Methods and compositions for treating diabetic retinopathy

Abstract

The present disclosure provides methods of treating diabetic retinopathy and ocular inflammatory diseases with anti-ceramide antibodies and antibody fragments. Also provided are methods for treating subjects who have previously received treatment for diabetic retinopathy. In some embodiments, the disclosure further provides methods of treating diabetic retinopathy with a single dose of an anti-ceramide antibody or antigen-binding fragment thereof.

1 . A method of treating or preventing diabetic retinopathy in a subject in need thereof comprising ocularly administering an anti-ceramide antibody or antigen-binding fragment thereof to the subject. 
     
     
         2 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a single-chain variable fragment (scFv). 
     
     
         3 . The method of  claim 1 , wherein the ocular administration is selected from the group consisting of topical administration, intraocular administration, sub conjunctival administration, intracameral administration, injection into the anterior chamber via the temporal limbus, intrastromal administration, intracorneal administration, subretinal administration, aqueous humor injection, subtenon administration, administration to the suprachoroidal space (SCS), administration to the supraciliary space, and intravitreal administration. 
     
     
         4 . The method of  claim 1 , wherein the administration is intravitreal administration. 
     
     
         5 . The method of  claim 1 , wherein the subject has received a prior treatment for diabetic retinopathy. 
     
     
         6 . The method of  claim 5 , wherein the subject failed to respond to the prior treatment for diabetic retinopathy. 
     
     
         7 . The method of  claim 5 , wherein the prior treatment is a therapeutic procedure selected from a vitrectomy and laser surgery, or a therapeutic agent selected from a steroid and an anti-vascular endothelial growth factor (VEGF) therapy. 
     
     
         8 . The method of  claim 7 , wherein the anti-VEGF therapy is an anti-VEGF antibody selected from the group consisting of bevacizumab, ranibizumab, and aflibercept. 
     
     
         9 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered as a single dose. 
     
     
         10 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least two weeks, at least three weeks, or at least four weeks. 
     
     
         11 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about two weeks to about four weeks. 
     
     
         12 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, or at least eleven months. 
     
     
         13 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about one month to about six months. 
     
     
         14 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one year. 
     
     
         15 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered before the onset of one or more symptoms of diabetic retinopathy. 
     
     
         16 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered after the onset of one or more symptoms of diabetic retinopathy. 
     
     
         17 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a non-proliferative stage of diabetic retinopathy. 
     
     
         18 . The method of  claim 17 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a proliferative stage of diabetic retinopathy. 
     
     
         19 . A method of treating or preventing diabetic retinopathy in a subject in need thereof comprising administering an anti-ceramide antibody or antigen-binding fragment thereof to the subject, wherein the subject has received a prior treatment for diabetic retinopathy. 
     
     
         20 . The method of  claim 19 , wherein the subject failed to respond to the prior treatment for diabetic retinopathy. 
     
     
         21 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a single-chain variable fragment (scFv). 
     
     
         22 . The method of  claim 19 , wherein the administration is ocular administration. 
     
     
         23 . The method of  claim 22 , wherein the ocular administration is selected from the group consisting of topical administration, intraocular administration, subconjunctival administration, intracameral administration, injection into the anterior chamber via the temporal limbus, intrastromal administration, intracorneal administration, subretinal administration, aqueous humor injection, subtenon administration, administration to the suprachoroidal space (SCS), administration to the supraciliary space, and intravitreal administration. 
     
     
         24 . The method of  claim 22 , wherein the ocular administration is intravitreal administration. 
     
     
         25 . The method of  claim 19 , wherein the prior treatment was a vitrectomy, laser surgery, a steroid, and/or an anti-vascular endothelial growth factor (VEGF) therapy. 
     
     
         26 . The method of  claim 25 , wherein the anti-VEGF therapy is an anti-VEGF antibody selected from the group consisting of bevacizumab, ranibizumab, and aflibercept. 
     
     
         27 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered as a single dose. 
     
     
         28 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least two weeks, at least three weeks, or at least four weeks. 
     
     
         29 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about two weeks to about four weeks. 
     
     
         30 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, or at least eleven months. 
     
     
         31 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about one month to about six months. 
     
     
         32 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one year. 
     
     
         33 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered before the onset of one or more symptoms of diabetic retinopathy. 
     
     
         34 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered after the onset of one or more symptoms of diabetic retinopathy. 
     
     
         35 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a non-proliferative stage of diabetic retinopathy. 
     
     
         36 . The method of  claim 19 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a proliferative stage of diabetic retinopathy. 
     
     
         37 . A method of treating or preventing diabetic retinopathy in a subject comprising administering a single dose of an anti-ceramide antibody or antigen-binding fragment thereof to the subject. 
     
     
         38 . A method of treating or preventing diabetic retinopathy in a subject comprising administering two or more doses of an anti-ceramide antibody or antigen-binding fragment thereof to the subject, wherein the two or more doses are separated by at least two weeks. 
     
     
         39 . The method of  claim 38 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least two weeks, at least three weeks, or at least four weeks. 
     
     
         40 . The method of  claim 38 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about two weeks to about four weeks. 
     
     
         41 . The method of  claim 38 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, or at least eleven months. 
     
     
         42 . The method of  claim 38 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about one month to about six months. 
     
     
         43 . The method of  claim 38 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one year. 
     
     
         44 . The method of  claim 37 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a single-chain variable fragment (scFv). 
     
     
         45 . The method of  claim 37 , wherein the administration is ocular administration. 
     
     
         46 . The method of  claim 45 , wherein the ocular administration is selected from the group consisting of topical administration, intraocular administration, subconjunctival administration, intracameral administration, injection into the anterior chamber via the temporal limbus, intrastromal administration, intracorneal administration, subretinal administration, aqueous humor injection, subtenon administration, administration to the suprachoroidal space (SCS), administration to the supraciliary space, or intravitreal administration. 
     
     
         47 . The method of  claim 45 , wherein the ocular administration is intravitreal administration. 
     
     
         48 . The method of  claim 37 , wherein the subject has received a prior treatment for diabetic retinopathy. 
     
     
         49 . The method of  claim 48 , wherein the subject failed to respond to the prior treatment for diabetic retinopathy. 
     
     
         50 . The method of  claim 48 , wherein the prior treatment was a vitrectomy, laser surgery, a steroid, and/or an anti-vascular endothelial growth factor (VEGF) therapy. 
     
     
         51 . The method of  claim 50 , wherein the anti-VEGF therapy is an anti-VEGF antibody selected from the group consisting of bevacizumab, ranibizumab, and aflibercept. 
     
     
         52 . The method of  claim 37 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered before the onset of one or more symptoms of diabetic retinopathy. 
     
     
         53 . The method of  claim 37 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered after the onset of one or more symptoms of diabetic retinopathy. 
     
     
         54 . The method of  claim 37 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a non-proliferative stage of diabetic retinopathy. 
     
     
         55 . The method of  claim 37 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered during a proliferative stage of diabetic retinopathy. 
     
     
         56 . A method of treating an ocular inflammatory disease comprising ocularly administering an anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         57 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a single-chain variable fragment (scFv). 
     
     
         58 . The method of  claim 56 , wherein the ocular administration is selected from the group consisting of topical administration, intraocular administration, subconjunctival administration, intracameral administration, injection into the anterior chamber via the temporal limbus, intrastromal administration, intracorneal administration, subretinal administration, aqueous humor injection, subtenon administration, administration to the suprachoroidal space (SCS), administration to the supraciliary space, or intravitreal administration. 
     
     
         59 . The method of  claim 56 , wherein the ocular inflammatory disease is selected from the group consisting of retinal neovascularization, choroidal neovascularization, corneal neovascularization, macular degeneration, age-related macular degeneration, diabetic retinopathy, vitreous hemorrhage, retinal hemorrhage, choroiditis, neovascular glaucoma, choroid diseases, telangiectasia, retinal artery occlusion, retinal vein occlusion, chorioretinitis, epiretinal membrane, choroid neoplasms, retinopathy of prematurity, cystoid macular edema, papilledema, recurrent ischemia, eye hemorrhage, and proliferative vitreoretinopathy. 
     
     
         60 . The method of  claim 56 , wherein the ocular administration is intravitreal administration. 
     
     
         61 . The method of  claim 56 , wherein the subject has received a prior treatment for diabetic retinopathy. 
     
     
         62 . The method of  claim 61 , wherein the subject failed to respond to the prior treatment for diabetic retinopathy. 
     
     
         63 . The method of  claim 61 , wherein the prior treatment was therapeutic procedure selected from a vitrectomy and laser surgery, or a therapeutic agent selected from a steroid and an anti-vascular endothelial growth factor (VEGF) therapy. 
     
     
         64 . The method of  claim 63 , wherein the anti-VEGF therapy is an anti-VEGF antibody selected from the group consisting of bevacizumab, ranibizumab, and aflibercept. 
     
     
         65 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered as a single dose. 
     
     
         66 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least two weeks, at least three weeks, or at least four weeks. 
     
     
         67 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about two weeks to about four weeks. 
     
     
         68 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one month, at least two months, at least three months, at least four months, at least five months, at least six months, at least seven months, at least eight months, at least nine months, at least ten months, or at least eleven months. 
     
     
         69 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by about one month to about six months. 
     
     
         70 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered in two or more doses separated by at least one year. 
     
     
         71 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered before the onset of one or more symptoms of the ocular inflammatory disease. 
     
     
         72 . The method of  claim 56 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is administered after the onset of one or more symptoms of the ocular inflammatory disease. 
     
     
         73 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ),
 a) wherein the V H  comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of GYTFTDHTIH (SEQ ID NO: 1), an HCDR2 comprising the amino acid sequence of YNYPRDGSTKYNEKFKG (SEQ ID NO: 2), and an HCDR3 comprising the amino acid sequence of GFITTVVPSAY (SEQ ID NO: 3), and   b) wherein the V L  comprises a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of RASKSISKYLA (SEQ ID NO: 4), an LCDR2 comprising the amino acid sequence of SGSTLQS (SEQ ID NO: 5), and an LCDR3 comprising the amino acid sequence of QQHNEYPWT (SEQ ID NO: 6).   
     
     
         74 . The method of  claim 1 , wherein the V H  comprises the amino acid sequence of SEQ ID NO: 7 and wherein the V L  comprises the amino acid sequence of SEQ ID NO: 8. 
     
     
         75 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a 6B5 antibody. 
     
     
         76 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a 6B5 scFv. 
     
     
         77 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ),
 a) wherein the V H  comprises a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence of GYTFTNYWMH (SEQ ID NO: 33), an HCDR2 comprising the amino acid sequence of AIYPGDSDTSYNQKFKG (SEQ ID NO: 34), and an HCDR3 comprising the amino acid sequence of GLYYGYD (SEQ ID NO: 35), and   b) wherein the V L  comprises a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of KSSQSLIDSDGKTFLN (SEQ ID NO: 36), an LCDR2 comprising the amino acid sequence of LVSKLDS (SEQ ID NO: 37), and an LCDR3 comprising the amino acid sequence of WQGTHFPYT (SEQ ID NO: 38).   
     
     
         78 . The method of  claim 1 , wherein the V H  comprises the amino acid sequence of SEQ ID NO: 39 and wherein the V L  comprises the amino acid sequence of SEQ ID NO: 40. 
     
     
         79 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a 2A2 antibody. 
     
     
         80 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a 2A2 scFv. 
     
     
         81 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ),
 a) wherein the V H  comprises a heavy chain complementarity determining region 1 (HCDR1) comprising or consisting of an amino acid sequence selected from SEQ ID NOS: 1 and 43, an HCDR2 comprising or consisting of an amino acid sequence selected from SEQ ID NOS: 44-47, and an HCDR3 comprising or consisting of an amino acid sequence of GFITTVVPSAY (SEQ ID NO: 3), and   b) wherein the V L  comprises a light chain complementarity determining region 1 (LCDR1) comprising or consisting of an amino acid sequence of RASKSISKYLA (SEQ ID NO: 4), an LCDR2 comprising or consisting of an amino acid sequence of SGSTLQS (SEQ ID NO: 5), and an LCDR3 comprising or consisting of an amino acid sequence of QQHNEYPWT (SEQ ID NO: 6).   
     
     
         82 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTIH (SEQ ID NO: 1), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDGSTKYNEKFQG (SEQ ID NO: 44). 
     
     
         83 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTIH (SEQ ID NO: 1), and the HCDR2 comprises or consists of the amino acid sequence of YNYPREGSTKYNEKFQG (SEQ ID NO: 45). 
     
     
         84 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTIH (SEQ ID NO: 1), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDVSTKYNEKFQG (SEQ ID NO: 46). 
     
     
         85 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTIH (SEQ ID NO: 1), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDGSTKYAEKFQG (SEQ ID NO: 47). 
     
     
         86 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTMH (SEQ ID NO: 43), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDGSTKYNEKFQG (SEQ ID NO: 44). 
     
     
         87 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTMH (SEQ ID NO: 43), and the HCDR2 comprises or consists of the amino acid sequence of YNYPREGSTKYNEKFQG (SEQ ID NO: 45). 
     
     
         88 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTMH (SEQ ID NO: 43), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDVSTKYNEKFQG (SEQ ID NO: 46). 
     
     
         89 . The method of  claim 81 , wherein the HCDR1 comprises or consists of the amino acid sequence of GYTFTDHTMH (SEQ ID NO: 43), and the HCDR2 comprises or consists of the amino acid sequence of YNYPRDGSTKYAEKFQG (SEQ ID NO: 47). 
     
     
         90 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 48 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 53. 
     
     
         91 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 48 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 54. 
     
     
         92 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 48 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 55. 
     
     
         93 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 49 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 53. 
     
     
         94 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 49 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 54. 
     
     
         95 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 49 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 55. 
     
     
         96 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 50 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 53. 
     
     
         97 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 50 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 54. 
     
     
         98 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 50 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 55. 
     
     
         99 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 51 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 53. 
     
     
         100 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 51 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 54. 
     
     
         101 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 51 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 55. 
     
     
         102 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 52 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 53. 
     
     
         103 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 52 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 54. 
     
     
         104 . The method of  claim 81 , wherein the VH comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 52 and the VL comprises or consists of an amino acid sequence that is at least 90%, at least 95%, at least 97% identical, or 100% identical to SEQ ID NO: 55. 
     
     
         105 . The method of  claim 81 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a humanized 6B5 (h6B5) antibody. 
     
     
         106 . The method of  claim 81 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a h6B5 scFv. 
     
     
         107 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 48, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         108 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 48, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 55. 
     
     
         109 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 49, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         110 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 49, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 54. 
     
     
         111 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 50, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         112 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 50, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 54. 
     
     
         113 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 51, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         114 . The method of  claim 1 , wherein the anti-ceramide antibody or antigen-binding fragment thereof comprises a variable heavy chain (V H ) and a variable light chain (V L ), wherein the V H  comprises an amino acid sequence of SEQ ID NO: 52, and wherein the V L  comprises an amino acid sequence of SEQ ID NO: 53. 
     
     
         115 . The method of  claim 107 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a humanized antibody. 
     
     
         116 . The method of  claim 107 , wherein the anti-ceramide antibody or antigen-binding fragment thereof is a humanized scFv. 
     
     
         117 . The method of  claim 1 , wherein preventing diabetic retinopathy or the ocular inflammatory disease comprises delaying the onset of diabetic retinopathy or the ocular inflammatory disease. 
     
     
         118 . The method of  claim 1 , wherein one or more symptoms of diabetic retinopathy or the ocular inflammatory disease are reduced in the subject compared to a control subject or compared to the subject prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         119 . The method of  claim 118 , wherein the one or more symptoms of diabetic retinopathy or the ocular inflammatory disease are selected from retinal inflammation, acellular capillary formation, retinal neovascularization, retinal endothelial cell death, retinal vascular permeability, retinal ischemia-reperfusion injury, retinal leakage area, and occludin disruption. 
     
     
         120 . The method of  claim 118 , wherein the one or more symptoms of diabetic retinopathy or the ocular inflammatory disease are reduced by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to the control subject or compared to the subject prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         121 . The method of  claim 1 , wherein the expression level of one or more inflammatory markers in the eye is reduced compared to the expression level in the eye of a control subject or compared to the expression level in the subject's eye prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         122 . The method of  claim 121 , wherein the one or more inflammatory markers is selected from a cytokine, a growth factor, and an adhesion molecule. 
     
     
         123 . The method of  claim 122 , wherein the cytokine is selected from TNFα, IL-1β, IL-6, or MCP1. 
     
     
         124 . The method of  claim 122 , wherein the growth factor is VEGF. 
     
     
         125 . The method of  claim 122 , wherein the adhesion molecule is ICAM-1 or VCAM-1. 
     
     
         126 . The method of  claim 121 , wherein the expression level of the one or more inflammatory markers in the subject's eye is decreased by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to the expression level in the eye of a control subject or compared to the expression level in the subject's eye prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         127 . The method of  claim 1 , wherein one or more vision parameters are increased in the subject compared to the vision parameters a control subject or compared to the vision parameters of the subject prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         128 . The method of  claim 127 , wherein the one or more vision parameters are selected from peripheral vision; night vision; color vision; distance vision; close-range vision; and vision clarity. 
     
     
         129 . The method of  claim 1 , wherein the retinal vascular permeability in the subject's eye is decreased by at least 10%, at least 20%, at least 30%, at least 40%, or at least 50% compared to the retinal vascular permeability in the eye of a control subject or compared to the expression level in the subject's eye prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof. 
     
     
         130 . The method of  claim 1 , wherein the average Early Treatment Diabetic Retinopathy Study (ETDRS) grading score in a group of the subjects is lowered by at least 0.2, at least 0.5, at least 1, at least 1.5, at least 2, or at least 2.5 compared to the average ETDRS grading score of a group of control subjects or compared to the average ETDRS grading score in the group of the subjects prior to treatment with the anti-ceramide antibody or antigen-binding fragment thereof.