WO2012162459A1 - Dispositif et procédé pour administrer des médications oculaires - Google Patents

Dispositif et procédé pour administrer des médications oculaires Download PDF

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Publication number
WO2012162459A1
WO2012162459A1 PCT/US2012/039267 US2012039267W WO2012162459A1 WO 2012162459 A1 WO2012162459 A1 WO 2012162459A1 US 2012039267 W US2012039267 W US 2012039267W WO 2012162459 A1 WO2012162459 A1 WO 2012162459A1
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Prior art keywords
chamber
eye
medication
iontophoresis
patient
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PCT/US2012/039267
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English (en)
Inventor
Jay PEPOSE
Randall Danta
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Pepose Jay
Randall Danta
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Publication of WO2012162459A1 publication Critical patent/WO2012162459A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A61N1/303—Constructional details
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
    • A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts

Definitions

  • This disclosure relates generally to the field of administering substances to tissue. More particularly, this application is directed to methods and apparatus for administering mydriatic medications to the eye.
  • One traditional method of delivering a medicament to the surface of the eye, either for treating a disorder or to aid in diagnosis, is through the use of eye drops.
  • the lower eyelid is held away from the bulbar conjunctiva and a drop of the medication is introduced into the pocket or cul-de-sac formed between the eyelid and the bulbar conjunctiva.
  • a drop of the medication is introduced into the pocket or cul-de-sac formed between the eyelid and the bulbar conjunctiva.
  • numerous types of drug may be delivered to the eye, such as, antibiotics, corticosteroid, or antihistamines.
  • eye drops may be used to administer drugs which control glaucoma and which either dilate or constrict the pupil.
  • an ophthalmologist during an eye examination may drop tropicamide or phenylephrine onto the eye in order to dilate the pupil. By doing this the ophthalmologist, will be able to fully view the crystalline lens and retina check for n ⁇ ' signs of pathology.
  • a surgeon may use topical drops to induce ocular anesthesia instead of performing a local retrobulbar or peribulbar anesthetic block with a needle.
  • a physician may place a number of similar drops onto the surface of the eye in order to dilate the pupil so that most of the lens is visible, thereby facilitating the surgical procedure under direct observation.
  • Medicated eyedrops often do not remain in long contact with the eye where it can lead to subconjunctival or intraocular absorption as intended. Rather, the medicated eyedrop quickly is pumped by blinking from the tear film down the nasolacrimal duct, where it can be absorbed into the bloodstream, sometimes leading to unwanted systemic side effects. Acute hypertension, tachycardia, or cardiac arrhythmias are reported examples of potentially serious systemic side effects following administration of topical epinephrine or phenylephrine drops to the eye to induce dilation.
  • Intraocular infection can lead to permanent blindness in some cases.
  • Making incisions or using needles to inject medications into the eye may not be practical in certain situations, such as prior to application of the laser interface for femtosecond cataract surgery, since pressure from application of the interface to the opened globe may lead to fluid to leaking from the anterior chamber and interfere with proper, efficient docking of the laser interface.
  • One alternate method for applying drugs to the eye is through direct absorption in which medication is brought into contact with the eye, possibly using a reservoir.
  • Direct absorption is especially useful for the cornea, which has virtual! ⁇ ' no blood supply and is easily accessible for topical application. Direct absorption can achieve higher concentrations of medication than possible using eye drops.
  • the reservoir can be configured to maintain a concentration of medication over a selected region of the eye. It may be possible to configure the reservoir with split chambers to provide multiple medications either side by side or concentric. It may be possible to support the reservoir on the sclera and provide a vaulted portion containing medication targeted to the cornea. It may also be possible to support the device on the cornea, with a vaulted portion containing medication targeted to the sclera. It may also be possible to support the reservoir on another device, such as the applanation cone or suction ring of a femtosecond laser.
  • iontophoresis One method used to enhance absorption of a drag to an eye is using an electric charge and is known as iontophoresis.
  • iontophoresis involves the application of an electromotive force to drive ionic chemicals through a tissue so that they can be absorbed by adjacent tissues and blood vessels. In general terms, this is performed by placing a first electrode containing an ionic medication solution in contact with a portion of the tissue which is to be phoresed. A second electrode is placed on a part of the body near to the first electrode, and a voltage is applied sufficient to cause current to pass through the tissue thereby completing the electrical circuit between the electrodes. As current flows, the ionized medication molecules migrate through the tissue under the influence of the second electrode.
  • ocular iontophoretic apparatus comes in one of two types, either an eyecup device or an applicator probe.
  • the traditional eyecup device is formed from a half-spherical element. Normally the interior of the element is hollow and an electrode extends from the top of the half-spherical element.
  • the eyecup is filled with a medicament solution and placed on the eye. As the voltage from a power source is applied, current passes from the electrode within the half-spherical element and flows into the surface of the eye.
  • an applicator probe may be used.
  • An applicator probe has an electrode which extends into a probe end that is filled with a medicament. The probe end is placed on the patient's afflicted area and medicament migrates from the probe end into the patient's tissue as current is applied,
  • Also medication which is placed within the eyecup may escape from beneath the edges of the eyecup due to conformability limitations of the eyecup and variations in the size and curvature of the eyeball. Additionally, contaminants, such as tears, saline, or other impurities may infiltrate the medicament thereby reducing the potency or pharmacological effectiveness of the medicament.
  • the eyecup may be forced against the surface of the eye to reduce the effects of leaking and containment infiltration; however, the required force may damage the eye.
  • Magnetic fields may be used to enhance penetration and absorption of drugs into tissue. Particular success has been found in administering long chain polynucleotides and polypeptides into mammalian tissue. Examples of use of magnetic fields are described in U.S. Patent Application Publication 2010/0249488.
  • Ultrasound may also be used to enhance penetration and absorption of drugs into tissue such as that described by Sundaram et al, An experimental and theoretical analysis of ultrasound- induced permeabilizatioii of cell membranes, 2003, Biophysical journal, vol. 84, p. 3087-101. US7,922,709, IJS7,758,561 , US7.662.629. US7,612,033.
  • Direct absorption is a non-invasive technique in which a quantity of a drug is held in contact with a tissue surface to promote drug penetration into the eye tissue.
  • direct, absorption can include optional addition of energy such as electricity (e.g., iontophoresis), magnetism, ultrasound, and/or light) to assist or promote surface penetration and cellular absorption of the drug.
  • the drug may be contained under a thin meniscus of elastomeric material vaulted over the cornea configured as a sclera contact lens.
  • the drug may be contained under a thin meniscus of elastonieric material configured as a contact lens vaulted over the sclera, in some embodiments, blinking helps to hold the thin meniscus configurations in place.
  • a larger reservoir is used, and blinking is precluded.
  • a portion of the reservoir may be configured to support a slight vacuum to hold the device in place, in some embodiments the vacuum may be produced to maintain contact between the device and the tissue by drawing air or liquid through a syringe or squeezing and releasing a bulb. In other embodiments, the vacuum may be produced by pressing the flexible portion of the reservoir into the eye and then releasing.
  • the device is configured to contain drug over the sclera and in contact with it.
  • the sponge is positioned over the sclera for example hydrogels or hydroxylated polyvinyl acetal sponges.
  • fluid resides over the sclera without the aid of sponges.
  • the device is configured with sponge over the sclera and fluid over the cornea. The area that is covered over the sclera could vary, and could range from 12,9 mm in diameter to greater than 1 8 rnm.
  • a syringe is used to apply the drugs.
  • the device is configured with a nipple through which drug may be applied into the chamber over the cornea.
  • the device is configured with a nipple through which drug may be applied into the chamber over the sclera.
  • the device is configured with a syringe pre-attached to the nipple.
  • a syringe is removable.
  • a syringe is configured to create a vacuum to apply the device and maintain contact with the eye.
  • the device enhances drug penetration by increasing contact time on the sclera and cornea, and the vasoconstrictors reduce the egress of drugs from the conjunctival and episcleral vessels.
  • Drugs may be selected that have further penetration enhancing characteristics. For example, they can be mixed within cationic, anionic or neutral liposomes, micelles, microemulsions, within micro- or nanoparticles or LGA or chitogan-coated micro or nanoparticles. They can be mixed in viscous or mucoadhesive excipients, such as hydroxyethyi cellulose, xan tham gum or gellan gum or in Durasite.
  • the drugs can be complexed to cyclodextrins to increase aqueous solubility or to surfactants or co-solvents.
  • vasoconstrictors are phenylephrine, epinephrine, etc.
  • Certain devices can use one or more medications alone or in combination, depending on the nature of the drug delivery to be provided. Adding a vasoconstrictor to a mydriatic drug enhances concentration and effectiveness.
  • the agents may be used in the form of a gel or liquid. In the gel form, the agent may be first placed into a chamber, and then the chamber may be inverted and placed onto the eye of a patient. If used in the form of a liquid of low viscosity, the chamber is first placed onto the eye of a patient, and then agent is introduced into the chamber through a fill tube.
  • a drain tube may be used to circulate liquid, remove air bubbles, and maintain a slight negative pressure to maintain contact with the eye.
  • the reservoir may be fashioned as a single piece, or split into multiple parts each with a specific chemical content. Once in place, the device is held in place for a period of time to allow the medications to diffuse into the tissues of the eye of a patient to achieve superior mydriasis than would be obtained by eye drops, topical gel, or intracameral application.
  • the reservoir may be fashioned as a single piece, or split into multiple parts each with a specific chemical content.
  • Iontophoresis is a non-invasive technique in which an electric current is applied to enhance ionized drug penetration into tissue.
  • the drug is applied with an electrode carrying a similar electric charge type (e.g., positive or negative charge) as the drug, and the ground electrode, which is of an opposite charge, is placed elsewhere on the body to complete the circuit.
  • the device is electrically charged by a controller for a period of time using a voltage and current.
  • Electrodes may be positioned within the device having one or more electrical polarities.
  • the electrical waveforms may be continuous over the treatment period, or may alternate, or have ramp-up, and/or ramp-down characteristics to best suit the application.
  • the voltage and current induce a charge to propel the medication into the tissues of the eye of a patient to achieve superior mydriasis than would be obtained by topical or intracameral application.
  • topical and intracameral methods are described by G, Morgado, et al., "Comparative study of mydriasis in cataract surgery; topical versus Mydriasert versus intracameral mydriasis in cataract surgery," Eur J Ophthalmol, 2010; 20 (6), 989-993.
  • Magnetic electroporation is a non-invasive technique in which a magnetic field is applied to enhance ionized drug penetration into tissue.
  • the magnetic field pulses do not require the use of contacting electrodes to conduct electric or ionic current. This method improves penetration of pharmaceutical substances without direct contact with tissue, and may be called rnagnetopermeabilization.
  • the magnet is activated by a controller for a period of time.
  • the waveforms may be continuous over the treatment period, or may alternate, or have ramp-up, and/or ramp-down characteristics to best suit the application.
  • the magnetic field propels the medication into the tissues of the eye of a patient to achieve superior mydriasis than would be obtained by topical or intracameral application. Examples of magnetic electroporation are described by U.S. Patent Application Publications 2010/0249488 and 2009/0326366.
  • Ultrasound poration is a non-invasive technique in which high frequency energy is applied to enhance ionized drug penetration into tissue.
  • the ultrasound pulses do not require the use of contacting electrodes to conduct electric or ionic current. This method improves penetration of pharmaceutical substances without direct contact with tissue.
  • the ultrasound transducer is activated by a controller for a period of time.
  • the waveforms may be continuous over the treatment period, or may alternate, or have ramp-up, and/or ramp-down characteristics to best suit the application.
  • the ultrasound energy propels the medication into the tissues of the eye of a patient to achieve superior mydriasis than would be obtained by topical or intracameral application.
  • Figure 1 A is a perspective view of an embodiment of a direct absorption device with a single chamber as described herein.
  • Figure IB is a perspective view of the direct absorption device of Figure
  • Figure 1C is a cross-sectional view of the direct absorption device of
  • Figure 2 A is an isometric view of an embodiment of a direct absorption device with a fill port as described herein.
  • Figure 2B is a perspective view of the direct absorption device of Figure 2A positioned on an eye of a patient.
  • Figure 2C is a cross-sectional view of the direct absorption device of Figure 2B.
  • Figure 3A is a perspective view of an embodiment of a direct absorption device with two chambers as described herein.
  • Figure 3B is a perspective view of the direct absorption device of Figure 3 A positioned on an eye of a patient.
  • Figure 3C is a cross-sectional view of the direct absorption device of Figure 3B.
  • Figure 4A is a perspective view of an embodiment of an direct absorption device with fill ports on each of the chambers as described herein.
  • Figure 4B is a perspective view of the direct absorption device of Figure 4A positioned on an eye of a patient.
  • Figure 4C is a cross-sectional view of the direct absorption device of Figure 4B.
  • Figure 5A is a perspective view of an embodiment of a direct absorption device with a ring shaped chamber as described herein.
  • Figure 5B is a perspective view of the direct absorption device of Figure
  • Figure 5C is a cross-sectional view of the direct absorption device of Figure 5B.
  • Figure 6A is a perspective view of an embodiment of a direct absorption device with a fill port on a ring shaped chamber as described herein.
  • Figure 6B is a perspective view of the direct absorption device of Figure
  • Figure 6C is a cross-sectional view of the direct absorption device of Figure 6B.
  • Figure 7 A is a perspective view of an embodiment of a direct absorption device with two chambers that form a ring shape as described herein.
  • Figure 7B is a perspective view of the direct, absorption device of Figure
  • Figure 7C is a cross-sectional view of the direct absorption device of Figure 7B.
  • Figure 8 A is a perspective view of an embodiment of a direct absorption device with fill ports on each of the chambers that form a ring shape as described herein.
  • Figure 8B is a perspective view of the direct, absorption device of Figure 8A positioned on an eye of a patient.
  • Figure 8C is a cross-sectional view of the direct absorption device of Figure 8B.
  • Figure 9A is a perspective view of an embodiment of a direct absorption device with two ring shaped chambers as described herein.
  • Figure 9B is a perspective view of the direct absorption device of Figure 9 A positioned on an eye of a patient.
  • Figure 9C is a cross-sectional view of the direct absorption device of Figure 9B.
  • Figure 10A is a perspective view of an embodiment of a direct absorption device with fill ports on each of the ring shaped chambers as described herein.
  • Figure 10B is a perspective view of the direct absorption device of Figure 10A positioned on an eye of a patient.
  • Figure IOC is a cross-sectional view of the direct absorption device of Figure 10B.
  • Figure 11 A is a perspective view of an embodiment of a femtosecond laser attachment as described herein.
  • Figure 1 I B is a perspective view of an embodiment of a direct absorption device configured to receive the femtosecond laser attachment of Figure 11 A as described herein.
  • Figure 11C is a perspective view of the direct absorption device of Figure 1 IB coupled with the femtosecond laser attachment, of Figure 11 A.
  • Figure 11D is a cross-sectional view of the direct absorption device and femtosecond laser attachment of Figure 1 1 C.
  • Figure 12A is a perspective view r of an embodiment of a direct absorption device with two ring shaped chambers and configured to receive a femtosecond laser attachment as described herein.
  • Figure 12B is a perspective view of the direct absorption device of Figure 12A coupled with a femtosecond laser attachment.
  • Figure 12C is a cross-sectional view of the direct absorption device and femtosecond laser attachment of Figure 12B.
  • Figure 13A is a perspective view of an embodiment of a direct absorption device with fill ports on each of the ring shaped chambers and configured to receive a femtosecond laser attachment as described herein.
  • Figure 13B is a perspective view of the direct absorption device of Figure 13 A coupled with a femtosecond laser attachment.
  • Figure 13C is a cross-sectional view of the direct absorption device and femtosecond laser attachment of Figure I3B.
  • Figure 14A is a perspective view of an embodiment of a 2 -lead electric charge controller as described herein,
  • Figure 14B is a perspective view of an embodiment of a 3-lead electric charge controller as described herein.
  • Figure 15 is a perspective view of an embodiment of a syringe configured to dispense a medication as described herein.
  • Figure 16 is a cross-sectional view of an embodiment of a scleral contact lens as described herein.
  • Figure 17 is a cross-sectional view of an embodiment of a corneal contact lens as described herein.
  • Figure 18 is a cross-sectional view of an embodiment of a vaulted chamber as described herein.
  • Figure 19 is a cross-sectional view of an embodiment of a scleral contact lens with bulb as described herein.
  • Figure 20 is a cross-sectional view of an embodiment of a vaulted chamber with bulb as described herein.
  • Figure 21 is a cross-sectional view of a chamber similar to that of Figure 18 and an embodiment of a magnet positioned over the eye of a patient as described herein.
  • Figure 22 is a cross-sectional view of a chamber similar to that of Figure 18 and an embodiment of an ultrasound transducer positioned over the eye of a patient as described herein.
  • Figure 23 is a cross-sectional view of a chamber similar to that of Figure 18 and an embodiment of a lamp positioned over the eye of a patient as described herein.
  • mydriasis is generally accomplished by the instillation of dilating drops or gels.
  • the speed and efficacy of these drugs to dilate the pupil is limited by a number of factors, including low penetration through the cornea and/or sclera.
  • Intracameral injections may be incompatabie with certain types of cataract surgery, such as femtosecond-laser assisted cataract extraction where the globe must remain without perforation and tolerant of the application of pressure from the laser interface de vice being applied to the eye.
  • cataract surgery such as femtosecond-laser assisted cataract extraction where the globe must remain without perforation and tolerant of the application of pressure from the laser interface de vice being applied to the eye.
  • poor pupil dilation may preclude femtosecond laser cataract extractions because the poorly dilated iris covers much of the anterior surface of the lens, blocking the laser light from making incisions of adequate diameter into the cataractous lens.
  • alpha la inhibitors are used to enhance urinary flow in patients with prostate hypertrophy and for other purposes.
  • This class of drugs typified by tarnsulosin (Flomax)
  • Flomax tarnsulosin
  • This floppy iris syndrome is shown to significantly increase the rate of complications during cataract surgery.
  • Other drugs of this kind shown to cause floppy iris syndrome include terazoson, doxazosin, alfuzosin, rninipress, alphavase, hypovas and prazosin.
  • Certain devices described herein utilize direct absorption to deliver mydriatic medications transcleraliy or transcornealiy into the eye in order to enlarge the pupil.
  • the drug is applied with a reservoir that provides a seal with the eye while maintaining contact between at least a portion of the drug and the surface of the eye.
  • Figure 16 illustrates an embodiment of a direct absorption device 1600 with a chamber 1602 (e.g., reservoir).
  • the chamber 1602 includes an opening extending from a first surface 1603 of the chamber 1602 to a cavity 1601 configured to receive at least one medication.
  • the chamber 1602 can be configured with an outer annular portion to maintain a seal with the sclera of an eye 1606 of a patient while a central vaulted portion maintains a quantity of drug in contact with the cornea.
  • Figure 17 illustrates a further embodiment of direct absorption device 1700 with a chamber 1702 (e.g., reservoir).
  • the chamber 1702 includes an opening extending from a first surface 1703 of the chamber 1702 to a cavity 1701 configured to receive at least one medication.
  • the chamber 1702 can be configured with an outer annular portion to maintain a seal with the sclera while maintaining a quantity of drug in contact with the sclera.
  • the chamber 1702 can be configured to at least partially surround at least a portion of a cornea of an eye 1706.
  • the chamber 1702 can be configured to avoid contact with the cornea of the eye 1706.
  • the chamber 1702 can be configured to cover a portion of a sclera of the eye.
  • the chamber 1702 is at least a partial annulus.
  • the at least one opening and the first surface 1703 of the chamber 1702 can be configured as at least a partial annulus.
  • the chamber 1702 and/or the at least one opening and the first surface 1703 of the chamber is an annulus.
  • the annulus may have an inner diameter greater than about 12 mm to avoid contact with the cornea.
  • Figure 1 8 illustrates an embodiment of direct absorption device 1 800 with a chamber 1802 (e.g., reservoir).
  • the chamber 1 802 includes an opening extending from a first surface 1803 of the chamber 1802 to a cavity 1801 configured to receive at least one medication.
  • the chamber 1802 can be configured with an outer perimeter to maintain a seal with the sclera while maintaining a quantity of drug in contact with both the cornea and the sclera (e.g., corneal and scleral coverage with perimeter seal).
  • the chambers described herein can have a variety of configures such as those described herein.
  • the chamber can have a single reservoir or can be split with a plurality of reservoirs such as concentric reservoirs.
  • Figure 19 illustrates an embodiment of a direct absorption device 1900 similar to the direct absorption device 1600 of Figure 16.
  • the chamber 1902 e.g., reservoir
  • the chamber 1902 can be configured with an outer annular portion to maintain a seal with the sclera while a central vaulted portion maintains a quantity of drug in contact with the cornea.
  • a negative pressure device 1930 can be fluidly coupled to the chamber 1902 and configured to be able to create a vacuum in the chamber 1902 while in contact with the eye 1906.
  • the negative pressure device 1930 can be a squeeze bulb configured to provide a vacuum for holding the device in place against the eye.
  • Figure 20 illustrates an embodiment of a direct absorption device 2000 similar to the direct absorption device 1700 of Figure 17.
  • the chamber 2002 e.g., reservoir
  • a negative pressure device 2030 can be fluidly coupled to the chamber 2002 similar to that of the negative pressure device 1930 of Figure 19 such as a squeeze bulb configured to provide a vacuum for holding the device in place against the eye.
  • Negative pressure can be applied to selected regions of the eye.
  • scleral suction can be used with a vaulted cornea reservoir or corneal suction can be used with a sclera reservoir.
  • Other attachment means beyond suction are also possible.
  • relatively thin devices can be secured by weight, surface tension, suction, speculum, and/or eyelid blinking.
  • Figure 21 illustrates an embodiment of a magnet 2140 positioned over the eye 2106 of a patient and configured to assist with the penetration of drug through the tissue surface and absorption of the drug into the underlying cells.
  • a direct absorption device 2100 similar to those described above can be used with the magnet 2140.
  • Figure 22 illustrates an embodiment of an ultrasound transducer 2240 positioned over the eye 2206 of a patient configured to assist the penetration of drug through the tissue surface and absorption of the drug into the underlying cells.
  • a direct absorption device 2200 similar to those described above can be used with the ultrasound transducer 2240.
  • Figure 23 illustrates an embodiment of light source 2340 (e.g., lamp) positioned over the eye 2306 of a patient contigured to assist the penetration of drug through the tissue surface and absorption of the drug into the underlying cells.
  • a direct absorption device 2300 similar to those described above can be used with the light 2340.
  • Certain devices described herein utilize coulomb controlled iontophoresis to deliver mydriatic medications transclerally or transcorneally into the eye via electrorepulsion in order to enlarge the pupil.
  • Iontophoresis is a non-invasive technique in which an electric current is applied to enhance ionized drug penetration into tissue.
  • the drug is applied with an electrode carrying a similar electric charge type (e.g., positive or negative charge) as the drug, and the ground electrode, which is of an opposite charge, is placed elsewhere on the body to complete the circuit.
  • the drug serves as a conductor of the current through the tissue.
  • the sclera and cornea support a net negative charge under physiological pFI conditions and has an isoelectric point ( ⁇ ) between 3.5 and 4. Equally, the principles of transseleral and transeorneal iontophoretie transport of low molecular weight compounds are consistent with those observed for skin.
  • Transeorneal iontophoresis delivers a high concentration of drug to the anterior segment of the eye (e.g., cornea, aqueous humor, ciliary body, iris and lens) with the potential of treating anterior segment diseases, such as; keratitis, glaucoma, dry eyes, corneal ulcers and ocular inflammations.
  • anterior segment diseases such as; keratitis, glaucoma, dry eyes, corneal ulcers and ocular inflammations.
  • this procedure can produce complications, including epithelial edema, decrease in endothelial cells, inflammatory infiltration and burns. Such damage is reliant, upon the site of application, the current density and the iontophoretie duration.
  • Any damage to the cornea surface immediately affects the vision and comfort of the patient whieh is less pronounced when applied to the sclera.
  • the clarity of the cornea is essential for interaction with light while the sclera is not relevant for light interaction.
  • the cornea is an avascular and highly innervated tissue, thus sensitive to pain and hypoxia.
  • Transcorneal iontophoresis can affect the light gathering portion of the eye, while transscleral iontophoresis can affect the retina underneath the application site, whieh is essential for visual image formation.
  • the electric current can be programmed for controlled delivery of drugs by adjusting the current, as the flux of drug into the system is in proportion to the current.
  • This technique ma ⁇ ' overcome certain biological variables such as variable electrical resistance.
  • the electric current can be either positive or negative, depending on the characteristics of the drug.
  • Iontophoresis thus uses an electrode of same polarity as the charge on the drug to drive ionic (charged) drugs into the body by electrostatic repulsion.
  • the mechanism of iontophoresis is based on the physical phenomenon that "like charges repel and opposite charges attract".
  • the drugs are forced into the tissue by simple electronic repulsion of similar charges.
  • anionic drugs can enter the tissue by using a negatively charged working electrode.
  • cationic drugs enter the tissue more successfully when a positively charged electrode is used.
  • the drug is placed between the negative electrode (e.g., cathode) and the membrane.
  • the drug ion is then attracted through the membrane towards the positive electrode (e.g., anode) by the electromotive force provided by the cell.
  • the electrode polarities are opposite.
  • Drug Salt Form Different salt forms have different specific conductivities that affect the general suitability of a drug for iontophoresis.
  • the salt form of drugs along with the pH of the solution influence the amount of drug in the ionized state.
  • pH of the Drug Micro environment The pH of a solution influences the amount of drug present in the ionized state. For optimum iontophoresis, it can be desired to have a relatively large proportion of the drug in the ionized state. However, this may need to be counterbalanced with delivery of a drug at a pH that is tolerable and safe for the patient.
  • Competing ions in the Electrodes Electrical current is carried by positive and negative ions in solution. There is no major distinction between ions of the same charge even though they are composed of different chemical elements. Therefore, in certain embodiments, solutions for iontophoresis should be as pure as practical and generally contain as few extraneous substances as possible. Drug solutions can be prepared with purified water (e.g., deionized, distilled, reverse osmosis). It is has been shown that the presence of excipients in dosage forms, e.g., preservatives in injections as well as compounds used as external buffers, may alter the amount of drug delivered.
  • purified water e.g., deionized, distilled, reverse osmosis
  • the total current will be carried by drug ions along with the same charges as drug ions in the donor cell plus the counter ions present in the receptor cell. Therefore, the competing ions in the donor cell and the counter ions in the receptor cell can be affecting the actual current carried by the drug moiety.
  • the competing ions in the donor cell and the counter ions in the receptor cell can be affecting the actual current carried by the drug moiety.
  • Buffers may be built into the electrode to minimize this effect.
  • the buffer materials can be bound, or immobile, and configured to not be released for iontophoresis transport, as they would then compete with the active drug.
  • Electrodes may use an immobilized buffer to maintain a safe solution pH (for example, between 4 and 8) during treatment.
  • Buffers include ions or charged molecules. These buffer ions may compete with the target ions for iontophoretic delivery if they are not immobilized.
  • Electrodes may incorporate a layered design that separates the buffering layer from the ionic solution reservoir. In this design, the granular buffer is intentionally placed next to the conductor in the electrode to neutralize the acid or base molecules as soon as they are generated. The ions targeted for delivery are concentrated in the layer nearest the tissue.
  • Drag Stability In certain embodiments, the drug undergoing iontophoresis is stable in the solution environment before and during the iontophoretic process. Oxidation or reduction of a drug not only decreases the total drug available, but the degradation compounds, if they possess the same charge as the drag ion, may compete with the drug ion and reduce the overall rate of administration.
  • I Oi l 4 Current density: Higher current density may result in higher rates of drug delivery. However, current density may be limited for various considerations. For example, the current may be limited to not produce harmful effects to the tissue or affect electrochemical stability of the drug. [01.15] A few relationships that can be important in iontophoresis are described below.
  • D IT/VC
  • Medications Certain devices and methods described herein utilize one or more of the following medications alone or in combination.
  • the mydriatic agents may be neutral, negatively charged, or positively charged depending on the nature of the drug delivery to be provided by the composition.
  • As the iontophoretic device is dependent on utilizing drugs that, are cationic or anionic, neutrally charged molecules may be modified to increase their valence.
  • the device is configured with an inert electrode which eleetrolyzes water to produce hydroxide or hydronium ions. These ions propel charged drug molecules.
  • Iontophoresis of cationic drugs at physiologic pH utilizes anodic electrolysis, generating hydronium ions that promote the movement of the cation into ocular tissues and fluids.
  • the drug solution or hydrogel
  • the eleclxode can be kept a distance away from the portion of the gel or liquid opposing the ocular surface.
  • the iontophoretic delivery of an anionic drug at physiologic pH utilizes cathodic electrolysis, producing hydroxide ions that promote movement of the anionic drug into ocular tissues and fluids, while raising the pH of the drug solution.
  • the use of buffers and distal placement of the electrode away from the portion facing the ocular surface can mitigate large changes in pH.
  • Agents that are considered cationic may be administered using anodic iontophoresis with the return electrode on the patient's forehead or other part of the body.
  • Cationic mydriatic drugs include:
  • Agents that are considered anionic may be administered using cathodic iontophoresis.
  • Cathodic iontophoresis includes a negatively charged chamber acting as a cathode, and a neutral return electrode on the patient's forehead or other part of the body.
  • Anionic medications include:
  • nepafanac the prodrug of amfenac, is neutral at physiological pH and may require some modification to be used for iontophoresis).
  • lidocaine which provides mydriasis and analgesia
  • epinephrine or possibly phenylephrine
  • tropicamide a muscarinic antagonist
  • drugs in the epinephrine classification can be a nonsteroidal anti-inflammatory, which helps create and prolong mydriasis and also reduces inflammation and cystoid macular edema.
  • the iontophoresis of non-steroidal drugs may further enhance mydriasis, in addition to reducing postoperative inflammation and cystoid macular edema.
  • iontophoresing a steroid can reduce postoperative inflammation or cystoid macular edema.
  • Iontophoresis of a fluoroquinolone e.g., moxifloxacin, which is a cation
  • a glycopeptide antibiotic such as vancomycin (which is positively charged at physiological pH)
  • a steroid may not, create mydriasis, it can be iontophoresed preoperativeiy as an anti-inflammatory and to prevent cystoid macular edema.
  • Additional examples of using iontophoresis of a corticosteroid to treat postoperative intraocular inflammation are described in U.S. Patent Publication No. 2009/0206579, and additional examples of iontophoresis of ocular drugs are described by E. Elj arrat-Binstock, et al., "Iontophoresis: A non-invasive ocular drug delivery," Journal of Controlled Release, 1 30 (2006), 479-489, the entirety of each of which is hereby incorporated by reference.
  • Mydriatic medications are normally dissolved in non-saline water and the active agents adjusted by pH to have a valency of equal to or greater than 1.
  • the mydriatic medications described herein can be delivered in the form of a liquid, gel, foam, hydrogel, paste, film, contact lens, microsphere or mucoadherent formulation.
  • the agent can placed into a chamber, and the chamber is inverted and placed onto the eye of a patient after application of topical anesthetic drops, such as proparacaine.
  • topical anesthetic drops such as proparacaine.
  • the chamber is first placed onto the eye of a patient after administration of a topical anesthetic drop, then agent may be introduced into the chamber through a fill tube.
  • Most drugs are generally weak acids or bases.
  • they have at least one site that can reversibly dissociate a proton (e.g., hydronium ion) and create an anion.
  • a proton e.g., hydronium ion
  • bases they reversibly associate a proton and form a cation.
  • the fractionated protonated and unprotonated species of the drug can be shifted by the pH of the media.
  • the ease of proton dissociation is called the pKa (dissociation constant), which equals the pH + log (protonated/unprotonated drug).
  • Drugs that are anions including steroids can use cathodic iontophoresis.
  • Cathodic iontophoresis induces produced negatively charged hydroxide anions to repel the drug into the tissue.
  • cationic drugs like lidocaine, tropicamide, epinephrine or phenylephrine, anodic iontophoresis can be used, since this will create positive charge hydronium ions from the electrolysis of water and these will repel the drug.
  • Other interesting positively charged ocular drugs are moxifioxacin and vancomycin, which could be used for prophylactic treatment against endophthalmitis prior to cataract surgery.
  • the medium may also contain supplemental agents, such as electrolytes, pH regulating buffers, preservatives, stability additives PEGylating agents and other additives that may increase the half life and/or availability of the drugs.
  • supplemental agents such as electrolytes, pH regulating buffers, preservatives, stability additives PEGylating agents and other additives that may increase the half life and/or availability of the drugs.
  • NSAIDS includes 2-acetoxybenzoic acid, indomethacin, tolmetin, ibuprofen, flurbiprofen, ketoprofen, naproxen, axoprozin, pranoprofen, suprofen, piroxicam, and amide derivatives of amfenac, bromfenac, diclofenac, ketorolac, flurbiprofen and suprofen.
  • Some embodiments may use a corticosteroid for anti- inflammatory effect.
  • Inflammation after cataract surgery can lead to pain/discomfort, photophobia, corneal edema and cystoid macular edema (CME)
  • CME cystoid macular edema
  • PGE2 prostaglandins
  • PGE2 prostaglandins
  • CME cystoid macular edema
  • An embodiment may use a cocktail of cationic drugs (lidocaine, tropicamide, phenylephrine or epinephrine), possibly adding an antibiotic such as moxifioxacin.
  • Embodiments of these drugs ma ⁇ ' deliver them alone or in combination.
  • the anionic drugs e.g., the NSAID and possibly the corticosteroid
  • the anionic drugs may need to be mixed separately from the cationic, and could be delivered alone or in combination. While the NSAID has effects on dilation, the corticosteroid should affect only inflammation, pain, photophobia and development of CME.
  • the chemistry may he limited to lidocaine, tropicamide, epinephrine (or phenylephrine) and the NSAID separately.
  • the eye cup may have two ports. One port delivers the drug solution. The other aspirates air bubbles that may disrupt the current supply. In some embodiments, inflow and outflow pressures may be adjusted to maintain a slightly negative pressure to hold the applicator in place.
  • the ground electrode is attached to the patient and attached as close as possible to the former electrode to obtain minimal resistance.
  • the electrode may be placed on the forehead. In other embodiments, the electrode may be clipped to the ear.
  • a drug saturated gel is configured as the delivery probe.
  • the gel may be configured to make a direct contact with the eye.
  • a hydrogel comprising polyacetal sponge may be used.
  • the drug applicator includes a small silicone shell that contains a conductive element, a hydrogel pad to absorb the drug formulation, and a small, flexible wire to connect the conductive element to the dose controller.
  • the dry hydrogel matrix is hydrated with the drug solution and placed against the conjunctiva overlying the sclera in the lower cul-de-sac of the eye.
  • the return electrode can be positioned anywhere on the body to complete the electrical circuit.
  • the device may be configured with a selective membrane which increases drug transport by excluding the transport of non-drug ions, thus making drug-ions the primary carrier of electrical current through scleral tissue.
  • a polyacrylic-porous hydrogel saturated with gentamicin or dexamethasone solutions may be configured for transcorneal and transscleral iontophoresis.
  • the device may be configured as a probe, in this configuration, hydrogel is inserted into a well at the tip of the el ectrode, and the probe placed onto the eye. The use of a hydrogel probe applicator may have fewer current interruptions and be less harmful to the eye surface compared with the eye cup approach.
  • the reservoir is configured as a cup and placed over the cornea and a portion of the sclera.
  • the reservoir may be configured as annular shape with an opening to avoid contact with the cornea.
  • the opening may be in the range of about 13 mm.
  • the material may be a pliable elastomer, such as silicone.
  • the reservoir may be metallic.
  • Described below are examples of direct absorption devices. Although they may be described in the context of being an iontophoresis device, the devices can be used in other configurations.
  • the iontophoresis devices described below can also be used as a chamber for direct absorption without electrorep lsion (e.g., without, electrodes).
  • FIGs 1 A-C illustrate an embodiment of an iontophoresis device 100 with a chamber 102 (e.g., reservoir) having a cup shape.
  • the chamber 102 includes an opening extending from a first surface 103 of the chamber 102 to a cavity 101 configured to receive at least one medication.
  • the at least one opening and/or the first surface 103 can be configured to be placed in contact with an eye 106 of a patient.
  • the iontophoresis device 100 can also include an electrode 104 (e.g., anode or cathode) configured to be in electrical communication with the at least one medication when the at least one medication is within the cavity 303 of the chamber 102.
  • an electrode 104 e.g., anode or cathode
  • the electrode 104 can be in electrical communication with the chamber 102, and the chamber 102 can be in electrical communication with the at least one medication.
  • the at least one medication can include at least one active ingredient, and the at least one active ingredient can be configured to enter tissue of the eye 306 through a process of iontophoresis.
  • Figures 2A-C illustrate another embodiment of an iontophoresis device 200 that is similar to the iontophoresis device 100 in Figures 1A-C.
  • the chamber 202 includes an opening extending from a first surface 203 of the chamber 202 to a cavitv' 201 configured to receive at least one medication.
  • the at least one opening and/or the first surface 203 can be configured to be placed in contact with an eye 206 of a patient.
  • the iontophoresis device 200 can also include an electrode 204 configured to be in electrical communication with the at least one medication when the at least one medication is within the cavity 201 of the chamber 202.
  • the iontophoresis device 200 includes at least one fill tube 208 extending from the cavity 201 to a second surface 205 of the chamber 202 and configured to receive the at least one medication such that the cavity 201 can receive the at least one medication while the chamber 202 is in contact with the eye 206.
  • Figures 3A-C illustrate a further embodiment of an iontophoresis device 300 that includes a first, chamber 302a and a second chamber 302b.
  • the first chamber 302a includes at least one opening extending from a first surface 303a of the first chamber 302a to a cavity 30! configured to receive at least one first medication.
  • the at least one opening and/or the first surface 303a can be configured to be placed in contact with an eye 306 of a patient.
  • a first electrode 304a can be configured to be in electrical communication with the at least one first medication when the at least one first medication is within the cavity 301 a of the first chamber 302a.
  • the at least one first medication can include at least one active ingredient, and the at least one active ingredient can be configured to enter tissue of the eye 306 through a process of iontophoresis.
  • the second chamber 302b includes at least one opening extending from a first, surface 303b of the second chamber 302b to a cavity 301b configured to receive at least one second medication.
  • the at least one opening of the second chamber 302b also configured to be placed in contact with an eye of a patient.
  • a second electrode 304b can be configured to be in electrical communication with the at least one second medication when the at least one second medication is within the cavity 301b of the second chamber 302b.
  • the at least one second medication can include at least one active ingredient, and the at least one active ingredient can be configured to enter tissue of an eye through a process of iontophoresis.
  • the iontophoresis device 300 can include a coupling device 31 0 configured to couple together the first chamber 302a and the second chamber 302b while maintaining electrical isolation between the first chamber 302a and the second chamber 302b.
  • a gap is between the first chamber 302a and the second chamber 302b,
  • an electrically insulative material can be between or sandwiched between the first chamber 302a and the second chamber 302b.
  • the cavity 301a of the first chamber 302a is fluidly separate from the cavity 301 b of the second chamber 302b.
  • the at least one first medication can be different than the at least one second medication and/or the at least one active ingredient, of the at least one first medication can be different than the at least one active ingredient of the at least one second medication.
  • examples of medications and active ingredients are described above, and each chamber 302a, 302b can include a different medication and/or active ingredient.
  • iontophoresis devices can include more than two chambers.
  • FIGS 4A-C illustrate a further embodiment of an iontophoresis device 400 that includes a first chamber 402a and a second chamber 402b similar to the iontophoresis device 300 in Figures 3A-C,
  • Each chamber 402a, 402b includes an opening extending from a first surface 403a, 403b to a cavity' 401a, 401b configured to receive at least one medication.
  • the at least one opening and/or the first surface 403a, 403b can be configured to be placed in contact with an eye 406 of a patient.
  • Each chamber 402a, 402b can also include an electrode 404a, 404b configured to be in electrical communication with the at least one medication when the at least one medication is within the cavity 401a, 401b of the respective chamber 402a, 402b.
  • the iontophoresis device 400 can include a coupling device 410 as discussed above.
  • the first chamber 402a can includes at, least one first fill tube 408a extending from the cavity 401a to a second surface 405a of the first chamber 402a and configured to receive the at least one medication such that the first cavity 401 can receive the at least one medication while the first chamber 402a is in contact with the eye 406.
  • the second chamber 402b can also include at least, one second fill tube 408b extending from the cavity 401b to a second surface 405b of the second chamber 402b and configured to receive the at least one medication such that the second cavity 401b can receive the at least one medication while the second chamber 402b is in contact with the eye 406.
  • the chamber 502 is configured to at, least partially surround at least, a portion of a cornea of an eye 506.
  • the chamber 502 can be configured to avoid contact with the cornea of the eye, instead, the chamber 502 can be configured to cover a portion of a sclera of the eye.
  • the chamber 502 is at least a partial annul us.
  • the at, least one opening and the first surface 503 of the chamber 502 can be configured as at least a partial aniiulus.
  • the chamber 502 and/or the at least one opening and the first surface 503 of the chamber is an annulus.
  • the annuius may have an inner diameter greater than about 12 mm to avoid contact with the cornea.
  • the iontophoresis device 500 may further include a support, structure 512 coupled to the chamber 502 to, for example, provide a method of holding the iontophoresis device 500.
  • the electrode 504 can be in electrical communication with the support structure 512 which can also be in electrical communication with the chamber 502 and the at least one medication.
  • Figures 6A-C illustrate an embodiment of an iontophoresis device 600 similar to the iontophoresis device 500 in Figures 5A-C.
  • the chamber 602 includes an opening extending from a first surface 603 of the chamber 602 to a cavity 601 configured to receive at least one medication.
  • the chamber 602 is configured to at least partially surround at least a portion of a cornea of an eye 606.
  • the iontophoresis device 600 further includes a support structure 612 and an electrode 604.
  • the iontophoresis device 600 can include one or more fill tubes 608 extending from the cavity 601 to a second surface 605 of the chamber 602 and configured to receive the at least one medication such that the cavity 601 can receive the at least one medication while the chamber 602 is in contact with the eye 606.
  • FIGS 7A-C illustrate an embodiment of an iontophoresis device 700 similar to the iontophoresis device 500 in Figures 5A-C but with a first chamber 702a and a second chamber 702b similar to the iontophoresis device 300 in Figures 3A-C.
  • Each chamber 702a, 702b includes an opening extending from a first surface 703a, 70.3b to a cavity 701a, 701 b configured to receive at least one medication.
  • the at least one opening and/or the first surface 703a, 703b can be configured to be placed in contact with an eye 706 of a patient.
  • Each chamber 702a, 702b can also include an electrode 704a, 704b configured to be in electrical communication with the at least one medication when the at least one medication is within the cavity 701 a, 701 b of the respective chamber 702a, 702b.
  • the iontophoresis device 700 can include a coupling device 710 as discussed above.
  • a first support structure 712a can be coupled to the first chamber 702a and a second support structure 712b can be coupled to the second chamber 702b.
  • a gap is between the first support structure 712a and the second support structure 712b.
  • an electrically msulative material can be between or sandwiched between the first support structure 712a and the second support structure 712b.
  • FIGs 8A-C illustrate an embodiment of an iontophoresis device 800 similar to the iontophoresis device 700 in Figures 7A-C.
  • Each chamber 802a, 802b includes an opening extending from a first surface 803a, 803b to a cavity 801a, 801b configured to receive at least one medication. The at least one opening and/or the first surface 803a, 803b can be configured to be placed in contact with an eye 806 of a patient.
  • Each chamber 802a, 802b can also include an electrode 804a, 804b.
  • the iontophoresis device 800 can include a coupling device 810, a first support structure 812a, and a second support structure 712b, as discussed above.
  • the first chamber 802a can includes at least one first fill tube 808a and the second chamber 802b can also include at least one second fill tube 808b.
  • Figures 9A-C illustrate an embodiment of an iontophoresis device 900 similar to the iontophoresis device 700 in Figures 7A-C.
  • the first chamber 902a and the second chamber 902b have an annular shaped with the second chamber 902b being inside the first chamber 902a (e.g., concentric rings).
  • the chambers 902a, 902b are configured to at least partially surround at least a portion of a cornea of an eye 906, and the second chamber 902b is between the first chamber 902a and the cornea.
  • the second chamber 902b has an inner diameter greater than a diameter of the cornea (e.g., greater than about 12 mm) and the first chamber 902a has an inner diameter greater than an outer diameter of the second chamber 902b.
  • the first chamber 902a may have an inner diameter of about 14 mm and the second chamber 902b may have an inner diameter of about 13 mm.
  • each chamber 902a, 902b includes an opening extending from a first surface 903a, 903b to a cavity 901 a, 901 b configured to receive at least one medication.
  • the at least one opening and/or the first surface 903a, 903b can be configured to be placed in contact with an eye 906 of a patient.
  • the iontophoresis device 900 can include other features as discussed above such as electrodes 904a, 904b, a coupling device 910, and support structures 912a, 912b.
  • Figures l OA-C illustrate an embodiment of an iontophoresis device 1000 similar to the iontophoresis device 900 in Figures 9A-C.
  • Each chamber 1002a, 1002b includes an opening extending from a first surface 1003a, 1003b to a cavity 1001a, 1001b configured to receive at least one medication.
  • the at least one opening and/or the first surface 1003a, 1003b can be configured to be placed in contact with an eye 1006 of a patient.
  • the iontophoresis device 1000 can include other features as discussed above such as electrodes 1004a, 1004b, a coupling device 1010, and support structures 1012a, 912b. Furthermore, the iontophoresis device 1000 can include fill tubes 1008a, 1008b as previously discussed.
  • Figure 1 1A illustrates a femtosecond laser attachment 1 120 configured to receive a femtosecond laser for treating an eye of a patient.
  • Figure 1 I B illustrates an iontophoresis device 1 100 configured to receive the femtosecond laser attachment 1 120 in Figure 1 1 A.
  • the iontophoresis device 1 100 is similar to the iontophoresis device 800 in Figures 8A-C. However, the support structures 1 1 12a and 1 1 12b provide a larger opening between them to accommodate the femtosecond laser attachment 1 120.
  • Figure 1 1 C illustrates the femtosecond laser attachment 1 120 coupled with the iontophoresis device 1 100.
  • iontophoresis device 1 100 and the femtosecond laser attachment 1 120 are configured to be removably coupled, in certain embodiments, the iontophoresis device 1 100 includes a gasket 1 1 13 (e.g., o-ring) along an inside perimeter of the support structures 1 1 12a and 1 1 12b, as illustrated in Figure 1 I D, The gasket 1 1 13 can help to provide a snug fit between the iontophoresis device 1 100 and the femtosecond laser attachment 1 120.
  • a gasket 1 1 13 e.g., o-ring
  • Figures 12A-C illustrate an iontophoresis device 1200 configured to receive a femtosecond laser attachment 1220 similar to iontophoresis device 1 100 and femtosecond laser attachment 1 120 in Figures 1 1 A-D. Furthermore, the iontophoresis device 1200 is similar to the iontophoresis device 900 in Figures 9A-C; however, the support structures 1212a and 1212b provide a larger opening between them to accommodate the femtosecond laser attachment 1220.
  • Figures 13A-C illustrate another iontophoresis device 1300 configured to receive a femtosecond laser attachment 1320 similar to iontophoresis device 1200 and femtosecond laser attachment 1220 in Figures 12A-D.
  • the iontophoresis device 1300 further includes fill tubes 1308a, 1308b coupled to the respective chambers 1302a, 1302b similar to the iontophoresis device 1000 in Figures l OA-C.
  • the iontophoresis device can also be configured to receive other devices.
  • the iontophoresis device can be configured to surround an Intralase cone or replace an intralase suction device.
  • iontophoresis devices can include a controller in electrical communication with the electrodes and a portion of the patient, if the iontophoresis device includes a single chamber such as those illustrated in Figures lA-C, 2A-C, 5A-C, and 6A-C, a 2-lead controller 1430 can be used, as illustrated in Figure 14A.
  • the controller 1430 can include a first lead 1434 configured to be in electrical communication with an electrode of the iontophoresis device and a second lead 1436 configured to be in electrical communication with a portion of the patient.
  • the controller 1430 can further include an interface 1432 to control electrical potential applied to the leads 1434, 1436.
  • a 3 -lead controller 1440 can be used, as illustrated in Figure 14B. Similar to the controller 1430 in Figure I4A, the controller 1440 can include leads 1444, 1446, 1448 and an interface 1442.
  • a first lead 1444 can be configured to be in electrical communication with a first electrode of the iontophoresis device, a second lead 1446 can be configured to be in electrical communication with a second electrode of the iontophoresis device, and a third lead 1448 can be configured to be in electrical communication with a portion of the patient. If the iontophoresis device includes more than two chambers, the controller can also include additional leads.
  • a method includes contacting a first surface of a first chamber with the eye.
  • the first, chamber includes at least one opening extending from the first surface to a cavity.
  • the method can further include filling the cavity of the first chamber with at least one first medication and applying an electrical potential between the first chamber and the patient to cause at least one active ingredient of the at least one first medication to enter the eye.
  • the iontophoresis device can include two or more chambers.
  • the method further includes contacting a first surface of a second chamber with the eye.
  • the second chamber includes at least one opening extending from the first surface to a cavity.
  • the method may further include filling the cavity of the second chamber with at least one second medication and applying an electrical potential between the second chamber and the patient, to cause at least one active ingredient of the at least one second medication to enter the eye.
  • the at least one first medication can be different than the at least one second medication.
  • the first medication and the second medication may be administered serially (e.g., one medication at a time) or in parallel (e.g., both medications at the same time).
  • the cavity of the first chamber may be fluidly separate from the cavity of the second chamber.
  • the first chamber and the second chamber may be coupled together while maintaining electrical isolation between the first chamber and the second chamber.
  • the device is configured as a double chamber sclera cup with fill ports.
  • the device is placed onto the eye of a patient, then the chambers are each filled using syringes (such as the syringe 1500 illustrated in Figure 15) or other means.
  • the chambers are electrically activated for a period of time using a 3 -lead controller. If the mydriatic agent in one of the chambers is a cationic medication, the controller applies a positive voltage to that chamber. If the mydriatic agent in one of the chambers is an anionic medication, the controller applies a negative voltage to that chamber.
  • One or more return lines are attached to the forehead or other body part of the patient to complete the circuits,
  • the device is configured as a double chamber sclera cup without fill ports, in use, the chambers are filled with gels, then the device is placed onto the eye of a patient.
  • the chambers are then electrically activated for a period of time using a 3 -lead controller. If the mydriatic agent in one of the chambers is a cationic medication, the controller applies a positive voltage to that chamber. If the mydriatic agent in one of the chambers is an anionic medication, the controller applies a negative voltage to that chamber.
  • One or more return lines are attached to the forehead or other body part of the patient to complete the circuits.
  • the device is configured as a single chamber sclera cup with fill ports.
  • the device is placed onto the eye of a patient, then the chamber is filled using a syringe or other means.
  • the chamber is electrically activated for a period of time using a 2-Iead controller, if the mydriatic agent is a cationic medication, the controller applies a positive voltage to the chamber. If the mydriatic agent is an anionic medication, the controller applies a negative voltage to the chamber.
  • a return line is attached to the forehead or other body part of the patient to complete the circuit.
  • the device is configured as a single chamber sclera cup without fill ports.
  • the device is filled with gel, and then placed onto the eye of a patient.
  • the chamber is then electrically activated for a period of time using a 2-iead controller. If the mydriatic agent is a cationic medication, the controller applies a positive voltage to the chamber. If the mydriatic agent is an anionic medication, the controller applies a negative voltage to the chamber.
  • A. return line is attached to the forehead or other body part of the patient to complete the circuit.
  • the device is configured as a double chamber eye cup with fill ports.
  • the device is placed onto the eye of a patient, and then the chambers are filled using syringes or other means.
  • the chambers are electrically activated for a period of time using a 3-lead controller. If the mydriatic agent in one of the chambers is a cationic medication, the controller applies a positive voltage to that chamber. If the mydriatic agent in one of the chambers is an anionic medication, the controller applies a negative voltage to that chamber.
  • One or more return lines are attached to the forehead or other body part of the patient to complete the circuits.
  • the device is configured as a double chamber eye cup without fill ports.
  • the device is filled with gels, and then placed onto the eye of a patient.
  • the chambers are then electrically activated for a period of time using a 3-lead controller. If the mydriatic agent in one of the chambers is a cationic medication, the controller applies a positive voltage to that chamber. If the mydriatic agent in one of the chambers is an anionic medication, the controller applies a negative voltage to that chamber.
  • One or more return lines are attached to the forehead or other body part of the patient to complete the circuits.
  • the device is configured as a single chamber eye cup with fill ports.
  • the device In use, the device is placed onto the eye of a patient, then the chamber is filled using a syringe or other means. Next, the chamber is electrically activated for a period of time using a 2-lead controller. If the mydriatic agent is a cationic medication, the controller applies a positive voltage to the chamber. If the mydriatic agent is an anionic medication, the controller applies a negative voltage to the chamber. A return line is attached to the forehead or other body part of the patient to complete the circuit.
  • the device is configured as a single chamber eye cup without fill ports.
  • the device is filled with gel and then placed onto the eye of a patient.
  • the chamber is then electrically activated for a period of time using a 2-lead controller, if the mydriatic agent is a cationic medication, the controller applies a positive voltage to the chamber. If the mydriatic agent is an anionic medication, the controller applies a negative voltage to the chamber.
  • A. return line is attached to the forehead or other body part of the patient to complete the circuit.
  • the iontophoresis device can be stand alone or incorporated into the interface of a femtosecond laser used for cataract surgery,
  • the diameter of the sclera ring is configured to fit around the circumference of the patient interface.
  • the sclera cup is attached to the femtosecond laser patient interface, and the two functions are handled as a unit.
  • an O-Ring is configured to be retained by the device, with a portion thereof protruding within an inner diameter of the device.
  • a portion of the O-Ring is configured to interface with a portion of the femtosecond laser patient interface causing retention there between.
  • the electrode (either inert or active) is far away from the surface applied to the eye, since most of the pH changes occur near the electrode and the electrode may create thermal effects.
  • the electrode may be about 6 millimeters away from the surface of the eye.
  • the electrophoresis is just done serially with the various drugs, in further embodiments, a NSAID can be used and could be strong enough that it could obviate the need for the steroid. For example, if iontophoresing bromfenac is used. Some embodiments may add a hydrophilic foam to the drags in the device.

Abstract

La présente demande décrit des dispositifs et des procédés qui utilisent une absorption directe pour délivrer des médicaments mydriatiques par voie transclérale ou transcornéenne dans l'œil afin d'agrandir la pupille de l'œil d'un patient. Cela peut être effectué en préparation pour une chirurgie oculaire, pour un examen, pour un traitement d'un glaucome malin, ou d'autres applications. Le mécanisme d'absorption directe peut être assisté par électrorépulsion, répulsion magnétique, ou excitation ultrasonore.
PCT/US2012/039267 2011-05-26 2012-05-24 Dispositif et procédé pour administrer des médications oculaires WO2012162459A1 (fr)

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US201161490537P 2011-05-26 2011-05-26
US61/490,537 2011-05-26
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US61/576,290 2011-12-15

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CN110934743A (zh) * 2019-12-31 2020-03-31 黄立平 多腔眼药水瓶的制造方法、用途及使用方法
RU2725295C2 (ru) * 2015-04-14 2020-06-30 Айвенсис Устройство для электропорации
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RU2809801C2 (ru) * 2015-04-14 2023-12-18 Айвенсис Устройство для электропорации
CN117281684A (zh) * 2023-11-24 2023-12-26 超目科技(北京)有限公司 眼球吸附装置和眼球吸附系统
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EP4190395A4 (fr) * 2020-08-28 2024-02-21 Terumo Corp Outil d'administration de médicament
CN117281684A (zh) * 2023-11-24 2023-12-26 超目科技(北京)有限公司 眼球吸附装置和眼球吸附系统
CN117281684B (zh) * 2023-11-24 2024-03-29 超目科技(北京)有限公司 眼球吸附装置和眼球吸附系统

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