Methods and compositions for improving visual function in ocular diseases and disorders

Abstract

Provided herein is a method and composition for improving the visual function of the eye of an individual with eye disease.The method described herein generally comprises the method for improving the visual function (e.g., BCVA) of the eye of an individual with eye disease or disorder, comprising administering to the eye of the individual the peptide (e.g., the composition comprising the peptide) that comprises amino acid sequence HHIYLGAVNYIY or its variant sequence, or the pharma- ceutically acceptable salt of the peptide.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 221,329, filed July 13, 2021, and U.S. Provisional Patent Application No. 63 / 336,896, filed April 29, 2022, the entireties of which are incorporated by reference herein for all purposes. [Background technology]

[0002] Vision generally depends on maintaining the integrity of the eye's structures, and alterations in retinal homeostasis can lead to loss of vision and / or retinal disease or injury. Therapies for the treatment of ocular diseases and injuries are generally directed to preventing or reducing the deleterious changes associated with ocular dysfunction resulting from ocular diseases or injuries. Summary of the Invention

[0003] Targeting the halt or reduction of the adverse changes in visual function associated with eye disease may be useful in treatment programs, but recovery and improvement of visual function has been shown to be more favorable and is generally more difficult to achieve in patient outcomes.Herein, compositions and methods are described and provided that are useful for improving the visual function of the eye of individuals with eye disease and / or disorder.

[0004] Provided and described herein are methods of improving visual function (e.g., BCVA) of an eye of an individual with an eye disease or disorder, comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the eye disease or disorder comprises loss of visual function. In some embodiments, the eye disease or disorder comprises photoreceptor cell death or a symptom thereof (e.g., loss of visual function). In some embodiments, the eye disease or disorder comprises retinal pigment epithelial cell death or a symptom thereof (e.g., loss of visual function). In some embodiments, the eye disease or disorder comprises macular degeneration.

[0005] In some embodiments, the visual function comprises one or more measurements selected from the group consisting of best corrected visual acuity (e.g., readable number), visual field, contrast sensitivity, binocular function, low luminance visual acuity, low contrast visual acuity, color vision, perimetry, threshold sensitivity, reading speed, and light-dark adaptation. In some embodiments, the method comprises improving visual function without performing surgery.

[0006] In some embodiments, the method further comprises performing surgery (e.g., standard of care surgery) on the individual's eye. In some embodiments, the surgery is performed after administering the peptide or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the surgery comprises retinal reattachment surgery. In some embodiments, the surgery comprises vitreous surgery.

[0007] In some embodiments, improving visual function comprises improving visual function compared to a baseline visual function prior to administration of the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide.

[0008] Provided herein is a method for treating macular degeneration with geographic atrophy in the eye of an individual, comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharmaceutically acceptable salt of the peptide.Provided herein is a method for treating the loss of visual function (e.g., BCVA) in the eye of an individual with macular degeneration, comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharmaceutically acceptable salt of the peptide.

[0009] In some embodiments, treating comprises improving visual function. In some embodiments, improving visual function is compared to baseline visual function before administering the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the macular degeneration comprises age-related macular degeneration. In some embodiments, the macular degeneration comprises geographic atrophy.

[0010] In some embodiments, visual function comprises one or more measures selected from the group consisting of best corrected visual acuity (e.g., readable number), visual field, contrast sensitivity, binocular function, low luminance visual acuity, low contrast visual acuity, color vision, perimetry, threshold sensitivity, reading speed, and / or light-dark adaptation.

[0011] Provided and described herein is a method for treating retinal detachment in an individual's eye, comprising administering to the individual's eye a peptide (e.g., a composition comprising the peptide) comprising amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided and described herein is a method for treating loss of visual function in an individual's eye with retinal detachment, comprising administering to the individual's eye a peptide (e.g., a composition comprising the peptide) comprising amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0012] In some embodiments, treating comprises inhibiting the loss and / or loss of vision in the eye. In some embodiments, treating comprises improving visual function. In some embodiments, improving visual function is compared to baseline visual function before administering the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, treating comprises inhibiting photoreceptor cell death.

[0013] In some embodiments, the retinal detachment comprises a fully detached retina or a partially detached retina. In some embodiments, the retinal detachment comprises a fully detached retina. In some embodiments, the retinal detachment comprises a partially detached retina. In some embodiments, the surgery comprises retinal reattachment surgery. In some embodiments, the surgery comprises vitreous surgery.

[0014] In some embodiments, the individual's eye has a detached retina, and the retina has been detached for about (y) days or more (e.g., prior to administering a composition comprising the peptide), where (y) is at least 1. In some embodiments, (y) is 1 to 21. In some embodiments, (y) is 3 to 21. In some embodiments, (y) is 7 to 21.

[0015] In some embodiments, the surgery is performed about (z) days after administration of the composition comprising the peptide, where (z) is at least 1. In some embodiments, (z) is 1. In some embodiments, (z) is 1 to 3. In some embodiments, (z) is 1 to 7.

[0016] In some embodiments, the method comprises administering to the vitreous of the eye a peptide or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the variant sequence comprises an amino acid substitution. In some embodiments, the variant sequence comprises one amino acid substitution. In some embodiments, the variant sequence comprises two amino acid substitutions. In some embodiments, the variant sequence comprises three amino acid substitutions.

[0017] In some embodiments, the peptide further comprises a modification. In some embodiments, the modification comprises a modified amino acid. In some embodiments, the peptide comprises an amidated C-terminus. In some embodiments, the peptide has the structure of Formula I, or a pharma- ceutically acceptable salt thereof. In some embodiments, the peptide has the structure of Formula III, or a pharma- ceutically acceptable salt thereof.

[0018] In some embodiments, the pharma- ceutically acceptable salt is an acetate salt. In some embodiments, the pharma- ceutically acceptable salt is a polyacetate salt. In some embodiments, the polyacetate salt is a triacetate salt. In some embodiments, the pharma- ceutically acceptable salt is a hydrochloride salt.

[0019] In some embodiments, the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is formulated into a composition. In some embodiments, the composition further comprises one or more excipients. In some embodiments, the composition further comprises a surfactant. In some embodiments, the surfactant is a non-ionic surfactant. In some embodiments, the surfactant is a polysorbate, a polyethoxylated castor oil derivative, a polyethoxylated fatty acid, a polyethoxylated alcohol, a polyoxyethylene-polyoxypropylene block copolymer, or an oxyethylated tertiary octylphenol formaldehyde polymer. In some embodiments, the surfactant forms about 0.01% to about 20% by weight of the composition. In some embodiments, the surfactant forms about 0.05% to about 10% by weight of the composition. In some embodiments, the composition further comprises a tonicity modifier, a buffering agent, or a combination thereof. In some embodiments, the composition is buffered at a pH of 2.5 to 7.5.

[0020] In some embodiments, 5 micrograms (μg) to 10,000 μg of peptide or variant sequence thereof, or pharma- ceutically acceptable salt of peptide is administered. In some embodiments, at least 10 micrograms (μg), at least 25 μg, at least 50 μg, at least 100 μg, at least 150 μg, at least 200 μg, or at least 250 μg of peptide or variant sequence thereof, or pharma- ceutically acceptable salt of peptide is administered. In some embodiments, the peptide is present at a concentration of 0.1 milligrams per milliliter (mg / mL) to 10.0 mg / mL.

[0021] Further provided herein are methods for improving visual function in combination with surgery (e.g., retinal reattachment and / or vitreous surgery). For example, provided herein are methods and compositions for use in treating neural retinal detachment and / or inhibiting loss and / or loss of vision following neural retinal detachment. In some embodiments, the methods provided herein utilize administering a Fas inhibitor (e.g., a Fas inhibitor peptide) (e.g., to an individual's eye, e.g., to its vitreous) and performing surgery (e.g., retinal reattachment surgery). In certain embodiments, the Fas inhibitor is administered to an individual's eye (e.g., to its vitreous), e.g., an eye that has (or is suspected of having) a retina detached (e.g., partially or completely) (e.g., completely or partially detached). In some cases, the methods provided herein (including, e.g., administering a Fas inhibitor to an individual's eye) inhibit inflammation in an individual's eye, e.g., an eye that has a retina detached (e.g., completely or partially detached). As a further example, in certain cases, administering a Fas inhibitor to the eye (e.g., by suppressing ocular inflammation associated with neural retinal detachment and performing surgery (e.g., retinal reattachment surgery)) inhibits the loss of vision caused by and / or associated with neural retinal detachment (e.g., compared to surgery alone). In certain cases, the methods and compositions provided herein are useful for improving patient outcomes (e.g., inhibiting loss of vision) in patients with detached neural retina (e.g., compared to surgery alone).

[0022] Certain embodiments herein provide a method (e.g., a method of treating an ocular disorder) comprising administering a Fas inhibitor (e.g., a composition comprising the same) to the eye of an individual. Some embodiments herein provide a method (e.g., a method of treating an ocular disorder) comprising administering a Fas inhibitor (e.g., a composition comprising the same) to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Certain embodiments herein provide a method (e.g., a method of treating an ocular disorder) comprising administering a peptide (e.g., a composition comprising the same) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Further provided is a method comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of Formulas I to IX, or a pharma- ceutically acceptable salt thereof, to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Methods are provided that include administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of Formula I or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual. Methods are also provided that include administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of Formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0023] In some embodiments, provided herein are methods of treating retinal detachment in an eye of an individual, the methods comprising administering a Fas inhibitor (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof) to the eye of the individual, and (e.g., subsequently) performing surgery (e.g., standard of care surgery) on the eye of the individual (e.g., surgery to at least partially reattach the retina). In certain embodiments, the retinal detachment is a rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a macula-off rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a macula-on rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a tractional retinal detachment. In certain embodiments, the retinal detachment is an exudative detachment. In certain embodiments, the retinal detachment is due to retinal injury.

[0024] In some embodiments, the method is a method of treating loss and / or decline of vision. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing loss and / or decline of vision. In some embodiments, the method is a method of treating loss and / or decline of visual function. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing loss and / or decline of visual function.

[0025] In some embodiments, the method is a method of treating ocular photoreceptor cell loss. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing ocular photoreceptor cell loss. In some embodiments, the method is a method of treating ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the method is a method of inhibiting, reducing, and / or preventing ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the method is a method of treating an ocular disease, disorder, or condition. In some embodiments, the method is a method of inhibiting progression of an ocular disease, disorder, or condition, or a symptom associated therewith.

[0026] In some embodiments, the surgery includes vitreous surgery, scleral buckle, pneumatic retinopexy, laser surgery, or a combination thereof. In some embodiments, the surgery includes vitreous surgery. In certain embodiments, the vitreous surgery includes the use of silicone oil (e.g., replacing the vitreous with silicone oil). In certain embodiments, the vitreous surgery includes the use of a gas (e.g., replacing the vitreous with a gas). In some embodiments, the surgery includes a scleral buckle. In some embodiments, the surgery includes a pneumatic retinopexy. In some embodiments, the surgery includes a laser surgery. In some embodiments, the surgery includes one or more of vitreous surgery, scleral buckle, pneumatic retinopexy, and laser surgery, or a combination thereof.

[0027] In some embodiments, the individual has a detached neural retina. In certain embodiments, the neural retina is completely detached. In certain embodiments, the neural retina is partially detached. In certain embodiments, the neural retina is completely detached. In some embodiments, the degree of detachment is 0 to 1, greater than about 1, greater than about 2, greater than about 3, greater than about 4, greater than about 5, greater than about 6, greater than about 7, greater than about 8, greater than about 9, greater than about 10, greater than about 11, or greater than about 12 (on a scale ranging from 0 to 12 based on clock time). In some embodiments, the height of the detachment (measured from the central macula) is 0 to 1 millimeter, greater than about 1 millimeter, greater than about 2 millimeters, greater than about 3 millimeters, greater than about 4 millimeters, or greater than about 5 millimeters.

[0028] In some embodiments, the surgery is performed about (z) days after administration of the composition comprising the peptide, where (z) is at least 1. In certain embodiments, (z) is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or a number greater than 10. In some embodiments, the surgery is performed about (h) hours after administration of the composition comprising the peptide, where (h) is at least 1. In certain embodiments, (h) is 1, 2, 3, 4, 5, 6, 12, 18, 24, 30, or 36.

[0029] In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity (BCVA) of hand motion discrimination. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of index valve. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 100 (e.g., by Snellen chart, ETDRS, Tumbling C, Infant HOTV, etc.). In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 3 or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 2 logMAR or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 1 logMAR or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 0.5 logMAR or greater.

[0030] In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 200 or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 100 or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 70 or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 50 or greater.

[0031] In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 32 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 24 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 16 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 8 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 4 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of 2 minutes or more.

[0032] In some embodiments, the subject has a loss of central vision. In some embodiments, the individual's eye has a detached retina, and the retina has been detached for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1. In some embodiments, the individual's eye has a loss of central vision, and the loss of central vision has been present for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1. In certain embodiments, the individual's eye has retinal damage or symptoms thereof, and the retinal damage or symptoms thereof has been present for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1. In certain embodiments, (y) is 1 (e.g., about 1 day or more), 2, 3, 4, 5, 6, 7, 8, 14, 21, 28, or more than 28.

[0033] In some embodiments, the subject has a symptom associated with detached neural retina (e.g., loss or loss of visual function). In some embodiments, the eye of the individual has a symptom associated with detached neural retina (e.g., loss or loss of visual function), and the symptom associated with detached neural retina (e.g., loss or loss of visual function) has been present for about (s) or more days (e.g., before administering a composition comprising a Fas inhibitor or before performing surgery), where (s) is at least 1. In certain embodiments, (s) is 1 (e.g., about 1 day or more), 2, 3, 4, 5, 6, 7, 8, 14, 21, 28, or more than 28.

[0034] In some embodiments, the individual is 40 years of age or older. In some embodiments, the individual is about 50 years of age or older. In some embodiments, the individual is about 55 years of age or older. In some embodiments, the individual is about 60 years of age or older. In some embodiments, the individual is about 65 years of age or older. In some embodiments, the individual is 70 years of age or older.

[0035] In some embodiments, the eye of the individual comprises inflammation (eg, an increased amount of one or more biomarkers).

[0036] In some embodiments, the individual's eye has a cataract. In some embodiments, the individual's eye is likely to have a cataract. In some embodiments, the individual's eye is at risk for developing a cataract (e.g., by exhibiting one or more symptoms of a cataract, aging, experiencing trauma to the eye, etc.). In some embodiments, the individual's eye is likely to have a pseudophakic lens. In some embodiments, the individual has a pre-existing disease or disorder, including a non-ocular condition (e.g., diabetes).

[0037] In some embodiments, the composition is administered by intravitreal injection, intracameral injection, injection into the suprachoroidal space, injection into the subtenon's space, subconjunctival injection, retrobulbar injection, periocular injection, microneedle injection, subretinal injection, or subretinal injection.

[0038] In some embodiments, the variant sequence comprises an amino acid substitution. In some embodiments, the variant sequence comprises one amino acid substitution. In some embodiments, the variant sequence comprises two amino acid substitutions. In some embodiments, the variant sequence comprises three amino acid substitutions.

[0039] In some embodiments, the peptide further comprises a modification. In some embodiments, the peptide comprises a modified amino acid or a non-naturally occurring amino acid. In some embodiments, the peptide comprises an amidated C-terminus, wherein the peptide has the structure of Formula I, or a pharma- ceutically acceptable salt thereof.

[0040] In some embodiments, the composition comprises a pharma- ceutically acceptable salt of the peptide. In some embodiments, the pharma- ceutically acceptable salt is an acetate. In some embodiments, the pharma- ceutically acceptable salt is a polyacetate. In some embodiments, the polyacetate is a triacetate. In some embodiments, the pharma- ceutically acceptable salt is a hydrochloride.

[0041] In some embodiments, the composition further comprises one or more excipients. In some embodiments, the composition further comprises a surfactant. In some embodiments, the surfactant is a non-ionic surfactant.

[0042] In some embodiments, the surfactant is a polysorbate, a polyethoxylated castor oil derivative, a polyethoxylated fatty acid, a polyethoxylated alcohol, a polyoxyethylene-polyoxypropylene block copolymer, or an oxyethylated tertiary octylphenol formaldehyde polymer. In some embodiments, the surfactant is a polysorbate. In some embodiments, the surfactant is a polyethoxylated alcohol. In some embodiments, the surfactant is a polyoxyethylene-polyoxypropylene block copolymer. In some embodiments, the surfactant is an oxyethylated tertiary octylphenol formaldehyde polymer.

[0043] In some embodiments, the surfactant comprises polysorbate 20, poloxamer 407, tyloxapol, or cremophor. In some embodiments, the surfactant comprises polysorbate 20. In some embodiments, the surfactant comprises poloxamer 407. In some embodiments, the surfactant comprises tyloxapol. In some embodiments, the surfactant comprises cremophor. In some embodiments, the surfactant forms about 0.01% to about 20% by weight of the composition. In some embodiments, the surfactant forms about 0.05% to about 10% by weight of the composition. In some embodiments, the non-ionic surfactant is about 0.05% w / w of the composition to about 2% w / w of the composition. In some embodiments, the non-ionic surfactant is at least about 0.05% w / w of the composition.

[0044] In some embodiments, the composition further comprises a tonicity adjusting agent, a buffering agent, or a combination thereof (e.g., as described herein, including any of the recited ranges and / or values ​​within the recited ranges). In some embodiments, the composition is buffered at a pH of 2.5 to 7.5.

[0045] In some embodiments, the composition comprises 5 micrograms (μg) to 10,000 μg of peptide. In some embodiments, the composition comprises about 5 micrograms (μg) of peptide to about 300 μg of peptide. In some embodiments, the peptide is present in a concentration of 0.1 milligrams per milliliter (mg / mL) to 10.0 mg / mL.

[0046] Citation by reference

[0047] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief description of the drawings]

[0048] The novel features of the invention are set forth with particularity in the appended claims. To better understand the nature and advantages of the present invention, reference should be made to the following detailed description that sets forth illustrative embodiments in which the principles of the invention are utilized and the accompanying drawings. [Figure 1] Data are presented demonstrating improved visual outcomes in GA patients receiving Fas inhibitors. [Figure 2A] 2A-2B provide exemplary conversions of visual acuity measurements: Figure 2A shows a first exemplary conversion table of visual acuity measurements. [Figure 2B] 2A-2B provide exemplary conversions of visual acuity measurements: Figure 2B shows a second exemplary conversion table of visual acuity measurements. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0049] Described herein are compositions and methods useful for improving the visual function of the eye of an individual with ocular disease and / or disorder.In certain examples, the improvement of visual function is achieved by treating (e.g., inhibiting, reducing, and / or preventing) Fas-associated inflammation in the eye, thereby preventing, reducing, and / or inhibiting retinal degeneration.Retinal degeneration is a complex, multifactorial pathology in which cell death (e.g., cell apoptosis), glial cell activation, and inflammation in or around retinal tissue are linked to cell death in the retina (e.g., retinal pigment epithelium (RPE) cells and / or photoreceptors (PR)).Fas-mediated inflammation may directly or indirectly lead to retinal degeneration and may be associated with symptoms caused by retinal degeneration. Fas-mediated inflammatory signaling pathways are generally initiated by the interaction between membrane-bound Fas ligand (FasL, a type II transmembrane protein of the TNF family) and the Fas receptor, resulting in activation of proinflammatory signaling (e.g., cytokine signaling, interleukin signaling, caspase action, etc.) and / or cell death signaling (e.g., apoptosis signaling, necrosis signaling, etc.) pathways.

[0050] Fas inhibitors Provided herein are Fas inhibitors useful for modulating (e.g., inhibiting, preventing, and / or reducing) Fas-mediated signaling. In certain cases, Fas inhibitors are useful for treating, inhibiting, preventing, and / or reducing Fas-mediated inflammation. In certain cases, inhibiting, preventing, and / or reducing Fas-mediated inflammation allows for the treatment and / or prevention of cell loss in the retina (e.g., photoreceptors and / or retinal pigment epithelium). Thus, in certain cases, Fas inhibitors are also useful for treating and / or preventing retinal cell loss and / or symptoms associated with retinal cell loss. In certain cases, inhibiting, preventing, and / or reducing Fas-mediated inflammation further treats, inhibits, reduces, and / or prevents retinal cell loss (e.g., retinal epithelial (RPE) cells and / or photoreceptor (PR) cells). In some embodiments, the Fas inhibitors described herein are useful for treating, inhibiting, reducing, and / or preventing retinal cell loss and / or symptoms associated with retinal cell loss. In such cases, since the Fas inhibitors described herein are useful in the manner described above, the Fas inhibitors are useful in methods of treating ocular diseases and disorders.

[0051] In some embodiments, the Fas inhibitors described herein include Met-derived peptides and / or fragments thereof. In some embodiments, the Met protein, also called c-Met or hepatocyte growth factor receptor (HGF receptor), is encoded by the Met gene (NCBI gene ID 4233, location: NC_000007.14 (116672196..116798386), UniProtKB-P0858). The Met protein is constructed from two major subunits, an alpha subunit and a beta subunit, and Met and fragments of Met (including the extracellular domain of Met and its alpha subunit) have been shown to bind to Fas and prevent cells from undergoing apoptosis. In some embodiments, the Fas inhibitors include Fas inhibitory peptides (e.g., Met-derived peptides and / or fragments thereof). In some embodiments, the Fas inhibitors described herein include Met-derived compounds that include the amino acids HHIYLGAVNYIY (His-His-lle-Tyr-Leu-Gly-Ala-Val-Asn-Tyr-lle-Tyr) (e.g., SEQ ID NOs: 1-8). In some embodiments, the peptide includes the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof.

[0052] As used herein, peptide includes and / or refers to any of a variety of natural or synthetic compounds that contain two or more amino acids joined by a peptide bond that connects the carboxyl group of one amino acid to the amino group of another. Also, as used herein, amino acid refers and / or includes naturally occurring amino acids, non-natural amino acids, amino acid analogs and amino acid mimetics that function similarly to naturally occurring amino acids. Amino acids are generally referred to herein by either their name, i.e., their commonly known three-letter symbols, or the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission.

[0053] In some embodiments, a Fas inhibitory peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) comprises one or more naturally occurring amino acids. In some embodiments, a Fas inhibitory peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) consists of one or more naturally occurring amino acids. As used herein, naturally occurring amino acids include and / or refer to amino acids that are generally found in nature and have not been engineered by humans. In some embodiments, naturally occurring includes and / or further refers to the 20 conventional amino acids alanine (A or Ala), cysteine ​​(C or Cys), aspartic acid (D or Asp), glutamic acid (E or Glu), phenylalanine (F or Phe), glycine (G or Gly), histidine (H or His), isoleucine (I or Ile), lysine (K or Lys), leucine (L or Leu), methionine (M or Met), asparagine (N or Asn), proline (P or Pro), glutamine (Q or Gln), arginine (R or Arg), serine (S or Ser), threonine (T or Thr), valine (V or Val), tryptophan (W or Trp), and tyrosine (Y or Tyr).

[0054] In some embodiments, the Fas inhibitor comprises a variant sequence of a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY). In some embodiments, amino acid substitutions may be made to the sequence of any of the polypeptides described herein without necessarily reducing or eliminating the activity of the polypeptide. Thus, in some embodiments, the variant sequence comprises one or more amino acid substitutions. In some embodiments, the variant sequence comprises one amino acid substitution. In some embodiments, the variant sequence comprises two amino acid substitutions. In some embodiments, the variant sequence comprises three amino acid substitutions. In some embodiments, the substitutions comprise conservative substitutions (e.g., substitution with an amino acid of comparable chemical characteristics). In some embodiments, a nonpolar amino acid may be substituted or replaced with another nonpolar amino acid, where nonpolar amino acids include alanine, leucine, isoleucine, valine, glycine, proline, phenylalanine, tryptophan, and methionine. In some embodiments, a polar amino acid with a neutral charge can be replaced or substituted with another polar amino acid with a neutral charge, where the polar amino acid with a neutral charge includes serine, threonine, cysteine, tyrosine, asparagine, and glutamine.In some embodiments, a positively charged amino acid can be replaced or substituted with another positively charged amino acid, where the positively charged amino acid includes arginine, lysine, and histidine.In some embodiments, a negatively charged amino acid can be replaced or substituted with another negatively charged amino acid, where the negatively charged amino acid includes aspartic acid and glutamic acid.In addition, examples of amino acid replacement include replacing L-amino acids with their corresponding D-amino acids, replacing cysteine ​​with homocysteine ​​or other unnatural amino acids.

[0055] In some embodiments, the Fas inhibitory peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) comprises one or more non-naturally occurring amino acids. In some embodiments, the Fas inhibitory peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) is composed of non-naturally occurring amino acids. As used herein, non-naturally occurring amino acids and / or non-naturally occurring amino acids include and / or refer to amino acid structures that cannot be produced biosynthetically in any organism using unmodified genes or modified genes from any organism. In some embodiments, non-naturally occurring amino acids and / or non-naturally occurring amino acids further include and / or refer to amino acid residues that are not present in the naturally occurring (wild type) Met protein sequence. For example, non-naturally occurring amino acids and / or non-naturally occurring amino acids include, but are not limited to, modified amino acids and / or amino acid analogs that are not one of the 20 naturally occurring amino acids (e.g., non-natural side chain variant sequence amino acids), D-amino acids, homoamino acids, β-homoamino acids, N-methyl amino acids, α-methyl amino acids.As further examples, non-naturally occurring amino acids also include 4-benzoylphenylalanine (Bpa), aminobenzoic acid (Abz), aminobutyric acid (Abu), aminohexanoic acid (Ahx), aminoisobutyric acid (Aib), citrulline (Cit), diaminobutanoic acid (Dab), diaminopropanoic acid (Dap), diaminopropionic acid (Dap), gamma-carboxyglutamic acid (Gla), homoalanine (Hala), homoarginine (Harg), homoasparagine (Hasn), homoaspartic acid (Hasp), homocysteine ​​(Hcys), homoglutamic acid (Hglu), homoglutamine (Hgln), homoisoleucine (Hile). , homoleucine (Hleu), homomethionine (Hmet), homophenylalanine (Hphe), homoserine (Hser), homotyrosine (Htyr), homovaline (Hval), hydroxyproline (Hyp), isonipestic acid (Inp), naphthylalanine (Nal), nipecotic acid (Nip), norleucine (Nle), norvaline (Nva), octahydroindole-2-carboxylic acid (Oic), penicillamine (Pen), phenylglycine (Phg), pyroglutamic acid (Pyr), sarcosine (Sar), t-butylglycine (Tle), and tetrahydro-isoquinoline-3-carboxylic acid (Tic). Such non-naturally occurring amino acid residues can be introduced by substituting a naturally occurring amino acid and / or by inserting the non-naturally occurring amino acid into the naturally occurring (wild-type) Met protein sequence. Unnatural amino acid residues may also be incorporated to confer desired functionality onto the apelin molecule, for example, the ability to conjugate a functional moiety (eg, PEG).

[0056] In some embodiments, the variant sequence comprises one or more amino acid deletions. In some embodiments, the variant sequence comprises one amino acid deletion. In some embodiments, the variant sequence comprises two amino acid deletions. In some embodiments, the variant sequence comprises three amino acid deletions. In some embodiments, the variant sequence comprises four amino acid deletions. In some embodiments, the variant sequence comprises one or more additional amino acids. In some embodiments, the additional amino acids are additional amino acids from the Met sequence. In some embodiments, the variant sequence comprises a substitution and a deletion. In some embodiments, the variant sequence comprises a substitution and one or more additional amino acids. In some embodiments, the substitution comprises a naturally occurring or non-naturally occurring amino acid. In some embodiments, the variant sequence is a retro-inverso amino acid sequence. In some embodiments, the variant sequence comprises one or more additional amino acid residues (e.g., one, two, or three additions) at the N-terminus or C-terminus. In some embodiments, the variant sequence comprises one or more deletions (e.g., one, two, or three deletions) of amino acid residues at the N-terminus or C-terminus.

[0057] The functionality of a peptide variant sequence (e.g., a variant sequence of the amino acid sequence HHIYLGAVNYIY) may be determined by in vitro assays. For example, in some embodiments, the variant sequence competes with Fas Ligand (FasL) for binding to the Fas Receptor (FasR). In some embodiments, the variant sequence inhibits, reduces, or prevents activation of caspase 8 in cells treated with FasL (e.g., as measured by a commercially available luminescent tetrapeptide cleavage assay kit (Promega, Madison, Wis.)). In some embodiments, the variant sequence inhibits, reduces, or prevents cell death of cells treated with FasL. By way of further example, in some embodiments, the variant sequence competes with a Fas activating antibody (e.g., the Fas agonist Jo2 monoclonal antibody (BD Biosciences, San Jose, Calif.)) for binding to the Fas Receptor (FasR). In some embodiments, the mutant sequence inhibits, reduces, or prevents activation of caspase 8 in cells treated with a Fas activating antibody (e.g., as measured by a commercially available luminescent tetrapeptide cleavage assay kit (Promega, Madison, Wis.)). In some embodiments, the mutant sequence inhibits, reduces, or prevents cell death in cells treated with a Fas activating antibody. Thus, in some embodiments, the Fas inhibitor comprises a mutant sequence (e.g., any one of the mutant sequences described herein) of a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY), which competes with Fas ligand (FasL) for binding to the Fas receptor (FasR). In some embodiments, the Fas inhibitor comprises a mutant sequence (e.g., any one of the mutant sequences described herein) of a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY), which inhibits, reduces, or prevents activation of caspase 8 in cells treated with FasL.In some embodiments, the Fas inhibitor comprises a variant sequence (e.g., any one of the variant sequences described herein) of a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY), which inhibits, reduces, or prevents cell death in cells treated with FasL. In some embodiments, the Fas inhibitor comprises a variant sequence (e.g., any one of the variant sequences described herein) of a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY), which competes with a Fas activating antibody for binding to the Fas receptor (FasR). In some embodiments, the Fas inhibitor comprises a variant sequence (e.g., any one of the variant sequences described herein) of a peptide comprising the amino acid sequence HHIYLGAVNYIY, which inhibits, reduces, or prevents activation of caspase 8 in cells treated with a Fas activating antibody. In some embodiments, the Fas inhibitor comprises a variant sequence of a peptide comprising the amino acid sequence HHIYLGAVNYIY (e.g., any one of the variant sequences described herein), where the variant sequence inhibits, reduces, or prevents cell death in cells treated with a Fas activating antibody.

[0058] The peptide or its variant sequence may further comprise one or more modifications. In some embodiments, the peptide (e.g., one comprising the amino acid sequence HHIYLGAVNYIY or its variant sequence) comprises a modification. In some embodiments, the peptide is a modified peptide. As used herein, a modification or modified peptide comprises and / or refers to a modification of one or more amino acids of the peptide. In some embodiments, the modification is a species of stereoisomer. All stereoisomers of the above compounds are contemplated, either in mixture or in pure or substantially pure form. The compounds may have asymmetric centers at any of the atoms. Thus, the peptide compounds or components thereof may exist in enantiomeric or diastereomeric forms or mixtures thereof. The present invention contemplates the use of any racemate (i.e., a mixture containing equal amounts of each enantiomer), enantiomerically enriched mixture (i.e., a mixture enriched in one enantiomer), pure enantiomers or diastereomers, or any mixture thereof. The chiral center may be designated as R or S or R, S or d, D, 1, L or d, 1, D, or L. Compounds containing amino acid residues include residues of D-amino acids, L-amino acids, or racemic derivatives of amino acids. Compounds containing sugar residues include residues of D-sugars, L-sugars, or racemic derivatives of sugars. Non-limiting examples of modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, amidation, or lipidation. Modifications may be introduced at the C-terminus of the peptide, the N-terminus of the peptide, or anywhere in between. Thus, a modification or modified peptide includes and / or refers to a modification of the free amino and / or carboxyl termini (N-terminus and C-terminus, respectively). In some embodiments, N-terminal modifications include, but are not limited to, acetylation, formylation, pyroglutamylation, carbamidoation, lipidation, sulfonamidation, and alkylamination. In some embodiments, C-terminal modifications include, but are not limited to, amidation, esterification, and incorporation of an aldehyde group. In some embodiments, the modification comprises amidation.In some embodiments, the amidation occurs at the c-terminus. In some embodiments, the modification comprises a retro-inverso peptide (e.g., YIYNVAGLYIHH). In some embodiments, the modification changes the chirality of one or more amino acid residues of the peptide (e.g., from an L amino acid to a D amino acid).

[0059] Thus, in one embodiment, provided herein is a peptide comprising the sequence (a)-HHIYLGAVNYIY-(b) or (a)-YIYNVAGLYIHH-(b) or a variant sequence thereof, During the ceremony, (a) is -H, -OH, -NH2, G 1 (CH2) n -, R 1 CONH-, or R 2 O-, (b) -H, -CH2OH, -CH2OR 2 , -CHO, -COR 2 , -CONH2, -CONHR 2 , -CON(R 3 )2, -CONH(CH2) y NR( 3 )2, -(CH2) n -G 1 , -COCH2-G 1 , -CONHCH2-G 1 , -(CH2) n NH2, -(CH2) n NHR 2 , -(CH2) n N(R 3 )2, NH-Glu-His-OH, NH-Glu-His-NH2, -Ala-His-NH2, -Gly--His-NH2, -NH-Glu-His-OH, -NH-Glu-His-NH2, -Ala-His-NH2, -G ly-His-NH2, -NH-[D]Glu-[D]-His-OH, -NH-[D]Glu-[D]-His-NH2, -[D]Ala-[D]-His-NH2, -Gly-[D]-His-NH2, or -CONH(CH2) n -G 2 and G 1is, in each occurrence, independently -H, -C(=O)NH2, -C(=O)NHR 2 , -C(=O)N(R 3 )2, C(=O)OR 2 , or -C(=O)R 1 and G 2 represents, in each occurrence, a 4- to 6-membered heterocycle containing at least a tertiary amine functional group in the ring, or -N(R 3 ) 2 substituted 3- to 7-membered carbocyclic ring; R 1 is independently H, C, 1-6 Alkyl, -(CH2) x (OCH2CH2) m OR 5 , C 1-6 -alkoxy, or L; R 2 is, in each occurrence, independently C 1-6 Alkyl, OR 5 Or NR 5 C substituted with 2 2-6 Alkyl, -(CH2) x (OCH2CH2) m OR 5 , or L; L, in each occurrence, is independently H, R 5 is a polyvalent polyethylene glycol derivative having 2 to 4 terminals, which may be capped with R 3 is, in each occurrence, independently C 1-6 Alkyl, OR 5 Or N(R 5 )2 replaced by C 2-6 Alkyl, -(CH2) x (OCH2CH2) m OR 5 and Or, two R's 3 may be joined together with the N atom to which they are attached to form a 4-8 membered monocyclic ring, or a 6-10 membered fused, bridged or spiro bicyclic ring, in which -O-, -(C=O)-, NR 6 , S, SO, or SO2; R 4 is, in each occurrence, independently C 1-6 Alkyl, C 1-6 Acyl, or -OPO3(R 5 )2, R 5 is, in each occurrence, independently H or C 1-6 is alkyl, R 6 In each occurrence, H, C 1-6 Alkyl, C 2-6 Hydroxyalkyl, C 1-6 Alkoxy-, C 1-6 Alkyl, or C 1-6 It is acyl, m is 1 to 100; n is 0 to 3; x is 0 to 6; y is 2 to 4; R 1 and R 2 At most one of them is L.

[0060] In certain instances, provided herein is a peptide comprising the structure of Formula I or Formula II, or a pharma- ceutically acceptable salt thereof:

[0061] [ka]

[0062] [ka] In the formula, A is H-, -OH, -NH2, G 1 (CH2) n -, R 1 CONH-, or R 2 O-, B is -H, CH2OH, CH2OR 2 , -CHO, -COR 2 , -CONH2, -CONHR 2 , -CON(R 3 )2, -CONH(CH2) y N(R3 )2, -(CH2) n -G 1 , -COCH2-G 1 , -CONHCH2-G 1 , -(CH2) n NH2, -(CH2) n NHR 2 , -(CH2) n N(R 3 )2NH-Glu-His-OH, NH-Glu-His-NH2, -Ala-His-NH2, -Gly-His-NH2, NH-Glu--His-OH, NH-Glu-His-NH2, -Ala-His-NH2, -Gly-His-NH2, NH-[D]Glu-[D]-His-OH, NH-[D]Glu-[D]-His-NH 2 , -[D]Ala-[D]-His-NH2, -Gly-[D]-His-NH2, or CONH(CH2) n -G 2 and E, in each occurrence, is independently -H, -OH, -OR 4 , SH, -SR 4 or halogen, G 1 is, in each occurrence, independently -H, -C(=O)NH2, -C(=O)NHR 2 , -C(=O)N(R 3 )2, C(=O)OR 2 , or -C(=O)R 1 and G 2 In each occurrence, there is at least one tertiary amine functional group NR 2 or N(R 3 ) 2 substituted 3- to 7-membered carbocyclic ring; Q, in each occurrence, is independently 1-propyl, 2-propyl, 2-methyl-prop-2-yl, C 3-6 -Cycloalkyl, C 4-6-cycloalkenyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothienyl-2-yl, tetrahydrothienyl-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, or 1-CH(OR 5 )CH3, R 1 is independently H, C, 1-6 Alkyl, -(CH2) x (OCH2CH2) m OR 5 , C 1-6 alkoxy, or L; R 2 is, in each occurrence, independently C 1-6 Alkyl, OR 5 Or N(R 5 )2 replaced by C 2-6 Alkyl, -(CH2) x (OCH2CH2) m OR 5 , or L, L, in each occurrence, is independently H, R 5 or another molecule of a peptide of formula I or II, R 3 is, in each occurrence, independently C 1-6 -Alkyl, OR 5 Or N(R 5 )2 replaced by C 2-6 -Alkyl, -(CH2) x (OCH2CH2) m OR 5 and Or, two R's 3 may be joined together with the N atom to which they are attached to form a 4-8 membered monocyclic ring, or a 6-10 membered fused, bridged or spiro bicyclic ring, in which -O-, -(C=O)-, NR 6, S, SO, or SO2; R 4 is, in each occurrence, independently C 1-6 Alkyl, C 1-6 Acyl, or -OPO3(R 5 )2, R 5 is, in each occurrence, independently H or C 1-6 is alkyl, R 6 In each occurrence, H, C 1-6 Alkyl, C 2-6 Hydroxyalkyl, C 1-6 Alkoxy-, C 1-6 Alkyl, or C 1-6 It is acyl, m is 1 to 100; n is 0 to 3; x is 0 to 6; y is 2 to 4;

[0063] R 1 and R 2 At most one of them is L.

[0064] In some embodiments, a peptide is provided having the structure of Formula III, or a pharma- ceutically acceptable salt thereof.

[0065] [ka]

[0066] Formula III: His-His-Ile-Tyr-Leu-Gly-Ala-Val-Asn-Tyr-Ile-Tyr-amide (SEQ ID NO: 3).

[0067] In some embodiments, a peptide is provided having the structure of Formula IV, or a pharma- ceutically acceptable salt thereof.

[0068] [ka]

[0069] Formula IV: All [D]Tyr-Ile-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-Ile-His-His-amide (SEQ ID NO: 4).

[0070] In some embodiments, a peptide is provided having the structure of Formula V, or a pharma- ceutically acceptable salt thereof.

[0071] [ka]

[0072] Formula V: All[D]Tyr-allo-Ile-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-allo-Ile-His-His-amide (SEQ ID NO:5).

[0073] In some embodiments, a peptide is provided having the structure of Formula VI, or a pharma- ceutically acceptable salt thereof.

[0074] [ka]

[0075] Formula VI: All [D]Tyr-Val-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-Val-His-His-amide (SEQ ID NO: 6).

[0076] In some embodiments, a peptide is provided having the structure of Formula VII, or a pharma- ceutically acceptable salt thereof.

[0077] [ka]

[0078] Formula 7: All [D] (desamino Tyr)-Val-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-Val-His-His-amide (SEQ ID NO: 7).

[0079] In some embodiments, a peptide is provided having the structure of Formula VIII, or a pharma- ceutically acceptable salt thereof.

[0080] [ka]

[0081] Formula 8: All-[D](hydroxy-desaminoTyr)-allo-Ile-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-allo-Ile-His-histamine (SEQ ID NO: 8).

[0082] In some embodiments, a peptide is provided having the structure of Formula IX, or a pharma- ceutically acceptable salt thereof.

[0083] [ka]

[0084] Formula IX: All [D] (desamino Tyr)-Val-Tyr-Asn-Val-Ala-Gly-Leu-Tyr-Val-His-His-piperazineamide (SEQ ID NO: 9).

[0085] Fas inhibitory peptide salt Further provided herein is a peptide salt for inhibiting ocular Fas-mediated inflammation and for use in the methods described herein.As used herein, salt generally refers to and / or includes pharmaceutically acceptable salt.Examples of pharmaceutically acceptable salt include the salt with organic acid or inorganic acid, such as (but not limited to) acetic acid, aspartic acid, benzenesulfonic acid, benzoic acid, butyric acid, citric acid, fumaric acid, hydrochloric acid, hydrobromic acid, lactic acid, maleic acid, malonic acid, methanesulfonic acid, 4-methylbenzenesulfonic acid, nicotinic acid, phosphoric acid, succinic acid, sulfuric acid, or tartaric acid, which is prepared by using methods well known in the art.In some embodiments, the salt is hydrochloride.

[0086] In addition, these salts may be prepared by adding inorganic or organic bases to the free acid.Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, and magnesium salts.Salts derived from organic bases include, but are not limited to, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, and polyamine resins.

[0087] Salts and pharma- ceutically acceptable salts are described in J. Pharmaceutical Sciences, 66:1-19 (1977), the contents of which are incorporated herein by reference.

[0088] In some embodiments, the salt is an acetate salt. In some embodiments, the acetate salt is a polyacetate salt. In some embodiments, the polyacetate salt is a triacetate salt.

[0089] Pharmaceutical Compositions In some embodiments, pharmaceutical compositions (also referred to as compositions) comprising Fas inhibitory peptides are further provided. In some embodiments, the pharmaceutical compositions described herein comprise a peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) or a pharma- ceutically acceptable salt thereof. In some embodiments, the pharmaceutical compositions described herein comprise a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the pharmaceutical compositions described herein comprise a peptide having the structure of any one of formulas I to IX, or a pharma- ceutically acceptable salt thereof. In some embodiments, the pharmaceutical compositions described herein comprise a peptide having the structure of formula I, or a pharma- ceutically acceptable salt thereof. In some embodiments, the pharmaceutical compositions described herein comprise a peptide having the structure of formula III, or a pharma- ceutically acceptable salt thereof.

[0090] A pharmaceutical composition may include one or more excipients. As used herein, excipients include and / or refer to any pharma- ceutically acceptable additive, carrier, diluent, adjuvant, or other ingredient other than the active pharmaceutical ingredient (API), typically including those for formulation and / or administration to a patient. A pharmaceutical composition may include a single pharmaceutical formulation (e.g., sustained release, immediate release, delayed release, nanoparticles, etc.) or multiple formulations (e.g., immediate release and delayed release, nanoparticles and non-nanoparticles, etc.). Excipients further include and / or refer to agents that may be added to a formulation to provide a desired consistency (e.g., modify bulk properties), improve stability, and / or adjust osmolality. Examples of commonly used excipients include, but are not limited to, sugars, polyols, amino acids, surfactants, and polymers. In some embodiments, non-ionic excipients or non-ionizable excipients, as used herein, include and / or refer to agents that do not have a net charge.

[0091] In some embodiments, non-ionic excipients have no net charge under certain formulation conditions, such as pH. Examples of non-ionic excipients include, but are not limited to, sugars (e.g., sucrose), sugar alcohols (e.g., mannitol), and non-ionic surfactants (e.g., polysorbate 80).

[0092] In some embodiments, the composition includes an excipient suitable for application to the eye. Suitable excipients include, but are not limited to, isotonicity agents, preservatives, chelating agents, buffers, surfactants, cosolvents, and antioxidants. Suitable tonicity agents include mannitol, sodium chloride, glycerin, sorbitol, and the like. Suitable preservatives include p-hydroxybenzoic acid esters, benzalkonium chloride, benzododecinium bromide, polyquaternium-1, and the like. Suitable chelating agents include sodium edetate, and the like. Suitable buffers include phosphates, borates, citrates, acetates, tromethamine, and the like. Suitable surfactants include ionic surfactants and non-ionic surfactants. In some embodiments, the one or more excipients include non-ionic surfactants such as polysorbates, polyethoxylated castor oil derivatives, polyethoxylated fatty acids, polyethoxylated alcohols, polyoxyethylene-polyoxypropylene block copolymers (Poloxamers), and oxyethylated tertiary octylphenol formaldehyde polymers (Tyloxapols). Other suitable surfactants may also be included. Suitable antioxidants include sulfites, thiosulfates, ascorbates, BHA, BHT, tocopherol, and the like.

[0093] In some embodiments, the composition is a non-ionic surfactant. In some embodiments, the composition comprises a polysorbate, a polyethoxylated castor oil derivative, a polyethoxylated fatty acid, a polyethoxylated alcohol, a polyoxyethylene-polyoxypropylene block copolymer (Poloxamer), or an oxyethylated tertiary octylphenol formaldehyde polymer (Tyloxapol). In some embodiments, the composition comprises a polysorbate. In some embodiments, the composition comprises a polyethoxylated castor oil derivative. In some embodiments, the composition comprises a polyethoxylated fatty acid. In some embodiments, the composition comprises a polyethoxylated alcohol. In some embodiments, the composition comprises a polyoxyethylene-polyoxypropylene block copolymer (Poloxamer). In some embodiments, the composition comprises an oxyethylated tertiary octylphenol formaldehyde polymer (Tyloxapol). In some embodiments, the surfactant comprises 0.05% to 20% by weight (w / w) of the composition. In some embodiments, the non-ionic surfactant is from about 0.05% w / w of the composition to about 20% w / w of the composition. In some embodiments, the non-ionic surfactant is at least about 0.05% w / w of the composition. In some embodiments, the non-ionic surfactant is up to about 20% w / w of the composition.In some embodiments, the nonionic surfactant is present in an amount of from about 0.05% w / w of the composition to about 0.1% w / w of the composition, from about 0.05% w / w of the composition to about 0.5% w / w of the composition, from about 0.05% w / w of the composition to about 1% w / w of the composition, from about 0.05% w / w of the composition to about 2% w / w of the composition, from about 0.05% w / w of the composition to about 5% w / w of the composition, from about 0.05% w / w of the composition to about 0.05% w / w of the composition. from about 0.05% w / w of the composition to about 20% w / w of the composition, from about 0.1% w / w of the composition to about 0.5% w / w of the composition, from about 0.1% w / w of the composition to about 1% w / w of the composition, from about 0.1% of the composition to about 2% w / w of the composition, from about 0.1% of the composition to about 5% w / w of the composition, from about 0.1% of the composition to about 10% w / w of the composition, from about 0.1% from about 0.5% to about 20% w / w of the composition, from about 0.5% to about 1% w / w of the composition, from about 0.5% to about 2% w / w of the composition, from about 0.5% to about 5% w / w of the composition, from about 0.5% to about 10% w / w of the composition, from about 0.5% to about 20% w / w of the composition, from about 1% to about 2% w / w of the composition, from about 1% to about 5% w / w of the composition, The nonionic surfactant is present in an amount of about 1% to about 10% w / w of the composition, about 1% to about 20% w / w of the composition, about 2% to about 5% w / w of the composition, about 2% to about 10% w / w of the composition, about 2% to about 20% w / w of the composition, about 5% to about 10% w / w of the composition, about 5% to about 20% w / w of the composition, or about 10% to about 20% w / w of the composition. In some embodiments, the nonionic surfactant is present in an amount of about 0.05% w / w of the composition, about 0.1% w / w of the composition, about 0.5% w / w of the composition, about 1% w / w of the composition, about 2% w / w of the composition, about 5% w / w of the composition, about 10% w / w of the composition, or about 20% w / w of the composition.

[0094] In some embodiments, the non-ionic surfactant is from about 0.05% w / w of the composition to about 2% w / w of the composition. In some embodiments, the non-ionic surfactant is at least about 0.05% w / w of the composition. In some embodiments, the non-ionic surfactant is at most about 2% w / w of the composition. In some embodiments, the non-ionic surfactant is from about 0.05% w / w of the composition to about 0.1% w / w of the composition, from about 0.05% w / w of the composition to about 0.1% w / w of the composition, from about 0.05% w / w of the composition to about 0.2% w / w of the composition, from about 0.05% w / w of the composition to about 0.3% w / w of the composition, from about 0.05% w / w of the composition to about 0.4% w / w of the composition, from about 0.05% w / w of the composition to about 0.5% w / w of the composition, from about 0.05% w / w of the composition to about 0.05% w / w of the composition. 0.6% w / w of the composition, from about 0.05% w / w of the composition to about 1% w / w of the composition, from about 0.05% w / w of the composition to about 1.5% w / w of the composition, from about 0.05% w / w of the composition to about 2% w / w of the composition, from about 0.1% w / w of the composition to about 0.1% w / w of the composition, from about 0.1% w / w of the composition to about 0.2% w / w of the composition, from about 0.1% w / w of the composition to about 0.3% w / w of the composition, from about 0.1% w / w of the composition to about 0.4% w / w of the composition, from about 0.1% w / w of the composition to about 0.5% w / w of the composition, about 0.5% w / w, about 0.1% w / w of the composition to about 0.6% w / w of the composition, about 0.1% w / w of the composition to about 1% w / w of the composition, about 0.1% w / w of the composition to about 1.5% w / w of the composition, about 0.1% w / w of the composition to about 2% w / w of the composition, about 0.1% w / w of the composition to about 0.2% w / w of the composition, about 0.1% w / w of the composition to about 0.3% w / w of the composition, about 0.1% w / w of the composition to about 0.4% w / w of the composition, about 0.1% w / w of the composition to about 0.5% w / w, from about 0.1% w / w of the composition to about 0.6% w / w of the composition, from about 0.1% w / w of the composition to about 1% w / w of the composition, from about 0.1% w / w of the composition to about 1.5% w / w of the composition, from about 0.1% w / w of the composition to about 2% w / w of the composition, from about 0.2% w / w of the composition to about 0.3% w / w of the composition, from about 0.2% w / w of the composition to about 0.4% w / w of the composition, from about 0.2% w / w of the composition to about 0.5% w / w of the composition, from about 0.2% w / w of the composition to about 0.6% w / w, from about 0.2% w / w of the composition to about 1% w / w of the composition, from about 0.2% w / w of the composition to about 1.5% w / w of the composition, from about 0.2% w / w of the composition to about 2% w / w of the composition, from about 0.3% w / w of the composition to about 0.4% w / w of the composition, from about 0.3% w / w of the composition to about 0.5% w / w of the composition, from about 0.3% w / w of the composition to about 0. 6% w / w, from about 0.3% w / w of the composition to about 1% w / w of the composition, from about 0.3% w / w of the composition to about 1.5% w / w of the composition, from about 0.3% w / w of the composition to about 2% w / w of the composition, from about 0.4% w / w of the composition to about 0.5% w / w of the composition, from about 0.4% w / w of the composition to about 0.6% w / w of the composition, from about 0.4% w / w of the composition to about 1% of the composition. w / w, from about 0.4% w / w of the composition to about 1.5% w / w of the composition, from about 0.4% w / w of the composition to about 2% w / w of the composition, from about 0.5% w / w of the composition to about 0.6% w / w of the composition, from about 0.5% w / w of the composition to about 1% w / w of the composition, from about 0.5% w / w of the composition to about 1.5% w / w of the composition, from about 0.5% w / w of the composition to about 2% w / w of the composition from about 0.6% w / w of the composition to about 1% w / w of the composition, from about 0.6% w / w of the composition to about 1.5% w / w of the composition, from about 0.6% w / w of the composition to about 2% w / w of the composition, from about 1% w / w of the composition to about 1.5% w / w of the composition, from about 1% w / w of the composition to about 2% w / w of the composition, or from about 1.5% w / w of the composition to about 2% w / w of the composition. In some embodiments, the nonionic surfactant is about 0.05% w / w of the composition, about 0.1% w / w of the composition, about 0.1% w / w of the composition, about 0.2% w / w of the composition, about 0.3% w / w of the composition, about 0.4% w / w of the composition, about 0.5% w / w of the composition, about 0.6% w / w of the composition, about 1% w / w of the composition, about 1.5% w / w of the composition, or about 2% w / w of the composition.

[0095] In some embodiments, the nonionic surfactant comprises polysorbate 20, poloxamer 407, tyloxapol, or cremophor. In some embodiments, the nonionic surfactant is polysorbate 20. In some embodiments, the nonionic surfactant is poloxamer 407. In some embodiments, the nonionic surfactant is tyloxapol. In some embodiments, the nonionic surfactant is cremophor. The nonionic surfactants described herein may be present within any one of the ranges (e.g., percent w / w) described herein, i.e., within a particular value that falls within the described range.

[0096] In some embodiments, the composition further comprises a co-solvent (e.g., 0.5 to 50% w / w) such as N,N-dimethylacetamide, ethanol, PEG-400, propylene glycol, dimethyl sulfoxide (DMSO), and an oil or cyclodextrin may be added to the pharmaceutical formulation. In some embodiments, the composition further comprises a tonicity modifier. In some embodiments, the composition is an isotonic solution. In some embodiments, the tonicity modifier is mannitol, sorbitol, glucose or trehalose, or an inorganic salt such as sodium chloride. In some embodiments, the composition comprises mannitol. In some embodiments, the composition comprises sorbitol. In some embodiments, the composition comprises glucose or trehalose. In some embodiments, the composition comprises an inorganic salt. In some embodiments, the tonicity modifier is present in an amount suitable to bring the tonicity of the composition to the range of 250-400 mOsm / L. In some embodiments, the non-ionic surfactant is about 1% w / w of the composition to about 10% w / w of the composition. In some embodiments, the non-ionic surfactant is at least about 1% w / w of the composition. In some embodiments, the non-ionic surfactant is at most about 10% w / w of the composition. In some embodiments, the non-ionic surfactant is at most about 1% w / w of the composition, at most about 2% w / w of the composition, at most about 1% w / w of the composition, at most about 3% w / w of the composition, at most about 1% w / w of the composition, at most about 4% w / w of the composition, at most about 1% w / w of the composition, at most about 5% w / w of the composition, at most about 1% w / w of the composition, at most about 10% w / w of the composition, at most about 2% w / w of the composition, at most about 3% w / w of the composition, at most about 2% w / w of the composition, at most about 4% w / w of the composition, at most about 5% w / w of the composition, at most about 10% w / w of the composition, at most about 2% w / w of the composition, at most about 3% w / w of the composition, at most about 4% w / w of the composition, at most about 5 ... from about 2% w / w to about 5% w / w of the composition, from about 2% w / w of the composition to about 10% w / w of the composition, from about 3% w / w of the composition to about 4% w / w of the composition, from about 3% w / w of the composition to about 5% w / w of the composition, from about 3% w / w of the composition to about 10% w / w of the composition, from about 4% w / w of the composition to about 5% w / w of the composition, from about 4% w / w of the composition to about 10% w / w of the composition, or from about 5% w / w of the composition to about 10% w / w of the composition.In some embodiments, the non-ionic surfactant is about 1% w / w, about 2% w / w of the composition, about 3% w / w of the composition, about 4% w / w of the composition, about 5% w / w of the composition, or about 10% w / w of the composition.

[0097] In some embodiments, the composition comprises a buffering agent. In some embodiments, the buffering agent is an acidifying agent. In some embodiments, the acidifying agent is an acetate buffer at pH 4.5. In some embodiments, the concentration of the acetate buffer at pH 4.5 is about 10 millimolar (mM). Generally, pH control may be performed by a suitable buffer suitable for injection into the eye, for example, the pH of the composition may be in the range of 3.0 to 7.5 or in the range of 3.5 to 4.5.

[0098] As described herein, the composition may include one or more excipients.Thus, in some embodiments, the composition includes a non-ionic surfactant, a tonicity modifier, and a buffering agent in combination with the peptide.Any of the excipients described may be combined in the amounts and / or ranges described.

[0099] Dosage and Administration Schedule In certain embodiments, the compositions described herein include an amount of peptide suitable for inhibiting Fas-mediated inflammation in the eye and / or treating, inhibiting, reducing and / or preventing retinal degeneration or symptoms thereof in the eye. As used herein, dose or administration amount includes and / or refers to the amount of therapeutic agent, e.g., a described peptide, in a composition (e.g., a composition for administration to the eye). Dose may refer to either (i) the peptide (parent compound) or a pharma- ceutically acceptable salt thereof. In some embodiments, the amount of peptide in a composition (i.e., pharmaceutical composition) suitable for the methods described herein (e.g., treating retinal degeneration) ranges from 5 micrograms (μg) to 10,000 μg. Dosage forms including the compositions described herein are generally administered to the vitreous humor of the eye and may be further formulated for injection into the eye (e.g., intravitreal injection). In some embodiments, the amount of peptide (e.g., peptide comprising amino acid sequence HHIYLGAVNYIY) or a pharma- ceutically acceptable salt thereof suitable for the methods described herein ranges from 5 μg to 10,000 μg. In some embodiments, the amount of peptide comprising amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide suitable for the methods described herein ranges from 5 μg to 10,000 μg. In some embodiments, the amount of peptide having structure of formula I or a pharma- ceutically acceptable salt thereof suitable for the methods described herein ranges from 5 μg to 10,000 μg. In some embodiments, the amount of peptide having structure of formula III or a pharma- ceutically acceptable salt thereof suitable for the methods described herein ranges from 5 μg to 10,000 μg.

[0100] In some embodiments, the composition comprises about 5 μg peptide to about 10,000 μg peptide. In some embodiments, the composition comprises at least about 5 μg peptide. In some embodiments, the composition comprises up to about 10,000 μg peptide. In some embodiments, the composition comprises about 5 μg peptide to about 25 μg peptide, about 5 μg peptide to about 50 μg peptide, about 5 μg peptide to about 100 μg peptide, about 5 μg peptide to about 200 μg peptide, about 5 μg peptide to about 500 μg peptide, about 5 μg peptide to about 1,000 μg peptide, about 5 μg peptide to about 2,500 μg peptide, about 5 μg peptide to about 5,000 μg peptide, about 5 μg peptide to about 2,5 ... from about 25 μg peptide to about 10,000 μg peptide, from about 25 μg peptide to about 50 μg peptide, from about 25 μg peptide to about 100 μg peptide, from about 25 μg peptide to about 200 μg peptide, from about 25 μg peptide to about 500 μg peptide, from about 25 μg peptide to about 1,000 μg peptide, from about 25 μg peptide to about 2,500 μg peptide, from about 25 μg peptide to about 5,000 μg peptide, from about 25 μg peptide to about 10,000 μg peptide, From about 50 μg peptide to about 100 μg peptide, from about 50 μg peptide to about 200 μg peptide, from about 50 μg peptide to about 500 μg peptide, from about 50 μg peptide to about 1,000 μg peptide, from about 50 μg peptide to about 2,500 μg peptide, from about 50 μg peptide to about 5,000 μg peptide, from about 50 μg peptide to about 10,000 μg peptide, from about 100 μg peptide to about 200 μg peptide, from about 100 μg peptide About 500 μg peptide, about 100 μg peptide to about 1,000 μg peptide, about 100 μg peptide to about 2,500 μg peptide, about 100 μg peptide to about 5,000 μg peptide, about 100 μg peptide to about 10,000 μg peptide, about 200 μg peptide to about 500 μg peptide, about 200 μg peptide to about 1,000 μg peptide, about 200 μg peptide to about 2,500 μg peptide, about 200 μg peptide to about 5,000 μg peptide, about 200 μg peptide to about 10,000 μg peptide, about 500 μg peptide to about 1,000 μg peptide, about 500 μg peptide to about 2,500 μg peptide, about 500 μg peptide to about 5,000 μg peptide, about 500 μg peptide to about 10,000 μg peptide, about 1,000 μg peptide to about 2 ,500 μg of peptide, about 1,000 μg of peptide to about 5,000 μg of peptide, about 1,000 μg of peptide to about 10,000 μg of peptide, about 2,500 μg of peptide to about 5,000 μg of peptide, about 2,500 μg of peptide to about 10,000 μg of peptide, or about 5,000 μg of peptide to about 10,000 μg of peptide. In some embodiments, the composition comprises about 5 μg of peptide, about 25 μg of peptide, about 50 μg of peptide, about 100 μg of peptide, about 200 μg of peptide, about 500 μg of peptide, about 1,000 μg of peptide, about 2,500 μg of peptide, about 5,000 μg of peptide, or about 10,000 μg of peptide.

[0101] In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 10,000 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises at least about 5 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises up to about 10,000 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 100 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 200 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 500 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 1,0 ... μg of a pharma- ceutically acceptable salt of a peptide to about 2,500 μg of a pharma- ceutically acceptable salt of a peptide, about 5 μg of a pharma- ceutically acceptable salt of a peptide to about 5,000 μg of a pharma- ceutically acceptable salt of a peptide, about 5 μg of a pharma- ceutically acceptable salt of a peptide to about 10,000 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide to about 200 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide from about 100 μg of a pharma- ceutically acceptable salt of peptide to about 500 μg of a pharma- ceutically acceptable salt of peptide, from about 100 μg of a pharma- ceutically acceptable salt of peptide to about 1,000 μg of a pharma- ceutically acceptable salt of peptide, from about 100 μg of a pharma- ceutically acceptable salt of peptide to about 2,500 μg of a pharma- ceutically acceptable salt of peptide, from about 100 μg of a pharma- ceutically acceptable salt of peptide to about 5,000 μg of a pharma- ceutically acceptable salt of peptide, from about 100 μg of a pharma- ceutically acceptable salt of peptide from about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 1,000 μg of a pharma- ceutically acceptable salt of a peptide, from about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 500 μg of a pharma- ceutically acceptable salt of a peptide, from about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 1,000 μg of a pharma- ceutically acceptable salt of a peptide, from about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 2,500 μg of a pharma- ceutically acceptable salt of a peptide, from about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 5,000 μg of a pharma- ceutically acceptable salt of a peptide, about 200 μg of a pharma- ceutically acceptable salt of a peptide to about 10,000 μg of a pharma- ceutically acceptable salt of a peptide, about 500 μg of a pharma- ceutically acceptable salt of a peptide to about 1,000 μg of a pharma- ceutically acceptable salt of a peptide, about 500 μg of a pharma- ceutically acceptable salt of a peptide to about 2,500 μg of a pharma- ceutically acceptable salt of a peptide, about 500 μg of a pharma- ceutically acceptable salt of a peptide to about 5,000 μg of a pharma- ceutically acceptable salt of a peptide, about 500 μg of a pharma- ceutically acceptable salt of a peptide to about 10,000 μg of a pharma- ceutically acceptable salt of a peptide, about 1,000 μg of a pharma- ceutically acceptable salt of a peptide The pharma- ceutically acceptable salt of the peptide may range from about 2,500 μg of a pharma- ceutically acceptable salt of the peptide, from about 1,000 μg of a pharma- ceutically acceptable salt of the peptide to about 5,000 μg of a pharma- ceutically acceptable salt of the peptide, from about 1,000 μg of a pharma- ceutically acceptable salt of the peptide to about 10,000 μg of a pharma- ceutically acceptable salt of the peptide, from about 2,500 μg of a pharma- ceutically acceptable salt of the peptide to about 5,000 μg of a pharma- ceutically acceptable salt of the peptide, from about 2,500 μg of a pharma- ceutically acceptable salt of the peptide to about 10,000 μg of a pharma- ceutically acceptable salt of the peptide, or from about 5,000 μg of a pharma- ceutically acceptable salt of the peptide to about 10,000 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide, about 200 μg of a pharma- ceutically acceptable salt of a peptide, about 500 μg of a pharma- ceutically acceptable salt of a peptide, about 1,000 μg of a pharma- ceutically acceptable salt of a peptide, about 2,500 μg of a pharma- ceutically acceptable salt of a peptide, about 5,000 μg of a pharma- ceutically acceptable salt of a peptide, or about 10,000 μg of a pharma- ceutically acceptable salt of a peptide.

[0102] In some embodiments, the amount of peptide comprising amino acid sequence HHIYLGAVNYIY or variant sequence thereof, or pharma- ceutically acceptable salt of peptide suitable for the methods described herein, ranges from 5 μg to 300 μg. In some embodiments, the amount of peptide having structure of formula I or a pharma-ceutically acceptable salt thereof suitable for the methods described herein, ranges from 5 μg to 300 μg. In some embodiments, the amount of peptide having structure of formula III or a pharma-ceutically acceptable salt thereof suitable for the methods described herein, ranges from 5 μg to 300 μg.

[0103] In some embodiments, the composition comprises about 5 μg peptide to about 300 μg peptide. In some embodiments, the composition comprises at least about 5 μg peptide. In some embodiments, the composition comprises up to about 300 μg peptide. In some embodiments, the composition comprises about 5 μg peptide to about 10 μg peptide, about 5 μg peptide to about 25 μg peptide, about 5 μg peptide to about 50 μg peptide, about 5 μg peptide to about 75 μg peptide, about 5 μg peptide to about 100 μg peptide, about 5 μg peptide to about 150 μg peptide, about 5 μg peptide to about 200 μg peptide, about 5 μg peptide to about 250 μg peptide, about 5 μg peptide to about 300 μg peptide, about 1 0 μg peptide to about 25 μg peptide, about 10 μg peptide to about 50 μg peptide, about 10 μg peptide to about 75 μg peptide, about 10 μg peptide to about 100 μg peptide, about 10 μg peptide to about 150 μg peptide, about 10 μg peptide to about 200 μg peptide, about 10 μg peptide to about 250 μg peptide, about 10 μg peptide to about 300 μg peptide, about 25 μg peptide to about 50 μg peptide, about 25 μg peptide to about About 75 μg peptide, about 25 μg peptide to about 100 μg peptide, about 25 μg peptide to about 150 μg peptide, about 25 μg peptide to about 200 μg peptide, about 25 μg peptide to about 250 μg peptide, about 25 μg peptide to about 300 μg peptide, about 50 μg peptide to about 75 μg peptide, about 50 μg peptide to about 100 μg peptide, about 50 μg peptide to about 150 μg peptide, about 50 μg peptide to about 200 μg peptide peptide, about 50 μg peptide to about 250 μg peptide, about 50 μg peptide to about 300 μg peptide, about 75 μg peptide to about 100 μg peptide, about 75 μg peptide to about 150 μg peptide, about 75 μg peptide to about 200 μg peptide, about 75 μg peptide to about 250 μg peptide, about 75 μg peptide to about 300 μg peptide, about 100 μg peptide to about 150 μg peptide, about 100 μg peptide to about 200 μg peptide,The composition comprises about 100 μg peptide to about 250 μg peptide, about 100 μg peptide to about 300 μg peptide, about 150 μg peptide to about 200 μg peptide, about 150 μg peptide to about 250 μg peptide, about 150 μg peptide to about 300 μg peptide, about 200 μg peptide to about 250 μg peptide, about 200 μg peptide to about 300 μg peptide, or about 250 μg peptide to about 300 μg peptide. In some embodiments, the composition comprises about 5 μg peptide, about 10 μg peptide, about 25 μg peptide, about 50 μg peptide, about 75 μg peptide, about 100 μg peptide, about 150 μg peptide, about 200 μg peptide, about 250 μg peptide, or about 300 μg peptide.

[0104] In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 300 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises at least about 5 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises up to about 300 μg of a pharma- ceutically acceptable salt of the peptide. In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 25 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 50 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 100 μg of a pharma- ceutically acceptable salt of the peptide, about 5 μg of a pharma- ceutically acceptable salt of the peptide to about 150 μg of a pharma- ceutically acceptable salt of the peptide, ..., about 5 μg of a pharma- ceutically acceptable salt of the peptide, about from about 200 μg of a pharma- ceutically acceptable salt of a peptide, from about 5 μg of a pharma- ceutically acceptable salt of a peptide to about 250 μg of a pharma- ceutically acceptable salt of a peptide, from about 5 μg of a pharma- ceutically acceptable salt of a peptide to about 300 μg of a pharma- ceutically acceptable salt of a peptide, from about 25 μg of a pharma- ceutically acceptable salt of a peptide to about 50 μg of a pharma- ceutically acceptable salt of a peptide, from about 25 μg of a pharma- ceutically acceptable salt of a peptide to about 100 μg of a pharma- ceutically acceptable salt of a peptide a pharma- ceutically acceptable salt of about 25 μg peptide to about 150 μg peptide, a pharma-ceutically acceptable salt of about 25 μg peptide to about 200 μg peptide, a pharma-ceutically acceptable salt of about 25 μg peptide to about 250 μg peptide, a pharma-ceutically acceptable salt of about 25 μg peptide to about 300 μg peptide, or a pharma-ceutically acceptable salt of about 50 μg peptide. from about 100 μg of a pharma- ceutically acceptable salt of a peptide, from about 50 μg of a pharma-ceutically acceptable salt of a peptide to about 150 μg of a pharma-ceutically acceptable salt of a peptide, from about 50 μg of a pharma-ceutically acceptable salt of a peptide to about 200 μg of a pharma-ceutically acceptable salt of a peptide, from about 50 μg of a pharma-ceutically acceptable salt of a peptide to about 250 μg of a pharma-ceutically acceptable salt of a peptide, from about 50 μg of a pharma-ceutically acceptable salt of a peptide to about 300 μg of a pharma-ceutically acceptable salt of a peptide,about 100 μg of a pharma- ceutically acceptable salt of a peptide to about 150 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide to about 200 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide to about 250 μg of a pharma- ceutically acceptable salt of a peptide, about 100 μg of a pharma- ceutically acceptable salt of a peptide to about 300 μg of a pharma- ceutically acceptable salt of a peptide, about 150 μg of a pharma- ceutically acceptable salt of a peptide to about 200 μg of a pharma- ceutically acceptable salt of a peptide, about 15 The pharma- ceutically acceptable salt of the peptide may range from about 0 μg of a pharma- ceutically acceptable salt of peptide to about 250 μg of a pharma- ceutically acceptable salt of peptide, from about 150 μg of a pharma- ceutically acceptable salt of peptide to about 300 μg of a pharma- ceutically acceptable salt of peptide, from about 200 μg of a pharma- ceutically acceptable salt of peptide to about 250 μg of a pharma- ceutically acceptable salt of peptide, from about 200 μg of a pharma- ceutically acceptable salt of peptide to about 300 μg of a pharma- ceutically acceptable salt of peptide, or from about 250 μg of a pharma- ceutically acceptable salt of peptide to about 300 μg of a pharma- ceutically acceptable salt of peptide. In some embodiments, the dose comprises about 5 μg of a pharma- ceutically acceptable salt of a peptide, about 25 μg of a pharma-ceutically acceptable salt of a peptide, about 50 μg of a pharma-ceutically acceptable salt of a peptide, about 100 μg of a pharma-ceutically acceptable salt of a peptide, about 150 μg of a pharma-ceutically acceptable salt of a peptide, about 200 μg of a pharma-ceutically acceptable salt of a peptide, about 250 μg of a pharma-ceutically acceptable salt of a peptide, or about 300 μg of a pharma-ceutically acceptable salt of a peptide.

[0105] The concentration of the peptide in the composition may be adjusted in a manner suitable for ocular administration. In some embodiments, the concentration of the peptide in the composition ranges from about 0.1 milligrams per milliliter (mg / mL) to about 5 mg / mL. In some embodiments, the concentration of the peptide in the composition ranges from about 0.1 milligrams per milliliter (mg / mL) to about 10 mg / mL. In some embodiments, the concentration of the peptide in the composition ranges from about 0.1 milligrams per milliliter (mg / mL) to about 100 mg / mL. In some embodiments, the concentration of the peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) or a pharma- ceutically acceptable salt thereof ranges from about 0.1 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, ranges from about 0.1 milligrams per milliliter (mg / mL) to about 5 mg / mL. In some embodiments, the concentration of the peptide having the structure of Formula I or a pharma- ceutically acceptable salt thereof ranges from about 0.1 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the peptide having the structure of Formula III or a pharma- ceutically acceptable salt thereof ranges from about 0.1 mg / mL to about 5 mg / mL.

[0106] In some embodiments, the concentration of the peptide in the composition ranges from about 0.1 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the peptide in the composition is at least about 0.1 mg / mL. In some embodiments, the concentration of the peptide in the composition ranges up to about 5 mg / mL. In some embodiments, the concentration of the peptide in the composition ranges from about 0.1 mg / mL to about 0.5 mg / mL, from about 0.1 mg / mL to about 1 mg / mL, from about 0.1 mg / mL to about 1.5 mg / mL, from about 0.1 mg / mL to about 2 mg / mL, from about 0.1 mg / mL to about 2.5 mg / mL, from about 0.1 mg / mL to about 3 mg / mL, from about 0.1 mg / mL to about 4 mg / mL, from about 0.1 mg / mL to about 5 mg / mL, about 0.5 mg / mL to about 1 mg / mL, about 0.5 mg / mL to about 1.5 mg / mL, about 0.5 mg / mL to about 2 mg / mL, about 0.5 mg / mL to about 2.5 mg / mL, about 0.5 mg / mL to about 3 mg / mL, about 0.5 mg / mL to about 4 mg / mL, about 0.5 mg / mL to about 5 mg / mL, about 1 mg / mL to about 1.5 mg / mL, about 1 mg / mL to about 2 ... mL, about 1 mg / mL to about 2.5 mg / mL, about 1 mg / mL to about 3 mg / mL, about 1 mg / mL to about 4 mg / mL, about 1 mg / mL to about 5 mg / mL, about 1.5 mg / mL to about 2 mg / mL, about 1.5 mg / mL to about 2.5 mg / mL, about 1.5 mg / mL to about 3 mg / mL, about 1.5 mg / mL to about 4 mg / mL, about 1.5 mg / mL to about 5 mg / mL, about 2 mg / mL to about 2.5 mg / mL, about 2 mg / mL to about 3 mg / mL, about 2 mg / mL to about 4 mg / mL, about 2 mg / mL to about 5 mg / mL, about 2.5 mg / mL to about 3 mg / mL, about 2.5 mg / mL to about 4 mg / mL, about 2.5 mg / mL to about 5 mg / mL, about 3 mg / mL to about 4 mg / mL, about 3 mg / mL to about 5 mg / mL, or about 4 mg / mL to about 5 mg / mL. In some embodiments, the concentration of the peptide in the composition is about 0.1 mg / mL, about 0.5 mg / mL, about 1 mg / mL, about 1.5 mg / mL, about 2 mg / mL, about 2.5 mg / mL, about 3 mg / mL, about 4 mg / mL, or about 5 mg / mL.

[0107] Pharmacokinetics As contemplated herein, the compositions described herein are administered to the eye of an individual in need thereof. Administration to the eye (i.e., "ocular application" or "ocular administration") includes subconjunctival administration, intravitreal administration, retrobulbar administration, intracameral administration, subretinal administration, or suprachoroidal administration. In some embodiments, ocular administration includes subconjunctival administration, intravitreal administration, retrobulbar administration, or intracameral administration. In some embodiments, ocular administration includes intravitreal administration. In some embodiments, ocular administration includes subconjunctival administration. In some embodiments, ocular administration includes retrobulbar administration. In some embodiments, ocular administration includes intracameral administration.

[0108] In some embodiments, the dosage form comprising the composition described herein is generally administered to the vitreous humor of the eye. In some embodiments, the half-life of peptide (e.g., peptide comprising amino acid sequence HHIYLGAVNYIY) or its pharma- ceutically acceptable salt in the vitreous humor is more than about 30 days to more than about 275 days. In some embodiments, the peptide comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or the pharma- ceutically acceptable salt of the peptide, in the vitreous humor is more than about 30 days to more than about 275 days. In some embodiments, the peptide having the structure of formula I or its pharma- ceutically acceptable salt has a half-life of more than about 30 days to more than about 275 days in the vitreous humor. In some embodiments, the peptide having the structure of formula III or its pharma- ceutically acceptable salt has a half-life of more than about 30 days to more than about 275 days in the vitreous humor. In some embodiments, a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, has a half-life in the vitreous humor of greater than about 14 days to greater than about 275 days. In some embodiments, a peptide having the structure of formula I or a pharma- ceutically acceptable salt thereof has a half-life in the vitreous humor of greater than about 14 days to greater than about 275 days. In some embodiments, a peptide having the structure of formula III or a pharma- ceutically acceptable salt thereof has a half-life in the vitreous humor of greater than about 14 days to greater than about 275 days.

[0109] In some embodiments, the half-life of the peptide is greater than about 14 days in the eye. In some embodiments, the half-life of the peptide is greater than about 30 days in the eye. In some embodiments, the half-life of the peptide is greater than about 60 days in the eye. In some embodiments, the half-life of the peptide is greater than about 90 days in the eye. In some embodiments, the half-life of the peptide is greater than about 120 days in the eye. In some embodiments, the half-life of the peptide is greater than about 150 days in the eye. In some embodiments, the half-life of the peptide is greater than about 180 days in the eye. In some embodiments, the half-life of the peptide is greater than about 210 days in the eye. In some embodiments, the half-life of the peptide is greater than about 240 days in the eye. In some embodiments, the half-life of the peptide is greater than about 270 days in the eye.

[0110] In some embodiments, the half-life of the peptide is greater than about 14 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 30 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 60 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 90 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 120 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 150 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 180 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 210 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 240 days in the vitreous humor. In some embodiments, the half-life of the peptide is greater than about 270 days in the vitreous humor.

[0111] Determining the amount of peptide in the vitreous humor generally requires taking all or a substantial portion of the vitreous humor from the eye to sample the vitreous humor or sacrificing the eye. In some embodiments, taking all or a substantial portion of the vitreous humor from the human eye or sacrificing the eye is not feasible for maintaining the health of the human eye. Thus, in some embodiments, the half-life of the peptide in the human eye is determined by measuring and / or estimating the half-life of the peptide in the mammalian eye. In some embodiments, the mammal is a rabbit. In some embodiments, the mammal is a pig (e.g., a miniature pig). In some embodiments, the mammal is a monkey. Various methods of detecting the presence of drugs are also suitable for detecting peptides. For example, a suitable method for detecting peptides includes performing mass spectrometry (e.g., liquid chromatography / mass spectrometry (LC-MS) or high performance LC-MS (HPLC-MS)) on a sample from the vitreous humor.

[0112] method Provided herein are methods advantageous for use in improving visual function in individuals with ocular diseases and / or disorders. In some embodiments, the ocular disease and / or disorder comprises loss of visual function (e.g., best corrected visual acuity, visual field, contrast sensitivity, binocular vision function, low luminance visual acuity, low contrast visual acuity, color vision, perimetry, threshold sensitivity, reading speed, and / or light-dark adaptation). In some embodiments, the ocular disease and / or disorder comprises photoreceptor cell death. In some embodiments, the ocular disease and / or disorder comprises retinal pigment epithelium cell death. In some embodiments, the ocular disease and / or disorder comprises macular degeneration. In some embodiments, the ocular disease and / or disorder comprises inflammation in ocular and / or retinal tissue (e.g., as measured by proinflammatory markers in samples from the vitreous).

[0113] Herein, a method is described and provided for improving the visual function (e.g., BCVA) of an individual's eye with an eye disease or disorder, comprising administering a Fas inhibitor to the eye of the individual.Further, herein, a method is described and provided for improving the visual function (e.g., BCVA) of an individual's eye with an eye disease or disorder, comprising administering a peptide (e.g., a composition comprising a peptide) comprising the amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharma- ceutically acceptable salt of the peptide to the eye of the individual.Further, herein, a method is described and provided for improving the visual function (e.g., BCVA) of an individual's eye with an eye disease or disorder, comprising administering a peptide (e.g., a composition comprising a peptide) having the structure of formula I or a pharma-ceutically acceptable salt thereof to the eye of the individual. Described and provided herein are methods of improving visual function (e.g., BCVA) of an eye of an individual having an ocular disease or disorder, the method comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) having a structure of Formula III or a pharmaceutically acceptable salt thereof. In some embodiments, the ocular disease or disorder comprises loss of visual function. In some embodiments, the ocular disease or disorder comprises photoreceptor cell death or a symptom thereof (e.g., loss of visual function). In some embodiments, the ocular disease or disorder comprises loss of visual function. In some embodiments, the ocular disease or disorder comprises photoreceptor cell death or a symptom thereof (e.g., loss of visual function). In some embodiments, the ocular disease or disorder comprises retinal pigment epithelial cell death or a symptom thereof (e.g., loss of visual function). In some embodiments, the ocular disease or disorder comprises macular degeneration. In some embodiments, the method comprises improving visual function without performing surgery. In some embodiments, the surgery is performed after administering the peptide or a variant sequence thereof, or a pharmaceutically acceptable salt of the peptide. In some embodiments, the surgery comprises retinal reattachment surgery. In some embodiments, the surgery comprises vitreous surgery.

[0114] Further, herein, a method for treating the loss of visual function (e.g., BCVA) of an individual's eye with macular degeneration is described and provided, comprising administering a Fas inhibitor to the eye of the individual.Also, a method for treating the loss of visual function (e.g., BCVA) of an individual's eye with macular degeneration is described and provided, comprising administering a peptide (e.g., a composition comprising a peptide) comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharmaceutically acceptable salt of the peptide to the eye of the individual.Further, herein, a method for treating the loss of visual function (e.g., BCVA) of an individual's eye with macular degeneration is described and provided, comprising administering a peptide (e.g., a composition comprising a peptide) having the structure of formula I or a pharmaceutically acceptable salt thereof to the eye of the individual. Described herein is a method for treating the loss of visual function (e.g., BCVA) of an eye of an individual with macular degeneration, comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) having the structure of formula III or a pharma-ceutically acceptable salt thereof. In some embodiments, the macular degeneration comprises age-related macular degeneration. In some embodiments, the macular degeneration comprises geographic atrophy.

[0115] Also described herein is a method for treating macular degeneration in the eye of an individual with geographic atrophy (e.g., AMD characterized by geographic atrophy), comprising administering a Fas inhibitor to the eye of the individual.Furthermore, described herein is a method for treating macular degeneration in the eye of an individual with geographic atrophy (e.g., AMD characterized by geographic atrophy), comprising administering a peptide (e.g., a composition comprising a peptide) comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharmaceutically acceptable salt of the peptide to the eye of the individual.Furthermore, described herein is a method for treating macular degeneration in the eye of an individual with geographic atrophy (e.g., AMD characterized by geographic atrophy), comprising administering a peptide (e.g., a composition comprising a peptide) having the structure of formula I or a pharmaceutically acceptable salt of the peptide to the eye of the individual. Described herein is a method for treating macular degeneration in an eye of an individual with geographic atrophy (e.g., AMD characterized by geographic atrophy), comprising administering to the eye of the individual a peptide (e.g., a composition comprising the peptide) having the structure of formula III or a pharma-ceutical acceptable salt thereof. In some embodiments, the macular degeneration comprises age-related macular degeneration.

[0116] In some embodiments, treating visual function comprises improving visual function compared to a baseline visual function prior to administration of the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, visual function comprises one or more measurements selected from the group consisting of best corrected visual acuity (e.g., readability), visual field, contrast sensitivity, binocular function, low luminance visual acuity, low contrast visual acuity, color vision, perimetry, threshold sensitivity, reading speed, and light-dark adaptation. In some embodiments, visual function comprises best corrected visual acuity (e.g., an increase in visual acuity from 20 / 200 to 20 / 100, or an increase in visual acuity from 20 / 50 to 20 / 40, and / or an increase in visual acuity measured by a decrease in logMAR value). In some embodiments, visual function comprises visual field. In some embodiments, visual function comprises contrast sensitivity. In some embodiments, visual function comprises binocular visual function. In some embodiments, visual function comprises low luminance visual acuity. In some embodiments, visual function comprises low contrast visual acuity. In some embodiments, visual function comprises color vision. In some embodiments, visual function comprises perimetry. In some embodiments, the visual function comprises threshold sensitivity. In some embodiments, the visual function comprises reading speed. In some embodiments, the visual function comprises light-dark adaptation. In some embodiments, improving visual function comprises improving visual function compared to a baseline visual function prior to administration of the peptide or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide.

[0117] In some embodiments, the methods described herein include methods of treating vision loss associated with ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, retinal inflammation may be determined by observing symptoms associated with ocular inflammation (e.g., loss and / or diminution of vision, loss of central vision, blurred vision, distorted vision, etc.) and / or by biological assays that detect the presence of inflammatory molecules (e.g., inflammatory cytokines) in a sample taken from the eye (e.g., a vitreous humor sample). Exemplary inflammatory molecules include, but are not limited to, Fas-mediated inflammation-related molecules (e.g., TNFa, IL-1b, IP-10, IL-18, MIP-1a, IL-6, GFAP, MIP2, MCP-1, or MIP-1b), Fas-mediated complement-related molecules (complement component 3 (C3) or complement component 1q (Clq)), caspase 8, components of the inflammasome (e.g., NLRP3 or NLRP2), C-X-C motif chemokines (e.g., CXCL2 (MIP-2α) or chemokines with a C-X-3-C motif (e.g., CX3CL1 (fractalkine)), chemokines with a C-C motif (CCL2 (MCP-1), CCL3 (MIP-1a), and CCL4 (MIP-1b)), toll-like receptor 4 (TLR4), interleukin cytokines (e.g., IL-1b, IL-18, and IL-6), TNF superfamily cytokines (e.g., TNFa), or GFAP.

[0118] In some embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by intravitreal injection, intracameral injection, injection into the suprachoroidal space, injection into the sub-Tenon's space, subconjunctival injection, retrobulbar injection, periocular injection, microneedle injection, subretinal injection, or subretinal injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by intravitreal injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by intracameral injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by injection into the suprachoroidal space. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by injection into the sub-Tenon's space. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by subconjunctival injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by retrobulbar injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by periocular injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by microneedle injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by subretinal injection. In certain embodiments, the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide is administered by subretinal injection.

[0119] In some embodiments, the variant sequence comprises an amino acid substitution. In some embodiments, the variant sequence comprises one amino acid substitution. In some embodiments, the variant sequence comprises two amino acid substitutions. In some embodiments, the variant sequence comprises three amino acid substitutions.

[0120] In some embodiments, the peptide further comprises a modification. In some embodiments, the peptide comprises a modified amino acid or a non-naturally occurring amino acid. In some embodiments, the peptide comprises an amidated C-terminus. In some embodiments, the peptide has the structure of Formula I, or a pharma- ceutically acceptable salt thereof. In some embodiments, the peptide has the structure of Formula III, or a pharma- ceutically acceptable salt thereof.

[0121] In some embodiments, a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, the pharma- ceutically acceptable salt is an acetate. In some embodiments, the pharma- ceutically acceptable salt is a polyacetate. In some embodiments, the polyacetate is a triacetate. In some embodiments, the pharma- ceutically acceptable salt is a hydrochloride.

[0122] In some embodiments, the pharma- ceutically acceptable salt is an acetate salt. In some embodiments, the pharma- ceutically acceptable salt is a polyacetate salt. In some embodiments, the polyacetate salt is a triacetate salt. In some embodiments, the pharma- ceutically acceptable salt is a hydrochloride salt.

[0123] In some embodiments, the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is formulated into a composition (eg, a pharmaceutical composition described herein).

[0124] In some embodiments, about 5-1,000 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 5-500 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 5-200 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 5-100 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 5-50 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 50-500 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 50-200 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 50-100 μg of the peptide or its variant sequence, or a pharma- ceutically acceptable salt of the peptide, is administered.

[0125] In some embodiments, about 5 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 25 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 50 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 100 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 200 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 500 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered. In some embodiments, about 1000 μg of the peptide or variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide is administered.

[0126] In some embodiments, the peptide is present at a concentration of 0.1 milligrams per milliliter (mg / mL) to 10 mg / mL. In some embodiments, the peptide is present at a concentration of 0.1 milligrams per milliliter (mg / mL) to 5.0 mg / mL.

[0127] As used herein, the term "best corrected visual acuity" or "BCVA" generally refers to the smallest visual angle subtended by a certain arc minute. In a particular case, the subtended visual angle of an object is the angle formed by the light rays projected from the eye above and below (or to the left and right) the object. In such a case, such visual angle is used to indicate the size of the retinal image of the object (e.g., the larger the visual angle, the larger the retinal image). In a particular case, the visual angle is influenced by two parameters: the size of the object and the distance of the object from the eye. A larger object projects a larger image on the retina than a smaller object. Thus, the larger the object, the larger its visual angle. A closer object projects a larger image on the retina than a smaller object. Thus, the closer the object is to the eye, the larger its visual angle. Thus, as an example, standard visual acuity is the ability to distinguish a point that is 1 arc minute away. As a further example, the ability to distinguish a set of lines that are 1 arc minute away is 20 / 20 visual acuity, and the ability to distinguish a set of lines that are 2 arc minutes away is 20 / 40 visual acuity. In some embodiments, visual acuity is measured by Snellen Index, ETDRS chart, Landolt C chart, Tumbling E chart, HOTV chart, and / or logMAR (minimum visual angle). Figures 2A-2B show exemplary, but non-limiting, conversion charts for comparing BCVA values.

[0128] As used herein, macular degeneration generally includes and / or refers to any of a number of conditions in which the retina macula degenerates and / or malfunctions (e.g., resulting from decreased proliferation of macular cells, increased death or remodeling of macular cells (e.g., RPE cells), loss of normal biological function, or a combination thereof). Macular degeneration generally causes loss of integrity of normal macular cells and / or extracellular matrix histology and / or loss of macular cell function. As used herein, macular degeneration also includes and / or refers to changes outside the macula that occur before or after macular dysfunction and / or macular degeneration. In some embodiments, the method includes treating symptoms associated with macular degeneration (e.g., retinal degeneration, elevated intraocular pressure, loss and / or reduction of visual acuity, blurred vision, distorted vision, etc.). In some embodiments, treating includes improving visual function (e.g., compared to baseline visual function measured before treatment). In some embodiments, the macular degeneration is age-related macular degeneration. In some embodiments, the macular degeneration comprises geographic atrophy. In some embodiments, the macular degeneration comprises loss and / or death of retinal pigment epithelial cells, photoreceptors, or a combination thereof. In some embodiments, the macular degeneration comprises loss and / or death of retinal pigment epithelial cells. In some embodiments, the macular degeneration comprises loss and / or death of photoreceptors. In some embodiments, the macular degeneration comprises loss and / or death of a combination of retinal pigment epithelial cells and photoreceptors.

[0129] Methods including surgery Despite advances in surgical techniques to treat neuroretinal detachments (e.g., retinal reattachment surgery), functional outcomes are often poor and / or suboptimal. Even considering such advances in surgical procedures, less than half of all patients achieve 20 / 40 visual acuity, and only about one-quarter of patients have a similar outcome when considering only cases involving the macula. Generally, visual recovery worsens with increasing detachment time. The loss of vision and sometimes permanent damage in such patients is generally due to photoreceptor cell death and retinal anoxia caused by the effects of the retinal detachment condition. Further challenges in effectively treating retinal detachments also arise because, in some cases, the diagnosis of retinal detachment is often delayed due to patients lacking access to treatment or knowledge of the symptoms. Further challenges also arise when other factors such as detachment time (measurable, for example, by loss of central vision), the extent of detachment, size of the detachment, the age of the individual, and / or the inflammatory state of the eye are considered. Generally, as such factors increase, the outcome of treatment associated with surgery alone (e.g., best corrected visual acuity after treatment) worsens.The methods and compositions described herein provide a solution to the problem of treating neuroretinal detachment and ocular diseases or disorders associated with neuroretinal detachment.Furthermore, in certain cases, the methods and compositions described herein provide the advantage of meeting such problems associated with standard treatment surgery alone (e.g., surgery to reattach retina).

[0130] Provided herein are methods that are advantageous for use in treating patients with detached (e.g., completely or partially detached) retinas. In some embodiments, the methods described herein include a combination of administering a Fas inhibitor (e.g., a Fas inhibitor peptide) to the eye of an individual and performing surgery on the eye. In some embodiments, the methods described herein include a method of treating retinal detachment. In some embodiments, the method includes treating symptoms associated with retinal detachment (e.g., loss and / or diminution of vision, loss of central vision, blurred vision, distorted vision, etc.). As used herein, retinal detachment generally includes and refers to ocular conditions and / or disorders in which the neural retina detaches (e.g., peels, separates, etc.) from the underlying support tissue. In some embodiments, retinal detachment refers to when the neural retina detaches (e.g., peels, separates, etc.) from the underlying support tissue. In some embodiments, retinal detachment refers to a disease or disorder in which the neural retina detaches (e.g., peels, separates, etc.) from the underlying support tissue. In some embodiments, types of retinal detachment include, but are not limited to, rhegmatogenous retinal detachment (RRD), tractional retinal detachment, and exudative detachment. As used herein, rhegmatogenous retinal detachment (RRD) generally includes and refers to a condition in which the vitreous fluid becomes less viscous and the retina is pulled from its attachment to the vitreous and retina, resulting in detachment of the retina during the liquefaction stage. In addition, further trauma to the eye caused by blunt force may cause rhegmatogenous retinal detachment (RRD). As used herein, tractional retinal detachment generally includes and refers to contraction of cell membranes that may form on the retina as a result of disease processes (e.g., neovascularization due to proliferative diabetic retinopathy). As used herein, exudative detachment generally includes and refers to a condition in which fluid accumulates between the retinal pigment epithelium and the neural retina (e.g., due to ocular inflammation, hemorrhage, or tumor growth). Retinal detachments may be relatively small and discrete or may involve large areas of the retina. Retinal detachments may include partial or complete detachments. In some embodiments, the retinal detachment is chronic. In some embodiments, the retinal detachment is acute.In some cases, the size and location of the detachment (macular or extramacular) determines the extent of vision loss. In some embodiments, the retinal detachment includes retinal detachment with macular detachment. In some embodiments, the retinal detachment includes retinal detachment without macular detachment (macula-on). In some embodiments, the methods described herein include methods of treating retinal damage, where the retinal damage includes detachment of the neural retina. In certain embodiments, the retinal damage includes an external force to an individual (e.g., damage from laser light, impact with an object, trauma from force, etc.) that causes damage to the eye (e.g., retinal detachment). In certain embodiments, the retinal damage includes an internal force to an individual (e.g., disease, inflammation, aging, etc.) that causes damage to the eye (e.g., retinal detachment).

[0131] In some embodiments, the methods described herein include methods of treating loss and / or decline in vision. In some embodiments, the methods described herein include methods of inhibiting, reducing, and / or preventing loss and / or decline in vision. In some embodiments, the loss and / or decline in vision is characterized and / or corresponds to a decline in vision (e.g., a decline in vision from 20 / 100 to 20 / 200, or a decline in vision from 20 / 40 to 20 / 50, and / or a decline in vision measured by an increase in logMAR value).

[0132] In some embodiments, the methods described herein include methods of treating loss and / or decline of visual function. In some embodiments, the methods described herein include methods of inhibiting, reducing, and / or preventing loss and / or decline of visual function. In some embodiments, the loss of visual function is characterized and / or corresponds to a decline in visual function assessment (e.g., visual acuity, visual field, contrast sensitivity, binocular function, low luminance visual acuity, low contrast visual acuity, color vision, perimetry, threshold sensitivity, and / or light-dark adaptation).

[0133] In some embodiments, the methods described herein include methods of treating ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the methods described herein include methods of inhibiting, reducing, and / or preventing ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the methods include treating symptoms associated with ocular inflammation (e.g., increased intraocular pressure, loss and / or decreased vision, loss of central vision, blurred vision, distorted vision, etc.). In some embodiments, retinal inflammation may be determined by observing symptoms associated with ocular inflammation (e.g., loss and / or decreased vision, loss of central vision, blurred vision, distorted vision, etc.) and / or by biological assays that detect the presence of inflammatory molecules (e.g., inflammatory cytokines) in a sample taken from the eye (e.g., a vitreous humor sample). Exemplary inflammatory molecules include, but are not limited to, Fas-mediated inflammation-related molecules (e.g., TNFa, IL-1b, IP-10, IL-18, MIP-1a, IL-6, GFAP, MIP2, MCP-1, or MIP-1b), Fas-mediated complement-related molecules (complement component 3 (C3) or complement component 1q (Clq)), caspase 8, components of the inflammasome (e.g., NLRP3 or NLRP2), C-X-C motif chemokines (e.g., CXCL2 (MIP-2α) or chemokines with a C-X-3-C motif (e.g., CX3CL1 (fractalkine)), chemokines with a C-C motif (CCL2 (MCP-1), CCL3 (MIP-1a), and CCL4 (MIP-1b)), toll-like receptor 4 (TLR4), interleukin cytokines (e.g., IL-1b, IL-18, and IL-6), TNF superfamily cytokines (e.g., TNFa), or GFAP.

[0134] In certain cases, treating ocular inflammation and / or detached neural retina is useful for treating retinal cell loss. In certain cases, inhibiting, reducing, and / or preventing ocular inflammation is useful for treating, inhibiting, reducing, and / or preventing retinal cell loss. In some embodiments, the methods described herein include methods for treating ocular retinal cell loss (e.g., retinal pigment epithelial cells and / or photoreceptors). In some embodiments, the methods described herein include methods for inhibiting, reducing, and / or preventing ocular retinal cell loss (e.g., retinal pigment epithelial cells and / or photoreceptors). In some embodiments, the methods include treating symptoms associated with ocular retinal cell loss (e.g., retinal pigment epithelial cells and / or photoreceptors) (e.g., loss and / or reduction of vision, loss of central vision, blurred vision, distorted vision, etc.). In some embodiments, the methods include inhibiting, reducing, and / or preventing symptoms associated with loss of retinal cells (e.g., retinal pigment epithelial cells and / or photoreceptors) in the eye (e.g., loss and / or diminution of vision, loss of central vision, blurred vision, distorted vision, etc.).

[0135] In certain cases, ocular inflammation, detached neural retina, and / or retinal cell loss are treated. In certain cases, inhibiting, reducing, and / or preventing ocular inflammation and / or retinal cell loss is useful for treating, inhibiting, reducing, and / or preventing the pathology of ocular diseases, disorders, or conditions. As used herein, ocular diseases, disorders, or conditions generally include and / or refer to ocular disorders or pathological conditions that are not normal to a healthy eye. In some embodiments, the methods described herein include methods of treating ocular diseases, disorders, or conditions. In some embodiments, the methods described herein include methods of inhibiting, reducing, and / or preventing ocular diseases, disorders, or conditions. In some embodiments, the methods include treating symptoms associated with ocular diseases, disorders, or conditions (e.g., loss and / or reduction of vision, loss of central vision, blurred vision, distorted vision, etc.). In some embodiments, the methods include inhibiting, reducing, and / or preventing symptoms associated with an ocular disease, disorder, or condition (e.g., loss and / or diminution of vision, loss of central vision, blurred vision, distorted vision, etc.) In some embodiments, the ocular disease, disorder, or condition includes loss and / or death of photoreceptors.

[0136] In some embodiments, the methods described herein include administering a Fas inhibitor (e.g., a Fas inhibitory peptide). In some embodiments, the methods described herein include administering a Fas inhibitory peptide (e.g., a peptide comprising the amino acid sequence HHIYLGAVNYIY) or a pharma- ceutically acceptable salt thereof. In some embodiments, the methods described herein include administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide. In some embodiments, the methods described herein include administering a peptide (e.g., a composition comprising the peptide) having the structure of any one of formulas I to IX, or a pharma- ceutically acceptable salt thereof. In some embodiments, the methods described herein include administering a peptide (e.g., a composition comprising the peptide) having the structure of formula I, or a pharma- ceutically acceptable salt thereof. In some embodiments, the methods described herein include administering a peptide (e.g., a composition comprising the peptide) having the structure of formula III, or a pharma- ceutically acceptable salt thereof.

[0137] Provided herein is a method comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formula I to IX or a pharma- ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a method comprising administering a peptide (e.g., a composition comprising the peptide) comprising the structure of formula I or a pharma- ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method that includes administering to an eye of an individual a peptide having a structure of Formula III or a pharma- ceutically acceptable salt thereof (e.g., a composition comprising the peptide) and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0138] Provided herein is the use of a Fas inhibitor in a method comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is the use of a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- tically acceptable salt of the peptide, in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- tically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma- tically acceptable salt thereof, in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- tically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having the structure of formula I, or a pharma- tically acceptable salt thereof, in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- tically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula III, or a pharma- ceutical acceptable salt thereof, in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutical acceptable salt thereof to an eye of an individual, and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0139] Provided herein is a Fas inhibitor for use in a method comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide for use in a method comprising administering a peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method comprising administering a peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula III, or a pharma- ceutically acceptable salt thereof, for use in a method comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0140] In some embodiments, the method is a method of treating retinal detachment. In some embodiments, the method is a method of treating retinal detachment. In certain embodiments, the retinal detachment is rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is macula-off rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is macula-on rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is tractional retinal detachment. In certain embodiments, the retinal detachment is exudative detachment. In certain embodiments, the retinal detachment is due to retinal damage. In some embodiments, the method is a method of treating loss and / or decline in vision. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing loss and / or decline in vision. In some embodiments, the method is a method of treating loss and / or decline in visual function. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing loss and / or decline in visual function. In some embodiments, the method is a method of treating ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the method is a method of inhibiting, reducing, and / or preventing ocular inflammation (e.g., Fas-mediated inflammation). In some embodiments, the method is a method of treating loss of ocular photoreceptor cells in the eye. In some embodiments, the method is a method of inhibiting, reducing, and / or preventing loss of ocular photoreceptor cells. In some embodiments, the method is a method of treating an ocular disease, disorder, or condition. In some embodiments, the method is a method of inhibiting progression of an ocular disease, disorder, or condition, or symptoms associated therewith.

[0141] Provided herein is a method for treating retinal detachment, comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method for treating retinal detachment, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method for treating retinal detachment, comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formula I to IX or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a method for treating retinal detachment, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the structure of formula I or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method of treating retinal detachment comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of Formula III or a pharma- ceutical acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0142] Provided herein is the use of a Fas inhibitor in a method for treating retinal detachment, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharma- ceutically acceptable salt of the peptide, in a method for treating retinal detachment, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for treating retinal detachment, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of treating retinal detachment comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of treating retinal detachment comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0143] Provided herein is a Fas inhibitor for use in a method for treating retinal detachment, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method for treating retinal detachment, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method for treating retinal detachment, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of treating retinal detachment comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide), or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of treating retinal detachment comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide), or a pharma-ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0144] In certain embodiments, the retinal detachment is a rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a macula-off rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a macula-on rhegmatogenous retinal detachment (RRD). In certain embodiments, the retinal detachment is a traction retinal detachment. In certain embodiments, the retinal detachment is an exudative detachment. In certain embodiments, the retinal detachment is due to retinal injury.

[0145] Provided herein is a method for treating vision loss and / or decline, comprising administering a Fas inhibitor to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Also provided is a method for treating vision loss and / or decline, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Further provided is a method for treating vision loss and / or decline, comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formulas I to IX or a pharma-ceutically acceptable salt thereof to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Methods of treating loss and / or decline in vision are provided that include administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula I or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual. Methods of treating loss and / or decline in vision are also provided that include administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0146] Provided herein is the use of a Fas inhibitor in a method for treating vision loss and / or decline, comprising administering the Fas inhibitor to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Also provided is the use of a peptide comprising amino acid sequence HHIYLGAVNYIY or its variant sequence, or a pharma- ceutically acceptable salt of the peptide, in a method for treating vision loss and / or decline, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for treating vision loss and / or decline, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of treating loss and / or impairment of vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of treating loss and / or impairment of vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0147] Provided herein is a Fas inhibitor for use in a method for treating vision loss and / or decline, comprising administering the Fas inhibitor to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method for treating vision loss and / or decline, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method for treating vision loss and / or decline, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is a peptide having the structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of treating loss and / or decline in vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is a peptide having the structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of treating loss and / or decline in vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0148] Provided herein is a method for inhibiting, reducing, and / or preventing vision loss and / or decline, comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method for inhibiting, reducing, and / or preventing vision loss and / or decline, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method for inhibiting, reducing, and / or preventing vision loss and / or decline, comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formulas I to IX, or a pharma-ceutically acceptable salt thereof, to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Methods are provided for inhibiting, reducing, and / or preventing loss and / or deterioration of vision comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula I or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual. Also provided are methods for inhibiting, reducing, and / or preventing loss and / or deterioration of vision comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0149] Provided herein is the use of a Fas inhibitor in a method for inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, in a method for inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0150] Provided herein is a Fas inhibitor for use in a method of inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method of inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or deterioration of vision, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline in vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline in vision comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0151] Provided herein is a method for inhibiting, reducing, and / or preventing the loss and / or decline of visual function, comprising administering a Fas inhibitor to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Also provided is a method for inhibiting, reducing, and / or preventing the loss and / or decline of visual function, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.Further provided is a method for inhibiting, reducing, and / or preventing the loss and / or decline of visual function, comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formulas I to IX or a pharma-ceutically acceptable salt thereof to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Methods are provided for inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula I or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual. Also provided are methods for inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0152] Provided herein is the use of a Fas inhibitor in a method for inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, in a method for inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0153] Provided herein is a Fas inhibitor for use in a method of inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline of visual function, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing loss and / or decline in visual function comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0154] Provided herein is a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formulas I to IX, or a pharma-ceutically acceptable salt thereof, to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Methods are provided for inhibiting, reducing, and / or preventing loss of photoreceptor cells comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula I or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual. Also provided are methods for inhibiting, reducing, and / or preventing loss of photoreceptor cells comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0155] Provided herein is the use of a Fas inhibitor in a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, in a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of inhibiting, reducing, and / or preventing loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0156] Provided herein is a Fas inhibitor for use in a method of inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method of inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing the loss of photoreceptor cells, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing photoreceptor cell loss comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting, reducing, and / or preventing photoreceptor cell loss comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0157] Provided herein is a method of treating an ocular disease, comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method of treating an ocular disease, comprising administering to an individual's eye a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method of treating an ocular disease, comprising administering to an individual's eye a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formula I to IX, or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a method of treating an ocular disease, comprising administering to an individual's eye a peptide (e.g., a composition comprising the peptide) comprising the structure of formula I, or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method of treating an eye disease comprising administering to an eye of an individual a peptide (e.g., a composition comprising the peptide) comprising the structure of Formula III or a pharma- ceutically acceptable salt thereof and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0158] Provided herein is the use of a Fas inhibitor in a method for treating an ocular disease, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, in a method for treating an ocular disease, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for treating an ocular disease, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt thereof to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of treating an ocular disease comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is the use of a peptide having a structure of Formula III, or a pharma- ceutically acceptable salt thereof, in a method of treating an ocular disease comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of the individual and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0159] Provided herein is a Fas inhibitor for use in a method of treating an ocular disease, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, for use in a method of treating an ocular disease, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, for use in a method of treating an ocular disease, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of treating an ocular disease comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide), or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having the structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of treating an ocular disease comprising administering to an individual's eye the peptide (e.g., a composition comprising the peptide), or a pharma-ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye.

[0160] Provided herein is a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering a Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Also provided is a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering to an individual's eye a peptide (e.g., a composition comprising the peptide) comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, and performing surgery (e.g., standard of care surgery) on the individual's eye. Further provided is a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering to an individual's eye a peptide (e.g., a composition comprising the peptide) comprising any one of the structures of formulas I to IX, or a pharma-ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the individual's eye. Methods are provided for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering to the eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of Formula I, or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the eye of the individual. Also provided are methods for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering to the eye of an individual a peptide (e.g., a composition comprising the peptide) comprising a structure of Formula III, or a pharma- ceutically acceptable salt thereof, and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0161] Provided herein is the use of a Fas inhibitor in a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is the use of a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharma- ceutically acceptable salt of the peptide, in a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is the use of a peptide having the structure of any one of formulas I to IX, or a pharma-ceutically acceptable salt thereof, in a method for inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma-ceutically acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is the use of a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, in a method of inhibiting the progression of an ocular disease, disorder, or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual, and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is the use of a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, in a method of inhibiting the progression of an ocular disease, disorder, or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual, and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0162] Provided herein is a Fas inhibitor for use in a method of inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the Fas inhibitor to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Also provided is a peptide comprising the amino acid sequence HHIYLGAVNYIY or a variant sequence thereof, or a pharmacologic acceptable salt of the peptide, for use in a method of inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharmacologic acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye.Further provided is a peptide having the structure of any one of formulas I to IX, or a pharmacologic acceptable salt thereof, for use in a method of inhibiting the progression of an ocular disease, disorder or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharmacologic acceptable salt of the peptide to an individual's eye and performing surgery (e.g., standard of care surgery) on the individual's eye. Provided is a peptide having a structure of Formula I, or a pharma- ceutically acceptable salt thereof, for use in a method of inhibiting the progression of an ocular disease, disorder, or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual, and performing surgery (e.g., standard of care surgery) on the eye of the individual. Provided is a peptide having a structure of Formula III, or a pharma-ceutically acceptable salt thereof, for use in a method of inhibiting the progression of an ocular disease, disorder, or condition, or a symptom associated therewith, comprising administering the peptide (e.g., a composition comprising the peptide) or a pharma- ceutically acceptable salt thereof to the eye of an individual, and performing surgery (e.g., standard of care surgery) on the eye of the individual.

[0163] In some embodiments, the surgery (e.g., standard of care surgery) involves surgically reattaching the neural retina. In general, various surgical procedures are available to repair neural retinal detachment. In certain cases, the surgical procedure depends on the location and size of the retinal break and the subsequent detachment. For example, in the case of an isolated retinal break without associated subretinal fluid (e.g., a break that has not progressed to detachment), laser photocoagulation is usually used (e.g., a specially designed small laser is shined through a lens or ophthalmoscope to cauterize the tissue around the break, create a scar, and in essence, "weld" the retina to the retinal pigment epithelium). In addition to laser photocoagulation, in certain cases, cryocoagulation is used to freeze the retina around the break and also create a scar around the break to hold the retina in place. If the break progresses to detachment, other techniques are presented. In certain cases, pneumatic retinopexy is performed, in which a small amount of inert gas (SF6 or C2F8) is injected into the vitreous as a way to seal retinal breaks and reabsorb subretinal fluid by the RPE. In certain cases, a scleral buckle is used alone or in combination with another procedure, which involves placing a silicone band around the eye and under the external rectus muscle. In some cases, the procedure involves a pars plana vitrectomy (PPV), which involves removing vitreous fluid and applying homogenous pressure to press the retina against the RPE using a gas (C3F8 or SF6) or silicone oil tamponade. In such cases, the PPV procedure is often combined with a scleral buckle to improve the outcome of the intervention. In certain cases, PPV utilizes three therapeutic mechanisms: (1) removing the potential causative agent (liquefied vitreous), (2) compressing the eyeball against the retina, and (3) compressing the retina back against the RPE, thereby causing reattachment. In certain cases, any of the surgical procedures described herein may be used in the methods described herein.

[0164] In some embodiments, the surgery includes vitreous surgery, scleral buckle, pneumatic retinopexy, laser surgery, or a combination thereof. In some embodiments, the surgery includes vitreous surgery. In certain embodiments, the vitreous surgery is partial vitreous surgery. In certain embodiments, the vitreous surgery is full vitreous surgery. In certain embodiments, the vitreous surgery includes the use of silicone oil (e.g., replacing the vitreous with silicone oil). In certain embodiments, the vitreous surgery includes the use of a gas (e.g., replacing the vitreous with a gas). In some embodiments, the surgery includes a scleral buckle. In some embodiments, the surgery includes a pneumatic retinopexy. In some embodiments, the surgery includes laser surgery. In some embodiments, the surgery includes one or more of vitreous surgery, scleral buckle, pneumatic retinopexy, and laser surgery, or a combination thereof.

[0165] In some embodiments, the individual has a detached neural retina. In certain cases, the extent of detachment is associated with a greater decline in vision and visual function after surgery alone. In such cases, the effectiveness of surgical treatment or inhibition of vision loss generally declines with the size or extent of the detachment, but the methods provided herein are useful for inhibiting the decline in vision and visual function in patients with greater detachment. In certain embodiments, the neural retina is completely detached. In certain embodiments, the neural retina is partially detached. In certain embodiments, the neural retina is completely detached. Retinal detachment is generally indicated by clock time, with the extent or magnitude of detachment ranging from 1 to 12, with 12 being a complete detachment. In some embodiments, the extent of detachment is 12. In some embodiments, the extent of detachment is 11 or greater. In some embodiments, the extent of detachment is 10 or greater. In some embodiments, the extent of detachment is 9 or greater. In some embodiments, the extent of detachment is 8 or greater. In some embodiments, the extent of detachment is 7 or greater. In some embodiments, the extent of detachment is 6 or greater. In some embodiments, the degree of peeling is 5 or greater. In some embodiments, the degree of peeling is 4 or greater. In some embodiments, the degree of peeling is 3 or greater. In some embodiments, the degree of peeling is 2 or greater. In some embodiments, the degree of peeling is 1 or greater.

[0166] In some embodiments, the degree of peeling is from about 1 to about 12. In some embodiments, the degree of peeling is from about 1 to about 2, from about 1 to about 3, from about 1 to about 4, from about 1 to about 5, from about 1 to about 6, from about 1 to about 7, from about 1 to about 8, from about 1 to about 9, from about 1 to about 10, from about 1 to about 11, from about 1 to about 12, from about 2 to about 3, from about 2 to about 4, from about 2 to about 5, from about 2 to about 6, from about 2 to about 7, from about 2 to about 8, from about 2 to about 9, from about 2 to about 10, from about 2 to about 11, from about 2 to about 12, from about 3 to about 4, from about 3 to about 5, from about 3 to about 6, from about 3 to about 7, from about 3 to about 8, from about 3 to about 9, from about 3 to about 10, from about 3 to about 11, from about 3 to about 12, from about 4 to about 5, from about 4 to about 6, from about 4 to about 7, from about 4 to about 8, about 4 to about 9, about 4 to about 10, about 4 to about 11, about 4 to about 12, about 5 to about 6, about 5 to about 7, about 5 to about 8, about 5 to about 9, about 5 to about 10, about 5 to about 11, about 5 to about 12, about 6 to about 7, about 6 to about 8, about 6 to about 9, about 6 to about 10, about 6 to about 11, about 6 to about 12, about 7 to about 8, about 7 to about 9, about 7 to about 10, about 7 to about 11, about 7 to about 12, about 8 to about 9, about 8 to about 10, about 8 to about 11, about 8 to about 12, about 9 to about 10, about 9 to about 11, about 9 to about 12, about 10 to about 11, about 10 to about 12, or about 11 to about 12. In some embodiments, the degree of peeling is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, or about 12. In some embodiments, the degree of peeling is at least about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, or about 11.

[0167] In certain cases, increasing detachment height is associated with a greater decline in visual acuity and visual function after surgery alone. In such cases, the effectiveness of surgical treatment or inhibition of visual loss generally decreases with increasing detachment height, but the methods provided herein are useful for inhibiting the decline in visual acuity and visual function in patients with greater detachment height. In some embodiments, the detachment height is between 0 and 1 millimeter. In some embodiments, the detachment height is 1 millimeter or more. In some embodiments, the detachment height is 2 millimeters or more. In some embodiments, the detachment height is 3 millimeters or more. In some embodiments, the detachment height is 4 millimeters or more. In some embodiments, the detachment height is 5 millimeters or more. In some embodiments, the detachment height is 7 millimeters or more.

[0168] In some embodiments, the surgery is performed about (z) days after administration of the composition comprising the peptide, where (z) is at least 1. In certain cases, providing a Fas inhibitor before surgery results in improved outcomes (e.g., vision and visual function) compared to surgery alone. In certain cases, the time of ablation is associated with a greater decline in vision and visual function after surgery alone. Furthermore, the effectiveness of treating or inhibiting vision loss by surgery generally declines with the time of ablation, but patients do not always undergo surgery immediately or within a reasonable time (e.g., less than about 8 days). In such cases, the methods provided herein are useful for safely extending the time during which surgery is performed while inhibiting the decline in vision and visual function in patients. In some embodiments, (z) is 1 or more (e.g., about 1 day or more). In some embodiments, (z) is 2 or more (e.g., about 2 days or more). In some embodiments, (z) is 3 or more (e.g., about 3 days or more). In some embodiments, (z) is 4 or more (e.g., about 4 days or more). In some embodiments, (z) is 5 or greater (e.g., about 5 days or greater). In some embodiments, (z) is 6 or greater (e.g., about 6 days or greater). In some embodiments, (z) is 7 or greater (e.g., about 7 days or greater). In some embodiments, (z) is 8 or greater (e.g., about 8 days or greater). In some embodiments, (z) is 10 or greater (e.g., about 10 days or greater). In some embodiments, (z) is 14 or greater (e.g., about 14 days or greater).

[0169] In certain embodiments, (z) is from about 0.5 to about 21. In certain embodiments, (z) is from about 0.5 to about 1, from about 0.5 to about 2, from about 0.5 to about 3, from about 0.5 to about 4, from about 0.5 to about 5, from about 0.5 to about 7, from about 0.5 to about 10, from about 0.5 to about 14, from about 0.5 to about 21, from about 1 to about 2, from about 1 to about 3, from about 1 to about 4, from about 1 to about 5, from about 1 to about 7, from about 1 to about 10, from about 1 to about 14, from about 1 to about 21, from about 2 to about 3, from about 2 to about 4, from about 2 to about 5, from about 2 to about 7, from about 2 to about 10, from about 1 to about 14, from about 1 to about 21, to about 10, about 2 to about 14, about 2 to about 21, about 3 to about 4, about 3 to about 5, about 3 to about 7, about 3 to about 10, about 3 to about 14, about 3 to about 21, about 4 to about 5, about 4 to about 7, about 4 to about 10, about 4 to about 14, about 4 to about 21, about 5 to about 7, about 5 to about 10, about 5 to about 14, about 5 to about 21, about 7 to about 10, about 7 to about 14, about 7 to about 21, about 10 to about 14, about 10 to about 21, or about 14 to about 21. In certain embodiments, (z) is about 0.5, about 1, about 2, about 3, about 4, about 5, about 7, about 10, about 14, or about 21. In certain embodiments, (z) is at least about 0.5, about 1, about 2, about 3, about 4, about 5, about 7, about 10, or about 14.

[0170] In some embodiments, the surgery is performed about (h) hours after administration of the composition comprising the peptide, where (h) is at least 1. In some embodiments, (h) is 1 or more (e.g., about 1 hour or more). In some embodiments, (h) is 2 or more (e.g., about 2 hours or more). In some embodiments, (h) is 3 or more (e.g., about 3 hours or more). In some embodiments, (h) is 6 or more (e.g., about 6 hours or more). In some embodiments, (h) is 12 or more (e.g., about 12 hours or more). In some embodiments, (h) is 18 or more (e.g., about 18 hours or more). In some embodiments, (h) is 24 or more (e.g., about 24 hours or more). In some embodiments, (h) is 30 or more (e.g., about 30 hours or more). In some embodiments, (h) is 36 or more (e.g., about 36 hours or more). In some embodiments, (h) is 48 or more (e.g., about 48 hours or more).

[0171] In certain embodiments, (h) is from about 1 to about 42. In certain embodiments, (h) is from about 1 to about 2, from about 1 to about 3, from about 1 to about 6, from about 1 to about 12, from about 1 to about 18, from about 1 to about 24, from about 1 to about 30, from about 1 to about 36, from about 1 to about 42, from about 2 to about 3, from about 2 to about 6, from about 2 to about 12, from about 2 to about 18, from about 2 to about 24, from about 2 to about 30, from about 2 to about 36, from about 2 to about 42, from about 3 to about 6, from about 3 to about 12, from about 3 to about 18, from about 3 to about 24, from about 3 to about 30, from about 3 to about 36, from about 3 to about 42, about 6 to about 12, about 6 to about 18, about 6 to about 24, about 6 to about 30, about 6 to about 36, about 6 to about 42, about 12 to about 18, about 12 to about 24, about 12 to about 30, about 12 to about 36, about 12 to about 42, about 18 to about 24, about 18 to about 30, about 18 to about 36, about 18 to about 42, about 24 to about 30, about 24 to about 36, about 24 to about 42, about 30 to about 36, about 30 to about 42, or about 36 to about 42. In certain embodiments, (h) is about 1, about 2, about 3, about 6, about 12, about 18, about 24, about 30, about 36, or about 42. In certain embodiments, (h) is at least about 1, about 2, about 3, about 6, about 12, about 18, about 24, about 30, or about 36.

[0172] As used herein, the term "best corrected visual acuity" or "BCVA" generally refers to the smallest visual angle subtended by a certain arc minute. In a particular case, the subtended visual angle of an object is the angle formed by the light rays projected from the eye above and below (or to the left and right) the object. In such a case, such visual angle is used to indicate the size of the retinal image of the object (e.g., the larger the visual angle, the larger the retinal image). In a particular case, the visual angle is influenced by two parameters: the size of the object and the distance of the object from the eye. A larger object projects a larger image on the retina than a smaller object. Thus, the larger the object, the larger its visual angle. A closer object projects a larger image on the retina than a smaller object. Thus, the closer the object is to the eye, the larger its visual angle. Thus, as an example, standard visual acuity is the ability to distinguish a point that is 1 arc minute away. As a further example, the ability to distinguish a set of lines that are 1 arc minute away is 20 / 20 visual acuity, and the ability to distinguish a set of lines that are 2 arc minutes away is 20 / 40 visual acuity. In some embodiments, visual acuity is measured by Snellen Index, ETDRS chart, Landolt C chart, Tumbling E chart, HOTV chart, and / or logMAR (minimum visual angle). Figures 2A-2B show exemplary, but non-limiting, conversion charts for comparing BCVA values.

[0173] In certain cases, the degree of vision loss due to retinal detachment is associated with the final visual outcome after surgical treatment (e.g., worsening baseline vision is associated with decreased visual acuity). In certain cases, the methods described herein are useful for treating patients with extensive baseline vision loss (e.g., vision limited to manual or index valves). In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of hand motion discrimination. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of index valves. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of 20 / 100 or less (e.g., poor visual acuity such as 20 / 200) on the Snellen scale. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of 3 logMAR or greater (e.g., poor visual acuity such as 3.5 logMAR). In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of 2 logMAR or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of 1 logMAR or greater. In some embodiments, the individual has a baseline (e.g., pre-treatment) best corrected visual acuity of 0.5 logMAR or greater.

[0174] In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 200 or less (e.g., low visual acuity such as 20 / 400). In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 100 or less. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 70 or less. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA of 20 / 50 or less.

[0175] In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 32 minutes or more (e.g., low visual acuity such as a 40 minute angle). In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 24 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 16 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 8 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 4 minutes or more. In some embodiments, the individual has a baseline (e.g., pre-treatment) BCVA angle of 2 minutes or more.

[0176] In certain embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of about 1 minute to about 32 minutes. In certain embodiments, the individual has a baseline (e.g., pre-treatment) BCVA visual angle of about 1 minute to about 2 minutes, about 1 minute to about 4 minutes, about 1 minute to about 8 minutes, about 1 minute to about 12 minutes, about 1 minute to about 16 minutes, about 1 minute to about 20 minutes, about 1 minute to about 24 minutes, about 1 minute to about 28 minutes, about 1 minute to about 32 minutes, about 2 minutes to about 4 minutes, about 2 minutes to about 8 minutes, about 2 minutes to about 12 minutes, about 2 minutes to about 16 minutes, about 2 minutes to about 20 minutes, about 2 minutes to about 24 minutes, about 2 minutes to about 28 minutes, about 2 minutes to about 32 minutes, about 4 minutes to about 8 minutes, about 4 minutes to about 12 minutes, about 4 minutes to about 16 minutes, about 4 minutes to about 20 minutes, about 4 minutes to about 2 minutes. 4 minutes, about 4 minutes to about 28 minutes, about 4 minutes to about 32 minutes, about 8 minutes to about 12 minutes, about 8 minutes to about 16 minutes, about 8 minutes to about 20 minutes, about 8 minutes to about 24 minutes, about 8 minutes to about 28 minutes, about 8 minutes to about 32 minutes, about 12 minutes to about 16 minutes, about 12 minutes to about 20 minutes, about 12 minutes to about 24 minutes, about 12 minutes to about 28 minutes, about 12 minutes to about 32 minutes, about 16 minutes to about 20 minutes, about 16 minutes to about 24 minutes, about 16 minutes to about 28 minutes, about 16 minutes to about 32 minutes, about 20 minutes to about 24 minutes, about 20 minutes to about 28 minutes, about 20 minutes to about 32 minutes, about 24 minutes to about 28 minutes, about 24 minutes to about 32 minutes, or about 28 minutes to about 32 minutes. In certain embodiments, the individual has a baseline (e.g., before treatment) BCVA visual angle of about 1 minute, about 2 minutes, about 4 minutes, about 8 minutes, about 12 minutes, about 16 minutes, about 20 minutes, about 24 minutes, about 28 minutes, or about 32 minutes.In certain embodiments, the individual has a baseline (e.g., before treatment) BCVA visual angle of at least about 1 minute, about 2 minutes, about 4 minutes, about 8 minutes, about 12 minutes, about 16 minutes, about 20 minutes, about 24 minutes, about 28 minutes, or about 32 minutes.In certain embodiments, the individual has a baseline (e.g., before treatment) BCVA visual angle of at most about 2 minutes, about 4 minutes, about 8 minutes, about 12 minutes, about 16 minutes, about 20 minutes, about 24 minutes, about 28 minutes, or about 32 minutes.

[0177] In some embodiments, the subject has central vision loss. In certain cases, providing a Fas inhibitor before surgery results in improved outcomes (e.g., vision and visual function) in patients with central vision loss when compared to surgery alone. In certain such cases, providing a Fas inhibitor before surgery results in improved outcomes (e.g., vision and visual function) in patients with central vision loss over the long term (e.g., 3 days, 5 days, 7 days, 10 days, 14 days, 21 days, etc.) when compared to surgery alone. In certain cases, the time of detachment is measured by central vision loss. In certain cases, the time of central vision loss is associated with a greater decrease in vision and visual function after surgery alone. Furthermore, the effectiveness of treating or inhibiting vision loss by surgery generally decreases with increasing time of central vision loss. In such cases, the methods provided herein are useful for treating patients with central vision loss over the long term (e.g., 3 days, 5 days, 7 days, 10 days, 14 days, 21 days, etc.). In some embodiments, the individual's eye has a detached retina, and the retina has been detached for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1. In some embodiments, the individual's eye has a loss of central vision, and the loss of central vision has been present for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1. In certain embodiments, the individual's eye has retinal damage or symptoms thereof, and the retinal damage or symptoms thereof have been present for about (y) days or more (e.g., before administering a composition comprising a Fas inhibitor or performing surgery), and (y) is at least 1.

[0178] In certain embodiments, (y) is 1 (e.g., about 1 day or more). In certain embodiments, (y) is 3 (e.g., about 3 days or more). In certain embodiments, (y) is 5 (e.g., about 5 days or more). In certain embodiments, (y) is 7 (e.g., about 7 days or more). In certain embodiments, (y) is 10 (e.g., about 10 days or more). In certain embodiments, (y) is 14 (e.g., about 14 days or more). In certain embodiments, (y) is 20 (e.g., about 20 days or more). In certain embodiments, (y) is 30 (e.g., about 30 days or more). In certain embodiments, (y) is from about 0.5 days to about 40 days. In certain embodiments, (y) is from about 0.5 to about 1 day, from about 0.5 to about 3 days, from about 0.5 to about 5 days, from about 0.5 to about 7 days, from about 0.5 to about 10 days, from about 0.5 to about 14 days, from about 0.5 to about 20 days, from about 0.5 to about 30 days, from about 0.5 to about 40 days, from about 1 to about 3 days, from about 1 to about 5 days, from about 1 to about 7 days, from about 1 to about 10 days, from about 1 to about 14 days, from about 1 to about 20 days, from about 1 to about 30 days, from about 1 to about 40 days, from about 3 to about 5 days, from about 3 to about 7 days, from about 3 to about 10 days, from about 3 to about 14 days, from about 3 to about 20 days , about 3 to about 30 days, about 3 to about 40 days, about 5 to about 7 days, about 5 to about 10 days, about 5 to about 14 days, about 5 to about 20 days, about 5 to about 30 days, about 5 to about 40 days, about 7 to about 10 days, about 7 to about 14 days, about 7 to about 20 days, about 7 to about 30 days, about 7 to about 40 days, about 10 to about 14 days, about 10 to about 20 days, about 10 to about 30 days, about 10 to about 40 days, about 14 to about 20 days, about 14 to about 30 days, about 14 to about 40 days, about 20 to about 30 days, about 20 to about 40 days, or about 30 to about 40 days. In certain embodiments, (y) is about 0.5 days, about 1 day, about 3 days, about 5 days, about 7 days, about 10 days, about 14 days, about 20 days, about 30 days, or about 40 days. In certain embodiments, (y) is at least about 0.5 days, about 1 day, about 3 days, about 5 days, about 7 days, about 10 days, about 14 days, about 20 days, about 30 days, or about 40 days.

[0179] In some embodiments, the subject has symptoms associated with detached neural retina (e.g., loss or decline of visual function). In certain cases, the time of detachment is measured by the onset of symptoms associated with detached or detaching retina. In certain cases, the time of central vision loss is associated with a greater decline in visual acuity and visual function after surgery alone. In such cases, the effectiveness of treating or inhibiting the decline in visual acuity by surgery generally declines with increasing time of symptoms associated with detached or detaching retina, but the methods provided herein are useful for treating patients with symptoms associated with detached or detaching retina for extended periods (e.g., 3 days, 5 days, 7 days, 10 days, 14 days, 21 days or more, etc.). In some embodiments, the eye of the individual has a symptom associated with a detached neural retina (e.g., loss or reduction in visual function), and the symptom associated with a detached neural retina (e.g., loss or reduction in visual function) has been present for about (s) or more days (e.g., prior to administering a composition comprising a Fas inhibitor or prior to performing surgery), where (s) is at least 1.

[0180] In certain embodiments, (s) is 1 (e.g., about 1 day or more). In certain embodiments, (s) is 3 (e.g., about 3 days or more). In certain embodiments, (s) is 5 (e.g., about 5 days or more). In certain embodiments, (s) is 7 (e.g., about 7 days or more). In certain embodiments, (s) is 10 (e.g., about 10 days or more). In certain embodiments, (s) is 14 (e.g., about 14 days or more). In certain embodiments, (s) is 20 (e.g., about 20 days or more). In certain embodiments, (s) is 30 (e.g., about 30 days or more).

[0181] In certain embodiments, (s) is from about 1 to about 40 days. In certain embodiments, (s) is from about 1 to about 3 days, from about 1 to about 5 days, from about 1 to about 7 days, from about 1 to about 10 days, from about 1 to about 14 days, from about 1 to about 20 days, from about 1 to about 30 days, from about 1 to about 40 days, from about 3 to about 5 days, from about 3 to about 7 days, from about 3 to about 10 days, from about 3 to about 14 days, from about 3 to about 20 days, from about 3 to about 30 days, from about 3 to about 40 days, from about 5 to about 7 days, from about 5 to about 10 days, from about 5 to about 14 days, from about 5 to about 5 ... from about 20 days, from about 5 to about 30 days, from about 5 to about 40 days, from about 7 to about 10 days, from about 7 to about 14 days, from about 7 to about 20 days, from about 7 to about 30 days, from about 7 to about 40 days, from about 10 to about 14 days, from about 10 to about 20 days, from about 10 to about 30 days, from about 10 to about 40 days, from about 14 to about 20 days, from about 14 to about 30 days, from about 14 to about 40 days, from about 20 to about 30 days, from about 20 to about 40 days, or from about 30 to about 40 days. In certain embodiments, (s) is about 1 day, about 3 days, about 5 days, about 7 days, about 10 days, about 14 days, about 20 days, about 30 days, or about 40 days. In certain embodiments, (s) is at least about 1 day, about 3 days, about 5 days, about 7 days, about 10 days, about 14 days, about 20 days, about 30 days, or about 40 days.

[0182] In certain cases, increasing age of an individual may be associated with a greater decline in visual acuity and visual function. In such cases, the effectiveness of surgical treatment or prevention of visual loss generally decreases as the age of an individual with a detached or detaching retina increases, but the methods provided herein are useful for treating patients across age groups. In some embodiments, the individual is 40 years old or older. In some embodiments, the individual is about 50 years old or older. In some embodiments, the individual is about 55 years old or older. In some embodiments, the individual is about 60 years old or older. In some embodiments, the individual is about 65 years old or older. In some embodiments, the individual is 70 years old or older. In some embodiments, the individual is about 75 years old or older.

[0183] In certain embodiments, the individual is between about 20 and about 80 years of age. In certain embodiments, the individual is between about 20 and about 30 years of age, between about 20 and about 40 years of age, between about 20 and about 50 years of age, between about 20 and about 60 years of age, between about 20 and about 70 years of age, between about 20 and about 80 years of age, between about 30 and about 40 years of age, between about 30 and about 50 years of age, between about 30 and about 60 years of age, between about 30 and about 70 years of age, between about 30 and about 80 years of age, between about 40 and about 50 years of age, between about 40 and about 60 years of age, between about 40 and about 70 years of age, between about 40 and about 80 years of age, between about 50 and about 60 years of age, between about 50 and about 70 years of age, between about 50 and about 80 years of age, between about 60 and about 70 years of age, between about 60 and about 80 years of age, or between about 70 and about 80 years of age. In certain embodiments, the individual is about 20, about 30, about 40, about 50, about 60, about 70, or about 80 years old. In certain embodiments, the individual is at least about 20, about 30, about 40, about 50, about 60, or about 70 years old.

[0184] In certain cases, neural retinal detachment is associated with an inflammatory condition in the eye (e.g., in the retinal tissue). In further cases, inflammation causes or is associated with exacerbated cell death (e.g., photoreceptor cell death) in the eye. In these cases, surgery alone is not directed to reducing inflammation in the eye (e.g., in the retinal tissue). In such cases, the methods provided herein are useful for treating and / or inhibiting inflammation in an individual's eye. In some embodiments, the individual's eye comprises inflammation (e.g., an increased amount of one or more biomarkers). In certain embodiments, the inflammation comprises an increased amount of one or more biomarkers associated with inflammation. In certain embodiments, the increased amount of one or more biomarkers associated with inflammation is relative to an eye that does not have a detached neural retina or an undamaged eye. In certain embodiments, the one or more biomarkers associated with inflammation (i.e., inflammatory molecules) include, but are not limited to, Fas-mediated inflammation-related molecules (e.g., TNFa, IL-1b, IP-10, IL-18, MIP-1a, IL-6, GFAP, MIP2, MCP-1, or MIP-1b), Fas-mediated complement-related molecules (complement component 3 (C3) or complement component 1q (Clq)), caspase 8, components of the inflammasome (e.g., NLRP3 or NLRP2), C-X-C motif chemokines ( For example, CXCL2 (MIP-2α) or CXCL10 (IP-10)), C-X3-C motif chemokines (e.g., CX3CL1 (fractalkine)), CC motif chemokines (CCL2 (MCP-1), CCL3 (MIP-1a), and CCL4 (MIP-1b)), toll-like receptor 4 (TLR4), interleukin cytokines (e.g., IL-1b, IL-18, and IL-6), TNF superfamily cytokines (e.g., TNFa), or GFAP. In certain embodiments, the presence and / or amount of one or more biomarkers associated with inflammation may be by a biological assay (e.g., immunoassay, ELISA-based assay, etc.) that detects the presence of an inflammatory molecule (e.g., an inflammatory cytokine) in a sample taken from the eye (e.g., a vitreous humor sample).

[0185] In some embodiments, the eye of the individual has a cataract. In some embodiments, the eye of the individual is likely to have a cataract. In some embodiments, the eye of the individual is likely to have a pseudophakic lens. In some embodiments, the individual has a pre-existing disease or disorder, including a non-ocular condition (e.g., diabetes).

[0186] In some embodiments, the composition is administered by intravitreal injection, intracameral injection, injection into the suprachoroidal space, injection into the subtenon's space, subconjunctival injection, retrobulbar injection, periocular injection, microneedle injection, subretinal injection, or subretinal injection. In certain embodiments, the composition is administered by intravitreal injection. In certain embodiments, the composition is administered by intracameral injection. In certain embodiments, the composition is administered by injection into the suprachoroidal space. In certain embodiments, the composition is administered by injection into the subtenon's space. In certain embodiments, the composition is administered by subconjunctival injection. In certain embodiments, the composition is administered by retrobulbar injection. In certain embodiments, the composition is administered by periocular injection. In certain embodiments, the composition is administered by microneedle injection. In certain embodiments, the composition is administered by subretinal injection. In certain embodiments, the composition is administered by subretinal injection.

[0187] In some embodiments, the variant sequence comprises an amino acid substitution. In some embodiments, the variant sequence comprises one amino acid substitution. In some embodiments, the variant sequence comprises two amino acid substitutions. In some embodiments, the variant sequence comprises three amino acid substitutions.

[0188] In some embodiments, the peptide further comprises a modification. In some embodiments, the peptide comprises a modified amino acid or a non-naturally occurring amino acid. In some embodiments, the peptide comprises an amidated C-terminus, wherein the peptide has the structure of Formula I, or a pharma- ceutically acceptable salt thereof.

[0189] In some embodiments, the composition comprises a pharma- ceutically acceptable salt of the peptide. In some embodiments, the pharma- ceutically acceptable salt is an acetate. In some embodiments, the pharma- ceutically acceptable salt is a polyacetate. In some embodiments, the polyacetate is a triacetate. In some embodiments, the pharma- ceutically acceptable salt is a hydrochloride.

[0190] In some embodiments, a composition comprising a Fas inhibitor (e.g., a Fas inhibitor peptide) is administered to the eye of an individual. In some embodiments, a composition comprising a peptide is administered to the eye of an individual. In some embodiments, the composition further comprises one or more excipients. In some embodiments, the composition further comprises a surfactant. In some embodiments, the surfactant is a non-ionic surfactant.

[0191] In some embodiments, the surfactant is a polysorbate, a polyethoxylated castor oil derivative, a polyethoxylated fatty acid, a polyethoxylated alcohol, a polyoxyethylene-polyoxypropylene block copolymer, or an oxyethylated tertiary octylphenol formaldehyde polymer. In some embodiments, the surfactant is a polysorbate. In some embodiments, the surfactant is a polyethoxylated alcohol. In some embodiments, the surfactant is a polyoxyethylene-polyoxypropylene block copolymer. In some embodiments, the surfactant is an oxyethylated tertiary octylphenol formaldehyde polymer.

[0192] In some embodiments, the surfactant comprises polysorbate 20, poloxamer 407, tyloxapol, or cremophor. In some embodiments, the surfactant comprises polysorbate 20. In some embodiments, the surfactant comprises poloxamer 407. In some embodiments, the surfactant comprises tyloxapol. In some embodiments, the surfactant comprises cremophor. In some embodiments, the surfactant forms about 0.01% to about 20% by weight of the composition. In some embodiments, the surfactant forms about 0.05% to about 10% by weight of the composition. In some embodiments, the non-ionic surfactant is about 0.05% w / w of the composition to about 2% w / w of the composition. In some embodiments, the non-ionic surfactant is at least about 0.05% w / w of the composition. In some embodiments, the non-ionic surfactant is at most about 2% w / w of the composition. In some embodiments, the nonionic surfactant is from about 0.05% w / w of the composition to about 0.1% w / w of the composition, from about 0.05% w / w of the composition to about 0.1% w / w of the composition, from about 0.05% w / w of the composition to about 0.2% w / w of the composition, from about 0.05% w / w of the composition to about 0.3% w / w of the composition, from about 0.05% w / w of the composition to about 0.4% w / w of the composition, from about 0.05% w / w of the composition to about 0.5% w / w of the composition, from about 0.05% w / w of the composition to about 0.6% w / w of the composition, from about 0.05% w / w of the composition to about 1% w / w of the composition, from about 0.05% w / w of the composition to about 1.5 ... from about 0.1% w / w of the composition to about 0.1% w / w of the composition, from about 0.1% w / w of the composition to about 0.2% w / w of the composition, from about 0.1% w / w of the composition to about 0.3% w / w of the composition, from about 0.1% w / w of the composition to about 0.4% w / w of the composition, from about 0.1% w / w of the composition to about 0.5% w / w of the composition, from about 0.1% w / w of the composition to about 0.6% w / w of the composition, from about 0.1% w / w of the composition to about 1% w / w of the composition, from about 0.1% w / w of the composition to about 1.5% w / w of the composition, from about 0.1% w / w of the composition to about 2% w / w of the composition, from about 0.1% w / w of the composition to about 0.2% w / w of the composition, from about 0.from about 1% w / w to about 0.3% w / w of the composition, from about 0.1% w / w of the composition to about 0.4% w / w of the composition, from about 0.1% w / w of the composition to about 0.5% w / w of the composition, from about 0.1% w / w of the composition to about 0.6% w / w of the composition, from about 0.1% w / w of the composition to about 1% w / w of the composition, from about 0.1% w / w of the composition to about 1.5% w / w of the composition, from about 0.1% w / w of the composition to about 2% w / w of the composition, from about 0.2% w / w of the composition to about 0.3% w / w of the composition, from about 0.2% w / w of the composition to about 0.4% of the composition. w / w, from about 0.2% w / w of the composition to about 0.5% w / w of the composition, from about 0.2% w / w of the composition to about 0.6% w / w of the composition, from about 0.2% w / w of the composition to about 1% w / w of the composition, from about 0.2% w / w of the composition to about 1.5% w / w of the composition, from about 0.2% w / w of the composition to about 2% w / w of the composition, from about 0.3% w / w of the composition to about 0.4% w / w of the composition, from about 0.3% w / w of the composition to about 0.5% w / w of the composition, from about 0.3% w / w of the composition to about 0.6% w / w of the composition, from about 0.3% w / w of the composition to about 0.3% w / w of the composition to about 1% w / w of the composition, about 0.3% w / w of the composition to about 1.5% w / w of the composition, about 0.3% w / w of the composition to about 2% w / w of the composition, about 0.4% w / w of the composition to about 0.5% w / w of the composition, about 0.4% w / w of the composition to about 0.6% w / w of the composition, about 0.4% w / w of the composition to about 1% w / w of the composition, about 0.4% w / w of the composition to about 1.5% w / w of the composition, about 0.4% w / w of the composition to about 2% w / w of the composition, about 0.5% w / w of the composition to about 0.6% w / w of the composition, about 0.5% w / w to about 1% w / w of the composition, about 0.5% w / w of the composition to about 1.5% w / w of the composition, about 0.5% w / w of the composition to about 2% w / w of the composition, about 0.6% w / w of the composition to about 1% w / w of the composition, about 0.6% w / w of the composition to about 1.5% w / w of the composition, about 0.6% w / w of the composition to about 2% w / w of the composition, about 1% w / w of the composition to about 1.5% w / w of the composition, about 1% w / w of the composition to about 2% w / w of the composition, or about 1.5% w / w of the composition to about 2% w / w of the composition. In some embodiments, the nonionic surfactant is about 0.05% w / w of the composition, about 0.1% w / w of the composition, about 0.1% w / w of the composition, about 0.2% w / w of the composition, about 0.3% w / w of the composition, about 0.4% w / w of the composition, about 0.5% w / w of the composition, about 0.6% w / w of the composition, about 1% w / w of the composition, about 1.5% w / w of the composition, or about 2% w / w of the composition.

[0193] In some embodiments, the composition further comprises a tonicity adjusting agent, a buffering agent, or a combination thereof (e.g., as described herein, including any of the recited ranges and / or values ​​within the recited ranges). In some embodiments, the composition is buffered at a pH of 2.5 to 7.5.

[0194] In some embodiments, the composition comprises 5 micrograms (μg) to 10,000 μg of peptide. In some embodiments, the composition comprises about 5 μg of peptide to about 300 μg of peptide. In some embodiments, the composition comprises at least about 5 μg of peptide. In some embodiments, the composition comprises at least about 25 μg of peptide. In some embodiments, the composition comprises at least about 50 μg of peptide. In some embodiments, the composition comprises at least about 100 μg of peptide. In some embodiments, the composition comprises at least about 125 μg of peptide. In some embodiments, the composition comprises at least about 150 μg of peptide. In some embodiments, the composition comprises at least about 200 μg of peptide. In some embodiments, the composition comprises at least about 250 μg of peptide. In some embodiments, the composition comprises at least about 300 μg of peptide.

[0195] In some embodiments, the composition comprises about 5 μg peptide to about 10 μg peptide, about 5 μg peptide to about 25 μg peptide, about 5 μg peptide to about 50 μg peptide, about 5 μg peptide to about 75 μg peptide, about 5 μg peptide to about 100 μg peptide, about 5 μg peptide to about 150 μg peptide, about 5 μg peptide to about 200 μg peptide, about 5 μg peptide to about 250 μg peptide, about 5 μg peptide to about 300 μg peptide, about 10 μg peptide to about 25 μg peptide, about 10 μg peptide to about 250 μg peptide, about 10 μg peptide to about 300 μg peptide, about 10 μg peptide to about 25 μg peptide, about 10 μg peptide to about 30 ... g peptide to about 50 μg peptide, about 10 μg peptide to about 75 μg peptide, about 10 μg peptide to about 100 μg peptide, about 10 μg peptide to about 150 μg peptide, about 10 μg peptide to about 200 μg peptide, about 10 μg peptide to about 250 μg peptide, about 10 μg peptide to about 300 μg peptide, about 25 μg peptide to about 50 μg peptide, about 25 μg peptide to about 75 μg peptide, about 25 μg peptide to about 100 μg peptide, about 25 μg peptide to about 15 0 μg peptide, about 25 μg peptide to about 200 μg peptide, about 25 μg peptide to about 250 μg peptide, about 25 μg peptide to about 300 μg peptide, about 50 μg peptide to about 75 μg peptide, about 50 μg peptide to about 100 μg peptide, about 50 μg peptide to about 150 μg peptide, about 50 μg peptide to about 200 μg peptide, about 50 μg peptide to about 250 μg peptide, about 50 μg peptide to about 300 μg peptide, about 75 μg peptide to about 100 μg peptide , about 75 μg peptide to about 150 μg peptide, about 75 μg peptide to about 200 μg peptide, about 75 μg peptide to about 250 μg peptide, about 75 μg peptide to about 300 μg peptide, about 100 μg peptide to about 150 μg peptide, about 100 μg peptide to about 200 μg peptide, about 100 μg peptide to about 250 μg peptide, about 100 μg peptide to about 300 μg peptide, about 150 μg peptide to about 200 μg peptide, about 150 μg peptide to about 250 μg peptide,The composition comprises about 150 μg peptide to about 300 μg peptide, about 200 μg peptide to about 250 μg peptide, about 200 μg peptide to about 300 μg peptide, or about 250 μg peptide to about 300 μg peptide. In some embodiments, the composition comprises about 5 μg peptide, about 10 μg peptide, about 25 μg peptide, about 50 μg peptide, about 75 μg peptide, about 100 μg peptide, about 150 μg peptide, about 200 μg peptide, about 250 μg peptide, or about 300 μg peptide.

[0196] In some embodiments, the peptide is present at a concentration of 0.1 milligrams per milliliter (mg / mL) to 10 mg / mL. In some embodiments, the peptide is present at a concentration of 0.1 milligrams per milliliter (mg / mL) to 5.0 mg / mL.

[0197] As used herein, an individual is synonymous with a patient and / or subject, and includes and / or refers to a human, which may be a human diagnosed with a disease or condition as disclosed herein in need of treatment. However, examples are not limited to humans, and include chimpanzees, marmosets, cows, horses, sheep, goats, pigs, rabbits, dogs, cats, rats, mice, guinea pigs, etc. An individual is usually a human, which may be a human diagnosed with a disease or condition as disclosed herein in need of treatment.

[0198] As used herein, the terms "inhibition" or "inhibiting" include and / or refer to the reduction or suppression of a given condition, symptom, disorder, or disease and / or the reduction in baseline activity of a biological activity or process.

[0199] As used herein, the term "treating" or "treatment" includes and / or refers to ameliorating a disease or disorder or a symptom thereof (e.g., slowing, halting, or reducing the progression of a disease or at least one of its clinical symptoms). In certain embodiments, "treating" or "treatment" also includes and / or refers to alleviating or ameliorating at least one physical and / or biological parameter, including those that may not be discernible by the patient. In certain embodiments, "treating" or "treatment" includes and / or refers to modulating a disease, disorder, or biological process, either physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physical and / or biological parameter), or both. In certain embodiments, "treating" or "treatment" includes and / or refers to preventing or delaying the onset or development or progression of a disease or disorder. In certain embodiments, "treating" or "treatment" includes and / or refers to (i) a healthy physiological state, or (ii) preventing, slowing, or inhibiting the deterioration of a baseline physiological state (e.g., the progression of a disease or disorder).

[0200] As used herein, "a" or "an," when used in conjunction with the term "comprising" in the claims and / or specification, refers to "one" and / or includes "one," and is consistent with the meanings of "one or more," "at least one," and "one or more than one." Similarly, the word "another" may mean at least one or more of another.

[0201] As used herein, the terms "comprising" (and any form of "comprising", e.g., "comprise" and "comprises"), "having" (and any form of "having", e.g., "have" and "has"), "including" (and any form of "including", e.g., "includes" and "includes"), or "containing" (and any form of "containing", e.g., "contain" and "contains") are inclusive or open-ended and do not exclude additional, unrecited elements or process steps.

[0202] As used herein, the term "about" in the context of a given value or range includes and / or refers to a value or range within 20%, within 10%, and / or within 5% of the given value or range.

[0203] As used herein, the term "and / or" should be considered as a specific disclosure of each of the two specified features or components, regardless of the presence or absence of the other. For example, "A and / or B" should be considered as a specific disclosure of (i) A, (ii) B, and (iii) each of A and B, as if each were individually set forth herein.

[0204] As used herein, a "sample" includes and / or refers to any fluid or liquid sample that is being analyzed to detect and / or quantify an analyte. In some embodiments, the sample is a biological sample. Examples of samples include, but are not limited to, bodily fluids, extracts, solutions containing proteins and / or DNA, cell extracts, cell lysates, or tissue lysates. Non-limiting examples of bodily fluids include urine, saliva, blood, serum, plasma, cerebrospinal fluid, tears, semen, sweat, pleural fluid, liquefied fecal material, and lacrimal gland secretions.

[0205] As used herein, in any instance or embodiment described herein, "comprising" may be replaced with "consisting essentially of" and / or "consisting of." As used herein, in any instance or embodiment described herein, "comprises" may be replaced with "consists essentially of" and / or "consist of." EXAMPLES

[0206] Example 1 - Improved Vision in GA Patients the purpose The primary objective was to determine the safety of a peptide having the structure of Formula III (ONL1204) and subsequently select a dose in patients with macular degeneration characterized by geographic atrophy (GA).The primary endpoint was the safety profile demonstrated in this study, including reports of adverse events, clinical assessments including best corrected visual acuity (BCVA), and laboratory assessments.

[0207] Study design Patients exhibiting GA were enrolled in escalating dose groups and received a single intravitreal injection of a peptide having the acetate salt of the structure of formula III (ONL1204). Baseline best corrected visual acuity (BCVA) was measured prior to treatment with ONL1204. BCVA was then measured 1, 2, 4, 12, and 24 weeks after treatment with ONL1204. Doses of 50 μg and 100 μg were evaluated in vials to provide concentrations of formula III of 0.5 mg / mL and / or 2 mg / mL.

[0208] result All patients receiving doses containing 25 μg and 50 μg of ONL1204 demonstrated improved visual outcomes (e.g., visual acuity). Figure 1 shows study data on change in best corrected visual acuity (BCVA). Compared to baseline BCVA, an overall improvement in visual acuity was observed across patients receiving ONL1204 (solid line indicates study eye, dashed line indicates fellow / untreated eye).

[0209] Example 2 - Treatment of Retinal Detachment the purpose The primary objective was to determine the maximum tolerated dose (MTD) of a peptide with the amino acid sequence HHIYLGAVNYIY and the structure of formula III (ONL1204) and then select the dose for further clinical studies. Ocular fluid samples were also collected during the study at the time of investigational drug injection and at the time of vitreous surgery. These samples were used for pharmacokinetic and pharmacodynamic analyses. The primary endpoint was the safety profile demonstrated in the study, including reports of adverse events, clinical assessments including best corrected visual acuity (BCVA), and clinical laboratory assessments. Exploratory endpoints were pharmacokinetic and pharmacodynamic analyses performed in the study, including measurements of ONL1204 drug levels in plasma and vitreous fluid in PK analyses, and measurements of cytokines and other candidate molecular biomarkers in aqueous and vitreous samples collected by vitreous needle at the time of vitreous surgery.

[0210] Study design Patients were enrolled in the escalating dose groups. After patients signed informed consent and met all eligibility criteria, they underwent vitreous puncture for analysis of cytokines and other candidate molecular biomarkers, followed by a single intravitreal injection of a peptide having the acetate salt of the structure of formula III (ONL1204). The injection of ONL1204 was performed on the day of diagnosis (day 1). A safety visit was performed 1 day after injection and was deemed necessary by the investigator until visit 3 (at least one visit every 3 days). At visit 3 (≥3 days after injection, following standard of care), patients underwent surgical repair of their retinal detachment using vitrectomy (with or without scleral buckle) and gas or oil tamponade. At the time of surgery, undiluted vitreous samples were collected for pharmacokinetic and pharmacodynamic analysis, and aqueous samples were collected for pharmacodynamic analysis. Further safety visits were targeted and generally conducted 1 day after surgery, 7 days after surgery (± 3 days), 14 days after surgery (+4 days), and at weeks 6, 9, 12 (± 7 days each) and 24 (± 14 days, end of study).

[0211] Doses of 25 micrograms (μg) and 50 μg were evaluated in vials to provide concentrations of 0.5 mg / mL and / or 2 mg / mL of Formula III. Thus, the study eye was injected with a volume of 0.05 or 0.1 mL. Patient enrollment was approximately 24 weeks (6 months), which included a single injection treatment and a 24-week follow-up.

[0212] safety Planning decisions regarding dose-limiting toxicities included consideration of the following events: 1. A 2-unit increase in ocular inflammation from pre-injection on the Standardization of Uveitis Nomenclature (SUN) rating scale for aqueous humor or vitreous clouding associated with inflammation but not with the drug formulation itself was identified after ONL1204 injection and before retinal reattachment surgery. 2. Despite medical therapy, IOP was persistently elevated after ONL1204 injection and before retinal reattachment surgery, characterized by levels above 30 mmHg for three consecutive days. 3. A decrease in visual acuity from baseline following ONL1204 injection and prior to retinal reattachment surgery that, in the opinion of the investigator, is likely attributable to the investigational product and causes (a) a decrease in visual acuity from 20 / 200 or 20 / 400 to light perception without progression of underlying retinal detachment, or (b) a decrease in visual acuity from baseline to no light perception. 4. Any serious adverse event (SAE) occurring within the first 14 days of ONL1204 injection is, in the opinion of the investigator, related to ONL1204.

[0213] A total of 20 adverse events occurred in 7 of 8 patients (4 who received 25 micrograms (μg) of ONL1204 and 4 who received 50 μg of ONL1204). Most were mild and related to study procedures or surgery. After evaluating the data from each cohort, the SRC unanimously recommended proceeding with dose escalation to the 100 μg dose.

[0214] result All patients receiving doses containing 25 μg of ONL1204 and all patients receiving doses containing 50 μg of ONL1204 showed improved visual outcomes (e.g., visual acuity). Table 1 shows study data for best corrected visual acuity (BCVA) by Snellen. Table 2 shows study data for best corrected visual acuity (BCVA) by logMAR. As demonstrated in Tables 1 and 2, improved visual acuity was observed across all ages of patients in the study in all patients receiving 25 μg of ONL1204 and all patients receiving 50 μg of ONL1204. Table 3 shows the time between the date of (i) onset of symptoms or (ii) loss of central vision and the date of screening. Table 3 shows the time between the date of (i) onset of symptoms or (ii) loss of central vision and the date of administration of ONL1204. As demonstrated in Table 3, all patients who received ONL1204 had improved visual outcomes, even when ONL1204 was administered to patients with central vision loss greater than 10 days prior. Table 4 shows the time from administration of ONL1204 to surgery. Table 4 also shows the time between (i) the onset of symptoms or (ii) the date of central vision loss and the date of surgery. As demonstrated in Table 4, all patients had improved visual outcomes, even when the time from administration of ONL1204 to surgery was greater than 3 days (up to a maximum of 7 days). As demonstrated in Table 4, all patients who received ONL1204 had improved visual outcomes, even when ONL1204 was administered to patients with central vision loss greater than 15 days prior to the time of retinal reattachment surgery. Table 5 shows the degree of detachment (1-12, with 12 being complete detachment) and height. As demonstrated in Table 5, improved visual outcomes were observed in all patients who received ONL1204, across the range of detachment heights and severity of detachment.

[0215] Table 6 shows summary statistics for all patients, including sample size (n), mean, and standard deviation (sd). In comparison to surgery alone, a prospective population-based study of 291 Scottish patients with rhegmatogenous retinal detachment (RRD) with macular detachment and no pre-existing retinal disease who were successfully treated with a single surgical procedure reported a baseline mean logMAR visual acuity of 1.71, followed by mean logMAR visual acuity of 0.87, 0.66, 0.65, and 0.57 at 6 weeks, 3 months, 6 months, and 12 months after surgery, respectively (Mitry et al. “Long-term visual acuity and the duration of macular detachment: findings from a prospective population-based study” Br J Ophthalmol. 2013 Feb;97(2):149-52. doi:10.1136 / bjophthalmol-2012-302330. Epub 2012 Nov 17. PMID:23159447). Additionally, the study reported that for patients with detachment for 8 days or less, the baseline mean logMAR visual acuity was 1.73, followed by mean logMAR visual acuity of 0.81, 0.60, 0.55, and 0.45 at 6 weeks, 3 months, 6 months, and 12 months after surgery, respectively.For patients with detachment for more than 8 days, the study reported that the baseline mean logMAR visual acuity was 1.67, followed by mean logMAR visual acuity of 0.98, 0.82, 0.86, and 0.79 at 6 weeks, 3 months, 6 months, and 12 months after surgery, respectively.

[0216] Table 7 shows the change in cytokine levels from the time of ONL1204 administration to surgery. As demonstrated in Table 7, administration of ONL1204 resulted in a mean decrease in MCP1, ICAM, IL1RA, and IL18.

[0217] [Table 1]

[0218] [Table 2]

[0219] [Table 3]

[0220] [Table 4]

[0221] [Table 5]

[0222] [Table 6]

[0223] [Table 7]

[0224] While preferred embodiments of the present disclosure have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present disclosure. It is understood that various alternatives to the embodiments described herein can be utilized in implementing the present invention. The following claims define the scope of the embodiments disclosed herein, and it is intended that methods and structures within the scope of the claims and their equivalents be covered thereby.

[0225] [Table 8]

Claims

A composition comprising a peptide for use in a method of treating macular degeneration associated with geographic atrophy of the eye of an individual, wherein the peptide comprises the amino acid sequence HHILYGAVNYIY or a variant sequence thereof, or a pharmaceutically acceptable salt of the peptide, and the method comprises administering the peptide to the eye of the individual. A composition comprising a peptide for use in a method of treating loss of visual function of the eye of an individual having macular degeneration, wherein the peptide comprises the amino acid sequence HHILYGAVNYIY or a variant sequence thereof, or a pharmaceutically acceptable salt of the peptide, and the method comprises administering the peptide to the eye of the individual. The peptide according to any one of claims 1 to 2, wherein treating comprises improving visual function. The composition according to claim 3, wherein improving the visual function is compared with the baseline visual function before administering the peptide or a variant sequence thereof, or a pharmaceutically acceptable salt of the peptide. The composition according to any one of claims 1 to 2, wherein the macular degeneration includes age-related macular degeneration, and optionally, the macular degeneration includes geographic atrophy. The composition according to any one of claims 1 to 2, wherein visual function includes one or more measurements selected from the group consisting of best corrected visual acuity, visual field, contrast sensitivity, binocular function, low luminance vision, low contrast vision, color vision, visual field measurement, threshold sensitivity, reading speed, and / or light and dark adaptation. A composition comprising a peptide for use in a method of improving visual function of the eye of an individual having an eye disease or disorder, wherein the peptide comprises the amino acid sequence HHILYGAVNYIY or a variant sequence thereof, or a pharmaceutically acceptable salt of the peptide, and the method comprises administering the peptide to the eye of the individual. The composition according to claim 7, wherein the eye disease or disorder includes one or more of loss of visual function, photoreceptor cell death or its symptoms, retinal pigment epithelial cell death or its symptoms, and macular degeneration. **Claim 9**: The composition according to claim 7, wherein the visual function includes one or more measured values selected from the group consisting of best corrected visual acuity, visual field, contrast sensitivity, binocular function, low luminance visual acuity, low contrast visual acuity, color vision, visual field measurement, threshold sensitivity, reading speed, and light and dark adaptation. **Claim 10**: The composition according to claim 7, wherein improving the visual function includes improving the visual function without performing surgery. **Claim 11**: The composition according to claim 7, wherein surgery is performed on the eye of the individual, and optionally, the surgery is performed after administering the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide. **Claim 12**: The composition according to claim 11, wherein the surgery includes retinal reattachment surgery or vitreous surgery. **Claim 13**: The composition according to claim 7, wherein improving the visual function includes improving the visual function as compared to the baseline visual function before administering the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide. **Claim 14**: The composition according to any one of claims 1, 2, and 7, wherein the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide is administered to the vitreous of the eye. **Claim 15**: The composition according to any one of claims 1, 2, and 7, wherein the variant sequence includes amino acid substitution. **Claim 16**: The composition according to any one of claims 1, 2, and 7, wherein the peptide further includes a modification, and optionally, the modification includes a modified amino acid. **Claim 17**: The composition according to any one of claims 1, 2, and 7, wherein the peptide includes an amidated C-terminus. **Claim 18**: The peptide has the structure of Formula III: 【Chemical 1】 or a pharmaceutically acceptable salt thereof, and the composition according to any one of claims 1, 2, and 7. **Claim 19**: The composition according to any one of claims 1, 2, and 7, wherein the pharmaceutically acceptable salt is acetate, polyacetate, or hydrochloride. **Claim 20**: The composition according to any one of claims 1, 2, and 7, further including one or more excipients. **Claim 21**: The composition according to any one of claims 1, 2, and 7, further including a surfactant, and the surfactant forms a weight ratio of about 0.01% to about 20% of the composition. **Claim 22**: The composition according to any one of claims 1, 2, and 7, wherein the composition is buffered at a pH of 2.5 to 7.

5. **Claim 23**: The composition according to any one of claims 1, 2, and 7, wherein 5 micrograms (μg) to 10,000 μg of the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide, is administered. **Claim 24**: The composition according to claim 23, wherein about 50 μg to about 200 μg of the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide, is administered. **Claim 25**: The composition according to claim 24, wherein about 50 μg, about 100 μg, or about 200 μg of the peptide or its variant sequence, or a pharmaceutically acceptable salt of the peptide, is administered.

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