Thin film ocular implant with control structure for regulating aqueous humor flow

Abstract

Disclosed herein are devices, systems, and methods configured to safely regulate aqueous outflow in a patient's eye while dynamically maintaining the normal range of intraocular pressure. An exemplary membrane implant includes a plurality of topographical features implemented on first and second surfaces of the implant. The topographical features include an interconnected channel network configured to direct aqueous in the patient's eye to flow through and across the surfaces of the membrane implant to reduce intraocular pressure. A plurality of control structures are implemented on one or more selected locations of the first and second surfaces to regulate the aqueous in the patient's eye.

Description

[0001] Cross-reference to related applications This application claims the benefit of U.S. Provisional Patent Application No. 63 / 606,472, filed December 5, 2023, the entire contents of which are incorporated herein by reference. Background Technology

[0002] Glaucoma is a group of eye diseases that damage the optic nerve. It is a leading cause of irreversible blindness in people over 60 years of age, affecting more than 65 million people worldwide, a number projected to increase to 111.8 million by 2040. The most common form of glaucoma is primary open-angle glaucoma, in which aqueous humor cannot drain properly through the obstructed trabecular meshwork. As aqueous humor accumulates in the eye, intraocular pressure (IOP) increases and damages the optic nerve, leading to slow, asymptomatic vision loss. Importantly, IOP remains the only modifiable risk factor for glaucoma.

[0003] Permanent glaucoma drainage devices have been developed for different severities of the disease: tubular shunts are primarily used to treat refractory or severe glaucoma, while minimally invasive glaucoma surgery—an angle-based procedure that does not induce subconjunctival filtration—is approved for mild to moderate glaucoma. Tubular shunts are generally more effective over a 5-year period compared to the gold standard open filtration surgery (trabeculectomy) and are increasingly used as first-line filtration procedures; however, tubular shunts are thicker, still invasive, and are often retained as a last resort. Meanwhile, subconjunctival microscaffolds (e.g., Xen gel scaffolds, Preserflo) have poorer drainage maintenance compared to tubular shunts and often require resurfacing procedures such as needle removal. Furthermore, both tubular shunts and subconjunctival microscaffolds rely on a single-lumen tube to drain aqueous humor to reduce IOP. Single-lumen tubes are prone to blockage by scar tissue and can erode healthy tissue, potentially requiring resurfacing procedures.

[0004] Therefore, there is a need to provide an apparatus, system, and method configured to safely regulate aqueous humor outflow while dynamically maintaining the normal range of IOP. Summary of the Invention

[0005] Among other features, this disclosure relates to a thin-film implant for reducing intraocular pressure. The thin-film implant includes: a first surface opposite a second surface; a plurality of morphological features on each of the first and second surfaces, wherein the plurality of morphological features include a plurality of interconnected channels configured to guide aqueous humor from a patient's eye through and across the first and second surfaces of the thin-film implant to reduce intraocular pressure in the patient's eye; and a plurality of control structures implemented at one or more selected locations on the first and second surfaces to regulate aqueous humor in the patient's eye.

[0006] In one embodiment, the plurality of control structures may include a plurality of gates for opening and closing aqueous humor flow in a patient's eye. Each gate may be configured to open or close at a plurality of degrees to control aqueous humor flow, thereby reducing intraocular pressure to a target range, wherein the plurality of degrees corresponds to the aqueous humor flow rate detected in the patient's eye.

[0007] In some embodiments, the plurality of control structures may be implemented across the first and second surfaces of the membrane implant. In an alternative embodiment, the control structures may be positioned near the distal end of an extension of the membrane implant to form a gated inlet for aqueous humor in the patient's eye. In yet another embodiment, the plurality of control structures may be positioned in the region where the extension of the membrane implant connects to the body of the membrane implant.

[0008] In one aspect, the plurality of control structures may be configured to open in response to the detection of elevated intraocular pressure in the patient's eye and to deflect toward closing in response to the detection of decreased intraocular pressure in the patient's eye.

[0009] Furthermore, each of the plurality of control structures can be configured to have a specific size and position relative to each of the plurality of interconnecting channels to achieve different pressure gradients across different portions of the thin-film implant. For example, the ratio between the plurality of control structures and the plurality of interconnecting channels can be 1:1.

[0010] According to an embodiment, at least a portion of the control structure may include a cap configured to prevent aqueous humor leakage or tissue ingrowth.

[0011] According to another embodiment, at least a portion of the control structure may include a hinge portion, wherein each hinge portion associated with each control structure is configured to open or close at multiple degrees to control the flow of aqueous humor.

[0012] Furthermore, at least one of the plurality of gates has a vertical orientation or a horizontal orientation.

[0013] According to other embodiments, at least one of the plurality of gates may have a thickened wall implemented on a selected side surface of the hexagonal microstructure of the membrane implant. The thickened wall may be configured to form a movable hinge to adjust the dynamic resistance to aqueous humor flow in the patient's eye.

[0014] Additional features and advantages are described in the following detailed description and accompanying drawings, and will become apparent from them. The features and advantages described herein are not exhaustive, and in particular, many additional features and advantages will become apparent to those skilled in the art upon reading the drawings and specification. Furthermore, no particular embodiment need to possess all the advantages listed herein, and it is expressly intended that individual advantageous embodiments may be claimed separately. Moreover, it should be noted that the language used in the specification has been chosen primarily for readability and edutainment purposes and is not intended to limit the scope of the subject matter of the invention. Attached Figure Description

[0015] This disclosure will be more fully understood through the following detailed description and accompanying drawings, wherein: Figure 1 This is a perspective view of an apparatus according to one embodiment.

[0016] Figure 2 yes Figure 1 A close-up view of the device at section A marked in the middle.

[0017] Figure 3 It is along Figure 2 A cross-sectional view of the device taken from line III-III.

[0018] Figure 4 This is a perspective view of a device according to another embodiment.

[0019] Figure 5A According to one embodiment Figure 4 A portion of a cross-sectional view of part A of the device shown.

[0020] Figure 5B According to one embodiment Figure 4 A portion of a cross-sectional view of part A of the device shown.

[0021] Figure 5C According to one embodiment Figure 4 A portion of a cross-sectional view of part A of the device shown.

[0022] Figure 6 This is a diagram of a control structure on a thin-film implant for regulating aqueous humor in a patient's eye, according to an exemplary embodiment of this disclosure.

[0023] Figure 7 According to exemplary embodiments of this disclosure Figure 6 Side view of the control structure.

[0024] Figure 8 This is a diagram of a plurality of control structures implemented on a selected portion of a thin-film implant according to an exemplary embodiment of the present disclosure.

[0025] Figure 9A and Figure 9B The illustration shows multiple control structures implemented at two example locations of a thin-film implant according to an example embodiment of the present disclosure.

[0026] Figure 10 This is a side view of the closed or open state of a control structure with different degrees according to an example embodiment of this disclosure.

[0027] Figure 11 This is a diagram of multiple control structures at different locations on a thin-film implant, implemented according to exemplary embodiments of the present disclosure.

[0028] Figure 12A and Figure 12B A cover for a recess implemented in a control structure according to an example embodiment of the present disclosure is shown.

[0029] Figure 13 This is a side view of a control structure with a hinge portion according to an exemplary embodiment of the present disclosure.

[0030] Figure 14A and Figure 14B The vertical and horizontal orientations of the control structure according to an example embodiment of this disclosure are shown respectively.

[0031] Figure 15 According to exemplary embodiments of this disclosure Figure 14B A side view of the horizontal orientation of the control structure.

[0032] Figure 16 A control structure with thickened walls for gate construction is shown according to an example embodiment of the present disclosure. Detailed Implementation

[0033] Various aspects of this disclosure will be described with reference to the accompanying drawings, wherein the same reference numerals are used throughout to refer to the same elements. In the following description, numerous specific details are set forth for purposes of explanation in order to facilitate a thorough understanding of one or more aspects of this disclosure. However, in some or all cases it will be apparent that any of the aspects described below may be implemented without employing the specific design details described below.

[0034] It should be understood that the devices, systems, and methods of this disclosure can be used in any one or more medical or surgical procedures involving fragile, thin-film implants, such as cardiac surgery, anastomosis, non-surgical procedures, endoscopic procedures, non-invasive procedures, invasive procedures, transportation procedures, fluoroscopic procedures, off-pump cardiac surgery, vascular surgery, neurosurgery, electrophysiological procedures, diagnostic and therapeutic procedures, ablation procedures, ablation of arrhythmias, endovascular procedures, treatment of one or more organs and / or blood vessels, electrocardiographic examinations, pharmacological therapy, drug delivery procedures, delivery of biologics, and so on. Due to treatment, cell therapy, cancer treatment, radiation therapy, genetics, cell, tissue and / or organ manipulation or transplantation procedures, coronary angioplasty, placement or delivery of coated or uncoated stents, placement of cardiac enhancement devices, placement of cardiac assist devices, atherosclerotic plaque resection, atherosclerotic plaque manipulation and / or removal procedures, emergency procedures, cosmetic surgery, reconstructive surgery, biopsy procedures, autopsy procedures, surgical training, delivery procedures, congenital repair procedures, and medical procedures requiring manipulation and delivery of one or more fragile, thin-film implants to the surgical site.

[0035] In one embodiment, as will be fully described below, this disclosure relates to a film-based ocular implant, for example, for the treatment of glaucoma. A glaucoma drainage implant is a small device (i.e., a film device) placed in a patient's eye to treat glaucoma. Most glaucoma patients have abnormally high intraocular pressure (IOP) due to the inability to drain excess aqueous humor from the anterior chamber through the trabecular meshwork. Without adequate treatment to reduce IOP, high IOP will continue to damage the optic nerve as the disease progresses, leading to vision loss or even complete blindness. During glaucoma implantation surgery, a tiny drainage opening is formed in the sclera (the white part of the eye) of the patient's eye. This opening allows fluid to drain from the eye beneath a thin membrane called the conjunctiva that covers the eyeball. The opening can be kept open using topical medications or injections, and the film glaucoma drainage device is positioned outside the eye below the conjunctiva to drain excess fluid from the eye to a location where it can be reabsorbed back into the body by the patient's capillary and lymphatic systems, thereby reducing intraocular pressure.

[0036] To minimize scarring and postoperative patient discomfort, it is desirable to keep the conjunctival incision as small as possible, ideally less than 3 millimeters ("mm"). As used throughout this document, ranges are used as abbreviations to describe each value within a range. Any value within a range may be chosen as an endpoint of the range. Furthermore, all references cited herein are incorporated herein by reference in their entirety. In the event of any conflict between the definitions in this disclosure and those in the cited references, this disclosure shall prevail.

[0037] The description of illustrative embodiments according to the principles of the present invention is intended to be read in conjunction with the accompanying drawings, which are considered an integral part of the entire written description. Any references to directions or orientations in the description of the embodiments of the invention disclosed herein are merely for convenience of description and are not intended to limit the scope of the invention in any way. Relative terms such as “down,” “up,” “horizontal,” “vertical,” “above,” “below,” “upward,” “downward,” “top,” and “bottom,” and their derivatives (e.g., “horizontally,” “downward,” “upward,” etc.) should be interpreted as referring to the orientation described at the time or the orientation shown in the figures under discussion. These relative terms are merely for convenience of description and do not require the structure to be constructed or operated in a particular orientation unless explicitly stated otherwise.

[0038] Terms such as "attachment," "fixation," "connection," "coupling," and "interconnection" refer to relationships in which structures are directly or indirectly fixed or attached to each other through intermediate structures, as well as movable or rigid attachments or relationships, unless otherwise expressly stated. Furthermore, the features and benefits of the invention are illustrated with reference to exemplary embodiments. Therefore, the invention is not expressly limited to such 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.

[0039] Unless otherwise stated, all percentages and quantities expressed herein and elsewhere in the specification shall be understood as weight percentages. The quantities given 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 non-existent" means a total amount based on the referenced value of less than about 0.1% by weight.

[0040] The “subjects” in this article can be humans 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.

[0041] Treatment device embodiment refer to Figure 1-3 The treatment device 1 includes a plate structure 200 (or simply a plate) having a first main exposed surface 201, a second main exposed surface 202 opposite to the first main exposed surface 201, and a side surface 203 extending between the two. The plate structure 200 may include an extension portion 250 and a main body portion 240.

[0042] The plate structure 200 may be formed of any material having suitable implantation and therapeutic properties. In some embodiments, the plate structure 200 may be formed of metals, polymers, ceramics (e.g., alumina), 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, alloys may include steel and nickel-titanium (e.g., nitinol).

[0043] The polymer or polymeric material used to form the plate structure 200 may include any polymer described herein.

[0044] Composite materials, such as silicon composites, may also be used. In one embodiment, the composite material may include silicon nitride (Si3N4). Silicon nitride may have any known crystal structure, such as, but not limited to, trigonal α-Si3N4, hexagonal β-Si3N4, or cubic γ-Si3N4.

[0045] The thickness of the plate structure 200 or the plate may range from 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.

[0046] The plate structure 200 may include a multi-directional plate 210, which includes a first main surface 211 and a second main surface 212 opposite to the first main surface 211. The multi-directional plate 210 may form multiple morphological features (e.g., repeating honeycomb patterns) on each of the first and second main surfaces 211 and 212. Each of the first and second morphologies may independently include multiple channels 232 and / or multiple open cells 222.

[0047] Multiple channels 232 may be interconnected and may form a channel network. The channels may be open or closed, allowing fluid to easily enter and flow through each of the multiple channels 232. The network may include channels intersecting in any suitable configuration to optimally facilitate fluid flow across the plate structure 200 via the multiple channels 232. In one embodiment, the channels 232 may be configured to form a hexagonal pattern. Figure 1The treatment device 1 shown is implanted, and fluid (e.g., aqueous humor) can be driven by a pressure gradient to flow through the channel and across the surface of the plate structure 200.

[0048] In some embodiments, channel 232 may include a rib pattern. The geometry of the rib pattern and / or the channel in the plate may vary based on different degrees of disease severity (e.g., mild, moderate, or severe glaucoma). In one embodiment, larger or smaller channels may be used to reduce intraocular pressure to different degrees. Changing intraocular pressure by a smaller magnitude can reduce the risk of hypotension (a condition that may occur when intraocular pressure is reduced too much) and improve the effectiveness of reducing pressure to the target level. In some embodiments, the device described herein with smaller channels can reduce flow and reduce the risk of hypotension. Similarly, larger channels can increase flow and allow the device to reduce intraocular pressure to even lower levels.

[0049] 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 is inconsistent with the first morphology of the first primary surface 211 of the multi-directional plate 210.

[0050] The thickness of the first coating 280 can range from about 0.1 μm to about 10 μm or from about 0.1 μm to about 2 μm—inclusive of all thicknesses and subranges 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.

[0051] 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 on the second primary surface 212 of the multi-directional plate 210. In other embodiments, the second coating 290 may form a morphology inconsistent with a second morphology of the second primary surface 212 of the multi-directional plate 210.

[0052] The thickness of the second coating 290 can range from about 0.1 μm to about 10 μm or from about 0.1 μm to about 1 μm—inclusive of all thicknesses and subranges 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.

[0053] In some embodiments, the plate structure 200 may include only the first coating 280—that is, without the second coating. In other embodiments, the plate structure 200 may include only the second coating 290—that is, without the first coating. In other embodiments, the plate structure 200 may include a first coating 280 and a second coating 290, whereby the first and second coatings overlap to completely encapsulate the multidirectional plate 210. In such embodiments, the side surface 203 of the plate structure 200 may include at least one of the first coating 280 and the second coating 290.

[0054] 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 each coating or thicker than the sum of the thicknesses of the two coatings.

[0055] The coatings described herein can be applied by any suitable deposition method, such as, but not limited to, physical vapor deposition, chemical vapor deposition, atomic layer deposition, spraying, spin coating, self-assembly, dip coating, or brush coating.

[0056] The first coating 280 can be applied to the first master surface 211 by any suitable deposition method. In one non-limiting example, the first coating 280 can be applied to the first master surface 211 by chemical vapor deposition, physical vapor deposition, or plasma-enhanced chemical vapor deposition. In another non-limiting example, the first coating 280 can be applied to the first master surface 211 by atomic layer deposition. In another non-limiting example, the first coating 280 can be applied to the first master surface 211 by spraying. In another non-limiting example, the first coating 280 can be applied to the first master surface 211 by dip coating. In another non-limiting example, the first coating 280 can be applied to the first master surface 211 by brushing.

[0057] The second coating 290 can be applied to the second master surface 212 by any suitable deposition method. In one non-limiting example, the second coating 290 can be applied to the second master surface 212 by chemical vapor deposition, physical vapor deposition, or plasma-enhanced chemical vapor deposition. In another non-limiting example, the second coating 290 can be applied to the second master surface 212 by atomic layer deposition. In another non-limiting example, the second coating 290 can be applied to the second master surface 212 by spraying. In another non-limiting example, the second coating 290 can be applied to the second master surface 212 by dip coating. In another non-limiting example, the second coating 290 can be applied to the second master surface 212 by brushing.

[0058] 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 and second coatings 280 and 290 may be independently continuous. Each of the first and second coatings 280 and 290 may be independently discontinuous. In some embodiments, both the first and second coatings 280 and 290 may be hydrophobic. In some embodiments, both the first and second coatings 280 and 290 may be hydrophilic. In some embodiments, both the first and second coatings 280 and 290 may be either lipophilic or lipophobic.

[0059] 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.

[0060] In some embodiments, the first coating 280 is hydrophilic, while the second coating 290 is hydrophobic. Making at least one of the first and / or second coatings 280, 290 hydrophobic can help prevent the treatment device 1 from unintentionally adhering to tissue during implantation.

[0061] In some embodiments, the purpose of the first and / or second coating is to increase the toughness of the device. Furthermore, the first and / or second coating may increase the biocompatibility of the device and / or reduce scar formation 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 may be reduced by more than about 10%, 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 an uncoated plate.

[0062] In one non-limiting embodiment, the first and / or second coating may comprise a polymer, such as a poly(para-xylylene) polymer or a derivative thereof. In other embodiments, the first and / or second coating may comprise alumina, a biocompatible membrane, a porous coating, or a lubricating coating. In one embodiment, the poly(para-xylylene) polymer is chlorinated or fluorinated poly(para-xylylene). In one embodiment, the poly(para-xylylene) polymer may be poly(para-xylylene) C, poly(para-xylylene) D, poly(para-xylylene) N, derivatives thereof, or combinations thereof. In other embodiments, the first and / or second coating may comprise alumina.

[0063] In other embodiments, other polymers may be used, combined with, or substituted for parylene polymers and / or alumina. In some embodiments, other polymeric materials may include, but are not limited to, rubber, synthetic rubber, silicone polymers, thermoplastics, thermosetting plastics, polyolefins, polyisobutylene, acrylic polymers, ethylene-vinyl acetate copolymers, polybutyl methacrylate, ethylene halide polymers (e.g., polyvinyl chloride), polyvinyl ethers (e.g., polyvinyl methyl ether), polyvinylidene halide, polyacrylonitrile, polyvinyl ketone, polyvinyl aromatic hydrocarbons, polyvinyl ester, 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, rayon, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polytetrafluoroethylene (e.g., Teflon), poly(ether-ether-ketone), polylactide (such as PLA, PLGA, PLLA, etc.), their derivatives, or combinations thereof.

[0064] 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 may facilitate fluid flow through the channels after the treatment device 1 has been implanted into the subject's eye.

[0065] refer to Figure 4 , 5A Treatment device 1001 is generally shown according to another embodiment, 5B and 5C. Except as described below, treatment device 1001 is similar to treatment device 1. The above description of treatment device 1 generally applies to treatment device 1001 as described below, except for the differences specifically pointed out below. Except for the use of the "1000" series numbering, a similar numbering scheme as that used for treatment device 1 will be used for treatment device 1001.

[0066] The treatment device 1001 includes a plate structure 1200 having a first exposed main surface 1201 and a second exposed main surface 1202 opposite to the first exposed main surface 1201. The plate structure 1200 may include a multidirectional plate 1210, which includes a first main surface 1211 and a second main surface 1212 opposite to the first main surface 1211. The multidirectional plate 1210 may form multiple morphological features (e.g., repeating honeycomb patterns) on each of the first and second main surfaces 1211 and 1212. Each of the first and second morphologies may independently include multiple channels 1232 and / or multiple open units 1222.

[0067] Now for reference Figure 5B The plate structure 1200 may include a first drug delivery component 1070 present in open voids created by a first morphology formed by a first exposed surface 1211 of the multi-directional plate 1210. Specifically, the first delivery component 1070 may be present in open voids created by open units 1222 of the first morphology formed by the first main surface 1211 of the multi-directional plate 1210.

[0068] The first therapeutic delivery component 1070 may include one or more active agents, such as, but not limited to, therapeutic and / or pharmacological components. The first therapeutic delivery component 1070 may occupy part, all, or substantially all of the free volume present in the open unit 1222 formed by the first morphology.

[0069] In other embodiments, the active agent may include any compound or drug that has a therapeutic effect in the subject. Non-limiting active agents include antiproliferators (including, but not limited to, macrolide antibiotics, including FKBP-12-binding compounds), estrogens, chaperone protein inhibitors, protease inhibitors, protein tyrosine kinase inhibitors, lepromycin B, peroxisome proliferator-activated receptor gamma ligand (PPARγ), trachomycin, nitric oxide, bisphosphonates, epidermal growth factor inhibitors, antibodies, steroids, proteasome inhibitors, antibiotics, anti-inflammatory drugs, antisense nucleotides, transformed nucleic acids, messenger RNA, drugs that reduce IOP, prostaglandins, cell-inhibiting compounds, toxic compounds, anti-inflammatory compounds, chemotherapeutic agents, analgesics, antibiotics, protease inhibitors, statins, nucleic acids, peptides, growth factors, and delivery carriers, including recombinant microorganisms, cells, stem cells, liposomes, antimetabolites (such as mitomycin C), combinations thereof, prodrugs thereof, pharmaceutical salts thereof, derivatives thereof, etc.

[0070] 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 the first main surface 1211 of the multi-directional plate 1210 and a first drug delivery component 1070 present in open units 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 component 1070.

[0071] Now for reference Figure 5A The plate structure 1200 may include a second drug delivery component 1080 present in open voids created by a second morphology formed by a second exposed surface 1212 of the multi-directional plate 1210. Specifically, the second delivery component 1080 may be present in open voids created by open channels 1232 of the second morphology formed by the second main surface 1212 of the multi-directional plate 1210. The second delivery component 1080 may be the same as or different from the first delivery component 1070.

[0072] The second therapeutic 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 part, all, or substantially all of the free volume present in the channel 1232 formed by the first morphology.

[0073] 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 the second primary surface 1212 of the multi-directional plate 1210 and a second delivery component 1080 present in open channels 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 the underlying pattern formed by the multi-directional plate 1210 and the second delivery component 1080.

[0074] The second coating 1060 may be the same as or different from the first coating 1050. For each of the first and second coatings 1050, 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 the treatment device 1001 is implanted in the subject.

[0075] Now for reference Figure 5C In other embodiments, the treatment device 1001 may include first and second drug delivery components 1070, 1080, and first and second coatings 1050, 1060 for encapsulating the first and second delivery components 1070, 1080.

[0076] 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 and / or second delivery components 1070, 1080. In such embodiments, the first coating 1050 and / or the second coating 1060 may form a film covering the open cells 1222 and / or open channels 1232 generated by the multidirectional plate.

[0077] The presence of the film formed by the first and / or second coatings 1050, 1060 enhances the overall strength of the resulting treatment device. Specifically, the layered structure of the film formed by the first and second coatings 1050, 1060 and bonded to the first and second main surfaces 1211, 1212 of the multi-directional plate 1210 provides additional mechanical integrity to the resulting treatment device.

[0078] In addition to achieving basic flexibility that conforms to the curvature of the eye, the addition of the first and / or second coatings 1050, 1060 provides a mechanism that allows the entire therapeutic device to match the elastic modulus of surrounding tissues (e.g., conjunctival and scleral tissues) to maximize biocompatibility or biointegration. Findings in brain implant research confirm that flexibility in soft tissue implants improves the implant's compliance with microscale movements of surrounding tissues and reduces tissue displacement and trauma, while also facilitating implantation of the therapeutic device.

[0079] Control structure for regulating aqueous humor flow According to various aspects of this disclosure, the control structure (e.g., a laser-cutting gate) can be configured relative to the above description. Figure 1-4 The plate structure described in 5A, 5B, and 5C is implemented at selected locations to regulate the aqueous humor in the patient's eye. For example... Figure 6 and 7 As shown, a laser-cut gate 606 can be positioned at a channel 702 formed between two adjacent hexagonal microstructures 602, 604, such as a plate structure. As will be fully described below, the gate 606 can be configured to open or close at different degrees to control the flow of aqueous humor through the channel 702.

[0080] In one respect, the location of control structures on the plate structure can be determined and arranged in a way that optimizes the resistance to aqueous humor flow in the patient's eye, thereby reducing IOP to the target range. For example, as Figure 6 As shown, a control structure can be implemented within each channel formed between adjacent hexagonal microstructures.

[0081] As another example, such as Figure 8 As shown, multiple control structures can be installed throughout the entire extension of the plate structure 800 (e.g., similar to...). Figure 1 Implemented on the extension portion 250 shown. According to one embodiment, as Figure 9A As shown, multiple control structures 902 can be positioned near the distal end of an extension of the plate structure to form a gated inlet for aqueous humor flow in the patient's eye. According to another embodiment, as... Figure 9B As shown, multiple control structures 1002 can be positioned at the extension and the main body of the plate structure (e.g., similar to...). Figure 1 The area connected to the main body portion 240 shown. Regulating the aqueous humor flow may be optimal at the inlet of the membrane splitter (before the flow generates significant velocity and is at higher pressure) or further downstream (when the flow generates velocity within the channel and is at lower pressure).

[0082] In some aspects, the control structure of this disclosure can be used as a passively adjusting gate whose angle is adjusted to regulate dynamically changing IOP in the anterior chamber. For example, the gate can be configured to open in response to the detection of an increase in IOP or flow in a patient's eye. On the other hand, the gate can be configured to deflect toward closing in response to the detection of a decrease in IOP.

[0083] The control structure can be configured to generate resistance to flow through several design options. For example, the closing or opening degree of a gate can be configured to have different degrees. Figure 10As shown, the gate can have a fully open state 1002, which is approximately proportional to the high outflow rate of aqueous humor from the anterior chamber. As the upstream velocity of the aqueous humor decreases, the gate can gradually move to an intermediate state 1004. Once it is determined that the IOP has reached a selected threshold, the gate can be completely closed. Figure 10 The fully closed state shown is 1006. It should be understood that the gate can... Figure 10 The states shown, 1002, 1004, and 1006, have multiple intermediate positions to regulate aqueous humor flow.

[0084] According to another example, the dimensions (height and width) and position of each gate can be determined and implemented relative to each channel to achieve different pressure gradients across different sections of the plate structure. For example... Figure 11 As shown, multiple gates 1102, 1104, and 1106 can be positioned in selected channels to create different outflow paths and resistances for the aqueous humor. The number of gates can be determined based on the number of channels. Typically, a 1:1 gate-to-channel ratio is preferred, but higher or lower ratios can also be implemented. This can depend on various factors, such as the individual resistance provided by each gate, the geometry of the channels and gates, the relative resistance effect provided by each gate, and whether significant flow mixing occurs between the channel arrays along the diverter.

[0085] According to an alternative embodiment, the manufacturing result using cutting techniques (such as lasers) may result in the formation of holes for creating the gate. If the presence of holes is undesirable, for example because they would create a path for aqueous humor leakage, the cover element can be integrated into the device manufacturing process. (See reference) Figure 12A and 12B A gate recess cover 1206 can be implemented for the gate 1204 adjacent to the hexagonal microstructure 1202. In some embodiments, if the gate is constructed in a way that creates a hole in the gate recess, this hole may become a leakage point for aqueous humor and / or a path where tissue may grow and obstruct the gate's deflection or closure. The recess cover can be integrated as a separate component, such as as a coating on the bottom of the device, so that the cover prevents aqueous humor leakage or tissue ingrowth.

[0086] Figure 13 An adjustable gate 1302 with a hinge portion 1304 is shown. The torsional stiffness of the gate 1302 can be determined by the geometry and material of the movable hinge. Furthermore, the initial configuration of the gate (e.g., the initial angle θ between the gate 1302 and the horizontal surface of the plate structure) can be determined and formed by plastic deformation applied during manufacturing. The stiffness of the hinge portion 1304 can be adjusted or modified during manufacturing by selective ablation or material removal at the base (e.g., using lasers and / or etching, etc.).

[0087] On the other hand, the control structure of this disclosure can have different gate orientations. (See reference...) Figure 14AThe vertical gate 1402 can be implemented in the channel 1404 between two adjacent hexagonal microstructures 1406 and 1408. Figure 14B Another embodiment is shown, in which a horizontal gate 1410 is implemented in a channel formed between two adjacent hexagonal microstructures 1412, 1414. Figure 15 As shown, such a horizontal gate 1410 can be configured to partially or completely block the flow of aqueous humor.

[0088] According to other embodiments, the control structure of this disclosure may have thickened walls for gate construction. For example... Figure 16 As shown, the thickened wall 1602 can be implemented on selected side surfaces of the hexagonal microstructure 1604. Next, laser cutting and any other suitable cutting techniques can be performed on the thickened wall 1602 along the dashed line 1606, retaining some material in the region where the movable hinge 1608 of the gate 1610 is formed. As a result, the gate 1610 is formed with a partial wall thickness.

[0089] The table below shows various state conditions that indicate how a movable hinged gate affects aqueous humor flow, where P represents pressure, Q represents flow velocity, and R represents flow resistance.

[0090] As shown in the table, the dynamic resistance to aqueous humor flow can be adjusted by the control structure of this disclosure (e.g., a movable hinged gate) to accommodate lower R when P is high and higher R when P is low. The control structure can act as an effective diverter for high IOP and alleviate low IOP by automatically reducing the outflow resistance of aqueous humor. As a result, the control structure can smooth the IOP curve to reduce the risk of low intraocular pressure (excessively low IOP) while effectively diverting flow from the anterior chamber to reduce high IOP.

[0091] According to an additional embodiment, the control structure of this disclosure can be activated externally by a physician, for example using a laser or magnet, to allow more or less outflow based on treatment goals. Flow modulation using common ophthalmic lasers can be achieved by incorporating a temperature-sensitive material (e.g., nitinol) into the gate structure, allowing the gate structure to bend in response to heat generated by the laser and transition from one position to another to modulate flow, thereby achieving the target IOP. Similarly, a control structure incorporating paramagnetic materials can be incorporated to facilitate postoperative flow modulation by exposing the patient's eye to a magnetic field to allow the gate to transition from one position to another. For both implementations, ratchet and / or pawl mechanisms can be incorporated so that once the laser-induced heat or magnetic field is removed, the gate structure retains its new configuration and the new flow resistance can be permanently altered.

[0092] In another embodiment, a sensor system (not shown) can be implemented to actively monitor and control the flow of aqueous humor throughout the thin-film implant. The sensor material can be biocompatible and corrosion-resistant (e.g., platinum, gold, graphene, or conductive polymers). Depending on the parameter to be monitored, a variety of different sensors can be selected, such as micropaddlewheels, hot-wire anemometers or MEMS-based flow sensors, capacitive or piezoresistive pressure sensors, and ion-sensitive field-effect transistors (ISFETs) or optical sensors (pH / chemical sensors). Any suitable microfabrication technique (e.g., photolithography, etching, or 3D printing) can be used to make the sensor compatible with the microstructure of the thin-film implant. When integrating the sensor system, direct deposition techniques (e.g., sputtering, chemical vapor deposition (CVD), or inkjet printing) can be used to deposit the sensor material directly onto the thin-film surface. In another embodiment, prefabricated microsensors can be attached to the thin-film implant using adhesives or thermal bonding while ensuring minimal impact on the microstructure or flow regulation performance. In another embodiment, one or more sensors can be embedded within or arranged along the microstructure using soft lithography or laser ablation. Furthermore, sensors can be placed at critical points where flow regulation is most sensitive or feedback is required, while ensuring that the sensors do not obstruct or alter the designed flow dynamics, such as at the tip of the implant communicating with the anterior chamber. In some embodiments, flexible and low-profile conductive traces (e.g., printed silver or gold wires) can be used to connect the sensors to external circuitry. Wireless power transmission (e.g., inductive coupling) or thin-film batteries can be utilized to minimize size. For encapsulation and protection purposes, in some embodiments, a thin, transparent, and waterproof coating (e.g., parylene, PDMS, or epoxy) can be applied to protect the sensors from water and mechanical damage. Such coatings do not interfere with sensor functionality, particularly for chemical or optical sensors. In other embodiments, wireless communication modules (such as Bluetooth, NFC, or LoRa) can be incorporated into the sensor system for real-time monitoring without physical connection. If space is limited, flexible antennas can be printed directly on the thin film. One or more sensors can also be combined with control electronics (e.g., microcontrollers or custom ASICs) to process sensor data in real time and respond based on that data. If active flow regulation is required, one or more actuators or valves can be integrated based on sensor feedback.

[0093] Although the present invention has been described in detail based on embodiments currently considered most practical and preferred for illustrative purposes, it should be understood that such detailed description is for that purpose only, and the present invention is not limited to the disclosed embodiments, but rather is intended to cover modifications and equivalent arrangements within the spirit and scope of the appended claims. For example, it should be understood that the present invention contemplates that, where possible, one or more features of any embodiment may be combined with one or more features of any other embodiment.

[0094] Unless otherwise stated, all figures expressing quantities, etc., in the specification and claims should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters described in the specification and appended claims are approximate values ​​and may vary according to the desired characteristics sought to be obtained according to the invention. At least, and not in an attempt to limit the application of the doctrine of equivalence in the scope of the claims, each numerical parameter should be interpreted at least according to the number of significant figures reported and by applying conventional rounding techniques. Although the numerical ranges and parameters illustrating the broad scope of the invention are approximate values, the values ​​set forth in the specific examples should be reported as precisely as possible. However, any numerical value inherently contains some error that necessarily arises from the standard deviation found in its respective test measurement.

[0095] In the context of describing the invention (particularly in the context of the following claims), the terms "a," "an," "the," and similar pronouns should be interpreted to cover both singular and plural forms, unless otherwise stated herein or obviously contradictory to the context. References to numerical ranges herein are intended only as a way of abbreviating each individual value falling within that range. Each individual value is incorporated into the specification as if individually referenced herein, unless otherwise stated herein or obviously contradictory to the context. All methods described herein may be performed in any suitable order, unless otherwise stated herein or obviously contradictory to the context. The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the invention and does not constitute a limitation on the scope of the claimed invention. The language in the specification should not be construed as indicating that any unclaimed element is essential to carrying out the invention.

[0096] The grouping of alternative elements or embodiments of the invention disclosed herein should not be construed as limiting. Each member of a group may be mentioned and claimed individually, or in any combination with other members of that group or other elements described herein. For convenience and / or patentability reasons, it is contemplated that one or more members of a group may be included in or removed from the group. When any such inclusion or removal occurs, this specification is deemed to contain the group as so modified to satisfy the written description of all Markush groups used in the appended claims.

[0097] This document describes certain embodiments of the invention, including the best mode known to the inventors for carrying out the invention. Of course, variations of these embodiments will be apparent to those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to appropriately employ such variations, and the inventors intend that the invention be practiced in a manner different from that specifically described herein. Therefore, the invention includes all modifications and equivalents of the subject matter described in the appended claims as permitted by applicable law. Furthermore, unless otherwise stated herein or clearly contradicted by the context, any combination of the foregoing elements and all possible variations thereof are covered within the scope of this invention.

[0098] The specific exemplary embodiments disclosed herein may be further defined in the claims using the language of "consisting of" or "substantially consisting of". When used in the claims (whether at the time of filing or added by amendment), the transitional term "consisting of" excludes any element, step, or ingredient not specified in the claims. The transitional term "substantially consisting of" limits the scope of the claims to the specified materials or steps and those that do not substantially affect the basic and novel characteristics. Exemplary embodiments of the invention thus claimed are inherently or explicitly described and enabled herein.

[0099] Finally, it should be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the invention. Other modifications may be used within the scope of the invention. Therefore, alternative constructions of the invention may be utilized in accordance with the teachings herein, as examples rather than limitations. Thus, the invention is not limited to exactly as shown and described.

Claims

1. A thin-film implant for reducing intraocular pressure, the thin-film implant comprising: The first surface is opposite to the second surface; Multiple morphological features on each of the first and second surfaces, wherein the multiple morphological features include multiple interconnected channels configured to guide aqueous humor in the patient's eye through and across the first and second surfaces of the thin-film implant to reduce intraocular pressure in the patient's eye; as well as Multiple control structures are implemented at one or more selected locations on the first and second surfaces to regulate aqueous humor in the patient's eye.

2. The thin-film implant of claim 1, wherein the plurality of control structures include a plurality of gates for opening and closing the flow of aqueous humor in the patient's eye through the plurality of interconnected channels.

3. The thin-film implant of claim 2, wherein each of the plurality of gates is configured to open or close at a plurality of degrees to control the flow of aqueous humor, thereby reducing the intraocular pressure to a target range, wherein the plurality of degrees correspond to the aqueous humor flow rate detected in the patient's eye.

4. The thin-film implant of claim 1, wherein the plurality of control structures are implemented across the first surface and the second surface.

5. The thin-film implant of claim 1, wherein the plurality of control structures are positioned near the distal end of an extension of the thin-film implant to form a gated inlet for aqueous humor in the patient's eye.

6. The film implant of claim 1, wherein the plurality of control structures are located in the region where the extension of the film implant connects to the body of the film implant.

7. The thin-film implant of claim 1, wherein the plurality of control structures are configured to open in response to detection of elevated intraocular pressure in the patient's eye and to deflect toward closing in response to detection of decreased intraocular pressure in the patient's eye.

8. The thin-film implant of claim 1, wherein each of the plurality of control structures is configured to have a certain size and position relative to each of the plurality of interconnecting channels to achieve different pressure gradients across various portions of the thin-film implant.

9. The thin-film implant of claim 1, wherein the ratio between the plurality of control structures and the plurality of interconnecting channels is 1:

1.

10. The thin-film implant of claim 1, wherein at least a portion of the control structure includes a cap configured to prevent aqueous humor leakage or tissue ingrowth.

11. The thin-film implant of claim 1, wherein at least a portion of the control structure includes a hinge portion, wherein each hinge portion associated with each control structure is configured to open or close at a plurality of degrees to control the flow of aqueous humor.

12. The thin-film implant of claim 2, wherein at least one of the plurality of gates has a vertical orientation.

13. The thin-film implant of claim 2, wherein at least one of the plurality of gates has a horizontal orientation.

14. The thin-film implant of claim 2, wherein at least one of the plurality of gates has a thickened wall implemented on a selected side surface of the hexagonal microstructure of the thin-film implant.

15. The thin-film implant of claim 14, wherein the thickened wall is configured to form a movable hinge to adjust the dynamic resistance to aqueous humor flow in the patient's eye.

16. The thin-film implant of claim 1, wherein at least a portion of the plurality of control structures is made of a temperature-sensitive material that can be activated by laser-induced heat to transition from one location to another, thereby modulating the aqueous humor in the patient's eye.

17. The thin-film implant of claim 1, wherein at least a portion of the plurality of control structures is made of a paramagnetic material that can be activated by a magnetic field to transition from one location to another, thereby modulating the aqueous humor in the patient's eye.

18. The thin-film implant of claim 1, further comprising a sensor system implemented on at least one of the first surface and the second surface to monitor and control aqueous humor in the patient's eye via the plurality of interconnected channels.

19. The thin-film implant of claim 18, wherein the sensor system comprises at least one sensor selected from a flow sensor, a pressure sensor, or a pH / chemical sensor.

20. The thin-film implant of claim 19, wherein the at least one sensor is disposed at the tip portion of the thin-film implant, the tip portion communicating with the anterior chamber of the patient's eye.

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