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 inhibiting the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration in a human, the method comprising administering transsclerally to an eye of the human an amount of a therapeutic agent effective to inhibit the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration, wherein the therapeutic agent is a compound selected from the group consisting of rapamycin, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, AND ABT-578, and wherein the therapeutic agent is administered transsclerally by placement within or proximate to a sclera of the eye. 
     
     
         2 . The method of  claim 1 , wherein the therapeutic agent is rapamycin, and wherein the sclera has an outer scleral surface and the rapamycin is administered transsclerally by placement of a rapamycin containing delivery system proximate to the outer scleral surface. 
     
     
         3 . The method of  claim 2 , wherein the rapamycin containing delivery system comprises a solid rapamycin core. 
     
     
         4 . The method of  claim 3 , wherein the rapamycin containing delivery system further contains a backing portion that is substantially impermeable to rapamycin. 
     
     
         5 . The method of  claim 2 , wherein the rapamycin containing delivery system comprises a suspension of particles of rapamycin. 
     
     
         6 . The method of  claim 5 , wherein the particles of rapamycin have an average diameter of less than about 50 μm. 
     
     
         7 . The method of  claim 2 , wherein the rapamycin containing delivery system comprises rapamycin dispersed in a polymer implant. 
     
     
         8 . The method of  claim 7 , wherein the polymer implant is a biodegradable polymer implant. 
     
     
         9 . The method of  claim 7 , wherein the polymer implant is a non-biodegradable polymer implant. 
     
     
         10 . The method of  claim 8  or  claim 9 , wherein the polymer implant further comprises a rapamycin impermeable backing. 
     
     
         11 . The method of  claim 8  or  claim 9 , wherein the polymer implant is shaped as a suture. 
     
     
         12 . The method of  claim 11 , wherein the suture has a length of less than about 10 cm and a diameter of less than about 2 mm. 
     
     
         13 . The method of  claim 8  or  claim 9 , wherein the polymer implant is shaped as a coiled fiber. 
     
     
         14 . The method of  claim 13 , wherein the coiled fiber has a length of less than about 5 cm and a diameter of less than about 1 mm. 
     
     
         15 . The method of  claim 8  or  claim 9 , wherein the polymer implant is shaped as a disk. 
     
     
         16 . The method of  claim 8  or  claim 9 , 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 rapamycin is delivered to the outer scleral surface of less than about 0.5 cm 2 . 
     
     
         17 . The method of  claim 8  or  claim 9 , 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. 
     
     
         18 . The method of  claim 8  or  claim 9 , 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. 
     
     
         19 . The method of  claim 8  or  claim 9 , wherein the polymer implant comprises a rapamycin containing portion coated with a coating, and wherein the concentration of rapamycin in the coating is less than the concentration of rapamycin in the rapamycin containing portion. 
     
     
         20 . The method of  claim 19 , wherein the concentration of rapamycin in the coating is such that release of rapamycin from the coating does not deliver a wound healing inhibiting amount of rapamycin. 
     
     
         21 . The method of  claim 2 , wherein the rapamycin containing delivery system comprises rapamycin dissolved in a solvent. 
     
     
         22 . The method of  claim 2 , wherein the rapamycin containing delivery system delivers the rapamycin transsclerally in an amount sufficient to maintain an amount effective to inhibit the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration for an extended period of time. 
     
     
         23 . The method of  claim 22 , wherein the rapamycin containing delivery system delivers the rapamycin transsclerally in an amount sufficient to inhibit the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration for at least about three weeks. 
     
     
         24 . The method of  claim 2 ,  claim 5 , or  claim 21 , wherein the rapamycin is administered transsclerally to the eye by subconjunctival or subtenon placement of the rapamycin containing delivery system. 
     
     
         25 . The method of  claim 24 , wherein the rapamycin is administered transsclerally to the eye by subconjunctival injection of the rapamycin containing delivery system. 
     
     
         26 . A method for inhibiting the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration 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 a therapeutic agent effective to inhibit the transition from the dry form of age-related macular degeneration to the wet form of age-related macular degeneration, and wherein the therapeutic agent is a compound selected from the group consisting of rapamycin, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, and ABT-578. 
     
     
         27 . The method of  claim 26 , wherein the therapeutic agent is rapamycin. 
     
     
         28 . The method of  claim 27 , wherein the composition comprises a suspension of particles of rapamycin. 
     
     
         29 . The method of  claim 27 , wherein the composition comprises rapamycin dissolved in a solvent. 
     
     
         30 . The method of  claim 28  or  claim 29 , wherein the composition is administered to the eye by subconjunctival injection. 
     
     
         31 . The method of  claim 21  or  claim 29 , wherein the solvent comprises polyethylene glycol. 
     
     
         32 . The method of  claim 31 , wherein the solvent further comprises ethanol. 
     
     
         33 . The method of  claim 32 , wherein the composition is administered to the eye by subconjunctival injection. 
     
     
         34 . A method for treating dry age-related macular degeneration in a human, the method comprising administering transsclerally to an eye of the human an amount of a therapeutic agent effective to treat dry age-related macular degeneration, wherein the therapeutic agent is a compound selected from the group consisting of rapamycin, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, and ABT-578, and wherein the therapeutic agent is administered transsclerally by placement within or proximate to a sclera of the eye. 
     
     
         35 . The method of  claim 34 , wherein the therapeutic agent is rapamycin, and wherein the sclera has an outer scleral surface and the rapamycin is administered transsclerally by placement of a rapamycin containing delivery system proximate to the outer scleral surface. 
     
     
         36 . The method of  claim 35 , wherein the rapamycin containing delivery system comprises a solid rapamycin core. 
     
     
         37 . The method of  claim 36 , wherein the rapamycin containing delivery system further contains a backing portion that is substantially impermeable to rapamycin. 
     
     
         38 . The method of  claim 35 , wherein the rapamycin containing delivery system comprises a suspension of particles of rapamycin. 
     
     
         39 . The method of  claim 38 , wherein the particles of rapamycin have an average diameter of less than about 50 μm. 
     
     
         40 . The method of  claim 35 , wherein the rapamycin containing delivery system comprises rapamycin dispersed in a polymer implant. 
     
     
         41 . The method of  claim 40 , wherein the polymer implant is a biodegradable polymer implant. 
     
     
         42 . The method of  claim 40 , wherein the polymer implant is a non-biodegradable polymer implant. 
     
     
         43 . The method of  claim 41  or  claim 42 , wherein the polymer implant further comprises a rapamycin impermeable backing. 
     
     
         44 . The method of  claim 41  or  claim 42 , wherein the polymer implant is shaped as a suture. 
     
     
         45 . The method of  claim 44 , wherein the suture has a length of less than about 10 cm and a diameter of less than about 2 mm. 
     
     
         46 . The method of  claim 41  or  claim 42 , wherein the polymer implant is shaped as a coiled fiber. 
     
     
         47 . The method of  claim 46 , wherein the coiled fiber has a length of less than about 5 cm and a diameter of less than about 1 mm. 
     
     
         48 . The method of  claim 41  or  claim 42 , wherein the polymer implant is shaped as a disk. 
     
     
         49 . The method of  claim 41  or  claim 42 , 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 rapamycin is delivered to the outer scleral surface of less than about 0.5 cm 2 . 
     
     
         50 . The method of  claim 41  or  claim 42 , 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. 
     
     
         51 . The method of  claim 41  or  claim 42 , 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. 
     
     
         52 . The method of  claim 41  or  claim 42 , wherein the polymer implant comprises a rapamycin containing portion coated with a coating, and wherein the concentration of rapamycin in the coating is less than the concentration of rapamycin in the rapamycin containing portion. 
     
     
         53 . The method of  claim 52 , wherein the concentration of rapamycin in the coating is such that release of rapamycin from the coating does not deliver a wound healing inhibiting amount of rapamycin. 
     
     
         54 . The method of  claim 35 , wherein the rapamycin containing delivery system comprises rapamycin dissolved in a solvent. 
     
     
         55 . The method of  claim 35 , wherein the rapamycin containing delivery system delivers the rapamycin transsclerally in an amount sufficient to maintain an amount effective to treat dry age-related macular degeneration for an extended period of time. 
     
     
         56 . The method of  claim 55 , wherein the rapamycin containing delivery system delivers the rapamycin transsclerally in an amount sufficient to treat dry age-related macular degeneration for at least about three weeks. 
     
     
         57 . The method of  claim 35 ,  claim 38 , or  claim 54 , wherein the rapamycin is administered transsclerally to the eye by subconjunctival or subtenon placement of the rapamycin containing delivery system. 
     
     
         58 . The method of  claim 57 , wherein the rapamycin is administered transsclerally to the eye by subconjunctival injection of the rapamycin containing delivery system. 
     
     
         59 . A method for treating dry age-related macular degeneration 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 a therapeutic agent effective to treat dry age-related macular degeneration, and wherein the therapeutic agent is a compound selected from the group consisting of rapamycin, tacrolimus, everolimus, pimecrolimus, CCI-779, AP23841, and ABT-578. 
     
     
         60 . The method of  claim 59 , wherein the therapeutic agent is rapamycin. 
     
     
         61 . The method of  claim 60 , wherein the composition comprises a suspension of particles of rapamycin. 
     
     
         62 . The method of  claim 60 , wherein the composition comprises rapamycin dissolved in a solvent. 
     
     
         63 . The method of  claim 61  or  claim 62 , wherein the composition is administered to the eye by subconjunctival injection. 
     
     
         64 . The method of  claim 54  or  claim 62 , wherein the solvent comprises polyethylene glycol. 
     
     
         65 . The method of  claim 64 , wherein the solvent further comprises ethanol. 
     
     
         66 . The method of  claim 65 , wherein the composition is administered to the eye by subconjunctival injection.