Treatment of ocular disease

Abstract

A formulation to treat ocular conditions such as dry eye disease, as well as other conditions, is disclosed. Rapamycin and/or ascomycin is administered intraocularly, such as by topical application, injection into the eye, or implantation in or on the eye. For example, a topical administration may contain between about 50 pg/ml drug to about 50 μg/ml drug in a formulation which may be applied at bedtime or throughout the day. For injection, a dose of about 50 pg/ml to about 200 μg/ml may be used. Rapamycin and/or ascomycin may also be administered in milligram quantities as a surgical implant, for example, in a diffusible walled reservoir sutured to the wall of the sclera, or may be contained within an inert carrier such as microspheres or liposomes to provide a slow-release drug delivery system.

1 - 40 . (canceled)  
     
     
         41 . A method for treating an ocular condition in a patient comprising intraocularly implanting a composition comprising a sustained release matrix and a drug selected from the group consisting of rapamycin, ascomycin and combinations thereof, in an amount effective to treat the condition.  
     
     
         42 . The method of  claim 41 , wherein the condition is selected from the group consisting of a condition associated with an immunologic reaction, an ocular age related condition, an ocular degenerative condition, a condition associated with ocular moisture, a condition associated with post-ocular surgery, and combinations thereof.  
     
     
         43 . The method of  claim 41 , wherein the condition is selected from the group consisting of dry eye disease, scleritis, neuritis, papillitis, uveitis, retinopathy, retinitis pigmentosa, macular degeneration, pemphigus, Sjogren's syndrome, Behcet's syndrome, toxoplasmosis, Birdshot choroidopathy, histoplasmosis, pars planitis, sarcoidosis, sympathetic ophthalmia, serpiginous choroidopathy, diffuse pigment epitheliopathy, Vogt-Koyanagi syndrome, polyarteritis nodosa, and juvenile rheumatic arthritis.  
     
     
         44 . The method of  claim 41 , wherein the condition is uveitis.  
     
     
         45 . The method of  claim 41 , wherein the matrix releases the drug at a rate selected from the group consisting of (i) about 1 μg per day, (ii) less that about 50 μg/day, (iii) in a range between about 50 pg/day to about 50 μg/day, and (iv) in a range between about 1 pg/day to about 5 μg/day.  
     
     
         46 . The method of  claim 41 , wherein the composition comprises from about 3 mg of the drug to about 5 mg of the drug.  
     
     
         47 . A method for treating an ocular condition in a patient comprising intraocularly administering by intraocular implantation a composition comprising a sustained release matrix and a drug selected from the group consisting of rapamycin, ascomycin and combinations thereof, wherein the drug is at a concentration of up to about 200 μg/ml in a pharmaceutically acceptable formulation, effective to treat the condition without substantial toxicity.  
     
     
         48 . The method of  claim 47 , wherein the composition further comprises Cyclosporin A, tacrolimus, or combinations thereof.  
     
     
         49 . The method of  claim 47 , wherein the condition is selected from the group consisting of a condition associated with an immunologic reaction, an ocular age related condition, an ocular degenerative condition, a condition associated with ocular moisture, a post-corneal surgery condition, and combinations thereof.  
     
     
         50 . The method of  claim 47 , wherein the condition is selected from the group consisting of dry eye disease, scleritis, neuritis, papillitis, uveitis, retinopathy, macular degeneration, pemphigus, Sjogren's syndrome, Behcet's syndrome, toxoplasmosis, Birdshot choroidopathy, histoplasmosis, pars planitis, sarcoidosis, sympathetic ophthalmia, serpiginous choroidopathy, diffuse pigment epitheliopathy, Vogt-Koyanagi syndrome, polyarteritis nodosa, and juvenile rheumatic arthritis.  
     
     
         51 . The method of  claim 47 , wherein the condition is uveitis.  
     
     
         52 . A method for treating an ocular condition in a patient comprising intraocularly administering by intraocular implantation a composition comprising a sustained release matrix and a pharmaceutically acceptable formulation of rapamycin, ascomycin, or combinations thereof, in an amount of up to about 200 μg, effective to treat an ocular condition without substantial toxicity, and at least one antibiotic.  
     
     
         53 . The method of  claim 52 , wherein the composition further comprises Cyclosporin A, tacrolimus, or combinations thereof.  
     
     
         54 . The method of  claim 52 , wherein the condition is selected from the group consisting of a condition associated with an immunologic reaction, an ocular age related condition, an ocular degenerative condition, a condition associated with ocular moisture, a post-corneal surgery condition, and combinations thereof.  
     
     
         55 . The method of  claim 52 , wherein the condition is selected from the group consisting of dry eye disease, scleritis, neuritis, papillitis, uveitis, retinopathy, macular degeneration, pemphigus, Sjogren's syndrome, Behcet's syndrome, toxoplasmosis, Birdshot choroidopathy, histoplasmosis, pars planitis, sarcoidosis, sympathetic ophthalmia, serpiginous choroidopathy, diffuse pigment epitheliopathy, Vogt-Koyanagi syndrome, polyarteritis nodosa, and juvenile rheumatic arthritis.  
     
     
         56 . The method of  claim 52 , wherein the condition is uveitis.  
     
     
         57 . An ocular treatment method comprising intraocularly administering, by intraocular implantation, to a patient after corneal surgery, a composition consisting essentially of a sustained release matrix and rapamycin, in a pharmaceutically acceptable formulation, and in an amount effective to enhance post-surgical ocular moisture in the patient.  
     
     
         58 . An ocular treatment method comprising intraocularly administering, by intraocular implantation, to a patient after corneal surgery, a composition consisting essentially of a sustained release matrix and ascomycin, in a pharmaceutically acceptable formulation, and in an amount effective to enhance post-surgical ocular moisture in the patient.  
     
     
         59 . A composition for treating an ocular condition comprising a sustained release matrix and a drug selected from the group consisting of rapamycin, ascomycin and combinations thereof, for intraocular implantation.  
     
     
         60 . The composition of  claim 59 , wherein the drug is present in the composition in an amount ranging between about 3 mg and about 5 mg.  
     
     
         61 . The composition of  claim 59 , wherein the matrix releases the drug at a rate selected from the group consisting of (i) less that about 50 μg/day, (ii) in a range between about 50 pg/day to about 50 μg/day, and (iii) in a range between about 1 pg/day to about 5 μg/day.  
     
     
         62 . The composition of  claim 59 , wherein the matrix comprises a substance selected from the group consisting of lipid, polyvinyl alcohol, polyvinyl acetate, polycaprolactone, poly(glycolic)acid, poly(lactic)acid, and combinations thereof.  
     
     
         63 . The composition of  claim 59 , further comprising at least one antibiotic.  
     
     
         64 . The composition of  claim 59 , further comprising Cyclosporin A, tacrolimus, or combinations thereof.