Methods for reducing neovascularization or edema

Abstract

Biocompatible intraocular implants include a steroid and an auxiliary agent, where the auxiliary agent is present in an amount sufficient to lessen the severity of at least one side effect compared to the use of an otherwise identical implant lacking said auxiliary agent. The steroid and the auxiliary agent may be present on the same intraocular implant or on different implants. The steroid and auxiliary agent may be associated with a biodegradable polymer matrix, such as a matrix of a two biodegradable polymers. Or, the steroid may be associated with a polymeric coating having one or more openings effective to permit the steroid to be released into an external environment. The implants containing the steroid and an auxiliary agent may be placed in an eye to treat one or more ocular conditions while reducing the side effects otherwise accompanying steroid use.

1 . A biodegradable intraocular implant, comprising:
 a steroid; and   an auxiliary agent, wherein the steroid and the auxiliary agent are associated with a biodegradable polymer in the form of an intraocular implant.   
     
     
         2 . The implant of  claim 1 , wherein the steroid is selected from the group consisting of dexamethasone, fluocinolone, fluocinolone acetonide, triamcinolone, triamcinolone acetonide, salts thereof, and mixtures thereof 
     
     
         3 . The implant of  claim 1 , wherein the biodegradable polymer is a poly (lactide-co-glycolide) polymer. 
     
     
         4 . The implant of  claim 1 , wherein the auxiliary agent is selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof. 
     
     
         5 . The implant of  claim 1 , wherein the auxiliary agent is selected from the group consisting of pilocarpone, carbachol, echothiophate, epinephrine, dipivefrin, apracionidine, brimonidine, clonidine, apraclonidine, p-aminoclonidine, oxymetazoline, epinephrine, norepinephrine, and cirazoline, dexmedatomidine, mivazerol, xylazine, medatomidine, memantime, timolol, levobunolol, metipranilol, carteolol, betaxolol, dorzolamine, brinzolamide, dichlorphenamide, latanoprost, bimatoprost, travaprost, unoprostone, and mixtures thereof. 
     
     
         6 . The implant of  claim 1 , wherein the implant comprises a polymeric outer layer which is impermeable to an intraocular fluid. 
     
     
         7 . The implant of  claim 6 , wherein the outer layer comprises a plurality of openings or holes in the polymeric outer layer. 
     
     
         10 . A biodegradable intraocular implant system, comprising:
 a steroid associated with a biodegradable polymer in the form of a first intraocular implant; and   an auxiliary agent associated with a biodegradable polymer in the form of a second intraocular implant.   
     
     
         11 . A biodegradable intraocular implant system, comprising:
 a steroid associated with a biodegradable polymeric component in the form of an intraocular implant structured for intravitreal placement in an eye of an individual, the steroid being present in an amount effective in treating an ocular condition of the eye with a reduced toxicity relative to intravitreal injection of a liquid composition containing the same steroid; and   an auxiliary agent associated with a biodegradable polymeric component in the form of an intraocular implant structured for intravitreal placement in an eye of an individual, the auxiliary agent being present in an amount effective to reduce the occurrence of at least one side effect present upon otherwise identical administration of the steroid alone.   
     
     
         12 . The implant system of  claim 11 , wherein the steroid is selected from the group consisting of dexamethasone, fluocinolone, fluocinolone acetonide, triamcinolone, triamcinolone acetonide, salts thereof, and mixtures thereof 
     
     
         13 . The implant system of  claim 11 , wherein the auxiliary agent comprises an antiglaucoma drug is selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof. 
     
     
         14 . The implant system of  claim 11 , wherein the implant comprises steroid and auxiliary agent in alternating layers. 
     
     
         15 . The implant system of  claim 11 , wherein the steroid and the auxiliary agent are comprised in the same implant. 
     
     
         16 . The implant system of  claim 11 , wherein the steroid and the auxiliary agent are comprised in different implants. 
     
     
         17 . A method of treating an ocular disease in an eye of a patient comprising
 contacting an implant comprising a steroid with an ocular fluid in the eye of the patient; thereby releasing steroid from the implant into the ocular fluid, and   contacting an implant comprising an auxiliary agent with the ocular fluid in the eye of the patient, thereby releasing auxiliary agent from the implant into the ocular fluid,   wherein the steroid is present in an amount effective in treating the ocular disease, and   wherein the auxiliary agent is present in an amount effective to reduce the occurrence of at least one side effect present upon otherwise identical administration of the steroid alone.   
     
     
         18 . The method of  claim 17 , wherein the auxiliary agent comprises an antiglaucoma drug selected from the group consisting of a parasympathomimetic, a sympathomimetic, an alpha agonist, a beta blocker, a carbonic anhydrase inhibitor, a prostaglandin analog, a neuroprotectant, and mixtures thereof. 
     
     
         19 . The method of  claim 18 , wherein the antiglaucoma drug is selected from the group consisting of pilocarpone, carbachol, echothiophate, epinephrine, dipivefrin, apracionidine, brimonidine, clonidine, apraclonidine, p-aminoclonidine, oxymetazoline, epinephrine, norepinephrine, and cirazoline, dexmedatomidine, mivazerol, xylazine, medatomidine, memantime, timolol, levobunolol, metipranilol, carteolol, betaxolol, dorzolamine, brinzolamide, dichlorphenamide, latanoprost, bimatoprost, travaprost, unoprostone, and mixtures thereof. 
     
     
         20 . The method of  claim 17 , wherein the steroid and the auxiliary agent are released from the implant simultaneously. 
     
     
         21 . The implant system of  claim 17 , wherein the steroid and the auxiliary agent are released from the implant at different times. 
     
     
         22 . The implant system of  claim 11 , wherein the steroid and the auxiliary agent are released from the implant intermittently. 
     
     
         23 . The method of  claim 17 , wherein the ocular implant comprising the steroid and the ocular implant comprising the auxiliary agent are the same implant. 
     
     
         24 . The method of  claim 17 , wherein the ocular implant comprising the steroid and the ocular implant comprising the auxiliary agent are different implants.