Transscleral delivery

Abstract

Diseases associated with the tissues in the posterior segment of the eye can be effectively treated by administering therapeutic agents transsclerally to those tissues. Compositions, devices, and methods for delivering therapeutic agents so that they cross the sclera and reach these tissues include injecting solutions or suspensions adjacent to or within the sclera and implanting solid structures containing the therapeutic agent adjacent to or within the sclera. These methods may be used for administering rapamycin or related compounds to treat choroidal neovascularization associated with age-related macular degeneration.

1 . A method for treating macular edema in a human, the method comprising administering transsclerally to an eye of the human an amount of a mTOR inhibitor effective to treat macular edema, wherein the mTOR inhibitor is administered transsclerally by placement within or proximate to a sclera of the eye. 
     
     
         2 . The method of  claim 1 , wherein the mTOR inhibitor is a limus compound selected from the group consisting of tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, and ABT-578. 
     
     
         3 . The method of  claim 2 , wherein the sclera has an outer scleral surface and the limus compound is administered transsclerally by placement of a limus compound containing delivery system proximate to the outer scleral surface. 
     
     
         4 . The method of  claim 3 , wherein the limus compound containing delivery system comprises a solid limus compound core. 
     
     
         5 . The method of  claim 4 , wherein the limus compound containing delivery system further contains a backing portion that is substantially impermeable to limus compound. 
     
     
         6 . The method of  claim 3 , wherein the limus compound containing delivery system comprises a suspension of particles of limus compound. 
     
     
         7 . The method of  claim 6 , wherein the particles of limus compound have an average diameter of less than about 50 μm. 
     
     
         8 . The method of  claim 3 , wherein the limus compound containing delivery system comprises limus compound dispersed in a polymer implant. 
     
     
         9 . The method of  claim 8 , wherein the polymer implant is a biodegradable polymer implant. 
     
     
         10 . The method of  claim 8 , wherein the polymer implant is a non-biodegradable polymer implant. 
     
     
         11 . The method of  claim 9  or  claim 10 , wherein the polymer implant further comprises a limus compound impermeable backing. 
     
     
         12 . The method of  claim 9  or  claim 10 , wherein the polymer implant is shaped as a suture. 
     
     
         13 . The method of  claim 12 , wherein the suture has a length of less than about 10 cm and a diameter of less than about 2 mm. 
     
     
         14 . The method of  claim 9  or  claim 10 , wherein the polymer implant is shaped as a coiled fiber. 
     
     
         15 . The method of  claim 14 , wherein the coiled fiber has a length of less than about 5 cm and a diameter of less than about 1 mm. 
     
     
         16 . The method of  claim 9  or  claim 10 , wherein the polymer implant is shaped as a disk. 
     
     
         17 . The method of  claim 9  or  claim 10 , wherein the polymer implant has a scleral surface portion for placement on the outer scleral surface of the eye and the scleral surface portion has an area through which the limus compound is delivered to the outer scleral surface of less than about 0.5 cm 2 . 
     
     
         18 . The method of  claim 9  or  claim 10 , wherein the polymer implant has a scleral surface portion for placement on the outer scleral surface of the eye, and the scleral surface portion comprises a bioadhesive layer. 
     
     
         19 . The method of  claim 9  or  claim 10 , wherein the polymer implant has a scleral surface portion comprises a number of protrusions, and whereby the scleral surface portion of the polymer implant anchors the polymer implant to the outer scleral surface of the eye. 
     
     
         20 . The method of  claim 9  or  claim 10 , wherein the polymer implant comprises a limus compound containing portion coated with a coating, and wherein the concentration of limus compound in the coating is less than the concentration of limus compound in the limus compound containing portion. 
     
     
         21 . The method of  claim 20 , wherein the concentration of limus compound in the coating is such that release of limus compound from the coating does not deliver a wound healing inhibiting amount of limus compound. 
     
     
         22 . The method of  claim 3 , wherein the limus compound containing delivery system comprises limus compound dissolved in a solvent. 
     
     
         23 . The method of  claim 3 , wherein the limus compound containing delivery system delivers the limus compound transsclerally in an amount sufficient to maintain an amount effective to treat macular edema for an extended period of time. 
     
     
         24 . The method of  claim 23 , wherein the limus compound containing delivery system delivers the limus compound transsclerally in an amount sufficient to treat macular edema for at least about three weeks. 
     
     
         25 . The method of  claim 3 ,  claim 6 , or  claim 22 , wherein the limus compound is administered transsclerally to the eye by subconjunctival or subtenon placement of the limus compound containing delivery system. 
     
     
         26 . The method of  claim 25 , wherein the limus compound is administered transsclerally to the eye by subconjunctival injection of the limus compound containing delivery system. 
     
     
         27 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of tacrolimus effective to treat macular edema. 
     
     
         28 . The method of  claim 27 , wherein the composition comprises a suspension of particles of tacrolimus. 
     
     
         29 . The method of  claim 27 , wherein the composition comprises tacrolimus dissolved in a solvent. 
     
     
         30 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of everolimus effective to treat macular edema. 
     
     
         31 . The method of  claim 30 , wherein the composition comprises a suspension of particles of everolimus. 
     
     
         32 . The method of  claim 30 , wherein the composition comprises everolimus dissolved in a solvent. 
     
     
         33 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of pimecrolimus to treat macular edema. 
     
     
         34 . The method of  claim 33 , wherein the composition comprises a suspension of particles of pimecrolimus. 
     
     
         35 . The method of  claim 33 , wherein the composition comprises pimecrolimus dissolved in a solvent. 
     
     
         36 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of CCI-779 effective to treat macular edema. 
     
     
         37 . The method of  claim 36 , wherein the composition comprises a suspension of particles of CCI-779. 
     
     
         38 . The method of  claim 36 , wherein the composition comprises CCI-779 dissolved in a solvent. 
     
     
         39 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of AP23841 effective to treat macular edema. 
     
     
         40 . The method of  claim 39 , wherein the composition comprises a suspension of particles of AP23841. 
     
     
         41 . The method of  claim 39 , wherein the composition comprises AP23841 dissolved in a solvent. 
     
     
         42 . A method for treating macular edema in a human, comprising administering a composition to an eye of the human by subconjunctival or subtenon placement of the composition, wherein the composition comprises an amount of ABT-578 effective to treat macular edema. 
     
     
         43 . The method of  claim 42 , wherein the composition comprises a suspension of particles of ABT-578. 
     
     
         44 . The method of  claim 42 , wherein the composition comprises ABT-578 dissolved in a solvent. 
     
     
         45 . The method of any one of  claim 22 ,  claim 29 ,  claim 32 ,  claim 35 ,  claim 38 ,  claim 41 , and  claim 44 , wherein the solvent comprises polyethylene glycol. 
     
     
         46 . The method of  claim 45 , wherein the solvent further comprises ethanol.