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.

1 .- 241 . (canceled) 
     
     
         242 . A method of treating uveitis in a human subject in need thereof, the method comprising,
 non-surgically administering an effective amount of a drug formulation comprising an anti-inflammatory drug to the suprachoroidal space (SCS) of the eye of the human subject in need of treatment of the posterior ocular disorder,   wherein upon administration, the drug formulation flows away from the insertion site and is substantially localized to the posterior segment of the eye.   
     
     
         243 . The method of  claim 242 , wherein the uveitis is acute posterior uveitis. 
     
     
         244 . The method of  claim 242 , wherein the anti-inflammatory drug is a steroid. 
     
     
         245 . The method of  claim 242 , wherein the anti-inflammatory drug is mycophenolate, infliximab, nepafenac, azathioprine, cyclosphosphamide, dexamethasone, difluprednate, fluocinolone, fluorometholone, leteprednol, prednisolone acetate, prednisolone sodium phosphate, rimexolone, triamcinolone, bromfenac, diclofenac, fluibiprofen, ketorolac, adalimumab, etanercept, certolizumab, gotimumab, daclizumab, rituximab, abatacept, basiliximab, belimumab, anakinra, efalizuma, alefacept or natalizumab. 
     
     
         246 . The method of  claim 242 , wherein the anti-inflammatory drug is triamcinolone. 
     
     
         247 . The method of  claim 242 , wherein the effective amount of the drug sufficient to elicit a therapeutic response when administered to the SCS is less than the effective amount of the drug sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         248 . The method of  claim 242 , wherein the retention of the anti-inflammatory drug in the posterior segment of the eye is greater than the retention of the anti-inflammatory drug in the posterior segment of the eye when the anti-inflammatory drug is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         249 . The method of  claim 242 , wherein an intraocular C max  of the drug is greater than an intraocular C max  of the drug, when the drug is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         250 . The method of  claim 242 , wherein the systemic exposure of the drug is less than the systemic exposure of the drug when the drug is administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         251 . The method of  claim 242 , 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. 
     
     
         252 . The method of  claim 242 , wherein the drug formulation comprises a suspension of microparticles or nanoparticles. 
     
     
         253 . The method of  claim 242 , wherein the anti-inflammatory drug is triamcinolone acetonide. 
     
     
         254 . The method of  claim 242 , wherein the intraocular pressure of the eye of the subject varies by no more than about 10% during the administration of the drug formulation. 
     
     
         255 . The method of  claim 247 , wherein a dosage of the drug sufficient to elicit a therapeutic response when administered to the SCS is 50% or less of a dosage of the drug sufficient to elicit a therapeutic response when administered intravitreally, intracamerally, topically, parenterally or orally. 
     
     
         256 . The method of  claim 252 , wherein the microparticles have a D 50  of 2 μm or less. 
     
     
         257 . A composition comprising triamcinolone acetonide, carboxymethylcellulose sodium and polysorbate 80. 
     
     
         258 . The composition of  claim 257 , wherein triamcinolone is in particulate and the particles have a D 50  of about 2 μm. 
     
     
         259 . The composition of  claim 257 , wherein the microprticles have a D 99  of less than 10 μm. 
     
     
         260 . The composition of  claim 257 , wherein the triancinolone acetonide is present in the composition at 40 mg/mL. 
     
     
         261 . The composition of  claim 257 , further comprising sodium acetate.