WO2025029739A2 - Subconjunctival implants and methods using the same - Google Patents

Abstract

A subconjunctival implant and a method for treating an eye infection in an eye of a subject by placing the subconjunctival implant into a subconjunctival space of the eye. The subconjunctival implant includes an elongated body portion and a fin. At least one of the elongated body portion or the fin comprises a biocompatible polymer and a medication. The elongated body portion includes a leading edge and a trailing edge opposite the leading edge. The elongated body portion includes a dorsal surface and an anterior surface. The fin extends from the dorsal surface. The fin has a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface.

Description

SUBCONJUNCTIVAL IMPLANTS AND METHODS USING THE SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 63/529,603, filed July 28, 2023. and titled ‘ SUBCONJUNCTIVAL IMPLANTS AND METHODS USING THE SAME,’^? the entirety of which is incorporated herein by reference.

FIELD OF THE INVENTION

[0002] The invention relates to the treatment of ocular diseases and conditions.

BACKGROUND OF THE INVENTION

[0003] Ocular surface diseases such as, for example, herpes simplex virus ty pes 1 and 2 (HSV-1/2), varicella zoster virus (shingles), and feline herpes virus (FHV-1), can have symptoms ranging from discomfort and pain to blindness. Treatments for such diseases can include topical treatments.

SUMMARY OF THE INVENTION

[0004] In one aspect, the invention relates to an implant. The implant can be a subconjunctival implant used in a method for treating an eye infection in an eye of a subject by being placed into a subconjunctival space of the eye. The implant can include various features as discussed herein to help the implant maintain the position and orientation within the subconjunctival space of the eye.

[0005] In another aspect, the invention relates to a subconjunctival implant including an elongated body portion and a fin. At least one of the elongated body portion or the fin comprises a biocompatible polymer and a medication. The elongated body portion includes a leading edge and a trailing edge opposite the leading edge. The elongated body portion includes a dorsal surface and an anterior surface. The fin extends from the dorsal surface. The fin has a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface.

[0006] In a further aspect, the invention relates to a method for treating an eye infection in an eye of a subject. The method includes forming an opening in a conjunctiva of the subject, inserting a subconjunctival implant through the opening in the conjunctiva and into a subconjunctival space of the eye, and closing the opening in the conjunctiva.

[0007] These and other aspects of the invention will become apparent from the following disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is side view of a subconjunctival implant according to an embodiment of the disclosure.

[0009] FIG. 2 a dorsal view of the subconjunctival implant shown in FIG. 1.

[0010] FIG. 3 is a flow chart of a method of treating an eye infection in a subject.

[0011] FIG. 4 is a side view of an example subconjunctival implant.

[0012] FIG. 5 is a dorsal view of the example subconjunctival implant shown in FIG. 4. [0013] FIGS. 6A and 6B are examples of a mold that may be used to manufacture the example subconjunctival implant shown in FIG. 4. FIG. 6A is a side view' of the mold, and FIG. 6B is a top view' of the mold. [0014] FIGS. 7A to 7F depicts an implantation procedure for implanting the example subconjunctival implant shown in FIG. 4. FIG. 7A is a first step. FIG. 7B is a second step. FIG. 7C is a third step. FIG. 7D is a fourth step. FIG. 7E is a fifth step. FIG. 7F is a sixth step.

[0015] FIG. 8 depicts a line graph showing the clinical scores in each eye at each examination timepoint for the SHAM eye (right eye (OD)) and TREATMENT eye (left eye (OS)).

[0016] FIG. 9 depicts ocular clinical scores of TREATMENT group compared with SHAM group during acute HSV-1 ocular infection.

[0017] FIG. 10 depicts ocular clinical scores of TREATMENT group compared with SHAM group during acute HSV-1 ocular infection.

[0018] FIG. 11 depicts ocular viral shedding of TREATMENT group compared with SHAM group during acute infection.

[0019] FIG. 12 depicts ocular viral shedding of TREATMENT group compared with SHAM group during acute infection.

[0020] FIG. 13 depicts ocular clinical scores of TREATMENT group compared with SHAM group following ocular HSV-1 reactivation procedures according to.

[0021] FIG. 14 depicts ocular clinical scores of TREATMENT group compared with SHAM group following ocular HSV-1 reactivation procedures according to an embodiment of the disclosure.

[0022] FIG. 15 depicts ocular viral shedding of TREATMENT group compared with SHAM group following reactivation procedures.

[0023] FIG. 16 depicts time release of a medication from a subconjunctival implant.

[0024] FIG. 17 depicts an analytical method for ganciclovir detection. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] As used herein, a "substantially flat anterior surface" is a surface of a subconjunctival implant that is about as flat as the surface of the subject's eye.

[0026] As used herein, a "biocompatible polymer" is a polymer material that is not harmful to living tissue.

[0027] As used herein, a "biodegradable" polymer material that can be at least partially chemically degraded within a subconjunctival space by the subject.

[0028] The "subconjunctival space" has its ordinary' anatomical meaning referring to an extraocular space beneath the conjunctiva.

[0029] An eye, such as an eye of a human or a non-human animal, can be infected with various infections such as viral infections, bacterial infections, and/or fungal infections. As noted above, ocular surface diseases such as, for example, herpes simplex virus types 1 and 2 (HSV-1/2), varicella zoster virus (shingles), and feline herpes virus (FHV-1), can have symptoms ranging from discomfort and pain to blindness. While some topical treatments may be available for some ocular surface diseases, such treatments often require repeated application over long durations of time. There remains a need, however, for treatments for ocular surface diseases which ensure patient compliance and have improved convenience while inhibiting viral replication and reducing symptoms or clinical signs of the disease. Disclosed herein are subconjunctival implants for treating such diseases. The subconjunctival implants can include a biocompatible polymer and a medication dispersed within the biocompatible polymer for treatment of the infection. Also disclosed are methods for treating an eye infection using the subconjunctival implant.

[0030] FIG. 1 is a side view of a subconjunctival implant 100 according to an embodiment of the disclosure, and FIG. 2 is a dorsal view of the subconjunctival implant 100. The subconjunctival implant 100 includes a body portion 110. The body portion 110 has a leading edge 112 and a trailing edge 114. The body portion 110 extends in a longitudinal direction L and has a length 1 in the longitudinal direction. The length 1 can be a distance from the leading edge 112 to the trailing edge 114. The trailing edge 114 is opposite the leading edge 112 in the longitudinal direction L. The body portion 110 also has a first side 116 and a second side 118. The body portion 110 also has a width w in a width direction W. The width w can be a distance from the first side 116 to the second side 118. The width direction W can be orthogonal to the longitudinal direction L. As will be discussed further below, the length 1 can be greater than the width w. Thus, the subconjunctival implant 100 and, more specifically, the body portion 110 can be elongated and may be referred to herein as an elongated subconjunctival implant 100 or an elongated body portion 110.

[0031] Each of the leading edge 112 and the trailing edge 114 can be rounded having a curvilinear shape. Each of the leading edge 112 and the trailing edge 114 can also be tapered. While the leading edge 112 and the trailing edge 114 can be rounded to the same degree, the leading edge 112 and the trailing edge 114 can also be rounded to different degrees. In the depicted embodiment, for example, the leading edge 112 has a greater degree of curv ature (a smaller radius of curvature) than the trailing edge 114. The first side 116 and the second side 118 can be parallel to each other. The first side 116 and the second side 118 can each be rectilinear when viewed from the top or bottom as shown in FIG. 2, for example. The first side 116 and the second side 118 can extend in the longitudinal direction. Each of the first side 1 1 and the second side 1 18 can be a substantially flat surface.

[0032] The body portion 110 also includes a dorsal surface 122 and an anterior surface 124. The body portion 110 has a thickness t in a thickness direction T. The thickness can be a distance from the dorsal surface 122 to the anterior surface 124. The thickness direction T can be orthogonal to the longitudinal direction L, the width direction W, or both. As will be discussed further below, the length t can be less than the length 1, the width w, or both. The anterior surface 124 can be substantially flat and can be referred to as a substantially flat anterior surface 124.

[0033] The subconjunctival implant 100 can include one or more fins 130. In some embodiments, the subconjunctival implant 100 includes a plurality of fins 130. The plurality of fins may be arrayed in the longitudinal direction L of the subconjunctival implant 100, such as arrayed on the dorsal surface 122 in the longitudinal direction L of the body portion 110. The fins 130 can extend from the dorsal surface 122. The fins 130 can be directly attached to the dorsal surface 122 to extend therefrom. In some embodiments, and as discussed further below, the fins 130 can be a unitary⁷ body with the body portion 110, such as by being co-molded with the body portion 110, such as discussed in the example below. In some embodiments, the subconjunctival implant 100 has two or more fins 130. In some embodiments, the subconjunctival implant 100 has three or more fins 130. In some embodiments, the subconjunctival implant 100 has from one to ten fins 130 such as, for example, from two to five fins 130 or three fins 130. The subconjunctival implant 100 shown in FIGS. 1 and 2 has three fins 130, a first fin 132, a second fin 134, and a third fin 136. Each of the fins 130 can be similarly shaped and the following discussion of the shape of the third fin 136 applies equally⁷ to the other fins 130, such as the first fin 132 and the second fin 134. [0034] The third fin 136 has a leading portion 140. The leading portion 140 can extend from the dorsal surface 122 of the body portion 1 10 to an apex 142. The leading portion 140 can be sloped and be referred to as a sloped leading portion. The leading portion 140 includes a leading surface 144. The leading surface 144 is a surface of the fin that extends from the dorsal surface 122 to the apex 142. The leading surface 144 can be rounded or tapered from the dorsal surface 122 to the apex 142. The leading portion 140 also includes a leading edge, which is referred to herein as a fin leading edge 146. The fin leading edge 146 can be the edge of the third fin 136 where the leading surface 144 connects with the dorsal surface 122. The fin leading edge 146 can be rectilinear, in other embodiments, such as the embodiment depicted in FIGS. 1 and 2, the fin leading edge 146 can be curvilinear. The fin leading edge 146 can be rounded or tapered. When the fin leading edge 146 is rounded, the fin leading edge 146 can be semi-circular or arcuate having a curvature.

[0035] The third fin 136 also has a trailing surface 152. The trailing surface 152 can be transverse to the dorsal surface 122 extending from the dorsal surface 122 to the apex 142. In some embodiments, the trailing surface 152 is perpendicular to the dorsal surface 122. The trailing surface 152 can also include a trailing edge, which is referred to herein as a fin trailing edge 154. The fin trailing edge 154 can be the edge of the third fin 136 where the trailing surface 152 connects with the dorsal surface 122. The trailing surface 152 can be substantially flat, and the fin trailing edge 154 can be rectilinear or curvilinear extending in the width direction W of the subconjunctival implant 100. In some embodiments, the third fin 136 has a height profile above the dorsal surface 122, and the height profile is asymmetric from the fin leading edge 146 to the fin trailing edge 154.

[0036] In some embodiments, the third fin 136 extends laterally from the first side 116 to the second side 118. In some embodiments, the w idth w of the third fin 136 is the same as the width of the body portion 110. The third fin 136 also has a height h. The height h of the third fin 136 can be a distance in the thickness direction from the dorsal surface 122 to the apex 142. The apex 142 can be the portion of the third fin 136 that is the farthest from the dorsal surface 122. [0037] The subconjunctival implant 100 can have a variety of dimensions and shapes. For example, the length 1 of the subconjunctival implant 100 and, more specifically, the body portion 110 can range from 10 mm to 30 mm. In some embodiments, the width w of the subconjunctival implant 100 and, more specifically, the body portion 110 can range from 1 mm to 5 mm. In some embodiments, the thickness t of the body portion 110 can be from 0.5 mm to 4 mm. In some embodiments, the height h of the fins 130 can range from 0. 1 mm to 2 mm. In some embodiments, the length 1 of the subconjunctival implant 100 and, more specifically , the body portion 110 is greater than the width w of the subconjunctival implant 100 and, more specifically, the body portion 110. In some embodiments, the width w of the subconjunctival implant 100 and, more specifically, the body portion 110 is greater than the thickness t of the body portion 110.

[0038] In some embodiments, such as that depicted in FIGS. 1 and 2, the fins 130 can have different sizes. For example, the fins 130 depicted in FIGS. 1 and 2 progressively increase in height h from the leading edge 112 to the trailing edge 114. For example, the second fin 134 has a height h that is greater than the height h of the first fin 132, and the third fin 136 has a height h that is greater than the height h of the second fin 134. The first fin 132 is close to the leading edge 112 than either of the second fin 134 or the third fin 136. The third fin 136 is closer to the trailing edge 114 than either of the first fin 132 or the second fin 134. The second fin 134 is located between he first fin 132 and the third fin 136.

[0039] The first fin 132 can be contiguous with the leading edge 112 of the subconjunctival implant 100 and, more specifically, the body portion 1 10. For example, the leading edge 1 12 of the subconjunctival implant may be rounded or tapered and the leading surface 144, more specifically the fin leading edge 146, of the first fin 132 can smoothly join the rounded or tapered leading edge 112. The fins 130 are spaced apart from each other. The fins 130 can be spaced apart from each other by a distance greater than the height h of one or more of the fins 130. In some embodiments, the fins 130 are spaced apart from each other by a distance greater than the height of the tallest fin (e.g., the third fin 136 in FIGS. 1 and 2). The last fin (e.g., the third fin 136 in FIGS. 1 and 2) can be spaced forward (towards the leading edge 112) and away from the trailing edge 114. The third fin 136 is thus spaced apart from the trailing edge 114 and is not contiguous with the trailing edge 114. The third fin 136 can be spaced forward from the trailing edge 114 by a distance similar to that discussed above for the spacing between fins 130.

[0040] The subconjunctival implant 100 can be made from a biocompatible poly mer and a medication. The biocompatible polymer may be any polymer suitable for implantation into a subconjunctival space of an eye. For example, the biocompatible polymer include silicone, poly(ethylene glycol), polypropylene glycol), poly(lactic-co-glycolic acid), poly(ethylene- vinyl acetate), poly(caprolactone), poly(lactic acid), poly(glycolic acid), copolymers thereof, or combinations thereof. In some embodiments, the biocompatible polymer is biodegradable. For example, the biodegradable polymer may be poly(lactic-co-glycolic acid), poly(ethylene- vinyl acetate), poly (caprolactone), poly(lactic acid), poly(glycolic acid), copolymers thereof, or combinations thereof. In some embodiments, the biocompatible is crosslinked. In some embodiments, the biocompatible is an elastomer.

[0041] The medication may be dispersed throughout the biocompatible polymer and/or located on the subconjunctival implant 100 as a surface coating. The medication may be any medication suitable for treating an eye infection. For example, the medication may be an antiviral agent, an antibiotic, and/or an antifungal. In some embodiments, the medication is an antibiotic. In some embodiments, the antibiotic comprises ofloxacin. In some embodiments, the medication consists essentially of ofloxacin. In some embodiments, the medication consists of ofloxacin. In some embodiments, the medication is an antifungal. In some embodiments, the antifungal comprises voriconazole. In some embodiments, the medication consists essentially of voriconazole. In some embodiments, the medication consists of voriconazole. In some embodiments, the medication is an antiviral agent. In some embodiments, the antiviral agent comprises at least one active agent chosen from foscamet, cidofovir, and ganciclovir. In some embodiments, the antiviral agent comprises ganciclovir. In some embodiments, the medication consists essentially of ganciclovir. In some embodiments, the medication consists of ganciclovir.

[0042] In addition to the drug releasing properties of the subconjunctival implant 100, the subconjunctival implant 100 has additional beneficial properties. First, the use of a tapered or rounded leading edge 112 facilitates placement of the implant by removing encumbrances associated with other shapes. At the same time, having a more squared trailing edge 114 helps maintain positioning of the implant within the eye, minimizing the tendency for the subconjunctival implant 100 to slide out of the subconjunctival space during placement. The shape of the fins 130, particularly by being sloped from the fin leading edge 146 and higher toward the fin trailing edge 154, both allow for easier insertion and further minimizes sliding of the subconjunctival implant 100 out of the subconjunctival space during placement. The fins 130 can be visually detected after implantation as bumps on the surface of the conjunctiva. This allows for ready determination that the subconjunctival implant 100 is still properly positioned after insertion. Additionally, the fins 130 increase the surface area of the subconjunctival implant 100, maximizing potential for release of active drug into the surrounding tissue.

[0043] FIG. 3 is a flow chart of a method of treating an eye infection in a subject. The subconjunctival implant 100 can be used to treat an eye infection in a subject. The subject may be any human or non-human animal. In some embodiments, the subject is a human. In some embodiments, the subject is a domestic animal. In some embodiments, the subject is a cat.

[0044] The method for treating an eye infection can include forming an opening in the subjects conjunctiva in step S310. The opening in the subject's conjunctiva may be formed using various means. In some embodiments, the opening in the subject's conjunctiva is formed using an implanting device including the subconjunctival implant. In some embodiments, the opening in the subject's conjunctiva is formed using a scalpel blade or scissors.

[0045] In step S320, the subconjunctival implant 100 is implanted through the opening in the subject's conjunctiva and into a subconjunctival space of the subject’s eye. More specifically, the leading edge 112 of the subconjunctival implant 100 can be inserted through the opening first. The subconjunctival implant 100 can be positioned with the anterior surface 124 facing the subject’s eye. As noted above, the anterior surface 124 is a substantially flat (a substantially flat anterior surface) that is about as flat as the surface of the subject's eye. The subconjunctival implant 100 can be positioned with the dorsal surface 122 and the fins 130 extending away from the subject’s eye.

[0046] In step S330, the method includes closing the opening in the subject's conjunctiva. The opening in the subject's conjunctiva may be closed using various means. In some embodiments, the opening in the subject's conjunctiva is closed with at least one stich, the opening in the subject's conjunctiva is closed with an adhesive, or both.

[0047] In step S340, the subconjunctival implant 100 is used to treat the eye infection. The subconjunctival implant 100 may reside in the subconjunctival space for various treatment durations. In some embodiments, the treatment duration ranges from 1 day to 2 years. In some embodiments, the treatment duration ranges from 1 week to 2 years. In some embodiments, the treatment duration ranges from 1 month to 1 year. In some embodiments, the treatment duration ranges from 1 month to 6 months.

[0048] The subconjunctival implant 100 may continuously release a therapeutically effective amount of the medication into the subconjunctival space of the subject's eye for various durations. In some embodiments, the subconjunctival implant 100 may continuously release a therapeutically effective amount of the medication into the subconjunctival space of the subject’s eye for a duration ranging from 1 day to 2 years. In some embodiments, the subconjunctival implant 100 may continuously release a therapeutically effective amount of the medication into the subconjunctival space of the subject’s eye for a duration ranging from 1 week to 2 years. In some embodiments, the subconjunctival implant 100 may continuously release a therapeutically effective amount of the medication into the subconjunctival space of the subject’s eye for a duration ranging from 1 week to 1 year. In some embodiments, subconjunctival implant may continuously release a therapeutically effective amount of the medication into the subconjunctival space of the subject’s eye for a duration ranging from 1 week to 6 months.

[0049] The subconjunctival implant 100 may be used to treat various eye infections such as viral infections, bacterial infections, and/or fungal infections. In some embodiments, the eye infection is a viral infection. In some embodiments, the eye infection is at least one condition chosen from herpes simplex virus type 1, herpes simplex virus type 2, varicella zoster virus, and feline herpes virus.

EXAMPLES

[0050] The following examples are provided for illustrative purposes only and are not intended to limit the scope of the disclosure. [0051] FIGS. 4 and 5 show an example subconjunctival implant, such as the subconjunctival implant 100 discussed above. The implants were designed specifically to fit into the superior or inferior subconjunctival space of the human and feline eye.

[0052] The example subconjunctival implant measures approximately 3 mm (width) by 16 mm (length) by 2 mm (height). Each subconjunctival implant weighs approximately 54 mg total. The shape of the body portion 110 was designed, as discussed above, to ensure it could be unidirectionally inserted into the subconjunctival space and then left in-situ without unwanted movement following placement, such as through the use of the three rounded fins 130.

[0053] The base material of the implant is manufactured by NuSil of Carpinteria, CA. A NuSil pourable clear low viscosity' silicone elastomer (MED-6233) was used for the creation of these implants. This is a 50 ty pe A durometer silicone, with a viscosity of 73,500 cP and is suitable for long-term implantation. The silicone elastomer is directly mixed with the powdered antiviral agent then poured into molds.

[0054] The implants contain 30% w/w ganciclovir, a potent antiviral drug. The active drug used for the creation of the implants is powdered USP grade or similar (suitable for medical use) (store. usp.org/product/1288306). Each implant contains approximately 16 mg of ganciclovir. Ganciclovir has been demonstrated to be highly effective and well tolerated for therapeutic use against various viruses implicated in ocular surface disease in both humans and cats such as herpes simplex virus type 1 and 2 (HSV-1/2), Varicella zoster virus (Shingles), and Feline herpes virus (FHV-1).

[0055] The subconjunctival implants were prepared according to the following methods. Supplies used to prepare the example subconjunctival implant include: USP Grade Ganciclovir powder; silicone, specifically, Nusil MED-6233 50 ml SXS 2 part liquid silicone elastomer; and an implant mold (such as on produced by 3D printing. The equipment used included a vacuum pump, such as Robinair 15800 VacuMaster Economy Vacuum Pump - 2- Stage, 8 CFM, CHROME, Chamber - BACOENG 1.5 Gallon Stainless Steel Vacuum Chamber Silicone Kit for Degassing Resins. Silicone and Epoxies; a gravity convection oven (VWR), laboratory scale capable of mg units, a caulking gun; and a Nusil Device to fit silicone tube to caulking gun.

[0056] The silicone and the Ganciclovir were mixed. The Ganciclovir was stored in a freezer and, prior to mixing, the Ganciclovir was allowed to warm up at room temperature for 2-5 min. The amount of ganciclovir or other drug needed was weighted out. The system was set up to deliver the silicone such as by placing the Nusil MED-6233 50 ml SXS 2-part liquid silicone elastomer in a container of a caulking gun. Using the caulking gun with a NuSil static mixing tip, the amount of silicone needed is slowly added to the drug. The drug is then thoroughly mixed into the silicone to form a silicone and drug mixture. The amounts used to fill one mode in this example are shown in Table 1, below.

Table 1: Example of amounts needed to fill one mold

[0057] Once the drug and silicone are thoroughly mixed, the silicone and drug mixture are degassed. The silicone and drug mixture may be contained in a container, such as al 00 ml tri pour beaker, and this container is placed into a chamber of the vacuum pump. The camber is prepared and a vacuum is drawn, reaching close to total vacuum for less then 5 minutes at a time. The chamber is appropriately degassed when there are either no more bubbles in the container or the gauge has not changed. Then the vacuum is released and the container removed.

[0058] A brief protocol using the operating instructions above to remove the gas bubbles from the silicone follows: 1. Mix silicone and drugs in tri pour cup; 2. Degas #1; 3. Remove the cup from the chamber; 4. Using the spatula gently scrape down the silicone form the sides of the cup trying to create as few bubbles as possible; 5. Degas #2; 6. Remove the cup from the chamber; 7. Using the spatula gently scrape down the silicone form the sides of the cup trying to create as few bubbles as possible; 8. Degas #3; 9. Remove the cup from the chamber and do not mix.

[0059] After the silicone and drug mixture is degassed, the subconjunctival implant is prepared by filling a mold having the shape of the subconjunctival implant discussed above. An example mold used to produce these examples is shown in FIGS. 6A and 6B. FIG. 6A is a side view of the mold, and FIG. 6B is a top view of the mold. The mold shown in FIGS. 6 A and 6B is 134 mm x 63 mm x 4 mm and can be a polypropylene mold. The mold may be formed by a 3D printing process suitable for the material of the mold. Using an appropriate tool, such as spatula, the mold was filled such as by gently scooping a small amount of the silicone to place in each implant space. The spatula was used to scrape the extra off the top to ensure the mold isn’t overfilled, and the extra silicone was returned to the cup. Once the mold is filled, the silicon and drug mixture in the mold was degassed again, following the steps to degas the implants in the mold. The spatula was used to scrape the silicone off the edges and back into the mold after a degassing step and the degassing is repeated as necessary.

[0060] After filling the mold, the subconjunctival implants are cured using and oven. The oven was preheated to 80°C. The implant mold was placed into a 80°C oven for 45 minutes. After 45 minutes, the implant mold was removed from the oven. The implant mold was allowed to cool to room temperature on the counter ~5 min. The temperature of the oven was increased to 150°C. The implants were removed from the mold, using, for example a forceps and/or a needle remove and by scrape around the edge of each individual implant and slowly and gently pull the implants of the mold. Once removed from the mold, the subconjunctival implants are placed on a sheet of foil. Once the oven reaches 150°C, the subconjunctival implants (removed from the mold) were placed into the oven for 45 minutes. After 45 minutes the subconjunctival implants are removed from the oven and allowed to cool to room temperature on the counter ~5 min. The subconjunctival implants were then placed in a sterile beaker or immediately packaged for sterilization.

[0061] After curing, the subconjunctival implants were sterilized. Sterilization was performed using gamma sterilization. The subconjunctival implants were packaged for gamma sterilization by placing one subconjunctival implant inside an instant sealing sterilization pouch and sealing the pouch. The pouches can then be sterilized using gamma radiation sterilization (24.3 - 29.7 kGy). The sterilized (or unsterilized) subconjunctival implants containing the drug were stored in the refrigerator at 4°C.

[0062] The subconjunctival implant is intended for insertion into the superior or inferior bulbar subconjunctival space of a subject. The bulbar conjunctiva is the salmon-pink thin membrane which extends from the limbus (scleral-comeal junction) to the conjunctival fornix. The image sequence shown in FIGS. 7A to 7F outlines the intended placement procedure, using an ex-vivo porcine globe and lids. FIG. 7A shows the globe and eyelids prior to implant placement. As shown in FIG. 7B, a 4 mm snip incision is made in the dorsal bulbar conjunctiva with scissors. As shown in FIG. 7C, the bulbar conjunctiva is undermined with blunt dissection using tenotomy scissors, for a length of approximately 20 mm. As shown in FIG. 7D, the implant is introduced into the subconjunctival space using forceps, in the manner discussed above. In FIG. 7E, the conjunctival hole is closed with appropriate diameter suture material in a cruciate pattern. FIG. 7F shows the appearance of the globe and eyelids following the implant placement.

[0063] The tolerability of the implants was assessed using 12 normal New Zealand White Rabbits (NZWR: 2.8-3kg, 6 male, 6 female). The animals received a novel implant in the left eye (OS) (TREATMENT) and a surgical sham procedure (SHAM) in the right eye (OD) after being confirmed to have normal ocular examination findings. The surgical procedure was performed OS as outlined above (‘intended use of the technology’) using 8-0 polyglactin 910 suture for conjunctival wound closure. The sham procedure OD was identical (with no implant placed). Animals were assessed at multiple timepoints using ocular scoring over a 115 day period to determine tolerability⁷ of the implant. Ocular scoring scheme was performed by an experienced board-certified veterinary⁷ ophthalmologist (ACL) using slit lamp biomicroscopy, rebound tonometry, indirect fundoscopy and fluorescein staining.

[0064] To detect significant differences between the left and right eyes at each time point, a mixed ANOVA (fixed effects = eye and timepoint, random effects = animal) was utilized. FIG. 8 depicts Line graph showing the clinical scores in each eye at each examination timepoint for the SHAM eye (right eye (OD)) and TREATMENT eye (left eye (OS)). Note that there are no significant differences (p>0.05) between the OS and OD at any time point during the study.

[0065] Ocular clinical scores were similar between eyes receiving an implant (OS) and eyes receiving a sham procedure (OD) with no significant differences between groups (p>0.05). Therefore, the implant was found to be well tolerated in this animal model over a 115-day period. All lesions receiving a clinical score were attributed as being secondary⁷ to the surgical procedure of placing the implants or sham procedure, which subsequently fully resolved.

[0066] The acute infection efficacy was evaluated as follows. Twelve NZWR (2.8-3kg, 6 male. 6 female) received the implant (TREATMENT, AL14-AL25) and 12 NZWR (2.8-3kg, 6 male, 6 female) received a surgical sham procedure (SHAM, AL26-AL37) 7 days prior to viral challenge. Ocular viral load was assessed prior to challenge and all animals were negative for HSV-1. All animals received a challenge dose of 2 X 105 plaque forming units (PFU) HSV-1 (Synl7+ strain) per eye following uniform comeal grid epithelial debridement. Ocular scores were recorded, and viral load was assessed (using qPCR specific to HSV-1 UL30 gene and copy number calculated using customized UL30 carrying plasmid) at 3, 7, 10, 15 and 23 days following viral challenge.

[0067] When animals reached defined humane endpoints, they were removed from the study population. In these 3 cases (AL23; 15 days post challenge, AL26; 14 days post challenge, AL27; 9 days post challenge), ocular scores and viral load assessment was performed at the time of removal from study.

[0068] Three animals in the SHAM group failed to develop ocular disease consistent with infection and were removed from the SHAM control group. In all cases, both eyes shed no or very little HSV-1 (Ct>34, copy number <3500) at all time points following infection and had low ocular disease scores (maximum anterior ocular disease score <4) at all time points following infection. Based on this, animals AL33, AL35 and AL36 were removed from the SHAM control group as they did not develop ocular disease and shedding consistent with successful infection.

[0069] All animals in the TREATMENT group retained the implant in both eyes for the duration of the acute infection study period with no significant complications. [0070] Statistical comparisons between treatment and sham group clinical scores at each time point and over the entire study duration were made using a mixed ANOVA (fixed effects = treatment, time, random effects = eye x animal) with outliers removed as necessary (AL24, OD, day 7 and 10). Differences between treatment and sham group viral shedding at each time point were analyzed using a one tailed t test. Differences between the treatment and sham group viral shedding over the entire study duration were made using one tailed Mann- Whitney test (with day 3 post challenge results excluded).

[0071] FIG. 9 depicts ocular clinical scores of TREATMENT group compared with SHAM group during acute HSV-1 ocular infection. Note that the ocular scores are significantly lower overall in the TREATMENT group (p = 0.0063).

[0072] FIG. 10 depicts Ocular clinical scores of TREATMENT group compared with SHAM group during acute HSV-1 ocular infection. Note that the ocular scores are significantly lower at each individual timepoint in the TREATMENT group from day 7 post challenge onwards. In FIG. 10, * is p<0.05, ** is p<0.01, and *** is p<0.001.

[0073] The results in FIGS. 9 and 10 confirm that the ocular implant led to significantly reduced ocular clinical signs in treated eyes at each timepoint and over the course of the entire study. Therefore, the ocular implant was effective in preventing and alleviating symptoms of HSV-1 ocular surface disease in this animal model.

[0074] FIG. 11 depicts ocular viral shedding of TREATMENT group compared with SHAM group during acute infection. Note that viral shedding was significantly lower overall in the TREATMENT group (p = 0.049). FIG. 12 depicts ocular viral shedding of TREATMENT group compared with SHAM group during acute infection. Note that the viral shedding was significantly lower on day 23 in the TREATMENT group (p=0.0354). The results in FIGS. 11 and 12 confirm that the ocular implant was associated with significantly reduced viral shedding in treated animals, both overall and at a specific timepoint (day 23).

[0075] As reactivation of viral ocular disease is common in humans with ocular HSV-1, procedures were designed to induce reactivation according to established protocols in an animal model. All animals used in this reactivation study had completed the acute infection study (above). Animals previously infected with HSV-1 were chosen for inclusion in the viral reactivation study only if all of the following were true: No active ocular disease immediately prior to reactivation procedures; A history of confirmed and resolved HSV-1 infection and shedding (by qPCR); and TREATMENT group: implant present in both eyes at time of reactivation procedures.

[0076] Based on this, 5 animals met the inclusion criteria in the TREATMENT group: AL14, AL15, AL17, AL21, AL25. The following 7 animals met the inclusion criteria in the SHAM group: AL28, AL29, AL30, AL31, AL32, AL34, AL37.

[0077] All animals in both groups received identical reactivation challenge procedures. This entailed injection of 200pL sterile water into the cornea stroma to induce lamellar fracture, 0.5mg dexamethasone SP (subconjunctival) in each eye, 0.4mg epinephrine subcutaneously and topical administration of ophthalmic dexamethasone 0.1%. This was followed by once daily administration of topical ophthalmic dexamethasone 0.1% for 3 days, once daily 0.4mg epinephrine administered subcutaneously for 2 days and once daily 4mg dexamethasone SP administered subcutaneously for 2 days. Ocular scores were recorded and viral load was assessed at 4, 7, 17, and 32 days following reactivation.

[0078] All animals with implants at the time of reactivation retained the implant in both eyes for the duration of the viral reactivation study period. Following harvest, the trigeminal ganglia (TG) was assessed for the presence of HSV-1 DNA using qPCR in each animal to confirm that they were latently infected with HSV-1.

[0079] Statistical comparisons between treatment and sham group clinical scores at each time point were made using a one tailed t test. Differences between treatment and sham group clinical scores over the entire study were detected using a mixed ANOVA (fixed effects = time and treatment, random effect = eye x animal). Differences between treatment and sham group viral shedding over the entire study duration were analyzed using a Mann- Whitney test. A chi-squared test was used to compare the number of animals in each group which shed HSV-1 following challenge procedures.

[0080] FIG. 13 depicts ocular clinical scores of TREATMENT group compared with SHAM group following ocular HSV-1 reactivation procedures. Note that the ocular scores are significantly lower on days 7, 17 and 32 post reactivation in the TREATMENT group. In FIG. 13, * is p<0.05. FIG. 14 depicts ocular clinical scores of TREATMENT group compared with SHAM group following ocular HSV-1 reactivation procedures. Note that the ocular scores are significantly lower overall in the TREATMENT group (p = 0.0327). The trigeminal ganglia (TG) of all animals in both groups was assessed post-mortem with qPCR specific for HSV-1. In all animals (100%) in both groups, HSV-1 DNA was detected in the TG, indicating that they were latently infected. FIGS. 13 and 14 confirm that the ocular implant led to significantly reduced ocular clinical signs in treated eyes from 7 days onwards following reactivation procedures and over the course of the entire study. Therefore, the ocular implant was effective in preventing and alleviating symptoms of HSV-1 ocular surface disease following reactivation procedures in this animal model.

[0081] FIG. 15 depicts Ocular viral shedding of TREATMENT group compared with SHAM group following reactivation procedures. Note that viral shedding was significantly lower overall in the TREATMENT group (p = 0.0066). This result confirms that the ocular implant led to significantly reduced viral shedding overall in treated animals following reactivation procedures. No animals in the treatment group shed virus at any time point following reactivation procedures. This effect was also found to be statistically significant (p=0.0025). [0082] Drug elution from the implant was assessed both in vitro over a 6-month period. Whole implants were assessed by University' of Florida Translational Drug Development Core (UFTDDF) to assess in-vitro elution characteristics over time, using a simulated tear film substitute.

[0083] Simulated Tear Fluid (STF) consisting of 0.67 % sodium chloride, 0.20 % sodium bicarbonate, and 0.008 % calcium chloride dihydrate in water was made and mixed thoroughly. (Kesarla, et al., 2016). Five X 20 mL scintillation vials were filled with 10 mL of STF. The tubes were placed in an Incubator at 37°C and allowed to equilibrate before one implant was placed in each vial. For time points 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks, 100 pL of sample fluid was drawn after a brief vortex mixing. 100 pL of STF was replaced into each vial after drawing. The sample was diluted with methanol and buffered water at pH 6.8. Internal standard was added, and the solution was mixed and filtered. The samples were analyzed using UPLC-MS/MS method compared to a standard curve. Calibration standards were made from a stock of ganciclovir powder and diluted to a concentration range of 5-500 ng/rnL. Two sets of quality control standards were made in the same way at concentrations of 5, 15, 200, 400 ng/rnL.

[0084] As depicted in FIG. 16, the results of the 6-month drug release assessment showed that drug levels rose until about 8 weeks after study initiation. After this point, drug levels remained stable until study conclusion (figure 15). Approximately 10% of the total mass of ganciclovir was released from the implant during this timeframe. [0085] In-vitro testing to assess the ability of the implants to inhibit replication of herpes virus type 1 (McKrae strain) was performed. The McKrae strain is a notably virulent isolate and is associated with high mortality in animal models (which is why the Synl7+ strain was used in-vivo). The implants led to marked inhibition of HSV-1 in-vitro. Table 2 depicts how the implants (placed in the cell media) led to 100% viral replication inhibition over a 24-hour period. The cellular viability (Vero cells) was high (95%).

Table 2.

[0086] Feline herpesvirus type 1 (FHV-1) is an alphaherpesvirus (like herpes simplex virus) with a narrow host range, typically only affecting domestic and wild felines. Feline herpesvirus in a common cause of ocular disease in domestic cats, and instituting effective treatment protocols is frequently complicated by poor patient compliance. Clinical trials were initiated to assess the use of the implant as a treatment for FHV-1. Similar to the results presented above for assessment in-vivo using host clinical score and viral quantification, preliminary results indicate that the implant is efficacious for treatment of ocular feline herpesvirus in domestic cats.

[0087] A young adult female spayed domestic short hair cat was presented for assessment of persistent unilateral ocular discharge and blepharospasm (squinting). The cat was found to have unilateral (right eye, OD) comeal ulceration with associated comeal neovascularization and comeal stromal haze. A screening test for FHV-1 confirmed the presence of significant quantities of FHV-1 viral DNA on the OD ocular surface. Following obtaining informed consent from the owner of the animal, plans were set to implant the device in the OD subconjunctival space.

[0088] The following week, the cat was routinely anesthetized and the OD surgically prepared. Prior to anesthesia, the OD conjunctiva was swabbed to obtain a sample for FHV-1 viral DNA quantification. The implant was placed in the OD subconjunctival space as outlined above. The cat was brought back for recheck appointments 9 days and 29 days following the implant procedure for reassessment, which included clinical observation and conjunctival swabs of the OD for FHV-1 viral DNA quantification.

[0089] The quantity of viral DNA on the OD ocular surface decreased from the time of implantation, becoming undetectable by 29 days after implantation (see table below). The persistent comeal ulceration noted prior to implant placement had resolved by 9 days following the procedure. By 29 days after implantation, the cat’s ocular clinical signs had significantly improved and the implant was noted to be located in the expected position. The own er of the animal noted that the implant appeared to be well tolerated.

[0090] FIG. 18 depicts an analytical method for ganciclovir detection. Table 3 provides Results of FHV-1 DNA quantification following implant in a FHV-1 positive cat with ocular disease. Note that positive ddCt values indicate decreasing levels of FHV-1 DNA.

Table 3. [0091] The novel implants were well tolerated over a 16-week period in an established animal model for ocular tolerability in humans. The implants were efficacious against herpes simplex virus in cell culture-based tests. The implants were effective in reducing both viral shedding and ocular disease during acute infection with herpes simplex virus in an established animal model for herpes simplex keratitis in humans. The implants were effective in preventing herpes simplex virus reactivation (both shedding and ocular disease) in an established animal model for herpes simplex keratitis in humans. Drug was steadily released for approximately 8 weeks in a laboratory setting, with steady levels of drug thereafter up until the 6-month timepoint.

[0092] The novel implants were well tolerated over 115 days in an established NZWR model. No significant differences for ocular clinical scores (p>0.05) were found between eyes containing an implant and sham procedure eyes. The implants were efficacious in-vitro against herpes simplex virus. 100% reduction in viral grow th 24 hours following infection with HSV-1 (McKrae strain) was observed, with maintenance of a high degree of cellular viability (95%). The implants led to significant reduction in both viral shedding (p<0.05) and ocular disease (p<0.05) during acute infection with herpes simplex virus in a NZWR model for HSV-1 keratitis in humans. The implants led to significant reduction of herpes simplex virus reactivation (both shedding (p<0.01) and ocular disease (p<0.05)) in a NZWR model for HSV-1 keratitis in humans. No treated animals developed disease recrudescence following challenge procedures, which was statistically significant (p<0.01). Drug was steadily released for approximately 8 weeks in-vitro, with steady levels of drug thereafter up until the 6-month timepoint. Approximately 10% of the total mass of ganciclovir w as released from the implant during this timeframe. [0093] Further aspects of the present disclosure are provided by the subject matter of the following clauses.

[0094] A subconjunctival implant includes an elongated body portion and a fin. At least one of the elongated body portion or the fin comprises a biocompatible polymer and a medication. The elongated body portion includes a leading edge and a trailing edge opposite the leading edge. The elongated body portion includes a dorsal surface and an anterior surface. The fin extends from the dorsal surface. The fin has a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface.

[0095] The subconjunctival implant of the preceding clause, wherein the medication is dispersed within the biocompatible polymer.

[0096] The subconjunctival implant of any preceding clause, wherein the medication is coated on a surface of the biocompatible polymer.

[0097] The subconjunctival implant of any preceding clause, wherein the trailing surface is perpendicular to the dorsal surface.

[0098] The subconjunctival implant of any preceding clause, wherein the elongated body portion includes a first side and a second side, and the fin extends laterally from the first side to the second side.

[0099] The subconjunctival implant of any preceding clause, wherein the sloped leading surface of the fin is contiguous with the leading edge.

[0100] The subconjunctival implant of any preceding clause, wherein the sloped leading surface of the fin has a leading edge, the leading edge being arcuate at the dorsal surface. [0101] The subconjunctival implant of any preceding clause, wherein the sloped leading surface of the fin is rounded. [0102] The subconjunctival implant of any preceding clause, wherein the biocompatible polymer is biodegradable.

[0103] The subconjunctival implant of any preceding clause, wherein the biocompatible polymer comprises silicone.

[0104] The subconjunctival implant of any preceding clause, wherein the subconjunctival implant comprises crosslinked polymer and the medication is dispersed within the crosslinked polymer.

[0105] The subconjunctival implant of any preceding clause, wherein the medication comprises an antiviral agent.

[0106] The subconjunctival implant of any preceding clause, wherein the medication comprises ganciclovir.

[0107] The subconjunctival implant of any preceding clause, wherein the leading edge is rounded.

[0108] The subconjunctival implant of any preceding clause, wherein the leading edge is rounded with a radius of curvature, and the trailing edge is rounded is rounded with a radius of curvature, the radius of curvature of the trailing edge being greater than the radius of curvature of the leading edge.

[0109] The subconjunctival implant of any preceding clause, wherein the fin is one fin of a plurality of fins, each fin extending from the dorsal surface and each fin having a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface.

[0110] The subconjunctival implant of the preceding clause, wherein the plurality of fins includes three or more fins. [0111] The subconjunctival implant of any preceding clause, wherein the plurality of fins is from 3 to 10 fins.

[0112] The subconjunctival implant of any preceding clause, wherein each fin is spaced apart from each other.

[0113] The subconjunctival implant of any preceding clause, wherein the plurality of fins is arrayed on the dorsal surface in a longitudinal direction of the elongated body portion.

[0114] The subconjunctival implant of any preceding clause, wherein each fin has a height, and the height of each fin of the plurality' of fins progressively increases from the leading edge to the trailing edge.

[0115] The subconjunctival implant of any preceding clause, wherein the body portion has a length from the leading edge to the trailing edge ranging from 10 mm to 30 mm.

[0116] The subconjunctival implant of any preceding clause, wherein the body portion has a width from the first side to the second side ranging from 1 mm to 5 mm.

[0117] The subconjunctival implant of any preceding clause, wherein the body portion has thickness from the anterior surface to the dorsal surface ranging from 0.5 mm to 4 mm.

[0118] The subconjunctival implant of any preceding clause, wherein the length is greater than the width.

[0119] The subconjunctival implant of any preceding clause, wherein the width is greater than the thickness.

[0120] The subconjunctival implant of any preceding clause, wherein the fin has a height ranging from 0. 1 mm to 2 mm.

[0121] A method for treating an eye infection in an eye of a subject includes forming an opening in a conjunctiva of the subject, inserting a subconjunctival implant of any one of the preceding clauses through the opening in the conjunctiva and into a subconjunctival space of the eye, and closing the opening in the conjunctiva.

[0122] The method of the preceding clause, wherein the opening in the conjunctiva is formed using an implanting device comprising the subconjunctival implant.

[0123] The method of any preceding clause, wherein the opening in the conjunctiva is formed using a scalpel or scissors.

[0124] The method of any preceding clause, wherein the opening in the conjunctiva is closed with at least one stich, the opening in the conjunctiva is closed with an adhesive, or both.

[0125] The method of any preceding clause, wherein the subconjunctival implant continuously releases a therapeutically effective amount of the medication into the subconjunctival space of the eye for a duration ranging from 1 week to 6 months.

[0126] The method of any preceding clause, wherein the eye infection is at least one condition chosen from herpes simplex virus type 1, herpes simplex virus type 2, varicella zoster virus, and feline herpes virus.

[0127] The method of any preceding clause, wherein the subconjunctival implant is positioned with the anterior surface facing the eye.

[0128] The method of any preceding clause, wherein the subconjunctival implant is positioned with the dorsal surface and the fin extending away from the eye.

[0129] The method of any preceding clause, wherein inserting the subconjunctival implant through the opening includes inserting the leading edge of the subconjunctival implant first through the opening.

[0130] Although this invention has been described with respect to certain specific exemplary embodiments, many additional modifications and variations will be apparent to those skilled in the art in light of this disclosure. It is, therefore, to be understood that this invention may be practiced otherwise than as specifically described. Thus, the exemplary embodiments of the invention should be considered in all respects to be illustrative and not restrictive, and the scope of the invention to be determined by any claims supportable by this application and the equivalents thereof, rather than by the foregoing description.

Claims

What is claimed is:

1. A subconjunctival implant comprising: an elongated body portion including a leading edge and a trailing edge opposite the leading edge, the elongated body portion further including a dorsal surface and an anterior surface; and a fin extending from the dorsal surface and having a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface, wherein at least one of the elongated body portion or the fin comprises a biocompatible polymer and a medication.

2. The subconjunctival implant according to claim 1, wherein the medication is dispersed within the biocompatible polymer.

3. The subconjunctival implant according to claim 1, wherein the medication is coated on a surface of the biocompatible polymer.

4. The subconjunctival implant according to claim 1, wherein the trailing surface is perpendicular to the dorsal surface.

5. The subconjunctival implant according to claim 1, wherein the elongated body portion includes a first side and a second side, and the fin extends laterally from the first side to the second side.

6. The subconjunctival implant according to claim 1, wherein the sloped leading surface of the fin is contiguous with the leading edge.

7. The subconjunctival implant according to claim 1, wherein the sloped leading surface of the fin has a leading edge, the leading edge being arcuate at the dorsal surface.

8. The subconjunctival implant according to claim 1, wherein the sloped leading surface of the fin is rounded.

9. The subconjunctival implant according to claim 1, wherein the biocompatible polymer is biodegradable.

10. The subconjunctival implant according to claim 1, wherein the biocompatible polymer comprises silicone.

11. The subconjunctival implant according to claim 1, wherein the subconjunctival implant comprises crosslinked polymer and the medication is dispersed within the crosslinked polymer.

12. The subconjunctival implant according to claim 1, wherein the medication comprises an antiviral agent.

13. The subconjunctival implant according to claim 1, wherein the medication comprises ganciclovir.

14. The subconjunctival implant according to claim 1, wherein the leading edge is rounded.

15. The subconjunctival implant according to claim 1, wherein the leading edge is rounded with a radius of curvature, and the trailing edge is rounded is rounded with a radius of curvature, the radius of curvature of the trailing edge being greater than the radius of curvature of the leading edge.

16. The subconjunctival implant according to claim 1, wherein the fin is one fin of a plurality of fins, each fin extending from the dorsal surface and each fin having a sloped leading surface extending from the dorsal surface to an apex of the fin and a trailing surface transverse to the dorsal surface and extending from the apex to the dorsal surface.

17. The subconjunctival implant according to claim 1 , wherein the plurality of fins includes three or more fins.

18. The subconjunctival implant according to claim 16, wherein the plurality of fins is from 3 to 10 fins.

19. The subconjunctival implant according to claim 16, wherein each fin is spaced apart from each other.

20. The subconjunctival implant according to claim 16, wherein the plurality of fins is arrayed on the dorsal surface in a longitudinal direction of the elongated body portion.

21. The subconjunctival implant according to claim 16, wherein each fin has a height, and the height of each fin of the plurality of fins progressively increases from the leading edge to the trailing edge.

22. A method for treating an eye infection in an eye of a subject, wherein the method comprises: forming an opening in a conjunctiva of the subject, inserting the subconjunctival implant according to claim 1 through the opening in the conjunctiva and into a subconjunctival space of the eye, and closing the opening in the conjunctiva.

23. The method according to claim 22, wherein the opening in the conjunctiva is formed using an implanting device comprising the subconjunctival implant.

24. The method according to claim 22, wherein the opening in the conjunctiva is formed using a scalpel or scissors.

25. The method according to claim 22, wherein the opening in the conjunctiva is closed with at least one stich, the opening in the conjunctiva is closed with an adhesive or both.

26. The method according to claim 22, wherein the subconjunctival implant continuously releases a therapeutically effective amount of the medication into the subconjunctival space of the eye for a duration ranging from 1 week to 6 months.

27. The method according to claim 22, wherein the eye infection is at least one condition chosen from herpes simplex virus type 1, herpes simplex virus type 2, varicella zoster virus, and feline herpes virus.

28. The method according to claim 22, wherein the subconjunctival implant is positioned with the anterior surface facing the eye.

29. The method according to claim 22, wherein the subconjunctival implant is positioned with the dorsal surface and the fin extending away from the eye.

30. The method according to claim 22, wherein inserting the subconjunctival implant through the opening includes inserting the leading edge of the subconjunctival implant first through the opening.