Methods and devices for treating eye disease

Abstract

This article describes a device used to treat high intraocular pressure and glaucoma.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 794,139, filed January 18, 2019, the entire disclosure of which is incorporated herein by reference. Background Technology

[0003] Millions suffer from eye diseases, especially glaucoma. Most glaucoma patients have abnormally high intraocular pressure (IOP) because they lack the ability to drain excess aqueous humor from the anterior chamber of the eye through the trabecular meshwork. If high IOP is not adequately treated to reduce it, the disease will continue to damage the optic nerve as the disease progresses, leading to vision loss or even complete blindness. Current drug treatments, surgeries, and implants have been proven insufficient to consistently reduce or maintain normal intraocular pressure over the years. Therefore, new methods to alleviate IOP are needed to treat glaucoma. Summary of the Invention

[0004] This document describes a therapeutic device (or simply device) for treating eye conditions. In one embodiment, the eye condition is elevated intraocular pressure, and the device described herein lowers the intraocular pressure. The device typically includes a plate structure or core component comprising a first main surface coated with a first material and a second main surface coated with a second material. In some embodiments, the plate or core component is simply coated, thus not limiting the first and second coatings.

[0005] The plate structure or plate may have a thickness ranging from about 1 nm to about 1,000 nm or from about 50 nm to about 800 nm.

[0006] The plate structure may include channels that assist in the movement of fluid in the eye, thereby reducing intraocular pressure.

[0007] Other embodiments include methods for reducing intraocular pressure. In one embodiment, the method includes securing a device as described herein to the eye, thereby displacing ocular fluid and reducing intraocular pressure.

[0008] In some embodiments, the described device is used to reduce or decrease intraocular pressure. The device may include: a plate structure comprising opposing first and second surfaces, wherein the first surface includes a series of fluid channels, a first coating on the first surface, and a second coating on the second surface.

[0009] In some embodiments, the plate structure is formed of a ceramic material. The ceramic material may be selected from alumina, silicon nitride, silicon dioxide, hafnium dioxide, titanium nitride, and titanium.

[0010] In some embodiments, the first coating is a polymer material. The polymer material may be a parylene polymer. The parylene polymer may be parylene C, parylene D, parylene N, derivatives thereof, or combinations thereof.

[0011] In other embodiments, the polymeric material includes rubber, synthetic rubber, siloxane polymers, parylene, thermoplastics, thermosetting plastics, polyolefins, polyisobutylene, acrylic polymers, ethylene-vinyl acetate copolymers, polymethyl methacrylate, vinyl halogenated polymers, polyethers, polyethylene halides, polyacrylonitrile, polyvinyl ketone, polyvinyl alcohol aromatics, polyvinyl alcohol esters, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides, alkyd resins, polycarbonates, polyoxymethylene, polyimide, polyethers, epoxy resins, polyurethanes, synthetic fibers, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polytetrafluoroethylene, polyetheretherketone, polylactic acid, such as PLA, PLGA, PLLA, their derivatives, or combinations thereof.

[0012] In some embodiments, the second coating comprises alumina and / or a poly(p-xylene) polymer.

[0013] In some embodiments, the second coating comprises alumina combined with the following: rubber, synthetic rubber, siloxane polymers, thermoplastics, thermosetting plastics, polyolefins, polyisobutylene, acrylic polymers, ethylene-vinyl acetate copolymers, polymethyl methacrylate, vinyl halogenated polymers, polyethers, polyethylene halides, polyacrylonitrile, polyvinyl ketone, polyvinyl alcohol aromatics, polyvinyl alcohol esters, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides, alkyd resins, polycarbonates, polyoxymethylene, polyimide, polyethers, epoxy resins, polyurethanes, synthetic fibers, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polytetrafluoroethylene, polyetheretherketone, polylactic acid, such as PLA, PLGA, PLLA, derivatives thereof, or combinations thereof.

[0014] The series of fluid channels may include multiple open channels that are interconnected to form a cross network of fluid pathways. In some embodiments, the channels are microchannels.

[0015] In some embodiments, the device further includes a drug. In some embodiments, the drug may be located within a microchannel. In some embodiments, the drug may be secured within the microchannel by a coating.

[0016] A method of treatment is also described. In one embodiment, the described method includes: injecting a device into an eye with high intraocular pressure, the device comprising a plate structure including opposing first and second surfaces, wherein the first surface includes a series of fluid channels, a first coating on the first surface, and a second coating on the second surface; and treating high or elevated intraocular pressure.

[0017] The method may also include fastening the device to the eye. Fastening may be to the sclera of the eye or any other part thereof.

[0018] In some embodiments, at least a portion of the first surface faces the conjunctiva of the eye, and at least a portion of the second surface faces the sclera of the eye.

[0019] In other embodiments, the device forms a fluid passage that provides fluid flow between the anterior chamber of the eye and the device location.

[0020] In addition, the fluid pathway includes a series of fluid channels.

[0021] In some implementations, treating high intraocular pressure is a form of glaucoma treatment.

[0022] Other applications of the invention will become apparent from the description provided below. It should be understood that the detailed descriptions and specific embodiments are intended for illustrative purposes only and are not intended to limit the scope of the invention. Attached Figure Description

[0023] The invention will be more fully understood through detailed embodiments and accompanying drawings, in which:

[0024] Figure 1 This is a perspective view of an apparatus according to one embodiment;

[0025] Figure 2 The device is based on Figure 1 A close-up view of the identified cross-section;

[0026] Figure 3 The device is along Figure 2 Cross-sectional view shown at centerline III-III;

[0027] Figure 4 This is a perspective view of an apparatus according to another embodiment;

[0028] Figure 5A According to one implementation method Figure 4 A portion of the cross-sectional view of section A of the device shown;

[0029] Figure 5B According to one implementation method Figure 4A portion of the cross-sectional view of section A of the device shown;

[0030] Figure 5C According to one implementation method Figure 4 A portion of the cross-sectional view of section A of the device shown;

[0031] Figure 6 This is a perspective view of an apparatus according to another embodiment of the present invention;

[0032] Figure 7 The device according to one embodiment is along Figure 6 Cross-sectional view shown by centerline XII-XII;

[0033] Figure 8 This is a top view of an apparatus according to another embodiment of the present invention;

[0034] Figure 9 The device according to one embodiment is along Figure 8 Cross-sectional view shown by centerline XIV-XIV;

[0035] Figure 10 This is a perspective view of an apparatus according to another embodiment;

[0036] Figure 11 The device according to one embodiment is along Figure 10 Cross-sectional view shown by the midline XVI-XVI;

[0037] Figure 12 The device according to one embodiment is along Figure 10 Cross-sectional view shown along centerline XVII-XVII;

[0038] Figure 13 This is a close-up view of an implantation device used for implanting devices as described herein;

[0039] Figure 14A Is using Figure 13 A cross-sectional view of the eye into which the implantation device is inserted;

[0040] Figure 14B Is using Figure 13 A close-up cross-sectional view of the eye into which the implantation device is inserted;

[0041] Figure 15 yes Figure 13 A cross-sectional view of the device during implantation;

[0042] Figure 16 yes Figure 13 A cross-sectional view of the device during implantation;

[0043] Figure 17It is an implantation device for implanting a device as described herein, said implantation device in a first state;

[0044] Figure 18 It is an implantation device for implanting a device as described herein, said implantation device in a second state;

[0045] Figures 19 to 20 It is an implantation device for an implantation device according to another embodiment;

[0046] Figure 21 Is using Figures 19 to 20 Close-up cross-sectional view of the eye to which an implantable device, such as the device described herein, is inserted;

[0047] Figure 22 Embodiments of the apparatus as described herein are shown;

[0048] Figure 23 Embodiments of inserters or insertion devices as described herein are shown;

[0049] Figure 24 Intraocular pressure is shown after insertion of the device as described herein; and

[0050] Figure 25 The intraocular pressure comparison between the device described in this article and the SIBS device is shown. Detailed Implementation

[0051] The following description of the embodiments is merely exemplary in nature and is not intended to limit the invention, its application, or its use.

[0052] As used throughout, a range is used as a shorthand to describe each individual value within the range. Any value within the range can be chosen as an endpoint of the range. Furthermore, the full text of all references cited herein is incorporated herein by reference. In the event of any conflict between the definitions in this disclosure and those in the cited references, the definitions in this disclosure shall prevail.

[0053] The description of exemplary embodiments of the invention is intended to be understood in conjunction with the accompanying drawings, which are considered part of the complete written description. Any references to direction or orientation in the description of embodiments of the invention herein are intended merely for descriptive convenience and are not intended to limit the scope of the invention. Relative terms such as “lower,” “upper,” “horizontal,” “vertical,” “above,” “below,” “up,” “top,” and “bottom,” and their derivatives (e.g., “horizontally,” “downward,” “upward,” etc.) should be understood to refer to the orientation described below or shown in the discussed figures. These relative terms are for descriptive convenience only, and unless explicitly indicated otherwise, do not require the structure to be constructed or operated in a particular orientation.

[0054] Unless otherwise explicitly stated, terms such as “attachment,” “attachment,” “connection,” “link,” “interconnection,” and similar terms mean a relationship in which structures are directly or indirectly fastened or attached to each other, either through an intermediary structure, and that the attachment or relationship is movable or rigid. Furthermore, the features and benefits of the invention are illustrated with reference to the exemplary embodiments. Therefore, the invention should not be explicitly limited to the exemplary embodiments, which illustrate some possible non-limiting combinations of features that may exist alone or in combination with other features; the scope of the invention is defined by the appended claims.

[0055] Unless otherwise specified, all percentages and quantities expressed herein and elsewhere in the specification shall be understood to mean weight percentages. Given quantities are based on the weight of the material. According to this application, the term "about" means + / - 5% of a reference value. According to this application, the term "substantially none" means less than 0.1 wt.% based on a total amount of a reference value.

[0056] The “subjects” in this article may be human or non-human animals, such as, but not limited to, rodents, such as mice, rats, hamsters, and guinea pigs; rabbits; dogs; cats; sheep; pigs; goats; cattle; horses; and non-human primates, such as apes and monkeys, etc.

[0057] refer to Figures 1 to 3 The treatment device 1 (or simply device) may include a plate structure 200 (or simply plate) having opposing first main exposed surfaces 201 and second main exposed surfaces 202, and a side surface 203 extending therebetween. The plate structure 200 may include an extension portion 250 and a main body portion 240.

[0058] The plate structure 200 can be formed of any material having suitable properties for implantation and treatment. In some embodiments, the plate structure 200 can be formed of metals, polymers, ceramics, other composite materials, or combinations thereof. Metals may include, but are not limited to, aluminum, titanium, zinc, platinum, tantalum, copper, nickel, rhodium, gold, silver, palladium, chromium, iron, indium, ruthenium, osmium, tin, iridium, or combinations thereof and alloys thereof. In some embodiments, the alloy may include steel and nickel-titanium, such as nitinol.

[0059] The polymer or polymeric material used to form the plate structure 200 may include any of the polymers described herein.

[0060] Composites, such as silicon composites, may also be used. In one embodiment, the composite may include silicon nitride (Si3N4). Silicon nitride may have any known crystalline structure, such as, but not limited to, trigonal α-Si3N4, hexagonal β-Si3N4, or cubic γ-Si3N4.

[0061] The plate structure or plate may have a thickness in the range of about 1 nm to about 1,000 nm, about 1 nm to about 500 nm, about 1 nm to about 400 nm, about 100 nm to about 1,000 nm, about 200 nm to about 1,000 nm, about 300 nm to about 1,000 nm, about 400 nm to about 1,000 nm, about 1 nm to about 900 nm, about 1 nm to about 800 nm, about 1 nm to about 700 nm, about 1 nm to about 600 nm, about 300 nm to about 500 nm, about 300 nm to about 600 nm, about 400 nm to about 600 nm, about 200 nm to about 600 nm, about 200 nm to about 500 nm, or about 50 nm to about 800 nm.

[0062] The plate structure 200 may include a multidirectional plate 210, which includes opposing first main surfaces 211 and second main surfaces 212. The multidirectional plate 210 may form multiple morphological features (e.g., repeating honeycomb patterns) on each of the first main surfaces 211 and the second main surfaces 212. Each of the first and second morphologies may independently include multiple channels 232 and / or multiple open chambers 222.

[0063] Multiple channels 232 can be interconnected and can form a channel network. The channels can be open, allowing fluid easy access and flow through each of the multiple channels 232. The network can include intersecting channels in any suitable configuration to greatly facilitate fluid flow through the plate structure 200 via the multiple channels 232. In one embodiment, the channels can be configured to form a hexagonal pattern. Once implanted... Figure 1 In the illustrated treatment device 1, fluid (e.g., aqueous humor) can be driven by a pressure gradient to flow through channels and onto the surface of the plate structure 200.

[0064] In some embodiments, the channels may include a ribbed pattern. The ribbed pattern and / or geometry of the channels in the plate may vary based on different degrees of glaucoma severity. In one embodiment, larger or smaller channels may be used to lower intraocular pressure by different amounts. A smaller change in intraocular pressure reduces the risk of hypotension (a condition that can occur when intraocular pressure decreases excessively) and improves the effectiveness of pressure reduction. In some embodiments, a device with smaller channels, as described herein, may reduce flow rate and reduce the risk of hypotension. Similarly, larger channels may increase flow rate and improve the effectiveness of the device in lowering intraocular pressure.

[0065] The plate structure 200 may further include a first coating 280 applied to a first primary surface 211 of the multi-directional plate 210. The first coating 280 may conform to a first morphology of the first primary surface 211 of the multi-directional plate 210. In other embodiments, the first coating 280 may form a morphology that does not conform to the first morphology of the first primary surface 211 of the multi-directional plate 210.

[0066] The first coating 280 may have a thickness ranging from about 0.1 μm to about 10 μm or from about 0.1 μm to about 1 μm (inclusive of all thicknesses and sub-ranges therein). In one embodiment, the thickness is between about 0.4 μm (400 nm) and 0.6 μm (600 nm). In another embodiment, the thickness is about 0.4 μm (400 nm). In other embodiments, the thickness is between about 1 μm and about 5 μm, between about 1 μm and about 3 μm, between about 2 μm and about 5 μm, or between about 2 μm and about 4 μm. In one embodiment, the thickness is about 2 μm.

[0067] The plate structure 200 may further include a second coating 290 applied to a second primary surface 212 of the multi-directional plate 210. The second coating 290 may conform to a plurality of surface features of the second primary surface 212 of the multi-directional plate 210. In other embodiments, the second coating 290 may form a morphology that does not conform to a second morphology of the second primary surface 212 of the multi-directional plate 210.

[0068] The second coating 290 may have a thickness ranging from about 0.1 μm to about 10 μm or from about 0.1 μm to about 1 μm (inclusive of all thicknesses and sub-ranges therebetween). In one embodiment, the thickness is between about 0.4 μm (400 nm) and 0.6 μm (600 nm). In another embodiment, the thickness is about 0.4 μm (400 nm). In other embodiments, the thickness is between about 1 μm and about 5 μm, between about 1 μm and about 3 μm, between about 2 μm and about 5 μm, or between about 2 μm and about 4 μm. In one embodiment, the thickness is about 2 μm.

[0069] In some embodiments, the plate structure 200 may include only the first coating 280, i.e., without the second coating. In other embodiments, the plate structure 200 may include only the second coating 290, i.e., without the first coating. In other embodiments, the plate structure 200 may include both the first coating 280 and the second coating 290, whereby the first and second coatings overlap to completely encapsulate the multidirectional plate 210. In this embodiment, the side surface 203 of the plate structure 200 may include at least one of the first coating 280 and the second coating 290.

[0070] In some embodiments, the first and second coatings, as well as any edge coatings, may be thicker than the plate itself. In some embodiments, the coating thickness may be one, two, or three orders of magnitude thicker than the plate structure. However, in other embodiments, the plate may be thicker than the sum of the thickness of each coating or the two coatings.

[0071] The coatings described herein can be applied by any suitable deposition method, such as, but not limited to, chemical vapor deposition, atomic layer deposition, spraying, dip coating, or brushing.

[0072] The first coating 280 can be applied to the first main surface 211 by any suitable deposition method. In a non-limiting embodiment, the first coating 280 can be applied to the first main surface 211 by chemical vapor deposition. In another non-limiting embodiment, the first coating 280 can be applied to the first main surface 211 by atomic layer deposition. In another non-limiting embodiment, the first coating 280 can be applied to the first main surface 211 by spraying. In another non-limiting embodiment, the first coating 280 can be applied to the first main surface 211 by dip coating. In another non-limiting embodiment, the first coating 280 can be applied to the first main surface 211 by brushing.

[0073] The second coating 290 can be applied to the second primary surface 212 by any suitable deposition method. In a non-limiting embodiment, the second coating 290 can be applied to the second primary surface 212 by chemical deposition. In another non-limiting embodiment, the second coating 290 can be applied to the second primary surface 212 by atomic layer deposition. In another non-limiting embodiment, the second coating 290 can be applied to the second primary surface 212 by spraying. In another non-limiting embodiment, the second coating 290 can be applied to the second primary surface 212 by dip coating. In another non-limiting embodiment, the second coating 290 can be applied to the second primary surface 212 by brushing.

[0074] The first coating 280 may be the same as the second coating 290. The first coating 280 and the second coating 290 may be different. The first coating 280 may be hydrophilic. The first coating 280 may be hydrophobic. The first coating 280 may be lipophilic. The first coating 280 may be lipophobic. The second coating 290 may be hydrophilic. The second coating 290 may be hydrophobic. The second coating 290 may be lipophilic. The second coating 290 may be lipophobic. Each of the first coating 280 and the second coating 290 may be independently continuous. Each of the first coating 280 and the second coating 290 may be independently discontinuous. In some embodiments, both the first coating 280 and the second coating 290 may be hydrophobic. In some embodiments, both the first coating 280 and the second coating 290 may be hydrophilic. In some embodiments, both the first coating 280 and the second coating 290 may be lipophilic.

[0075] The first coating 280 can be organic. The first coating 280 can be inorganic. The second coating 290 can be organic. The second coating 290 can be inorganic.

[0076] In some embodiments, the first coating 280 is hydrophilic and the second coating 290 is hydrophobic. Making at least one of the first coating 280 and / or the second coating 290 hydrophobic can help prevent the treatment device 1 from adversely adhering to tissue during implantation.

[0077] In some embodiments, the purpose of the first and / or second coating is to increase the toughness of the device. Additionally, the first and / or second coating can increase the biocompatibility of the device and / or reduce scarring by reducing tissue and / or fibroblast adhesion. In some embodiments, the coatings described herein are hydrophobic and reduce tissue adhesion. In some embodiments, tissue adhesion can be reduced by more than about 50%, more than about 60%, more than about 70%, more than about 80%, more than about 90%, more than about 95%, more than about 96%, more than about 97%, more than about 98%, or more than about 99% compared to the uncoated plate.

[0078] In a non-limiting embodiment, the first coating and / or the second coating may comprise a parylene polymer, such as a parylene polymer (poly(p-xylene)) or a derivative thereof. In other embodiments, the first coating and / or the second coating may comprise alumina. In one embodiment, the parylene polymer is chlorinated poly(p-xylene). In one embodiment, the parylene polymer may be parylene C, parylene D, parylene N, derivatives thereof, or combinations thereof. In other embodiments, the first coating and / or the second coating may comprise alumina.

[0079] In other embodiments, other polymers may be used as supplements to or alternatives to, or in combination with, parylene polymers and / or alumina. In some embodiments, other polymeric materials may include, but are not limited to, rubber, synthetic rubber, siloxane polymers, thermoplastics, thermosetting plastics, polyolefins, polyisobutylene, acrylic polymers, ethylene-vinyl acetate copolymers, polymethyl methacrylate, vinyl halogenated polymers (e.g., polyvinyl chloride), polyethers (e.g., polyethylene methyl ether), polyethylene halides, polyacrylonitrile, polyvinyl ketone, polyvinyl alcohol aromatics, polyvinyl alcohol esters, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides (e.g., Nylon 66 and polycaprolactam), alkyd resins, polycarbonates, polyoxymethylene, polyimide, polyethers, epoxy resins, polyurethanes, synthetic fibers, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polytetrafluoroethylene (e.g., Teflon), polyetheretherketone, polylactic acid, such as PLA, PLGA, PLLA, their derivatives, or combinations thereof.

[0080] The resulting treatment device 1 may include a first plurality of channels 222 present on a first exposed main surface 201 of the plate structure 200, wherein the first plurality of channels 222 are hydrophilic due to the presence of a first coating 280. The resulting treatment device 1 may include a second plurality of channels 232 present on a second exposed main surface 202 of the plate structure 200, wherein the second plurality of channels 232 are hydrophilic due to the presence of a second coating 290. As discussed, the hydrophilic channels can facilitate fluid flow through the channels after the treatment device 1 is implanted into the subject's eye.

[0081] refer to Figure 4 , Figure 5A , Figure 5B as well as Figure 5CThis example illustrates a treatment device 1001 according to another embodiment. Treatment device 1001 is similar to treatment device 1, except as described herein. The foregoing description of treatment device 1 generally applies to treatment device 1001 as described below, except for the differences explicitly stated below. A similar numbering scheme to treatment device 1 will be used for treatment device 1001, except that a numbering system of "1000" will be used.

[0082] The treatment device 1001 includes a plate structure 1200 having a first exposed main surface 1201 opposite to a second exposed main surface 1202. The plate structure 1200 may include a multidirectional plate 1210, which includes opposing first main surfaces 1211 and second main surfaces 1212. The multidirectional plate 1210 may have multiple morphological features (e.g., repeating honeycomb patterns) formed on each of the first main surface 1211 and the second main surface 1212. Each of the first and second morphologies may independently include multiple channels 1232 and / or multiple open chambers 1222.

[0083] Now refer to Figure 5B The plate structure 1200 may include a first delivery member 1070, which is present in an opening void created by a first morphology formed by a first exposed surface 1211 of the multidirectional plate 1210. Specifically, the first delivery member 1070 may be present in an opening void created by an opening chamber 1222 of the first morphology formed by the first main surface 1211 of the multidirectional plate 1210.

[0084] The first delivery component 1070 may include one or more active agents, such as, but not limited to, therapeutic and / or pharmacological components. The first delivery component 1070 may occupy some, all, or substantially all of the free volume present in the open chamber 1222 formed by the first morphology.

[0085] In other embodiments, the active agent may include any compound or drug that has a therapeutic effect on the subject. Non-limiting active agents include antiproliferative agents, including but not limited to macrolide antibiotics including FKBP-12 binding compounds, estrogen, chaperone inhibitors, protease inhibitors, protein tyrosine kinase inhibitors, leucine B, peroxidase proliferator-activated receptor gamma ligand (PPARγ), teratomycin, nitric oxide, bisphosphonates, epidermal growth factor inhibitors, antibodies, steroids, proteasome inhibitors, antibiotics, anti-inflammatory agents, antisense nucleic acids, converted nucleic acids, IOP-lowering drugs, prostaglandins, cell growth inhibitory compounds, toxic compounds, anti-inflammatory compounds, chemotherapeutic agents, analgesics, antibiotics, protease inhibitors, statins, nucleic acids, peptides, growth factors, and delivery carriers including recombinant microorganisms, liposomes, antimetabolites such as mitomycin C, combinations thereof, their prodrugs, their pharmaceutical salts, their derivatives, etc.

[0086] The treatment device 1001 may further include a first coating 1050 applied to a first main surface 1211 of the multi-directional plate 1210. The first coating 1050 may cover both the first main surface 1211 of the multi-directional plate 1210 and a first delivery member 1070 present in an open chamber 1222 formed in the first main surface 1211 of the multi-directional plate 1210. The first coating 1050 may be in the form of a continuous film. The first coating 1050 may be planar. In other embodiments, the first coating 1050 may conform to an underlying pattern formed by the multi-directional plate 1210 and the first delivery member 1070.

[0087] Now refer to Figure 5A The plate structure 1200 may include a second delivery member 1080, which exists in an opening gap created by a second morphology formed by the second exposed surface 1212 of the multi-directional plate 1210. Specifically, the second delivery member 1080 may exist in an opening gap created by an opening channel 1232 of the second morphology formed by the second main surface 1212 of the multi-directional plate 1210.

[0088] The second delivery component 1080 may be the same as or different from the first delivery component 1070.

[0089] The second delivery component 1080 may include one or more therapeutic and / or pharmacological components, including but not limited to anti-inflammatory agents, steroids, antibiotics, and analgesics. The second delivery component 1080 may occupy some, all, or substantially all of the free volume present in the channel 1232 formed by the first morphology.

[0090] The treatment device 1001 may further include a second coating 1060 applied to a second primary surface 1212 of the multi-directional plate 1210. The second coating 1060 may cover both the second primary surface 1212 of the multi-directional plate 1210 and a second delivery member 1080 present in an opening channel 1232 formed in the second primary surface 1212 of the multi-directional plate 1210. The second coating 1060 may be in the form of a continuous film. The second coating 1060 may be planar. In other embodiments, the second coating 1060 may conform to an underlying pattern formed by the multi-directional plate 1210 and the second delivery member 1080.

[0091] The second coating 1060 may be the same as or different from the first coating 1050. For each of the first coating 1050 and the second coating 1060, the resulting membrane may be formed of a slow-release material that dissolves slowly upon exposure to aqueous humor or other biological fluids, thereby releasing the first delivery component 1070 from the channel 1232 of the treatment device 1001 after implantation into the subject.

[0092] Now refer to Figure 5C In other embodiments, the treatment device 1001 may include both a first delivery component 1070 and a second delivery component 1080, as well as a first coating 1050 and a second coating 1060 for encapsulating the first delivery component 1070 and the second delivery component 1080.

[0093] In other embodiments, the plate structure 1200 may include at least one of a first coating 1050 and / or a second coating 1060, without the first delivery member 1070 and / or the second delivery member 1080. In this embodiment, the first coating 1050 and / or the second coating 1060 may form a film covering the open chambers 1222 and / or open channels 1232 created by the multidirectional plate.

[0094] The presence of the film obtained by the first coating 1050 and / or the second coating 1060 can enhance the overall strength of the resulting treatment device. Specifically, the layered structure of the film formed by the first coating 1050 and the second coating 1060 (bonded to the first main surface 1211 and the second main surface 1212 of the multi-directional plate 1210) provides additional mechanical integrity to the resulting treatment device.

[0095] In addition to achieving baseline flexibility to conform to the curvature of the eye, the addition of the first coating 1050 and / or the second coating 1060 can provide a mechanism to allow the overall therapeutic device to match the elastic modulus of the surrounding conjunctival and scleral tissues, thereby maximizing biointegration. Results from brain implant research confirm that the flexibility of the implant in soft tissue improves the implant's compliance with the micro-movements of surrounding tissues, reduces tissue displacement and trauma, and facilitates the implantation of the therapeutic device.

[0096] refer to Figure 6 and Figure 7 This example illustrates a treatment device 2001 according to another embodiment. Treatment device 2001 is similar to treatment devices 1 and 1001, except as described herein. The foregoing description of treatment devices 1 and 1001 generally applies to treatment device 2001 as described below, except for the differences explicitly stated below. A similar numbering scheme to that of treatment devices 1 and 1001 will be used for treatment device 2001, except that a numbering system of "2000" will be used.

[0097] The treatment device 2001 may include a penetrating element 2100 and a plate structure 2200 provided as separate components, wherein the penetrating element 2100 is coupled to the plate structure 2200. The penetrating element 2100 and the plate structure 2200 may be coupled together by any suitable component, such as, but not limited to, adhesives, fasteners, etc. Non-limiting embodiments of adhesives include glues, acrylic resins such as acrylates, epoxy resins, thermosetting plastics, thermoplastic plastics, elastomers, polydimethylsiloxane (PDMS), silicone resins, siloxanes, polyurethanes, etc. Non-limiting embodiments of fasteners include anchors, latches, buckles, or any other restraints. In some embodiments, fasteners may be used in conjunction with adhesives.

[0098] The plate structure 2200 may include opposing first exposed main surfaces 2201 and second exposed main surfaces 2202, and an exposed side surface 2203 extending between the first exposed main surfaces 2201 and the second exposed main surfaces 2202. When viewed with the naked eye, the first exposed main surface 2201 of the plate structure 2200 may be substantially continuous and appear smooth. Similarly, when viewed with the naked eye, the second exposed main surface 2202 of the plate structure 2200 may be substantially continuous and appear smooth.

[0099] The penetrating element 2100 may include an outer surface 2101 and an inner surface 2102. The penetrating element 2100 may include an elongated body 2110. The elongated body 2110 may include an outer surface 2112 and an inner surface 2111. The penetrating element 2100 may also include a path 2140 (also referred to herein as an "internal cavity path") extending through the elongated body 2110. The inner surface 2111 may be continuous and form a D-shaped cross-section. The D-shaped cross-section may result in the outer surface 2112 having a rounded portion 2118 and a generally flat portion 2117, whereby the generally flat portion 2117 is engaged with at least one of a first exposed main surface 2201 or a second exposed main surface 2202 of the plate structure. The flat portion 2117 provides a good fit with the smooth and / or flat main surfaces 2201, 2202 of the plate structure.

[0100] refer to Figures 8 to 9 This example illustrates a treatment device 3001 according to another embodiment. Treatment device 3001 is similar to treatment devices 1, 1001, and 2001, except as described herein. The foregoing description of treatment devices 1, 1001, and 1002 generally applies to treatment device 3001 described below, except for the differences explicitly stated below. A similar numbering scheme to that used for treatment devices 1, 1001, and 1002 will be used for treatment device 3001, except that a numbering system of "3000" will be used.

[0101] The treatment device 3001 may include a penetrating element 3100 and a plate structure 3200 provided as separate components, wherein the penetrating element 3100 is coupled to the plate structure 3200. The penetrating element 3100 and the plate structure 3200 may be coupled together by any suitable component, such as, but not limited to, adhesives, fasteners, etc. Non-limiting embodiments of fasteners include anchors, plates, buckles, latches, or any other restraints.

[0102] The plate structure 3200 may include a first exposed main surface 3201 opposite to the second exposed main surface 3202. When viewed with the naked eye, the first exposed main surface 3201 of the plate structure 3200 may appear to be or substantially continuous and appear smooth. When viewed with the naked eye, the second exposed main surface 3202 of the plate structure 3200 may appear to be substantially continuous and appear smooth.

[0103] The first exposed main surface 3201 may include a first region 3211 and a second region 3212. The first region 3211 may be offset relative to the second main surface 3202 by a first thickness t1. The second region 3212 may be offset relative to the second main surface 3202 by a second thickness t2. The first thickness t1 and the second thickness t2 may be different. The second thickness t2 may be less than the first thickness t1, such that the second region 3212 forms a recess in the first exposed main surface 3201 of the plate structure 3200.

[0104] The penetrating element 3100 may include an outer surface 3101 and an inner surface 3102. The penetrating element 3100 may include an elongated body 3110. The elongated body 3110 may include an outer surface 3111 and an inner surface 3112. The penetrating element 3100 may also include a path 3140 (also referred to herein as an "internal cavity path") extending through the elongated body 3110. The inner surface 3112 may be continuous and form a circular cross-section. The circular cross-section may result in an outer surface 3111 that is also circular in shape. A recess formed by the second region 3212 on the first exposed main surface 3201 may accommodate at least a portion of the circular cross-section of the penetrating element 3100, thereby allowing the penetrating element to extend into the plate structure 3200, such that the penetrating element 3100 has an internal cavity path 3140 to allow fluid flow without the penetrating element 3100 protruding too far beyond the first region 3211 of the first exposed main surface 3201 of the plate structure 3200.

[0105] refer to Figures 10 to 12 This example illustrates a treatment device 4001 according to another embodiment. Treatment device 4001 is similar to treatment devices 1, 1001, 2001, and 3001, except as described herein. The foregoing description of treatment devices 1, 1001, 2001, and 3001 generally applies to treatment device 4001 described below, except for the differences explicitly stated below. A similar numbering scheme to that of treatment devices 1, 1001, 2001, and 3001 will be used for treatment device 4001, except that a numbering system of "4000" will be used.

[0106] The treatment device 4001 includes a first plate structure 4200a and a second plate structure 4200b. The first plate structure 4200a may include a first main surface 4201a and a second main surface 4202a opposite to each other. The second plate structure 4200b may include a second main surface 4202b and a first main surface 4201b opposite to each other.

[0107] The first main surface 4201a of the first plate structure 4200a may include a first morphology. The second main surface 4202a of the first plate structure 4200a may include a second morphology. The first main surface 4201b of the second plate structure 4200b may include a first morphology. The second main surface 4202b of the second plate structure 4200b may include a second morphology.

[0108] The second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b may face each other. In some embodiments, at least portions of the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b may contact each other. In some embodiments, at least portions of the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b may be in free-floating contact with each other. In some embodiments, at least portions of the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b may be offset from each other, such that there is no contact between the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b.

[0109] The treatment device 4001 may further include a penetrating element 4100 positioned between the first plate structure 4200a and the second plate structure 4200b. The penetrating element 4100 may be coupled to at least one of the first plate structure 4200a and the second plate structure 4200b by any suitable component (such as, but not limited to, one of the aforementioned adhesives, fasteners, etc.). The penetrating element 4100 may be coupled to portions of the second main surfaces 4202a, 4202b of the first plate structure 4200a and the second plate structure 4200b.

[0110] According to this embodiment, the penetrating element 4100 extends between the first plate structure 4200a and the second plate structure 4200b, such that the path 4140 formed by the elongated body 4110 of the penetrating element 4100 also extends between the plate structures 4200a and 4200b. In this configuration, fluid can enter the elongated body 4110, travel along the path 4140, and exit between the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b. The portions of the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b in free-floating contact can separate in the presence of fluid, allowing the fluid to spread along the second main surfaces 4202a and 4202b of the first plate structure 4200a and the second plate structure 4200b.

[0111] The first main surface 4201a and the second main surface 4202a of the first plate structure 4200a may have a first surface area, and the first main surface 4201b and the second main surface 4202b of the second plate structure 4200b may have a second surface area. The first surface area and the second surface area may be the same. In other embodiments, the first surface area and the second surface area may be different. The second surface area may be greater than the first surface area.

[0112] The first plate structure 4200a may have a first width and a first length L1. The second plate structure 4200b may have a second width and a second length L2. The first width and the second width may be the same. In other embodiments, the first width and the second width may be different. The first length L1 and the second length L2 may be the same (not shown). In other embodiments, such as Figure 10 As shown, the first length L1 and the second length L2 can be different. The second length L2 can be greater than the first length L1, so that at least a portion of the second main surface 4202b of the second plate structure 4200b does not overlap with the second main surface 4202a of the first plate structure 4200a.

[0113] refer to Figure 13 , Figure 14A and Figure 14B The embodiment also includes an implantation device 90 configured to implant the treatment device 1 into the eye 900. The following discussion will refer to the treatment device 1, but is also applicable to treatment devices 1001, 2001, 3001, 4001 exemplified according to other embodiments of the invention.

[0114] The implantation device 90 may include a handle portion 93 and an insertion portion 91, the insertion portion 91 including a body 92 for securing the treatment device 1. The housing 92 may be configured to any geometry suitable for securing the treatment device 1. In a non-limiting embodiment, the housing 92 may be an open cavity for housing the treatment device 1.

[0115] During implantation, the implantation device 90 can be inserted into the eye 900 so that the treatment device 1 can be positioned to contact the eye 900 for treating eye diseases such as glaucoma. Specifically, the insertion portion 91 can be inserted through the sclera 913 and into the anterior chamber 988 of the eye 900, such that the distal portion of the treatment device 1 is located within the anterior chamber 988 of the eye 900. Once the treatment device 1 is in place, the implantation device 90 can be removed from the eye 900, thereby removing the treatment device 1 from its housing 92 and leaving it in the eye 900.

[0116] When in place, the plate structure 200 of the treatment device 1 can be located between the sclera 913 and the conjunctival tissue 950. In this configuration, the plate structure 200 can serve as a tissue separator and / or an external reservoir for excess fluid when fluid is absorbed into the subject's surrounding tissues.

[0117] Now refer to Figure 15 and Figure 16 The release decal 400 can be attached to at least one of the main surfaces of the treatment device 1. The release decal 400 can be flipped to one of the main surfaces 201, 202 of the plate structure 200 of the treatment device 1 so that the release decal 400 can be removed by peeling it off from the main surface of the treatment device 1, but will resist shear separation from the main surface of the treatment device 1.

[0118] Release decal 400 may be formed from materials including but not limited to: polytetrafluoroethylene (PTFE), one or more metals, siloxanes, PDMS, glass, and / or one or more plastics.

[0119] The release decal 400 may include decal knots 410 that provide features to allow a user to directly or indirectly manipulate the position of the treatment device 1 relative to the underlying ocular tissue (specifically, the sclera 913). For example, after the treatment device 1 has been released from the housing 92 on the implantation device 1, the decal knots can be manipulated via the insertion portion 91 of the implantation device 1. In other embodiments, a separate tool may be used to engage the decal knots 410 to manipulate the position of the treatment device 1 on the sclera 913.

[0120] The position of the plate structure 200 of the treatment device 1 can be precisely adjusted along the sclera 913 by means of the decal knots 410, and Figures 6 to 12 The penetrating elements 100, 2100, 3100, 4100 or in the embodiments thereof Figure 1 The extension 250 of the illustrated embodiment can be precisely placed within the anterior chamber 988 to provide optimal release of excess fluid present in the eye 900.

[0121] The bond strength between the release decal 400 and the treatment device 1 is strong enough to resist shearing, thereby allowing lateral movement of both the release decal 400 and the treatment device 1. However, once the treatment device 1 is precisely positioned, the release decal 400 can be removed from the treatment device 1 by lifting it in a direction substantially orthogonal to the main surface of the treatment device 1, that is, by peeling the release decal 400 off the treatment device 1.

[0122] Now refer to Figure 17 and Figure 18The embodiment also includes an implantation device 80, which can be configured to implant the treatment device 1 into the eye 900. The following discussion will refer to the treatment device 1, but is also applicable to treatment devices 1001, 2001, 3001, and 4001.

[0123] According to this embodiment, the support frame can be used in conjunction with the treatment device 1. Specifically, the treatment device 1 can be placed on top of the support frame, and the implantation tool, including a first support member 81 and a second support member 82, can simultaneously grasp the treatment device and the support frame. In a non-limiting embodiment, the implantation device 80 can be forceps. Figure 17 This indicates that, in the first state, the first support 81 and the second support 82 clamp the treatment device 1 and the bracket.

[0124] During implantation, an opening can be formed in the scleral tissue 913 on the eye 900. Then, the implantation device 80 in its first state can be inserted into the opening, such that the first support 81 and the second support 82 are positioned within the opening. The implantation device 80 can then be switched to a second state (e.g., ...). Figure 18 (As shown), the first support 81 and the second support 82 separate, thereby releasing the treatment device 1. The implantation device 80 can be switched from the first state to the second state manually or by means of a machine.

[0125] Once in the second state, the treatment device 1 can be transferred from the first support 81 to the eye 900. In one embodiment, both the treatment device 1 and the support can be transferred to the eye, and once correctly positioned, the support can be removed, leaving only the treatment device in its final implantation location. In another embodiment, the treatment device 1 can be transferred to the eye without the support, which remains on the first support 81. The transfer of the treatment device 1 can be accomplished by moving the implantation device 80 (e.g., a slight oscillating movement) to push the treatment device 1 from the first support 81.

[0126] Now refer to Figures 19 to 21 The embodiment also includes an implantation device 70, which is configured to implant the treatment device 1 into the eye 900. The following discussion will refer to the treatment device 1, but is also applicable to treatment devices 1001, 2001, 3001, and 4001.

[0127] According to this embodiment, the device described herein may further include an injectable therapeutic device 71, which includes a support rod 72 for use in conjunction with the therapeutic device 1. Specifically, the therapeutic device 1 may be wound around the support rod 72 to form an elongated cylindrical shape. In other embodiments, the injectable therapeutic device 71 may not include the support rod 72, and instead, the therapeutic device 1 may be self-winding.

[0128] The injectable therapeutic device 71 can then be placed in an injection device 74 configured to inject the injectable therapeutic device 71 into the eye 900 via a fluid passage 75. In a non-limiting embodiment, the injection device 74 may be a syringe, and the fluid passage 75 may be formed of a needle.

[0129] During implantation, the fluid pathway 75 can enter the bottom portion of the anterior chamber 988 and extend upward toward the sclera 913, thereby expelling the treatment device 1 from the implantation device 70 and delivering it to the sclera 913 via a pumping mechanism. Once delivered, the treatment device 1 can unfold from its coiled position around the support rod 72, thereby creating a fluid pathway from the anterior chamber 988 to the location between the conjunctiva and sclera 913 to allow excess aqueous humor to leave the anterior chamber 988.

[0130] In one implementation method Figure 22 An example of the apparatus described herein is shown. Apparatus 2200 includes a plate structure 2202 having opposing first main exposed surfaces 2204 and second main exposed surfaces (not shown), and side surfaces 2206 extending therebetween. Plate structure 2202 includes an extension portion 2208 and a main body portion 2210.

[0131] Generally speaking, in Figure 22 In this embodiment, the extension 2208 includes two generally parallel side surfaces 2212, 2212' that meet a generally flat end face 2214. This portion may be referred to as the core or neck. In this embodiment, the junction of the parallel side surfaces 2212, 2212' and the generally flat end face 2214 is rounded. These rounded corners may have radii between about 0.2 mm and about 0.8 mm, between about 0.3 mm and about 0.8 mm, between about 0.4 mm and about 0.8 mm, between about 0.5 mm and about 0.8 mm, between about 0.6 mm and about 0.8 mm, between about 0.7 mm and about 0.8 mm, between about 0.4 mm and about 0.6 mm, or between about 0.3 mm and about 0.7 mm. However, in other embodiments, these junctions are not rounded.

[0132] Similarly, the main body portion 2210 includes two generally parallel side surfaces 2216, 2216'. These parallel side surfaces are joined by generally rounded end faces 2218. In other embodiments, the generally rounded end faces 2218 may be generally flat end faces with rounded or unrounded joints.

[0133] The distance 2220 between two generally parallel side surfaces 2212, 2212' is less than the distance 2222 between generally parallel side surfaces 2216, 2216'. In some embodiments, the distance 2220 is between about 1 mm and about 10 mm, between about 1 mm and about 9 mm, between about 1 mm and about 8 mm, between about 1 mm and about 6 mm, between about 2 mm and about 6 mm, between about 3 mm and about 6 mm, between about 3 mm and about 7 mm, between about 3 mm and about 8 mm, or between about 4 mm and about 6 mm. In some embodiments, the distance 2222 is between about 5 mm and about 10 mm, between about 5 mm and about 9 mm, between about 5 mm and about 8 mm, between about 5 mm and about 7 mm, or between about 5 mm and about 6 mm. In some embodiments, the generally rounded end face 2218 may have a radius between about 1 mm and about 5 mm, between about 1 mm and about 4 mm, between about 1 mm and about 3 mm, or between about 1 mm and about 2 mm.

[0134] The distance 2224 between the generally flat end face 2214 and the interface between the extension portion 2208 and the main body portion 2210 is between about 1 mm and about 5 mm, between about 1 mm and about 4 mm, between about 1 mm and about 3 mm, or between about 1 mm and about 2 mm. The distance 2226 between the interface between the extension portion 2208 and the main body portion 2210 and the generally rounded end face 2218 is between about 5 mm and about 15 mm, between about 5 mm and about 14 mm, between about 5 mm and about 13 mm, between about 5 mm and about 12 mm, between about 5 mm and about 10 mm, between about 5 mm and about 9 mm, between about 6 mm and about 15 mm, between about 7 mm and about 15 mm, between about 8 mm and about 15 mm, between about 9 mm and about 15 mm, between about 10 mm and about 15 mm, or between about 9 mm and about 11 mm.

[0135] Furthermore, the main body portion 2210 includes two generally rounded corners 2228 and 2228' at the interface between the extension portion 2208 and the main body portion 2210. However, these corners do not need to be rounded. In some embodiments, the generally rounded corners 2228 and 2228' may have radii between about 0.2 mm and about 1 mm, between about 0.3 mm and about 1 mm, between about 0.4 mm and about 1 mm, between about 0.5 mm and about 1 mm, between about 0.6 mm and about 1 mm, between about 0.7 mm and about 1 mm, between about 0.8 mm and about 1 mm, or between about 0.9 mm and about 1 mm. Additionally, the interface between the extension portion 2208 and the main body portion 2210 is curved. However, this portion does not need to be curved. The bend may have a radius between about 0.2 mm and about 0.8 mm, between about 0.3 mm and about 0.8 mm, between about 0.4 mm and about 0.8 mm, between about 0.5 mm and about 0.8 mm, between about 0.6 mm and about 0.8 mm, between about 0.7 mm and about 0.8 mm, between about 0.4 mm and about 0.6 mm, or between about 0.3 mm and about 0.7 mm.

[0136] In some embodiments, device 2200 may include a marking indentation 2212. The marking indentation 2212 may be located anywhere on the periphery of the upper surface 2206 of the extension 2208 or the main body portion 2210.

[0137] In some embodiments, device 2200 may include two or more marking indentations.

[0138] The marking indentation can have almost any shape. Shapes can include curved shapes, straight shapes, and so on. In one implementation, such as... Figure 22 As illustrated, the marking indentation 2212 has a semi-circular shape. However, the marking indentation 2212 may have a straight shape, such as a pyramid or a dot.

[0139] Marking indentations may be present to assist in correct placement during implantation. In some embodiments, having a single marking indentation provides a visual indication of the correct side-facing orientation of the device to the implanter.

[0140] Figure 23A non-limiting embodiment of an inserter for implanting a device as described herein is illustrated. The inserter 2300 includes a body or housing 2302. The housing includes a needle 2304 pinned to its proximal end 2306. The needle 2304 has a sharp proximal end 2308. The sharp proximal end 2308 is used to pierce eye tissue during device implantation. In some embodiments, the needle 2304 is a small-gauge needle, such as 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, or 20 gauge needles.

[0141] The needle 2304 includes a camera 2310. The camera 2310 is used to visualize the implantation process and can be a wired or wireless camera.

[0142] The device 2312 is housed within a compartment 2314 near its proximal end 2306 within the housing 2302. However, in other embodiments, the device 2312 may be housed within the needle 2304.

[0143] Slider 2316 can be located on the housing. Although slider 2316 is illustrated as being on the top of the housing, it can be located in almost any position on the housing. The shape of the slider is also shown for illustrative purposes and can be almost any shape that allows it to slide. Furthermore, a mechanical slider may not be necessary. In some embodiments, slider 2316 may be replaced by a button and an electronic sliding mechanism (not illustrated).

[0144] Circuit board 2318 may include a memory and a processor for executing programs stored in the memory. For example, if a button is used instead of a slider, the circuit board can perform this function. Circuit board 2318 is powered by battery 2320. Battery 2318 can be any battery capable of powering inserter 2300. Batteries may include, but are not limited to, cylindrical batteries such as AA, AAA, AAAA, C, D, and button batteries (such as lithium button batteries), coin cells, and non-cylindrical batteries such as 4.5V and 9V box batteries, etc. Alternatively, button batteries or coin cells may also be used. The battery can be removed as needed. In some embodiments, the battery may be rechargeable.

[0145] The wireless interface 2322 is also associated with the circuit board 2318. This interface can be any type of wireless interface, such as WiFi, Bluetooth, cellular, etc. This interface can transmit camera data, device data, etc.

[0146] In some embodiments, the inserter 2300 is disposable. In other embodiments, the inserter 2300 may be a multipurpose device that can be cleaned and sterilized between uses.

[0147] During use, device 2312 is located within compartment 2314. In some embodiments, device 2312 is pre-loaded in the inserter. As the slider moves, the device is extruded from the sharp proximal end 2308 of needle 2304. In some embodiments, winding device 2324 is located within compartment 2314 or needle 2304 for winding the device after extrusion. In other embodiments, the device is pre-wound or wound when the pre-loaded inserter is factory-loaded.

[0148] In some embodiments, the device described herein can be used to enhance glaucoma treatment even when using other devices and methods. The device can be inserted before or after the insertion of another ocular device (such as a stent). The device can be used with another glaucoma stent, wherein the current device acts as a tissue separator for ocular tissue. Such tissue separation can enhance the effectiveness of the ocular stent in treating glaucoma.

[0149] In some embodiments, the current device can be used as an alternative to mitomycin C injections following ocular surgery. In some embodiments, the device is inserted into the eye during surgery. In other embodiments, the device is inserted in a subsequent procedure following surgery. The device can help reduce intraocular pressure associated with surgery.

[0150] Example 1

[0151] Studies were conducted to evaluate the ability of the device described in this paper to reduce ocular pressure and protect the optic nerve. The device was implanted to determine whether aqueous humor flowed slowly and in a controlled manner through a network of microchannels within the device into the subconjunctival space, thereby forming low-lying, diffuse vesicles.

[0152] Experimental Design

[0153]

[0154]

[0155] A parylene-alumina composite material, fabricated via atomic layer deposition and chemical vapor deposition as described herein, was provided as a test article. The article was stored at room temperature and standard atmospheric pressure.

[0156] Before being included in the study, each animal will undergo an ophthalmic examination (slit-lamp microscopy and indirect ophthalmoscopy) by the study leader or principal investigator. Ocular findings will be scored using a modified McDonald-Shadduck scoring system. The acceptance criterion for inclusion in the study is a score of "0" for all variables.

[0157] Prior to the study, intraocular pressure (IOP) measurement was performed on each animal once daily for 5 to 7 days before the study began. This allowed the animals to become accustomed to the IOP procedure and establish a baseline IOP level. IOP measurements were performed daily at the same time (±1 hour) using a Tonovet rebound tonometer. At least three measurements were taken for each eye for each measurement event.

[0158] Anesthetized animals are administered via intramuscular (IM) injection of ketamine hydrochloride (up to approximately 50 mg / kg) and acetaminophen (up to approximately 10 mg / kg) or dexmedetomidine (approximately 0.25 mg / kg). Ganro bromide (approximately 0.01 mg / kg, IM) may be administered concurrently. Atemexazole hydrochloride (up to 1 mg / kg) may be used as a reversal agent.

[0159] After surgical preparation for the eye, apply one to two drops of local promecaine hydrochloride anesthetic (0.5%) to the animal's eye. If necessary, additional local eye anesthetics may be administered during the surgery.

[0160] On day 0, the test product was implanted into the subconjunctival space of the right eye (OD).

[0161] Clean the eyes with povidone-iodine, then rinse with balanced salt solution (BSS). Apply one to two drops of local promecaine hydrochloride anesthetic (0.5%) to the animal's eyes. Additional local eye anesthetics may be administered during surgery if necessary. The eyes may be covered, and a sterile speculum may be inserted to allow the eyelids to retract.

[0162] The conjunctival flap, based on a 60- to 90-degree fornix, is located in the superior temporal quadrant, with the initial conjunctival incision placed 2 mm posterior to the limbus. The length of the fovea should be 8 mm from the initial incision.

[0163] A puncture incision is made 1 mm from the limbus using a corneal scalpel blade, extending into the anterior chamber, to create a scleral tunnel between the subconjunctival fossa and the anterior chamber.

[0164] Gently grasp the test specimen using tweezers. Handle the test specimen with care, as the material is very delicate and may stick to wet surfaces. Gently insert the implant into the subconjunctival sac.

[0165] Carefully insert the implant through the rounded notch on the left side, ensuring the implant is correctly oriented, i.e., the channel is facing upwards. Gently guide the neck of the implant into the scleral tunnel to ensure easy access. The body of the implant can be gently smoothed to ensure it is properly positioned and lying flat. If necessary, use BSS to moisten the tissue.

[0166] If the anterior chamber collapses or there is a decrease in the tension of the spherical structure, then use a 27-gauge needle and a 3mL syringe to enlarge the anterior chamber with BSS. Enlarging the AC with viscoelastic materials may make it difficult to retain the neck of the implant in the AC, but viscoelastic materials can be used to lubricate the implant.

[0167] The implant is anchored to the sclera using 10-0 nylon or Prism sutures, which is achieved by passing the suture through the device at each of the corners and the tail.

[0168] Use 10.0 nylon sutures or similar thread to close the conjunctiva so that a simple, continuous pattern can be used to create a waterproof closure, thus avoiding the implant body as much as possible.

[0169] If the test specimen is difficult to see, a felt-tip surgical marker can be used to mark the spherical body portion of the implant.

[0170] Animals recovered immediately after administration of the test product and were monitored during recovery until they were fully recovered.

[0171] Administer a single injection of buprenorphine (0.02-0.05 mg / kg IM / SC) for pain relief shortly before surgery. Administer additional buprenorphine twice daily (approximately 12 hours apart) from day 1 to day 3 following administration of the test product. Alternatively, sustained-release buprenorphine (approximately 0.1 mg / kg SC) may be administered on day 1.

[0172] On day 0 after the implantation procedure, apply one drop of 0.3% ofloxacin and one drop of 1% prednisolone acetate, and then apply four times daily from day 1 to day 7 after the test product is administered.

[0173] Clinical ophthalmological examinations (slit-lamp only) were performed on both eyes (OU) of all study animals at baseline (before test product administration), on day 0 immediately following test product implantation, and on days 1, 3, 7 (±1), 14 (±1), and 21 (±3). Additional examinations were performed on days 35 (±3), 49 (±3), 63 (±3), 77 (±3), and 91 (±3) in the optional study extension scenario.

[0174] Intraocular pressure (IOP) measurements were performed in both eyes (OU) of all study animals at baseline (before test article administration), immediately following test article implantation on day 0, and on days 1, 3, 7 (±1), 14 (±1), and 21 (±3). With the option of study extension, additional IOP measurements were performed on days 35 (±3), 49 (±3), 63 (±3), 77 (±3), and 91 (±3).

[0175] IOP measurements were performed using the same technique at the same time (±1 hour) daily using a Tonovet rebound tonometer. At least three measurements were taken for each eye for each measurement event.

[0176] Slit-lamp photographs were taken of both eyes (OU) of all study animals at baseline (before administration of the test article), and immediately following day 0, day 1, day 7 (±1), and day 21 (±3) after implantation of the test article.

[0177] On day 21 (±3), a fluorescein test was performed on all right eyes (OD) to assess the non-closure of the test product and the path of aqueous humor from the anterior chamber to the subconjunctival space.

[0178] A small (approximately 30 gauge) needle is inserted into the anterior chamber, allowing aqueous humor to drain out to avoid excessive intraocular pressure (IOP). A second small needle is then introduced into the anterior chamber, and approximately 0.5 mL of 0.01% sodium fluorescein solution in balanced saline (BSS) is slowly infused into the anterior chamber over 20 minutes. IOP is monitored during the procedure to ensure it does not exceed safe levels.

[0179] Post-injection observations will be recorded in the raw data, including a description of the pathway (or absence) of the fluorescein into the test article and into the subconjunctival space.

[0180] Digital photographs of the eye can be taken using a slit lamp or DSLR camera as needed to document research findings. Additional photographs can be taken using fluorescein filters and / or cobalt blue filters.

[0181] like Figure 24 As illustrated, on day 7, intraocular pressure in the treated eye decreased by an average of 25% relative to baseline and remained below baseline and below the control. The baseline score was the average intraocular pressure over the 5 days prior to implantation.

[0182] Blisters were present on all implants.

[0183] Furthermore, according to the McDonald-Shadduck scoring system, all eye observations received low scores.

[0184] Example 2

[0185] The results of Example 1 were compared with those using the InnFocus SIBS device. Figure 25 As illustrated, 22 days post-surgery, the intraocular pressure in the test eye using the device currently described was lower than that in the control.

[0186] Conversely, no statistically significant reduction in intraocular pressure was observed between the eyes with SIBS implants and the control eyes within 7 days post-surgery.

[0187] Example 3

[0188] The population from Example 1 was used for further studies. On day 22, 0.5 mL of 0.01% sodium fluorescein was injected into the anterior chamber over 20 minutes. The fluorescein dye flowed into the subconjunctival blister created by the current device, indicating that the channel was not closed. Furthermore, a large, diffuse infiltration area remained outside the device surface area and the anatomical area, thus illustrating outflow from the anterior chamber.

[0189] Example 4

[0190] Using an ab-interno and minimally-invasive approach, such as, but not limited to, a gel scaffold, a single or multi-layered plate is implanted into the subconjunctival space. A small portion of the device (a few millimeters in length) is located in the anterior chamber, allowing aqueous humor to flow along it via capillary action into the subconjunctival space (between the conjunctival sac and sclera).

[0191] Fluid flows through microchannels in and above / below the plate. The microchannels can be oriented toward the conjunctiva or sclera to maximize flow.

[0192] The device is pre-loaded into the capsule or cassette in which it is inserted. The insertion device helps to deposit in the correct position in the eye, and then the insertion device is withdrawn from the eye, leaving the device in place.

[0193] The insertion device has a tapered, flat / rectangular blade that forms a minimally invasive incision, starting in the cornea of ​​the lower nasal quadrant of the eye, moving upwards, and pushing tissue in the superior temporal quadrant aside. The blade can be tapered or open to prevent tissue from blocking the opening and to prevent plate deposition. The tip of the insertion device or the body of the blade has ridges to prevent tissue from being cut too deeply. The ridges also aid in blade positioning and cutting.

[0194] Once the blade has opened the outflow pathway from the anterior chamber to the subconjunctival space, the insertion device is pushed into the open space by the blade or via some systemic deposition, such that the plate is mostly within the tissue, but extends a few millimeters into the anterior chamber. The insertion device is then removed, and the surgeon closes any openings left in the eye.

[0195] Example 5

[0196] This embodiment illustrates the use of the device to lower intraocular pressure and the tolerability of the device when implanted under the conjunctiva of a New Zealand white rabbit.

[0197] Surgical methods:

[0198] Three young experimental New Zealand white rabbits (one male and two females) were assigned to the treatment group. At the start of the study, they were approximately 5 months old and weighed between 2.8 and 3.3 kg (regardless of sex), as shown in Table 1 below.

[0199] Table 1

[0200]

[0201] For implantation of the treatment device, each rabbit was subcutaneously anesthetized with a combination of chlorpheniramine (40 mg / kg) and acetaminophen (4 mg / kg). Anesthetic was supplemented as needed. All medications used are documented in the original data. At this point, several drops of 1% promecaine (local anesthetic) were instilled into each eye. Once anesthetized, the rabbit was placed on its side, and the area around the eyes was prepared with a swapstick containing 10% povidone-iodine. The eyes were then flushed with 0.9% sterile saline and several additional drops of promecaine. A sterile drape was placed over the rabbit to allow exposure of the eyes. Sterile instruments were used (autoclaved before the initial surgery, then chemically sterilized in chlorhexidine solution between animals, and rinsed with sterile water / saline). Sterile gloves were worn.

[0202] The eyelids are kept open manually or with a speculum for surgery. Using Colibri forceps, the eye is rotated inward, and a small incision is made in the conjunctiva on the lateral side of the iris. A subconjunctival sac is created anteriorly, and the treatment device is placed within it. After placement, the eye is allowed to rotate back to its normal position, and the placement of the treatment device is observed to ensure it lies well flat within the subconjunctival sac. The rabbit is then rotated to the other side, and a similar sham surgery is performed on the contralateral eye without implanting the treatment device or other materials. Sterile ophthalmic ointment is applied to both eyes during the recovery period.

[0203] Observation and measurement:

[0204] On day 1, the treatment device was implanted into the subject's eye through a conjunctival incision between the sclera and conjunctiva. Mortality and clinical observation were assessed daily. Ocular inflammation scores were recorded daily on days 1 before administration, days 2 through 5, day 12, and day 19. Body weight was recorded weekly. Food consumption was recorded daily. On day 21, all animals were euthanized. The eyes with optic nerves were obtained from all animals at necropsy and evaluated microscopically.

[0205] Histological analysis:

[0206] On day 21, animals were euthanized by intravenous administration of an overdose of barbiturate. All animals underwent necropsy. Eyes with optic nerves were collected and immediately fixed in Davidson's fixative for 24 to 48 hours. After dehydration of the nerve samples with increased concentrations of ethanol (30–100%), the nerves were sectioned with a sharp blade. These sections were then embedded in paraffin in descending order and cut into 3 mm thick sections. These sections were stained with hematoxylin and eosin. Two sections with pupil-optic disc orientation (two halves of the sphere) were cut from each eye, and each paraffin block was sliced ​​in two layers, resulting in four slides per eye available for microscopic examination.

[0207] Results and discussion

[0208] On day 1, a treatment device was administered once to one male and two female New Zealand white rabbits via a conjunctival incision between the sclera and conjunctiva.

[0209] Mortality / morbidity: No premature deaths occurred during the study period. All animals survived until their planned euthanasia on day 21.

[0210] Clinical observations: On day 1, a mild to moderate reduction in postoperative behavioral activity was observed, and all animals closed or partially closed their eyes 2 to 4 hours after administration. These findings were considered independent of the test product and secondary to the anesthetic and surgery. From day 2 to day 21 of the study, all animals appeared normal.

[0211] Eye observation: Prior to administration on day 1, the eye Draize scores of all animals (left and right eyes) were 0. Minimum overall Draize scores were recorded on days 2 and 3 of the study. Note the scores for the left and right eyes (respectively, the expulsion device implant and the sham surgery). Eye scores were no longer noted by day 4. Table 2 below summarizes the overall eye Draize scores recorded during the study.

[0212] Table 2

[0213]

[0214] Weight: It was noted that there was no significant test article-related effect on weight or weight gain.

[0215] Food loss: There was no significant test-product-related effect on food loss. The animals essentially consumed all their food throughout the day.

[0216] Autopsy observation

[0217] Results of visual autopsy: On the 21st day, the results of the visual autopsy were not noticed when the execution was planned.

[0218] Histopathology: The treatment device was not visible under a microscope in any of the animals. Focal scleral changes were observed near the limbus in several eyes, consisting of elevation and separation of conjunctival and superficial collagen fibers relative to deeper collagen fibers in the sclera, forming empty spaces. No noticeable tissue reaction was observed other than collagen fragmentation. Although the lowest (grade 1) severity defect was observed in two control (right) eyes, a mild (grade 2) to moderate (grade 3) severity defect was clearly present in two of the three treated (left) eyes, thus the tissue defects in the eye receiving the treatment device could at least partially indicate suspicion of the implantation site, which was broken or washed away during treatment. Lowest severity conjunctival hyperplasia, lymphoplasmacytic infiltration, and / or fibrosis were observed near the limbus in the right and left eyes of all three animals. These lesions could be interpreted as spontaneous findings of background technical studies and / or associated with surgical manipulation.

[0219] Overall, no effects were observed on clinical observations related to the test, weight or weight gain, or food loss. By day 4, the overall Draize score was lowest post-surgery, and all eyes appeared normal. No gross autopsy results were observed at the planned euthanasia on day 21. The treatment device was not visible after tissue processing, and no tissue reaction was observed at the implantation site. In conclusion, the treatment device was well tolerated when implanted subconjunctivally in New Zealand White rabbits.

[0220] It should be understood that the foregoing only indicates the tolerability of the treatment device when implanted in the eye and only illustrates the principles of this disclosure, and various modifications can be made by those skilled in the art without departing from the scope and spirit of this disclosure.

[0221] Example 6

[0222] Fibroblasts were cultured on the surfaces of ordinary plastic cell culture dishes, patterned silicon wafers coated with parylene-C, and cell culture dishes coated with parylene-C. After holding the samples for 24 hours, they were attached to the surfaces at 37°C. Cell culture medium was added, and the samples were then kept in the culture for another 48 hours. Fibroblasts attached to the ordinary plastic dishes and grew normally, but floated in the total cell clumps and were uncountable on the parylene-coated samples. These results indicate that the hydrophobicity of parylene prevents the adhesion of fibrotic cells. Furthermore, the results suggest that parylene can prevent tissue adhesion.

[0223] Example 7

[0224] The device with a parylene-C coating, as described herein, was implanted into the subconjunctival space of New Zealand white rabbits, the subconjunctival space being connected to the anterior chamber. After an 83-day cycle, the implant and blister were sectioned, fixed, and subjected to histological examination.

[0225] The thickness of fibrotic blisters in three rabbits was measured, and the results are recorded in Table 3.

[0226] Table 3

[0227]

[0228] The thickness of the fibrosis was the average of four measurements: anterior, scleral, posterior, and conjunctival. The thickness of the fibrosis on the scleral and conjunctival sides was the average of four evenly distributed measurements on the corresponding sides of the implant.

[0229] The results in Table 4 are compared with those of glaucoma valves (AGVs) implanted in the same space (with or without an amnion). The device of the present invention exhibits a much lower fibrotic capsule thickness than the AGV.

[0230] Table 4

[0231]

[0232] These results indicate that hydrophilic coatings (such as parylene and / or patterned surfaces, such as the surface of the device described) reduce fibrosis growth and scarring.

[0233] Although the invention has been described in detail for illustrative purposes based on specific embodiments now considered the most practical and preferred, it should be understood that such details are for illustrative purposes only, and the technology is not limited to the disclosed specific embodiments, but rather is intended to cover modifications and equivalent implementations within the spirit and scope of the appended claims. For example, it should be understood that the invention covers the possibility of combining one or more features of any specific embodiment with one or more features of any other specific embodiment to the extent possible.

[0234] Unless otherwise specified, all figures used in the specification and claims regarding the amount of components, properties such as molecular weight, reaction conditions, etc., should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters listed in the specification and appended claims are approximate values, which may vary depending on the desired properties the invention aims to obtain. To a minimum, and without attempting to limit the application of the teachings of equivalents to the scope of the claims, each numerical parameter should be understood at least based on the number of significant digits reported and by applying conventional rounding. Although the numerical ranges and parameters illustrating the broad scope of the invention are approximate, the values ​​set forth in the specific embodiments are reported as precisely as possible. However, any numerical value inherently includes some errors that inevitably arise from the standard deviation obtained in the corresponding test measurements.

[0235] The terms “a / an” and “the,” and similar designations, used in the context of describing the invention (particularly in the context of the appended claims), are to be regarded as encompassing both the singular and plural forms simultaneously, unless otherwise indicated herein or clearly contradicted by the context. The application of ranges of values ​​herein is intended merely as a contractual method for individually referring to each independent value falling within the range. Each individual value is incorporated into the specification as if it were individually referenced herein, unless otherwise indicated herein or clearly contradicted by the context. All methods described herein may be performed in any suitable order, unless otherwise indicated herein or clearly contradicted by the context. The use of any and all exemplary or illustrative language (e.g., “such as”) provided herein is intended only to better illustrate the invention and, unless otherwise required, does not limit the scope of the invention. The language in this specification should not be construed as indicating any non-claimed element as necessary for practicing the invention.

[0236] The grouping of alternative elements or embodiments of the invention disclosed herein should not be construed as limiting. Each group member may refer to other members of the group or other elements mentioned herein, and may claim protection for such other members or elements individually or in any combination. One or more members of a group may be included in or removed from the group for convenience and / or patentability. When any such inclusion or removal occurs, the specification is deemed to include the modified grouping, thereby completing the written specification of all Markush groups used in the appended claims.

[0237] Certain embodiments of the invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations of these described embodiments will become apparent to those skilled in the art after reading the foregoing description. The inventors encourage those skilled in the art to adopt such variations as appropriate, and the inventors intend to practice the invention in ways other than those specifically described herein. Therefore, the invention includes all modifications and equivalents of the subject matter set forth in the appended claims, as permitted by applicable law. Furthermore, the invention covers any combination of the foregoing elements in all possible variations thereof, unless otherwise indicated herein or otherwise clearly contradicted by the context.

[0238] The specific embodiments and implementations disclosed herein may be further limited to claims using the language of "consisting of..." and "substantially consisting of...". When used in claims, whether at the time of application or added according to amendments, the transitional term "consisting of..." excludes any element, step, or ingredient not specified in the claim. The transitional term "substantially consisting of..." limits the scope of the claim to the specified materials or steps and those that do not substantially affect the basic and novel features. Embodiments and implementations of the invention thus claimed are inherently or explicitly described and practiced herein.

[0239] Finally, it should be understood that the embodiments of the invention disclosed herein exemplify the principles of the invention. Other modifications may be employed within the scope of the invention. Therefore, alternative configurations of the invention can be utilized based on the teachings herein, rather than as examples or limitations. Thus, the invention is not limited to what is precisely shown and described.

Claims

1. A device for lowering intraocular pressure, the device comprising: A plate having a first end and a second end, the plate including opposing first and second surfaces, wherein the first surface includes a series of fluid channels configured in an open, cross-network pattern extending from the first end of the plate to the second end of the plate, the width of the first end of the plate being narrower than the width of the second end of the plate, so that the first end of the plate can be inserted into the anterior chamber of a patient, the fluid channels forming a hexagonal pattern, and... The second surface includes a plurality of open chambers formed by the fluid channels in a hexagonal pattern; A first coating on the first surface, the first coating conforming to the morphology of the series of fluid channels, and The second coating on the second surface, The plate has a thickness between about 50 nm and about 800 nm, and the first coating has a thickness between 0.1 μm and 1 μm.

2. The device according to claim 1, wherein the plate is formed of a ceramic material.

3. The apparatus of claim 2, wherein the ceramic material is selected from the group consisting of: alumina, silicon nitride, silicon dioxide, hafnium dioxide, titanium nitride, and titanium carbide.

4. The apparatus of claim 1, wherein the first coating is a parylene polymer.

5. The apparatus of claim 4, wherein the parylene polymer is parylene C, parylene D, parylene N, derivatives thereof, or combinations thereof.

6. The apparatus of claim 1, wherein the first coating is a polymer material selected from the group consisting of: synthetic rubber, siloxane polymers, parylene, thermoplastics, thermosetting plastics, polyolefins, polyisobutylene, acrylic polymers, ethylene-vinyl acetate copolymers, polymethyl methacrylate, vinyl halogenated polymers, polyethers, polyethylene halides, polyacrylonitrile, polyvinyl ketone, polyvinyl alcohol aromatics, polyvinyl alcohol esters, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides, alkyd resins, polycarbonates, polyoxymethylene, polyimide, polyethers, epoxy resins, polyurethanes, synthetic fibers, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polytetrafluoroethylene, polyetheretherketone, PLA, PLGA, PLLA, derivatives thereof, or combinations thereof.

7. The apparatus of claim 1, wherein the second coating has a thickness of about 0.1 µm to about 1 µm.

8. The apparatus of claim 1, wherein the second coating is alumina or a poly(p-xylene) polymer.

9. The apparatus of claim 1, wherein the second coating comprises alumina, synthetic rubber, siloxane polymer, parylene, thermoplastic, thermosetting plastic, polyolefin, polyisobutylene, acrylic polymer, ethylene-vinyl acetate copolymer, polymethyl methacrylate, vinyl halogenated polymer, polyether, polyethylene halide, polyacrylonitrile, polyvinyl ketone, polyvinyl alcohol aromatics, polyvinyl alcohol ester, acrylonitrile-styrene copolymer, ABS resin, ethylene-vinyl acetate copolymer, polyamide, alkyd resin, polycarbonate, polyoxymethylene, polyimide, polyether, epoxy resin, polyurethane, synthetic fiber, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ether, carboxymethyl cellulose, polytetrafluoroethylene, polyetheretherketone, PLA, PLGA, PLLA, derivatives thereof, or combinations thereof.

10. The apparatus of claim 1, further comprising a drug.

11. The apparatus of claim 1, wherein the first coating is a polymer material selected from the group consisting of rubber, cellulose, or polylactic acid.

12. The apparatus of claim 1, wherein the second coating comprises rubber, cellulose, or polylactic acid.

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