on the first eye of the patient and the second delivery system on the first eye of the patient. Can be used in two eyes. In other variations, the kit may comprise two different systems. For example, the first delivery system may be configured to deliver the fluid composition and the second delivery system may not be configured to deliver the fluid composition, but instead the elongated member. May be used to divide the trabecular meshwork. Kits with multiple systems can be packaged in any suitable manner. For example, FIG. 27A shows a kit with two delivery systems (2700, 2702) in a stacked configuration (shown without outer packaging), and FIG. 27B shows a kit with two delivery systems (2704, 2706) side by side. Shown in the configuration shown (without outer packaging). Again, the delivery systems (2700, 2702) may both be configured to deliver a fluid composition and both may not be configured to deliver a fluid composition (eg, deliver an elongate member). May be configured to disrupt the trabecular meshwork), or one may be configured to deliver the fluid composition and the other not. Similarly, the delivery systems (2704, 2706) may both be configured to deliver a fluid composition, both may be configured to not deliver a fluid composition, or one is a fluid composition. May be configured to deliver, and the other may not.

  Some kits may include an intraocular implant in addition to one or more delivery systems described herein. For example, the kit may comprise one or more devices configured to be embedded in Schlemm's canal, which generally do not significantly interfere with transmural fluid flow across the canal without significant interference with Schlemm's canal. Can be configured to maintain patency of the. The kit may include one or more intraocular implants, such as, but not limited to, a stent for placement in Schlemm's canal. In some variations, intraocular implants are described in US Pat. No. 7,909,789, which is hereby incorporated by reference in its entirety, and US Pat. It may be one or more of those disclosed in No. 8,529,622. In one variation, the device may comprise a twisted ribbon member, which is substantially with respect to the first elongated edge, the second elongated edge and the central longitudinal axis of the twisted ribbon member. And a plurality of struts extending between these elongated edges in a vertical direction. The struts may define a plurality of fenestrations spaced along at least a portion of the length of the twisted ribbon member.

III. Methods There are also methods for treating an ocular condition and / or implanting an intraocular device, delivering a fluid composition to Schlemm's canal and / or delivering an instrument to Schlemm's canal using the above system. Provided. In some examples, treating an ocular condition can lead to increased aqueous humor drainage, reduced resistance to aqueous humor outflow, and / or reduced intraocular pressure. Some methods described herein can expand Schlemm's canal, expand collector channels, and / or disrupt any septum that can occlude circumferential flow through Schlemm's canal. Expansion of Schlemm's canal can disrupt the occluded inner wall of the canal, pull the trabecular meshwork, and / or increase the porosity of the trabecular meshwork. This improves the natural outflow of aqueous humor. Expansion can be accomplished by advancing an instrument (eg, a slidable elongate member described herein). Additionally or alternatively, expansion may be accomplished by delivering a fluid composition (eg, a viscoelastic fluid described herein). Additionally or alternatively, some methods described herein may include performing travectomy to cut the trabecular meshwork. Additionally or alternatively, some methods described herein may include implanting the intraocular device in Schlemm's canal. In some examples, using the system described herein, abinterno trabectomy, abinterno transluminal trabectomy, transparent corneal travectomy, transparent corneal transluminal trabectomy, abinter Tube angioplasty and / or transparent corneal tube angioplasty may be performed. The delivery system may also, in some instances, dissolve anterior chamber adhesions, viscogonoplasty with viscoelastic substances, assist in intraocular lens replacement, raise a dropped lens or foreign body, and / or It may be used to relocate the escaped iris tissue.

  The method is generally minimally invasive and is a single operator, one-hand controlled method, for example, which may be advantageous over the more invasive ab externo procedures as described above. Adapted to the Intelno procedure. However, the use of the intraocular system in the Ab Externo method is contemplated in some examples and is not excluded here. Methods for delivering intraocular devices or fluids or methods for providing disruption forces may be used to treat or prevent glaucoma, pre-stage glaucoma, or ocular hypertension. When treating glaucoma, the method may also be used using the same incision during the same session, or at another time, in combination (before or after) with cataract surgery.

  Some of the methods, described in more detail below, use the delivery systems described herein to expand Schlemm's canal and / or aqueous humor collector channels (eg, by viscoelastic fluid). May be included. Another of the methods, also described in more detail below, may include tearing or cutting the trabecular meshwork of Schlemm's canal. These methods may be performed separately or combined into a single procedure. For example, in some examples, a portion (eg, half) of Schlemm's canal may be dilated (eg, using a fluid composition or device, or both), and the same or different portions of Schlemm's canal may be used. Trabecular meshwork can be torn or severed in the same eye. As another example, all of Schlemm's canal may be expanded and then all or part of the trabecular meshwork subsequently torn or severed. This may be desirable, for example, to both expand the collector channel and tear or cut the trabecular meshwork.

  In some of these variations, expanding and tearing or severing a single delivery system, such as those described herein, configured to deliver a fluid composition. Can be done using. For example, the elongate member of the delivery system configured to deliver the fluid composition is first used to deliver the fluid composition as described herein to a portion of Schlemm's canal (e.g. 180 degree arc, about 90 degree arc of the canal), followed by tearing or cutting of the trabecular meshwork in the same portion of the canal as described herein. As another example, the elongate member of the delivery system configured to deliver the fluid composition is first used to deliver the fluid composition to a portion of Schlemm's canal (eg, about a 180 degree arc of canal, canal). Of the trabecular meshwork in a different portion of the canal (eg, one about a 180 degree arc, the other at a 90 degree arc, etc.) . As yet another example, the elongate member of the delivery system configured to deliver the fluid composition is first used to deliver the fluid composition to all of Schlemm's canal (eg, about 180 degrees fluid composition). May be delivered in a first direction and then a fluid composition of about 180 degrees in a second direction), followed by subsequent tearing or cutting of the entire 360 degree trabecular meshwork (eg, , By tearing or cutting the trabecular meshwork of about 180 degrees in a first direction, and then tearing or cutting the trabecular meshwork of about 180 degrees in a second direction).

  In other variations, expanding and tearing or severing may be performed using different delivery systems (eg, expanding is configured to deliver a fluid composition. May be used, and the tearing or cutting may be performed using a delivery system that is not configured to deliver the fluid). As yet another example, in some cases the dilation may be performed in one eye of the patient while simultaneously tearing or cutting the trabecular meshwork in the other eye of the patient.

  Means for dilating Schlemm's canal and / or means for tearing or severing the trabecular meshwork deliver an intraocular device (discussed in more detail herein) to the same eye or to different eyes of the same patient. You may combine with a procedure. For example, the intraocular device may be inserted after dilating all or part of Schlemm's canal. As another example, a portion of the trabecular meshwork may be torn or severed while the intraocular implant may be delivered to another portion of Schlemm's canal. As yet another example, a portion of Schlemm's canal may be dilated and an intraocular implant may be delivered to another portion of Schlemm's canal at the same time. As yet another example, the intraocular implant may be delivered to a portion of Schlemm's canal, followed by dilation of Schlemm's canal to improve the function of the intraocular implant.

Intraocular Device Delivery Generally, methods for implanting an intraocular device in Schlemm's canal include first providing access to the anterior chamber of the eye through the eye wall (eg, sclera or cornea or corneal scleral limbus or junction). Creating an incision to make. As shown in the stylized depiction of the eye in FIG. 14, the cannula (1400) of the intraocular delivery system is then passed through the incision and at least partially across the anterior chamber (1402) to the trabecular meshwork ( (Not shown). The Schlemm's canal (ie, the lumen of Schlemm's canal) (1404) is then accessed by the distal curved portion (1406) of the cannula and the slidable positioning element (or, for example, a slidable instrument or guidewire). Or an elongate member (generally represented by element 1408) is advanced from the cannula to implant the intraocular device in Schlemm's canal or perform the procedure in either Schlemm's canal or adjacent trabecular tubule tissue. Alternatively, the fluid is delivered to the canal. However, in some instances, the elongated member may not be used, as any fluid delivered is delivered through the cannula. In yet a further variation, only the trabecular meshwork is pierced to deliver the fluid composition without having to go around Schlemm's canal.

  As mentioned above, in some variations, the cannula may be configured to include a proximal end and a distal curved portion, the distal curved portion including the proximal end, the distal end, and these ends. It has a radius of curvature defined between the parts. Here, the cannula may also include a body and a distal tip that directly engages the radius of curvature, eg, has a bevel adjacent the radius of curvature. In other variations, a straight cannula (ie, one that does not have a distal bend) may be used to access Schlemm's canal. The method also includes the steps of flowing fluid into the system (eg, to remove air from the system) and / or irrigating the surgical field to clear blood or improve visualization of the surgical field. But it's okay.

  Any suitable intraocular device that maintains the patency of Schlemm's canal or improves outflow of aqueous humor may be implanted by the systems described herein. For example, an intraocular device may be implanted that maintains the patency of Schlemm's canal without significantly interfering with fluid flow across, along, or out of the canal. Such a device may comprise a support having at least one fenestration, which has been previously incorporated by reference in US Pat. No. 7,909,789 and US Pat. No. 529,622. Intraocular devices that disrupt the inner wall of the proximal canalicular trabecular meshwork or the adjacent Schlemm's canal may also be implanted. In addition to intraocular devices made from metals or metal alloys, sutures, modified sutures, modified polymers, polymer filaments, or solid viscoelastic structures may be delivered. Fluid compositions such as saline, viscoelastic fluids, air, drug mixtures or solutions, and gases may also be delivered.

  When delivering a fluid composition to Schlemm's canal, the method generally involves creating an incision in the eye wall (eg, the sclera or cornea) that provides access to the anterior chamber of the eye, an intraocular delivery system. Advancing the cannula through this incision at least partially across the anterior chamber into the trabecular meshwork, using the cannula to access Schlemm's canal, and an elongated member slidable within the lumen of the cannula. Is used to deliver the fluid composition to the canal. The cannula may be configured to include a proximal end and a distal curved portion, the distal curved portion having a proximal end and a distal end and a radius of curvature defined between the ends. . Here, the cannula may also include a body and a distal tip that directly engages the radius of curvature, eg, has a bevel adjacent the radius of curvature. Further advantageous cannula features may be included and have been described above. The method also includes the steps of flowing fluid into the system (eg, to remove air from the system) and / or irrigating the surgical field to clear blood or improve visualization of the surgical field. But it's okay.

  When using the Abinterno method for implanting an intraocular device, the method may include the following steps. The surgeon may first view the anterior chamber and trabecular meshwork (Schlemm's canal underlying) using a surgical microscope and a gonioscope or gonioprism. The surgeon may then gain access to the anterior chamber using a corneal, limbal, or sclerotomy of 0.5 mm or greater. A saline solution or viscoelastic composition may then be introduced into the anterior chamber to prevent it from collapsing. Here, the saline solution or viscoelastic composition may be delivered through the delivery system cannula or otherwise, eg, by injection through an irrigation sleeve on the cannula. The surgeon then advances the delivery system cannula through the incision towards the anterior chamber angle under direct microscopy visualization. Upon approaching the angle (and thus the trabecular meshwork), the surgeon may apply a gonioscope or gonioprism to the cornea to visualize the angle. Application of fluids (eg viscous solutions or viscoelastic compositions as previously described) and / or gonioscopes or gonioprisms to the cornea is achieved by achieving good optical contact and eliminating total internal reflection. , May allow visualization of the anterior chamber angle. Once the surgeon visualizes the trabecular meshwork, the bevel at the distal end of the curved distal portion of the cannula may then be advanced to pierce the mesh and communicate with the lumen of Schlemm's canal. The surgeon may irrigate the canal or anterior chamber with saline or a viscoelastic composition to prevent the anterior chamber from collapsing, dilate Schlemm's canal, or interfere with cannula visualization and intraocular device delivery. Can wash away any blood. Once the intraocular device has been advanced to the extent desired by the surgeon, the device may disengage from the engagement mechanism resulting in its presence in Schlemm's canal. If repositioning of the intraocular device is needed or desired, the surgeon may use the positioning elements of the delivery system to retract and / or reposition the intraocular device. The surgeon may then withdraw the delivery system from the eye.

  Other variations of the Abinterno method for implanting intraocular devices include the use of endoscopes. Similar to the above method, the anterior chamber is first accessed by making an incision in the cornea, limbus, or sclera. Again, this may be done in conjunction with the cataract surgery, either before or after the cataract surgery, or independently. The anterior chamber may be infused with saline solution or the viscoelastic composition may be placed in the anterior chamber to prevent it from collapsing. The saline or viscoelastic material may be delivered as a separate step, or may be injected using an elongated member of the delivery system, an irrigation sleeve on the elongated member or cannula, or a separate infusion cannula. The surgeon then advances the endoscope through the incision toward the comer and trabecular meshwork under direct microscopy visualization. As the surgeon visualizes the trabecular meshwork using an endoscope or any associated video display, the bevel of the cannula is advanced to puncture the mesh. The intraocular device is then advanced using the positioning element under endoscopic visualization. The surgeon may irrigate the canal or anterior chamber with saline or a viscoelastic composition to prevent the anterior chamber from collapsing, dilate Schlemm's canal, or interfere with cannula visualization and intraocular device delivery. Can wash away any blood. Once the intraocular device has been advanced to the extent desired by the surgeon, the device may disengage from the engagement mechanism, resulting in its presence in Schlemm's canal. If repositioning of the intraocular device is needed or desired, the surgeon may use the positioning elements of the delivery system to retract and / or advance the intraocular device. The surgeon may then withdraw the delivery system from the eye.

Fluid Composition Delivery Some methods described herein may include delivering the fluid composition into the eye, such as within Schlemm's canal. In some methods, an elongate member with a lumen may be advanced into Schlemm's canal and the fluid composition may be delivered through the elongate member. Delivery of both the elongate member and fluid may expand Schlemm's canal and fluid delivery may further expand the collector channel. For delivery of fluid compositions, the method is similar to implanting an intraocular device. However, instead of using a positioning element, the delivery system may use a slidable elongate member to inject a fluid composition into Schlemm's canal.

  The fluid composition may be delivered to dilate Schlemm's canal. The entire length of Schlemm's canal or a portion thereof can be expanded by fluid. For example, at least 75%, at least 50%, at least 25%, at least 10%, or at least 1% of the canal may be expanded. The fluid composition may also be delivered to treat various medical conditions of the eye, including: glaucoma, pre-stage glaucoma, anterior or posterior neovascular disease, anterior or posterior vascular disease. Inflammatory diseases, ocular hypertension, uveitis, age-related macular degeneration, diabetic retinopathy, hereditary eye disorders, complications of cataract surgery, vascular occlusion, vascular diseases, or inflammatory diseases, It is not limited to these.

  The surgeon may first view the anterior chamber and trabecular meshwork (Schlemm's canal underlying) using a surgical microscope and a gonioscope or gonioprism. The surgeon may then gain access to the anterior chamber using a corneal, limbal, or sclerotomy of 0.5 mm or greater. A saline solution or viscoelastic composition may then be introduced into the anterior chamber to prevent it from collapsing. Here, the saline solution or viscoelastic composition may be delivered through the delivery system cannula or otherwise, eg, by injection through an irrigation sleeve on the cannula. The surgeon then advances the delivery system cannula through the incision towards the anterior chamber angle under direct microscopy visualization. Upon approaching the angle (and thus the trabecular meshwork), the surgeon may apply a gonioscope or gonioprism to the cornea to visualize the angle. Application of various fluids (e.g. viscoelastic compositions as described above) and / or gonioscopes or gonioprisms to the cornea is achieved by achieving good optical contact and eliminating total internal reflection. It may allow visualization of the anterior chamber angle. Once the surgeon visualizes the trabecular meshwork, the bevel at the distal end of the curved distal portion of the cannula may then be advanced to pierce the mesh and communicate with the lumen of Schlemm's canal.

  A slidable elongate member coaxially disposed within the lumen of the cannula may then be advanced into the canal under visualization with a goniscope. The elongate member may be advanced in any suitable amount and direction around the canal. For example, the elongate member may be about 1 degree to about 360 degrees around the canal, about 10 degrees to about 360 degrees around the canal, about 150 degrees to about 210 degrees around the canal, or any suitable distance from the canal. About 360 degrees around, about 270 degrees around the canal, about 180 degrees around the canal, about 120 degrees around the canal, about 90 degrees around the canal, about 60 degrees around the canal, around the canal You may advance about 30 degrees, or about 5 degrees around the canal. In some variations, the elongate member is configured in two steps, for example, first in a clockwise direction around the canal (eg, about 180 degrees, about 90 degrees, etc.) and then in a counterclockwise direction (eg, about 180 degrees, (Eg, about 90 degrees) (e.g., thereby achieving a 360 or 180 degree abinternobisco canalostomy or angioplasty). Fluid may be injected upon advancement or storage of the elongate member. Once the slidable elongate member is positioned within the canal, the fluid composition, eg, viscoelastic solution, may be delivered continuously or intermittently through the lumen of the elongate member. The fluid composition exits the lumen of the elongate member through its distal end (eg, through the distal tip), through an opening or fenestration provided along its shaft, or a combination of both. The openings or fenestrations can be spaced along the axial length of the elongate member in any suitable manner, eg, symmetrical or asymmetrical along its length. If desired, other substances such as drugs, air, or gases may be delivered in the same manner.

  In some variations, the slidable elongate member may be repositioned by retraction or repeated advancement and retraction. Some variations of the method may use the same or different incisions, but to access and dilate Schlemm's canal from different directions (eg, counterclockwise instead of clockwise). Use a delivery system cannula. Once the sufficient amount of fluid has been delivered, the surgeon may retract the slidable elongate member into the cannula and remove the delivery system from the eye. The cannula described herein may be specifically manufactured to have a two-surface configuration (ie, a sharp surface and a smooth surface) at the distal tip, which allows the elongate member to be located on the distal tip of the cannula. It should be appreciated that it may be possible to advance, reposition, and / or retract without disrupting it. It should also be appreciated that these steps may be used alone or in combination (at one time) with cataract surgery.

  Some of the delivery systems described herein can be configured to limit the cumulative amount of advancement and / or storage of the slidable elongate member. For example, as described above, the elongate member may have a certain cumulative distance (eg, about 39 mm to about 40 mm each for advancing and retracting, corresponding to an approximate circumference of Schlemm's canal; or about the circumference of Schlemm's canal). Corresponding to a doubling, after advancing and retracting by advancing and retracting, respectively, about 78 mm to about 80 mm; or any other suitable distance), no further advancement is possible. This advancement and storage can occur over multiple advancement storage cycles. For example, the elongate member may be advanced about 20 mm, then stored about 20 mm, then advanced about 20 mm, and then stored about 20 mm. If the cumulative distance is limited to about 40 mm, the elongate member may not be able to advance further after these two cycles of advancement and storage.

  In some variations of the Abinterno method, the fluid composition may be delivered at the same time as the elongate member is retracted (ie, the fluid composition is advancing fluid from the cannula of the system by retracting the system components. May be delivered in a manner that allows for). Referring again to FIGS. 11A-11C, the linear gear (1108) is retracted in the direction of the arrow (FIG. 11B) so that the reservoir (1102) remains pressurized. Retraction can be accomplished by rotation of the pinion gear mechanism (1120). Once a sufficient amount of pressure has been created in the reservoir (1102), the fluid composition contained therein is injected through the linear gear lumen (1114) and elongate member (1118) into Schlemm's canal. It should be appreciated that the intraocular delivery system may be configured to deliver the fluid composition continuously, passively, automatically, or actively by the surgeon. The fluid composition may also be delivered canal by a pump or an auxiliary plunger independent of movement of the gear shaft. In some variations, storage of the elongated member may correspond to a volume of fluid composition delivered through the lumen of the elongated member. The fluid composition may be delivered as it is stored through a distal opening in the lumen of the elongate member, such that the fluid is delivered evenly throughout the portion of the canal that the elongate member advances. obtain.

  The present fluid compositions that can be delivered by the intraocular devices described herein include, but are not limited to, saline and viscoelastic fluids. The viscoelastic fluid may include hyaluronic acid, chondroitin sulfate, cellulose, derivatives or mixtures thereof, or solutions thereof. In one variation, the viscoelastic fluid comprises sodium hyaluronate. In another variation, the viscoelastic composition may further include a drug. For example, the viscoelastic composition may include a drug suitable for treating glaucoma, reducing or reducing intraocular pressure, reducing inflammation, fibrosis, angiogenesis, or scarring, and / or preventing infections. The viscoelastic composition may also include agents that aid visualization of the viscoelastic composition. For example, dyes such as, but not limited to, fluorescein, trypan blue, or indocyanine green may be included. In some variations, fluorescent or bioluminescent compounds are included in the viscoelastic composition to aid in its visualization. In another variation, the system delivers only the drug without the viscoelastic composition. In this case, the drug may be loaded onto or into a sustained release biodegradable polymer that will elute the drug over weeks, months, or years. It is also contemplated to deliver air or gas using the system as described herein.

  Another variation of the Abinterno method for delivering a fluid composition involves the use of an endoscope. Similar to the method just described, the anterior chamber is first accessed by making an incision in the cornea, limbus, or sclera. Again, this may be done in conjunction with the cataract surgery, either before or after the cataract surgery, or independently. The anterior chamber may be infused with saline solution or the viscoelastic composition may be placed in the anterior chamber to prevent it from collapsing. The saline or viscoelastic material may be delivered as a separate step, or may be injected using an elongated member of the delivery system, an irrigation sleeve on the elongated member or cannula, or a separate infusion cannula. The surgeon then advances the endoscope through the incision toward the comer and trabecular meshwork under direct microscopy visualization. When the surgeon visualizes the trabecular meshwork with an endoscope or any associated display, the bevel of the cannula is advanced to puncture the mesh. Thereafter, the elongated member is advanced under endoscopic visualization. The elongate member may be advanced in any suitable amount and direction around the canal. For example, the elongate member may be advanced about 10 degrees to about 360 degrees around the canal in two steps, for example 180 degrees clockwise around the canal and 180 degrees counterclockwise (thus. Achieve all 360 degrees Abu Internobisco Kanalostomy), you may move forward. Once the elongate member is positioned within the canal, the fluid composition, eg, viscoelastic fluid, may be delivered continuously or intermittently through the lumen of the elongate member. The fluid composition exits the lumen of the elongate member through its distal end (eg, through the distal tip), through an opening or fenestration provided along its shaft, or a combination of both. The openings or fenestrations can be spaced along the axial length of the elongate member in any suitable manner, eg, symmetrical or asymmetrical along its length. If desired, other substances such as drugs, air, or gases may be delivered in the same manner. The elongate member may be repositioned by retracting or repeated advance and retract. Some variations of the method may use the same or different incisions, but to access and dilate Schlemm's canal from different directions (eg, counterclockwise instead of clockwise). Use a delivery system cannula. Once the sufficient amount of fluid has been delivered, the surgeon may retract the slidable elongate member into the cannula and remove the delivery system from the eye.

  One variation described herein is illustrated in Figures 28A-D, which may be performed using the delivery system described with respect to Figures 23A-23F. FIG. 28A shows a flow chart illustrating the method. The method shown therein allows for one-handed manual delivery of fluid (eg, viscoelastic fluid or gel) to Schlemm's canal via a slidable elongate member (eg, microcatheter) having a lumen. obtain. Viscoelastic fluid delivery can be metered such that a controlled small amount of viscoelasticity can be delivered to the eye. The method may allow 360 degree catheterization of the Schlemm's canal and a transluminal viscoelastic viscodulation using a single transparent corneal incision for access. This can reduce intraocular pressure, for example in patients suffering from glaucoma, such as open-angle glaucoma.

  First, the delivery system can be removed from its packaging. The delivery system may then be filled with the viscoelastic fluid. A filling device (eg, a nozzle) that can be supplied with the delivery system in the kit can be attached to the viscoelastic cartridge. Suitable commercially available viscoelastic materials include, but are not limited to, Healon ™, Healon GV ™, Amvisc ™, and PROVISC ™. The filling device can then be flushed with the viscoelastic material. The lock on the proximal end of the delivery system can then be rotated (while still attached to the handle of the device device) to expose the proximal opening in the device. The nozzle may then be inserted into the proximal opening and the viscoelastic fluid injected from the viscoelastic cartridge into the reservoir of the delivery system. It may be desirable to hold the delivery system and viscoelastic cartridge upright during injection. The viscoelastic fluid may be injected until the flow of viscoelastic material from the distal tip of the cannula is visible. The lock is then removed from the delivery system.

  The cannula may be advanced through the existing cornea or scleral incision into the anterior chamber to deliver the viscoelastic fluid into the eye. It may be desirable for the incision to be at least about 1 mm wide. The distal tip of the cannula may be used to puncture the trabecular meshwork and enter Schlemm's canal. The cannula may be held stationary with respect to the angle while advancing the elongate member into Schlemm's canal. One or more exposed portions of the wheels of the drive assembly have elongated members up to about 180 degrees around Schlemm's canal (about 18 mm, about 19 mm, about 20 mm, about 18 mm to about 20 mm, or about 15 mm to about 25 mm. Canal rotation in the circumferential direction). At this point, the elongate member may be fully extended and the wheel may not be allowed to rotate any further. During this procedure, visualization of the cannula tip by direct microscopy or gonioscopy may be maintained and the anterior chamber may be maintained by viscoelastic or continuous balanced saline infusion.

  Thereafter, one or more wheels may be rotated distally to retract the elongate member. When storing the elongate member, a particular predetermined volume of viscoelastic material may be continuously delivered from the lumen of the elongate member in a metered manner, which is due to the viscoelastic material of Schlemm's canal and / or the collector channel. Can cause expansion. In some variations, full containment of the elongate member results in delivery of about 2 μl to about 9 μl of viscoelastic fluid (eg, about 4.5 μl of viscoelastic fluid). The wheels may be configured to rotate incrementally with audible and / or tactile clicks during incremental rotation, and in some cases about 0.5 μl of viscoelastic fluid is delivered with each click. obtain. Delivery of viscoelastic material (2800) to Schlemm's canal (2802) and collector channel (2804) during storage of elongate member (2806) in cannula (2808) is shown in FIGS. 28B-28D. As seen in FIGS. 28C-28D, the angle and length of delivery of viscoelastic material (2800) into Schlemm's canal corresponds to the angle and length of advancement of the elongated member into the canal. In some examples, a viscoelastic material may be used to tamponade any backflow of blood back to the anterior chamber.

  The viscoelastic material may then optionally be delivered to the other half of Schlemm's canal. The cannula tip may be removed from Schlemm's canal and the delivery system may be inverted so that the cannula tip rotates 180 degrees and points in the opposite direction. In some examples, the delivery system can be inverted in the anterior chamber without removing the cannula from the eye. In another example, the delivery system may be removed from the eye, inverted and reinserted into the incision. The cannula tip may then be re-inserted into Schlemm's canal through the same incision in the trabecular meshwork, repeating the advancement, storage, and delivery of the viscoelastic fluid described above to the remaining 180 degrees of Schlemm's canal. May be expanded by a viscoelastic material. Upon completion of the procedure, a total of about 4 μl to about 18 μl of viscoelastic fluid (eg, about 9 μl of viscoelastic fluid can be delivered to the eye.

  At the end of the procedure, the anterior chamber may be irrigated through the corneal wound (eg, with balanced salt solution) (either manually or automatically). Balanced salt solutions or viscoelastic materials may be used to reshape the anterior chamber as needed to achieve physiological pressure and further tamponade any backflow of blood from the collector channel back to the anterior chamber. If necessary, sutures may be used to seal the cornea or scleral incision. Postoperatively, antibiotics or bactericides, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for weeks or months to help prevent adhesion formation and angle closure.

  More generally, in the methods described herein, exemplary volumes of viscoelastic fluid that can be delivered are, in some examples, from about 1 μl to about 200 μl, or in some examples, from about 1 μl to about 1 μl. It can be about 100 μl. In some examples, the volume sufficient to provide the disruption force can range from about 1 μl to about 50 μl, about 1 μl to about 30 μl, or about 2 μl to about 16 μl. In one variation, a volume of approximately 4 μl is sufficient to disrupt Schlemm's canal and / or surrounding tissue. In other variations, the volume of viscoelastic material sufficient to disrupt trabecular tubule tissue is about 2 μl, about 3 μl, about 4 μl, about 5 μl, about 6 μl, about 7 μl, about 8 μl, about 9 μl, about 10 μl. About 11 μl, about 12 μl, about 13 μl, about 14 μl, about 15 μl, about 16 μl, about 17 μl, about 18 μl, about 19 μl, about 20 μl, about 25 μl, about 30 μl, about 35 μl, about 40 μl, about 45 μl, or about 50 μl. obtain.

  Tissue disruption may be at least about 1 μl, at least about 2 μl, at least about 3 μl, at least about 4 μl, at least about 5 μl, at least about 6 μl, at least about 7 μl, at least about 9 μl, at least about 9 μl, at least about at least about 1 μl, at least about 2 μl, per 360 degree arc of the canal. 10 μl, at least about 11 μl, at least about 12 μl, at least about 13 μl, at least about 14 μl, at least about 15 μl, at least about 16 μl, at least about 17 μl, at least about 18 μl, at least about 19 μl, or at least about 20 μl of viscoelastic fluid, It can be caused by excessive and intentional expansion by viscoelastic substances. In some variations, at least about 20 μl, at least about 25 μl, at least about 30 μl, at least about 35 μl, at least about 40 μl, at least about 45 μl, or at least about 50 μl of viscoelastic fluid may be delivered.

  Depending on factors such as the type and severity of the condition being treated, the disruption force may be generated to partially and completely disrupt and / or remove the trabecular meshwork and the volume of viscoelastic fluid delivered. May be adjusted by changing. For example, 8 μl may be used to pierce or gently tear the web, while 16 μl may be used to maximally cut or tear the web. More specifically, about 1-2 μl may be used to dilate Schlemm's canal and collector channel, and about 2-4 μl to dilate Schlemm's canal and collector channel to pull proximal tubule tissue. Approximately 4-6 μl may be used to create all of the above as well as micro-tears or micro-perforations in the trabecular meshwork and adjacent tubule tissue (this further increases porosity and outflow). Increase). A volume of about 8-16 μl may be used to do all of the above and to significantly pierce / tear the trabecular meshwork and adjacent tubule tissue. A volume of about 16-50 μl may be used to substantially or completely tear or cut the trabecular meshwork.

  The total volume of the viscoelastic fluid is determined by 360 of Schlemm's canal during a single advance (eg, as shown in FIG. 16) or withdrawal of the elongate member (1604) from a single access point (1602) in the canal. It may be delivered along the arc of degrees (1600), or along the arc of lesser degrees in multiple advancements or withdrawals of the elongate member. For example, as shown in FIG. 17, the elongate member (1700) is advanced along the canal's 180 degree arc both clockwise (1702) and counterclockwise (1704) to move fluid, for example, It may be delivered from a single access point (1706) in the canal. Referring to FIGS. 16 and 17, an exemplary disruption volume of about 4 μl to about 18 μl can be delivered along the 360 ° arc of the canal while at the same time the elongate member is advanced from a single access point in the canal. , Or between two advancements (one clockwise and one counterclockwise) of the elongate member from a single access point in the canal, about 2 μl to about 9 μl into a 180 ° arc of the canal. Can be delivered along. More specifically, an exemplary disruption volume may be about 9 μl delivered along the 360-degree arc of the canal, or to the 180-degree arc of the canal during each of two advancements. It may be about 4.5 μl delivered along. The elongate member may be canal accessed from a single point or from multiple points.

  In addition, it delivers a fluid composition to restore the vasculature of Schlemm's canal, clear obstructions in the canal, disrupt the proximal canalicular trabecular meshwork or inner wall of Schlemm's canal, or expand the canal. May be. Here, the delivery system may include wires, tubes, balloons, devices that deliver energy to tissue, and / or other features to assist in these methods. It is contemplated that such a system with additional features may be used to treat glaucoma. The surface of these systems may be roughened or have protrusions to further disrupt the inner wall of Schlemm's canal and the adjacent trabecular meshwork to enhance outflow or permeability of aqueous humor. .

  The viscoelastic fluid may be withdrawn by the single operator while advancing the elongate member of the device controlled by one hand from Schlemm's canal, clockwise, counterclockwise, or both, and / or withdrawing the elongate member from Schlemm's canal. In between, it may be delivered. As mentioned above, viscoelastic fluid may be delivered to disrupt Schlemm's canal and surrounding trabecular tubule tissue. For example, the delivered viscoelastic fluid may expand Schlemm's canal, increase the porosity of the trabecular meshwork, pull the trabecular meshwork, form tiny tears or perforations in nearby tubule tissue, remove the septum from Schlemm's canal, The disruption may be caused by expanding the collector channel, or a combination thereof. The elongate member may be filled with a viscoelastic fluid at the beginning of the ophthalmic procedure so that the fluid may be delivered by a single device. Forceps or other advancement device for advancing the fluid delivery catheter into Schlemm's canal, and / or separate or independent of the delivery catheter or catheter advancement device and delivered by the surgeon during the procedure. In contrast to other systems that use a device containing a viscoelastic fluid, which must be tied to a delivery catheter or catheter advancement device by an assistant while the device is held.

Instrument delivery Prior to the introduction of goniotomy and trabeculotomy, both of which are typically used to treat obstructed trabecular meshwork, often young and genetic, congenital glaucoma remains blind Was connected to. Goniotomy (which is done at Abinterno, but uses a sharp scalpel to cut the omentum 30-60 degrees to improve outflow) and trabectomy (by deep scleral incision of Schlemm's canal). Despite the invasiveness of the ab externo method of stripping the roof and cutting the net with a probe, this procedure is considered effective, and many pediatric patients may avoid lifelong blindness. Has been made possible. In 1960, Burian and Smith each independently described the Abexterno trabecrotomy. In this highly invasive Ab-Externo procedure, the surgeon makes a deep scleral incision, finds Schlemm's canal, and uses a specially designed probe called a catheter, or trabectome, to deliver all 360 degrees of Schlemm's canal. Is externally cannulated and finally the ends of the catheter or probe are pulled until the travectome cuts through the trabecular meshwork to the anterior chamber to improve drainage.

  A more recent attempt to reduce the invasiveness of travectomy was developed by NeoMedix commercializing a device called "Trabectome". This Trabectome attempts to make travectomy easier by using ab intelno approach. This device and method involves removing the trabecular meshwork at Abinterno by electrocautery using a device that also provides injection and aspiration. Trafectome has three drawbacks. 1) This device uses an energy-based mechanism to clear the trabecular meshwork, which is believed to cause inflammation and scarring in the eye, which may also adversely affect outflow and pressure; 2). This device / procedure is ergonomically limited as it requires a foot pedal and power cord to activate the electrocautery and irrigation, plus 60-120 degree omentum per corneal or scleral incision. Limited to treatment; 3) Capital equipment is required as it involves energy-based removal and irrigation.

  Methods (as well as systems and devices) described herein, including methods for providing disruption forces to trabecular tubule tissue, allow them to avoid the use of electrocautery and to provide elongated members to larger than Schlemm's canal. Because it can be advanced over a power arc, it can be very suitable for trabectomy and goniotomy. If the system and device are adapted to provide a disruptive force to trabecular tubule tissue, implant-free methods may be used, such methods delivering, for example, a disrupted volume of viscoelastic fluid. And / or by advancing a cutting instrument, such as a cannula, elongate member, catheter or the like. In some examples, the disruption devices may include disruption components on their distal portions. Exemplary severing components include, but are not limited to, notches, hooks, barbs, balloons, or combinations thereof. In other examples, the disruption devices may not have disruption components on their distal portion and may have a blunt distal tip portion that is actually atraumatic. Exemplary atraumatic distal portions include, but are not limited to, umbrella or dome shaped distal portions.

  In some variants of ab innotravectomy and goniotomy, the procedure involves advancing the cannula at least partially through the anterior chamber of the eye, using the cannula at a single access point. A volume of viscoelastic fluid sufficient to enter Schlemm's canal and to disrupt the structure of Schlemm's canal and surrounding tissue to reduce intraocular pressure is slidable and extendable from the cannula with a lumen. Delivery through a deliverable elongate member. Another method that may be useful in treating an eye condition is to enter Schlemm's canal using an elongate member extendable from a single operator-controlled handle that includes a fluid reservoir; Delivering a volume of viscoelastic fluid from the fluid reservoir through the elongated member by increasing the pressure in the reservoir, the volume of delivered viscoelastic fluid being determined by the structure of Schlemm's canal and surrounding tissue. Is sufficient to divide the eye and reduce intraocular pressure. The disruption volume can be about 2 μl to about 16 μl. In one variation, the disruption volume is about 4 μl viscoelastic fluid. As mentioned above, in some examples, the disruption volume may range from about 20 μl to about 50 μl. Methods based on fluid delivery are described in more detail above.

  When using only the disruption device, without the use of fluid, the outer diameter of the elongate member or instrument will vary with respect to the disruption of tissue, similar to how the fluid volume may be varied to change the level of disruption. Can be sized. For example, an elongate member or device having a profile in the range of about 50 to about 100 microns is advanced through the canal to slightly expand the canal and destroy or remove the septum blocking the circumferential capillary flow. You can The foregoing may be performed with an elongate member or device having an outer diameter in the range of about 100-200 microns, and tensioning of the trabecular meshwork and adjacent tubule tissue may be initiated. An elongate member or device having an outer diameter in the range of about 200 to about 300 microns may be able to do the above, but may also create minute tears in the trabecular meshwork and adjacent tubule tissue, The collector channel can be expanded maximally. An elongate member or device having an outer diameter in the range of about 300 to about 500 microns can maximally divide the tissue and create tears or perforations along the trabecular meshwork and adjacent tubule tissue. In addition, the longer the elongate member or instrument is advanced through the canal, the more effective the procedure. For example, an elongate member or device may be advanced out of the tip of the cannula and into the canal around a 30 degree arc of the canal (eg, approximately 3 out of the cannula) for maximum effectiveness and maximum intraocular pressure reduction. ~ 4 mm advance), advance around a 60 degree arc of the canal (e.g., advance about 6-8 mm from the cannula) and advance around a 90 degree arc of the canal (e.g., advance about 10 mm from the cannula). ), Advancing around 120 arcs of the canal (eg, advancing about 15 mm from the cannula), advancing around 180 ° arc on the canal (eg, advancing about 20 mm from the cannula), or all 360 of the canal. It may be advanced about a degree (eg, about 36-40 mm advanced from the cannula). In some variations, the elongate member can have a non-uniform outer diameter. For example, the elongate member may have a tapered outer diameter such that the outer diameter increases from the distal end to the proximal end.

  In some variations, the methods disclosed herein can include advancing an elongate member (or instrument) around a 5 ° arc to a 360 ° arc of Schlemm's canal. In some variations, the method includes elongate members (or instruments) around a 360 degree arc of Schlemm's canal, around a 270 degree arc of Schlemm's canal, around a 120 degree arc of Schlemm's canal, Schlemm's canal. Around a 180-degree arc of, or around a 90-degree arc of Schlemm's canal. In yet a further variation, the advancement of the elongate member (or instrument) is about a 0-5 degree arc of Schlemm's canal, a 30 degree arc of Schlemm's canal, or a 60 degree arc of Schlemm's canal. May be. Advancement may occur from a single access point in Schlemm's canal or from multiple access points in the canal. It may be beneficial to advance the elongate member, both clockwise and counterclockwise, from a single access point in the canal about a 180 degree arc of Schlemm's canal when providing disruption forces. .

  Depending on factors such as the type and severity of the condition being treated, the disruption force may be created to partially or completely destroy and / or remove the trabecular meshwork by varying the instrument configuration. You may adjust. In some methods, the trabecular meshwork may be disrupted during advancement of the slidable elongate member. Also, customization of the body segment of the elongate member proximal to the tip with one or more notches, barbs, or balloons that captures the mesh as the distal tip is guided and advanced along Schlemm's canal. Upon use, the trabecular meshwork can be disrupted, partially torn, completely torn and / or removed during advancement. In addition, implants with edges specifically designed to cut the mesh may be used.

  In yet another method, the trabecular meshwork may be disrupted during storage of the slidable elongate member. Yet another method for disrupting tissue is the present system (e.g., an elongate member, any catheter or wire, such as to capture or grasp the mesh during storage after advancement through the canal is complete). Customizing the probe tip, etc.). It advances through the lumen of the catheter and then hooks the mesh during storage and either tears the mesh along its length or removes the mesh together, curved tips, hooks, notches, Alternatively, a wire with barbs at the ends may be used, or the tip (and / or the fuselage) may advance Schlemm's canal without tearing the net, but during storage, hook the net, tear the net, and / or Alternatively, it may be done only with metal or polymer wires or sutures (without catheter) that are hooks, notches, or barbs to completely remove the mesh. Alternatively, as shown in FIG. 18C, the elongate member (1806) has a sharp edged element () that can sever or tear the trabecular meshwork while stored in the disruption device, eg, the cannula (1800). 1808) may be provided, which is fixedly held. An exemplary sharp-edged element can be a hook, wire, or any other suitable shape memory component that can extend from the cannula to tear, cut, or remove the trabecular meshwork.

  Another method for severing tissue is to use an oversized elongate member (eg, one having an outer diameter of 300-500 microns) to tear the mesh during delivery, or the elongate member may be a Schlemm's canal. Can be fully advanced and then expanded or expanded to pull, split, rupture, or completely tear the net. For example, the outer diameter of the tip is 200-250 microns, but after 3 hours of Schlemm's canal (ie, approximately at the 5 or 10 mm mark of the catheter / elongate) up to about 300, up to about 400, or up to about 500. Use a catheter / elongate member, probe, or wire (with or without a lumen) with a micron, shaft that begins to spread outward, so that when the tip comfortably advances within Schlemm's canal, the expanded shaft is Follow it backwards and tear the trabecular meshwork as it advances.

  Alternatively, cutting, breaking, removing, etc. of the trabecular meshwork may be accomplished by tearing through the net by removing the cannula from the eye while leaving the elongate member in the canal. With reference to FIG. 18A, a cannula (1800) may be inserted into the anterior chamber (1802) and Schlemm's canal (1804) and an instrument (eg, a slidable elongate member (1806)) within the canal (1804). You may move forward. As shown in FIG. 18B, the cannula (1800) may be removed from the anterior chamber (1802) without retracting the elongate member (1806). This action itself may tear the trabecular meshwork. When the cannula (1800) is removed from the anterior chamber (1802), the elongate member (1806) may begin to tear the trabecular meshwork from the point where the cannula (1800) is inserted into Schlemm's canal (1804). The perimeter of the mesh may continue to tear towards the distal end of the elongate member.

  Variations of the methods described herein are illustrated in Figures 29A-29D, which may be performed using a delivery system such as those described with respect to Figures 23A-23F. FIG. 29A shows a flow chart illustrating the method. The method may be used to access the trabecular outflow system using a single transparent corneal incision and may allow transluminal trabecultomy up to 360 degrees. The method may use a flexible elongate member that may be advanced and retracted using a one-handed disposable hand instrument. First, the device can be removed from the package. The lock is then removed from the delivery system. The cannula may be advanced into the anterior chamber through an existing corneal or scleral incision. It may be desirable for the incision to be at least about 1 mm wide. The distal tip of the cannula may be used to puncture the trabecular meshwork and enter Schlemm's canal. The cannula may be held stationary with respect to the comer angle while advancing the flexible elongate member into Schlemm's canal. The exposed portion of one or more of the wheels may be rotated proximally such that the flexible elongate member advances about the Schlemm's canal by up to about 180 degrees (about 20 mm circumferential canal movement). At this point, the flexible elongate member may be fully extended and the wheel may not be allowed to rotate any further. During this procedure, visualization of the cannula tip by direct microscopy or gonioscopy may be maintained and the anterior chamber may be maintained by viscoelastic or continuous balanced saline infusion.

  Advancement of the flexible elongate member may remove the cannula from the eye through the incision without retracting the flexible elongate member. This may allow the flexible elongate member to cut through the trabecular meshwork. In some instances, it may be desirable to bias the distal tip of the cannula toward the trabecular meshwork being cut, which, in some instances, may result in flexible elongate members during cannula removal. Can help prevent the dog from slipping out of the canal. Removal of the cannula (2900) without retracting the flexible elongate member (2902) to tear the trabecular meshwork (2904) is illustrated in Figures 29B-29D. As can be seen there, the elongated member (2902) converts the force from the removal of the cannula (2900) into a force that tears the trabecular meshwork. Removal of the cannula (2900) provides a "zipper" effect that tears the trabecular meshwork. That is, the trabecular meshwork is split from its proximal end to its distal end by the body of the elongate member (2902). First, the force on the trabecular meshwork from the proximal end of the body of the elongated member (2902) causes the trabecular meshwork to tear near the insertion point of the cannula (2900). As the cannula (2900) continues to be withdrawn from the eye, the body of the elongate member (2902) continues to tear the trabecular meshwork toward the distal tip of the elongate member, as shown in FIGS. 29C and 29D. By this method, the trabecular meshwork is progressive from a first location (proximal end of extended elongate member, near cannula insertion point) to a second location (distal end of extended elongate member). Note that this is in contrast to simultaneous tears or tears along the distance from the first location to the second location. Further, in this method, each portion of the trabecular meshwork is not split by a single feature of the elongated member (eg, the distal end of the elongated member during advancement or storage), rather than each portion of the trabecular meshwork. Note that the portion is torn by the portion of the elongate member adjacent to it after the elongate member has been advanced.

  After complete removal of the delivery system from the eye, the flexible elongate member may be retracted back into the cannula by rotating one or more of the wheels distally. Once the flexible elongate member is fully retracted, the delivery system may be inverted so that the cannula tip rotates 180 degrees and points in the opposite direction. The cannula tip may then be advanced through the corneal or scleral incision into the anterior chamber and the distal tip may be advanced into the same entry into Schlemm's canal. The method described above may then be repeated for the second half of Schlemm's canal to cut the trabecular meshwork. In some examples, a viscoelastic material may be used to tamponade any backflow of blood back to the anterior chamber.

  At the end of the procedure, the anterior chamber may be irrigated through the corneal wound (eg, with balanced salt solution) (either manually or automatically). Balanced salt solutions or viscoelastic materials may be used to reshape the anterior chamber as needed to achieve physiological pressure and further tamponade any backflow of blood from the collector channel back to the anterior chamber. If necessary, sutures may be used to seal the cornea or scleral incision. Postoperatively, antibiotics or bactericides, mydriatics, or miotics may be used as appropriate. For example, miotic eye drops may be used for weeks or months to help prevent adhesion formation and angle closure.

  In yet a further method, tissue disruption may be accomplished by ab intelno delivery of sutures throughout Schlemm's canal, which in turn pulls the canal, disrupts the trabecular meshwork, and / or Or pulled enough to pierce the net ("abinterno suture travectomy"). Here, the distal suture ends are pulled inward when the cannula is withdrawn from the eye, to break all 360 degrees or segments of the trabecular meshwork, or by tying the suture ends together, An instrument including a gripping element may be used to provide tension to the web without having to tear it.

Ab-Externo Technique The Ab-Externo technique for implanting an intraocular device or delivering a fluid composition may include additional or slightly different steps. For example, tissue flap creation, suturing, etc. may be part of the Ab Externo procedure. In general, the Ab-Externo method for implanting an intraocular device may include the following steps. First, under microscopic visualization, the conjunctiva is dissected, the scleral flap is created, the tissue is dissociated, and the mouth to Schlemm's canal is identified. Saline may be individually injected into the anterior chamber, or the viscoelastic composition may be placed therein to prevent collapse of the anterior chamber angle. This operation may be performed as an independent procedure or in combination with cataract surgery. This may also be done before or after the cataract surgery site.

  The delivery system described herein is used to advance the cannula into Schlemm's canal and advance the intraocular device using a positioning element under direct microscopy visualization or through a gonioscope or gonioprism. You may let me. When advancing the intraocular device by the desired amount, the surgeon may activate the engagement mechanism to release the intraocular device from the positioning element and remove the delivery system from the eye and operative field. The scleral wound may be self-sealing, or it may be closed using, for example, sutures or tissue glue. If repositioning of the intraocular device is needed or desired, the surgeon may use the positioning elements of the delivery system to retract and / or advance the intraocular device.

  For delivery of fluid compositions, the Ab-Externo method is similar to Ab-Interno delivery. However, instead of using positioning elements, the delivery system uses slidable elongate members to inject the fluid composition into Schlemm's canal. First, under microscopic visualization, the conjunctiva is dissected, the scleral flap is created, the tissue is dissociated, and the mouth to Schlemm's canal is identified. Saline may be individually injected into the anterior chamber, or the viscoelastic composition may be placed therein to prevent collapse of the anterior chamber angle. This operation may be performed as an independent procedure or in combination with cataract surgery. This may also be done before or after the cataract surgery site.

  The delivery system described herein may be used to advance a cannula into Schlemm's canal and an elongate member coaxially disposed within the lumen of the cannula to the canal under visualization with a goniscope. . Once the elongate member is positioned within the canal, the fluid composition, eg, viscoelastic fluid, may be delivered continuously or intermittently through the elongate member. The fluid composition exits the lumen of the elongate member through its distal end (eg, through the distal tip), through an opening or fenestration provided along its shaft, or a combination of both. The openings or fenestrations can be spaced along the axial length of the elongate member in any suitable manner, eg, symmetrical or asymmetrical along its length. If desired, other substances such as drugs, air, or gases may be delivered in the same manner. The elongate member may be repositioned by retracting or repeated advance and retract. The delivery system can then be removed from the eye.

  The configuration of the present intraocular delivery system can be advantageous in many different ways. In one aspect, the delivery system can be used in the Abinterno method of implanting an intraocular device in Schlemm's canal or the ablinterno method of canal delivery of a fluid composition or device. In another aspect, the cannula of the delivery system is configured to allow easy and atraumatic access to Schlemm's canal. Moreover, the delivery system is configured in a manner that gives the surgeon more freedom of use, all in a single instrument. For example, the handle of the system is configured for use on either side (ie, by flipping the handle or rotating the cannula). For this reason, the delivery system is designed for clockwise or counterclockwise use with either hand or eye. For example, the delivery system may be used with either the right or left hand to access Schlemm's canal in a counterclockwise fashion, or with the right or left hand to access the canal in a counterclockwise fashion, for either eye. be able to. Thus, access to the canal from all four quadrants of the eye may be achieved. In yet a further aspect, the delivery system is configured to provide sufficient force to disrupt Schlemm's canal and surrounding tissue to improve flow through the trabecular tubule outflow tract. A single operator controlled device according to. The system generally includes an access cannula, a delivery elongate member, an elongate member advancement mechanism, a disruption device, and a viscoelastic device so that the elongate member or device can be advanced by one person or with one hand or fluid can be delivered. Fluids are combined into a single device.

Methods of Manufacturing the Cannula As described above, the cannulas described herein reversibly elongate the elongated member without piercing the trabecular meshwork or other tissue and without cutting, breaking, or damaging the elongated member. It can be configured to both deliver. To this end, the cannula may be manufactured with a distal end having both a pointed portion and a blunt or rounded portion. In general, the method of manufacturing a cannula described herein involves creating a bevel at the distal tip of the cannula, creating a sharp piercing tip by sharpening the distal end of the distal tip, and removing the distal end of the cannula. It may include smoothing a portion of the distal tip and bending a portion of the cannula along the longitudinal axis of the cannula. In some variations, the method also includes obtaining a cannula of suitable working length, roughening the outer surface of the cannula, applying a protective cover to a portion of the distal tip, polishing a portion of the cannula, and cannula. Cleaning may be included.

  FIG. 19 illustrates an exemplary method of manufacturing a cannula for use with the devices, systems, and methods described herein. As shown therein, a method of manufacturing a cannula (1900) includes obtaining a cannula of appropriate working length (1902), roughening the outer surface of the cannula (1904), and creating a bevel at the distal tip of the cannula (1906). Sharpening the distal tip of the cannula (1908), applying a protective cover to the distal tip of the cannula (1910), smoothing a portion of the distal tip of the cannula (1912), bending the cannula (1914), Polishing the cannula (1916) and cleaning the cannula (1918) may be included. Although the method steps in FIG. 19 are shown in a particular order, many of the steps may be completed in a different order, some of which may all be collectively optional, as discussed in more detail below. It should be appreciated that it may be an option.

  To begin the process, a cannula of suitable working length may be obtained (1902). The cannula may be purchased pre-cut to the desired working length, or the raw material used to create the cannula, such as a stainless steel hypodermic tube, may be purchased in bulk during the cannula manufacturing process. It may be cut to a suitable length. The cannula may be inspected for breakage or other visible defects upon acquisition and throughout the manufacturing process. In some variations, the working length (ie, the length suitable for handling the cannula during manufacture) may correspond to the desired final length of the cannula. In other variations, the working length may be greater than the desired length, for example, for ease of manufacturing, and the cannula may have a desired final length at any point during the manufacturing process, including the final step of the process. May be cut or shortened (eg, by cutting the proximal end of the cannula). Exemplary working lengths include, but are not limited to, about 50 mm to about 70 mm, about 40 mm to about 90 mm, and more specifically about 60 mm.

  The proximal end of the cannula may be cut, treated, and / or finished at any time during the manufacturing process. In some examples, the proximal end of the cannula may be cut at right angles (ie, cut substantially perpendicular to the longitudinal axis of the cannula). The edge of the proximal end may be smoothed or rounded using any suitable method, for example, by media ejection. Smoothing the proximal end of the cannula may prevent the elongate member from cutting, tearing or damaging. For example, smoothing the proximal end removes any sharp edges or wavy surfaces from the proximal end, leaving any debris or debris remaining at the proximal end of the lumen from the cutting process. Things can also be removed. The proximal end of the cannula may be inspected after smoothing to further smooth the proximal end if any sharp or serrated edges remain.

  In some variations, the outer surface of the cannula may optionally be roughened (1904) or textured, which may aid in adhesion of the cannula to the handle. For example, in some examples, the proximal or central portion of the outer surface of the cannula may be abrasively jetted to create a textured or roughened surface to which the adhesive is applied. Abrasive jetting of the outer surface of the cannula increases the surface area of the abradingly jetted portion, which may provide better adhesion between the handle and the cannula.

  As mentioned above, the distal end of the cannula may be beveled. The bevel may be created by cutting or sharpening the distal end of the cannula at an angle to the longitudinal axis of the cannula (1906). More specifically, the bevel may be placed transverse to and at a right angle to the lumen of the cannula. FIG. 3 shows a side view of a cannula (300) with a bevel (312) on the distal tip (306). The bevel (312) may comprise an angle (A) of about 5 degrees to about 85 degrees. As mentioned above, the angle (A) provides sufficient visualization of the trabecular meshwork properly without damaging other surrounding tissue, to access Schlemm's canal, and / or to advance and retract the elongate member. Can be important for. In some variations, the angle (A) is about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or 85 degrees. obtain. In some variations, angle (A) may be about 23 degrees to about 27 degrees. In some of these variations, angle (A) may be about 25 degrees.

  FIG. 20 shows a perspective view of the distal tip (2002) of the cannula (2000) after creating the bevel. As shown, the beveled distal tip (2002) now comprises a proximal end (2008) and a distal end (2010). In addition, creating a bevel at the distal tip (2002) causes the opening (2012) at the distal tip (2002) to stretch, creating an oval rather than a circular opening. For this reason, beveling the distal tip (2002) requires that the top of the oval opening be beveled closer to the proximal portion of the cannula than the bottom of the oval opening. Can create a cavity opening. The inner and outer peripheral edges (2004, 2006) are also shown in FIG.

  Bevel placement can create a pointed edge, and in some cases a pointed distal tip, but with a portion of the distal tip of the cannula further sharpened for greater precision. It may be desirable to achieve easier access to Schlemm's canal. Thus, in some examples, after the bevel is created, the distal tip may be further pointed (1908) to create a pointed piercing tip that may further aid in puncturing the trabecular meshwork. The distal tip may be sharpened using any suitable technique, for example, by sharpening or removing a portion of the outer surface and / or a portion of the outer periphery of the distal end of the distal tip of the cannula. You may let me. It may be desirable to keep the wall thickness at the distal tip as thick as possible to ensure that the wall thickness is uniform in order to minimize unwanted sharp edges that could damage the elongate member. . It may be beneficial to prevent cannula material or other sharpening by-products from forming, accumulating, adhering, or depositing on the inner surface of the cannula within the lumen. Such material can become debris, creating ridges or pointed surfaces or edges that can cut or damage the elongated member during use of the delivery system.

  21A and 21B show perspective and front views, respectively, of a variation of the distal tip (2100) of a cannula with both a bevel (2102) and a pointed piercing tip (2114). Distal tip (2100) also includes a proximal end (2108), a distal end (2110), inner and outer perimeter edges (2104, 2106), and a lumen opening (2112). The pointed piercing tip (2114) is created by sharpening the distal end (2110) of the distal tip (2100), thereby creating two beveled surfaces (2116) that merge to form a pointed tip. You can The beveled surface (2116) may be formed at any suitable angle that results in a sharp piercing tip (2114). For example, in some examples, the ramped surface (2116) may be about 20, 25, 30, 35, 40, 45, or 50 degrees, about 25 to about 50 degrees, or about 37.5 to about 42.5 degrees. May have an angle (B) with respect to the longitudinal axis of the distal tip (2100). Thus, in some variations, the angle between the two sloping surfaces (2116) may be about 50 to about 100 degrees. Although the distal tip (2100) is shown with two beveled surfaces, it should be understood that a distal tip having a single beveled surface could also be used.

  Returning to FIG. 19, the method (1900) for manufacturing a cannula may further include smoothing a portion of the distal tip (1912) of the cannula. In the variant with a sharpened distal tip of the cannula, as described above with respect to FIGS. 21A and 21B, the method includes a protective cover, prior to the smoothing (1912) of the distal tip, with a protective tip. May further include applying (1910) on a sharpened portion, eg, the distal end of the sharpened piercing tip (2114) and / or the beveled surface (2116). Even with the blunt distal tip variant after beveling, it may still be desirable to apply a protective cover on the distal end of the distal tip (as described above with respect to FIG. 20). The application of a protective cover can help maintain the sharp edge (s) during smoothing.

  As mentioned above, the distal tip of the cannula may be configured to both pierce tissue and deliver elongate members. The elongate member itself may be susceptible to cannula puncture, cutting, severing, or damage. To protect the elongate member, it may be important to smooth or chamfer the surface and / or edge of the distal tip of the cannula with which the elongate member may contact. For example, referring again to FIGS. 21A and 21B, in some variations, a portion of the inner and / or outer perimeter edges (2104, 2106), a surface between the edges (2118), and / or an opening (2112). The inner and / or outer surface of the cannula adjacent to may be smoothed. This may even and / or dull these edges and surfaces. For example, it may be desirable to smooth a portion of the inner peripheral edge (2104) at the proximal or distal ends (2108, 2110) of the distal tip (2100), or even the entire inner peripheral edge. Good. In some examples, a portion of the outer peripheral edge (2106) may also be smoothed while maintaining the sharp edge of the distal tip (eg, a sharp piercing tip). For example, a portion of the outer peripheral edge (2106) may be smoothed at the proximal end (2108) of the distal tip (2100), or the entire outer peripheral edge (2106) may be smoothed to the beveled surface (2116). Good. In addition, adjacent to or at the opening (2112) at the surface between the edges (2118) and / or at the proximal end (2108) or distal end (2110) of the distal tip (2100). It may be desirable to smooth or chamfer the inner or outer surface of the cannula around the circumference of 2112).

  A portion of the distal tip (2100) of the cannula may be chamfered, smoothed, homogenized, rounded, blunted, or the like using any suitable mechanism. For example, smoothing a portion of the distal tip of a cannula may include mechanical and / or manual chamfering, abrasive or soda media blasting, scouring, sharpening, wire brushing, laser ablation, polishing (eg, electrolysis). Polishing), combinations thereof, or the like.

  Returning to FIG. 19, the method of manufacturing the cannula (1900) may further include bending the distal portion of the cannula (1914) to form the distal curved portion described above. By bending the catheter, the distal tip can be properly oriented to atraumatically pierce the trabecular meshwork. Referring back to FIG. 3, in some variations, the distal portion of the cannula may be bent so that the pointed piercing tip is located along the outer radius (322) of the curved cannula. In some examples, the distal portion of the cannula may be bent at an angle of about 100 to about 125 degrees, about 115 to about 125 degrees, or about 118 degrees relative to the outer surface of the proximal portion of the cannula.

  The distal portion of the cannula may be bent using any suitable mechanical or manual bending process. It may be important to choose a bending process that does not alter the cross-sectional size and shape of the cannula during the bending process. In addition, the cannula may be flexed at any point during the manufacturing process, and flexion does not necessarily have to occur after smoothing the distal tip of the cannula, as shown in method (1900) in FIG. I want you to understand.

  The method of manufacturing a cannula (1900) may optionally include polishing (1916) all or a portion of the cannula, eg, the distal tip of the cannula. In the abrading cannula variant, abrading the cannula (1916) may remove residual debris, markings, nicks, grooves, or the like on the surface of the cannula. These markings may be relics from any part of the manufacturing process, in particular creating a bevel at the distal tip of the cannula (1906), sharpening the distal tip of the cannula (1908), And / or smoothing a portion of the distal tip of the cannula (1912). Polishing the cannula (1916), smoothing a portion of the distal tip of the cannula (1912), may be particularly useful in processes that generally leave debris or markings behind, such as deformations including laser ablation. . Polishing the cannula (1916) may be completed using any suitable method, such as electropolishing, stepped media ejection using increasing particle size media, or the like.

  If desired, the cannula may be cleaned (1918) prior to installation in the delivery system described herein. For example, in some variations, the cannula may be passivated to remove iron oxide or other contaminants. In some examples, the cannula may be passivated using an acid such as nitric oxide. In other variations, the cannula may be cleaned using a cleaning agent, ultrasonic bath, or any suitable cleaning process.

  The cannula and / or assembled delivery system may be sterilized using, for example, gamma irradiation. The dose range for gamma irradiation can be, for example, 25-40 kGy. Other irradiation energies, such as E-beam irradiation, may be used for sterilization. Alternative sterilization methods include gas sterilization, eg ethylene oxide gas sterilization. In variants in which all or part of the system is reusable, these parts may be sterilized and reused as described herein. For example, in a variant where the handle is reusable and the cannula and elongate member are disposable, after use, the used cannula and elongate member are removed, the handle is sterilized, and the new cannula and elongate member are sterilized into a sterilized handle. Can be attached.

  Although the inventive devices, systems, kits, and methods have been described in some detail for purposes of illustration, such illustrations are for purposes of clarity only. Given the teachings herein, it will be readily apparent to those skilled in the art that certain changes and modifications can be made therein without departing from the spirit and scope of the appended claims.

Claims (1)

  The invention described herein.