Methods and devices for the treatment of ocular diseases in human subjects

Abstract

Methods and devices are provided for targeted non-surgical administration of a drug formulation to the suprachoroidal space (SCS) of the eye of a human subject for the treatment of a posterior ocular disorder or a choroidal malady. In one embodiment, the method comprises inserting a hollow microneedle into the eye at an insertion site and infusing a drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused drug formulation flows within the suprachoroidal space away from the insertion site during the infusion. In one embodiment, the fluid drug formulation comprises drug nanoparticles or microparticles.

What is claimed is: 
     
         1 . A method of treating a posterior ocular disorder in a human subject in need thereof, the method comprising,
 non-surgically administering an effective amount of a drug formulation comprising lenalidomide to the suprachoroidal space (SCS) of the eye of the human subject.   
     
     
         2 . The method of  claim 1 , wherein the posterior ocular disorder is a retinal disease or a choroidal malady. 
     
     
         3 . The method of  claim 2 , wherein the choroidal malady is selected from the group consisting of ocular neovascularization, choroidal neovascularization, polypoidal choroidal vasculopathy, choroidal sclerosis, central sirrus choroidopathy, multi-focal choroidopathy, and choroidal dystrophy. 
     
     
         4 . The method of  claim 1 , wherein the posterior ocular disorder is selected from the group consisting of macular degeneration, retinopathy, macular edema, uveitis, scleritis, retinitis, and choroiditis. 
     
     
         5 . The method of  claim 4 , wherein the macular degeneration is selected from the group consisting of age related macular degeneration, dry age related macular degeneration, exudative age-related macular degeneration, geographic atrophy associated with age related macular degeneration, neovascular (wet) age-related macular degeneration, neovascular maculopathy and age related macular degeneration, occult with no classic choroidal neovascularization (CNV) in age-related macular degeneration, Stargardt's disease, subfoveal wet age-related macular degeneration, and Vitreomacular Adhesion (VMA) associated with neovascular age related macular degeneration. 
     
     
         6 . The method of  claim 4 , wherein the retinopathy is selected from the group consisting of diabetic retinopathy, hypersentitive retinopathy, sickle cell retinopathy, retinopathy of prematurity, and central serous retinopathy. 
     
     
         7 . The method of  claim 1 , wherein the posterior ocular disorder is selected from the group consisting of chorioretinal inflammation, chorioretinitis, retinochoroiditis, focal chorioretinal inflammation, focal chorioretinitis, focal choroiditis, focal retinitis, focal retinochoroiditis, disseminated chorioretinal inflammation, disseminated chorioretinitis, disseminated choroiditis, disseminated retinitis, disseminated reinochoroiditis, posterior cyclitis, Harada's disease, chorioretinal scars, choroidal degeneration, choroidal hemorrhage and rupture, choroidal detachment, retinal detachment, retinoschisis, epiretinal membrane, peripheral retinal degeneration, hereditary retinal dystrophy, retinitis pigmentosa, cytomegalovirus retinitis, retinal hemorrhage, separation of retinal layers, and glaucoma. 
     
     
         8 . The method of  claim 1 , wherein upon administration, the drug formulation is substantially localized to the posterior segment of the eye 
     
     
         9 . The method of  claim 1 , wherein an effective amount of lenalidomide sufficient to elicit a therapeutic response when administered to the SCS is less than the effective amount of lenalidomide sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         10 . The method of  claim 9 , wherein a dosage of lenalidomide sufficient to elicit a therapeutic response when administered to the SCS is 50% or less of a dosage of lenalidomide sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         11 . The method of  claim 1 , wherein the retention of lenalidomide in the posterior segment of the eye is greater than the retention of lenalidomide in the posterior segment of the eye when lenalidomide is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         12 . The method of  claim 1 , wherein an intraocular C max  of lenalidomide is greater than an intraocular C max  of lenalidomide when lenalidomide is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         13 . The method of  claim 1 , wherein the systemic exposure of lenalidomide is less than the systemic exposure of lenalidomide when lenalidomide is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         14 . The method of  claim 1 , wherein the non-surgically administering includes conveying the effective amount of the drug formulation to the SCS via a microneedle having a length of from about 500 μm to about 1500 μm. 
     
     
         15 . The method of  claim 1 , wherein the drug formulation comprises a suspension of microparticles or nanoparticles. 
     
     
         16 . The method of  claim 15 , wherein the microparticles have a D 50  of 2 μm or less. 
     
     
         17 . The method of  claim 1 , wherein the intraocular pressure of the eye of the subject varies by no more than about 10% during the administration of the drug formulation. 
     
     
         18 . The method of  claim 1 , wherein the method further comprises non-surgically administering a second drug to the eye of the subject. 
     
     
         19 . The method of  claim 18 , wherein the second drug comprises a vascular endothelial growth factor (VEGF) modulator. 
     
     
         20 . The method of  claim 19 , wherein the VEGF modulator is a VEGF antagonist. 
     
     
         21 . The method of  claim 20 , wherein the VEGF antagonist is selected from a VEGF-receptor kinase antagonist, an anti-VEGF antibody or fragment thereof, an anti-VEGF receptor antibody, an anti-VEGF aptamer, a small molecule VEGF antagonist, a thiazolidinedione, a quinoline or a designed ankyrin repeat protein (DARPin). 
     
     
         22 . The method of  claim 20 , wherein the VEGF antagonist is aflibercept. 
     
     
         23 . The method of  claim 18 , wherein the second drug comprises a platelet derived growth factor (PDGF) antagonist. 
     
     
         24 . The method of  claim 18 , wherein the second drug is administered to the SCS of the eye of the subject. 
     
     
         25 . The method of  claim 18 , wherein the second drug is administered intravitreally to the eye of the subject in a second drug formulation. 
     
     
         26 . The method of  claim 18 , wherein the drug formulation comprising lenalidomide and the second drug are administered to the subject in one dosing session.