Methods and devices for the treatment of ocular conditions

Abstract

Featured is a method for instilling one or more bioactive agents into ocular tissue within an eye of a patient for the treatment of an ocular condition, the method comprising concurrently using at least two of the following bioactive agent delivery methods (A)-(C): (A) implanting a sustained release delivery device comprising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more bioactive agents subretinally; and (C) instilling (e.g., injecting or delivering by ocular iontophoresis) one or more bioactive agents into the vitreous humor of the eye.

1 . A method for instilling one or more bioactive agents into ocular tissue within an eye of a patient for the treatment of an ocular condition, the method comprising concurrently using at least two of the bioactive agent delivery methods (A)-(C): 
 (A) implanting a sustained release delivery device comprising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more bioactive agents into a vitreous humor;    (B) instilling one or more bioactive agents subretinally; and    (C) instilling one or more bioactive agents into the vitreous humor.    
   
   
       2 . The method of  claim 1 , wherein method (A) is used concurrently with method (B).  
   
   
       3 . The method of  claim 2 , wherein the one or more bioactive agents delivered by the sustained release delivery device of method (A) are the same as the one or more bioactive agents instilled subretinally in method (B).  
   
   
       4 . The method of  claim 2 , wherein the one or more bioactive agents delivered by the sustained release delivery device of method (A) are different than the one or more bioactive agents instilled subretinally in method (B).  
   
   
       5 . The method of  claim 1 , wherein method (A) is used concurrently with method (C)  
   
   
       6 . The method of  claim 5 , wherein the one or more bioactive agents delivered by the sustained release delivery device of method (A) are the same as the one or more bioactive agents instilled into the vitreous humor of the eye in method (C).  
   
   
       7 . The method of  claim 5 , wherein the one or more bioactive agents delivered by the sustained release delivery device of method (A) are different than the one or more bioactive agents instilled into the vitreous humor of the eye in method (C).  
   
   
       8 . The method of  claim 1 , wherein method (B) is used concurrently with method (C).  
   
   
       9 . The method of  claim 8 , wherein the one or more bioactive agents instilled subretinally in method (B) are the same as the one or more bioactive agents instilled into the vitreous humor of the eye in method (C).  
   
   
       10 . The method of  claim 8 , wherein the one or more bioactive agents instilled subretinally in method (B) are different than the one or more bioactive agents instilled into the vitreous humor of the eye in method (C).  
   
   
       11 . The method of  claim 1 , wherein method (A) is used concurrently with both method (B) and method (C).  
   
   
       12 . The method of  claim 1 , wherein method (B) comprises injecting or implanting one or more bioactive agents subretinally.  
   
   
       13 . The method of  claim 1 , wherein method (B) comprises: 
 (a) forming a localized retinal detachment to define a subretinal space; and    (b) instilling one or more bioactive agents in the subretinal space formed by localized retinal detachment.    
   
   
       14 . The method of  claim 12  wherein the one or more bioactive agents are provided in a sustained release delivery device that is configured for implantation in the subretinal space.  
   
   
       15 . The method of  claim 14 , wherein the sustained release delivery device is tapered at a proximal end, a distal end, or both the proximal and distal ends.  
   
   
       16 . The method of  claim 14 , wherein the sustained release delivery device is a solid in the form of a capsule, pellet, rod, sheet, or film.  
   
   
       17 . The method of  claim 14 , wherein the sustained release delivery device is in the form of a flexible rod, thin film, foldable disc, biodegradable polymer with the bioactive agent embedded within, bioactive agent-eluting polymer coating over a rigid scaffold, compressed pellet of one or more bioactive agents, or one or more bioactive agents encapsulated in a semi-permeable membrane.  
   
   
       18 . The method of  claim 14 , wherein the sustained release delivery device is in the form of a biocompatible polymer capsule comprising (a) a core comprising one or more bioactive agents; and (b) a jacket surrounding the core comprising a membrane that is biocompatible and that permits diffusion of the one or more bioactive agents.  
   
   
       19 . The method of  claim 14 , wherein the sustained release delivery device comprises a core having an outer surface; and a coating layer of a polymer matrix and a least one bioactive agent applied over at least a portion of the outer surface of the core.  
   
   
       20 . The method of  claim 19 , wherein the coating layer is provided on a portion of the outer surface of the core.  
   
   
       21 . The method of  claim 19 , wherein the coating layer is provided on an intermediate portion of the core.  
   
   
       22 . The method of  claim 19 , wherein the coating includes proximal a transition segment, a distal transition segment, or both a proximal and a distal transition segment.  
   
   
       23 . The medical device according to  claim 19 , wherein the core is selected from titanium alloys, nickel-cobalt base alloys, stainless steel, cobalt-chromium alloys, and biodegradable magnesium alloys.  
   
   
       24 . The method of  claim 19 , wherein the polymer matrix comprises a first polymer and a second polymer wherein the first polymer is a poly(alkyl(meth)acrylates) or a poly(aromatic(meth)acrylates) and wherein the second polymer is poly(ethylene-co-vinyl acetate).  
   
   
       25 . The method of  claim 24 , wherein the first polymer comprises a poly(aromatic (meth)acrylates) selected from the group consisting of poly(aryl (meth)acrylates), poly(aralkyl(meth)acrylates), poly(alkaryl(meth)acrylates), poly(aryloxyalkyl (meth)acrylates), and poly (alkoxyaryl(meth)acrylates).  
   
   
       26 . The method of  claim 24 , wherein the first polymer comprises a poly(alkyl(meth)acrylates) selected from the group consisting of poly (n-butyl methacrylate), poly(n-butyl methacrylate-co-methyl methacrylate), poly(n-butyl methacrylate-co-isobutyl methacrylate), and poly(t-butyl methacrylate).  
   
   
       27 . The method of  claim 24 , wherein the first polymer is poly(butylmethacrylate) and the second polymer is poly(ethylene-co-vinyl acetate).  
   
   
       28 . The method of  claim 14 , wherein the sustained release delivery device has a total diameter of no greater than about 1000 μm and a length of no greater than about 6 mm.  
   
   
       29 . The method of  claim 14 , wherein the sustained release delivery device has a bioactive agent elution rate of at least 0.0001 μg per day.  
   
   
       30 . The method of  claim 1 , wherein the one or more bioactive agents are selected from antiproliferative agents, anti-inflammatory agents, anti-angiogenic agents, antibiotics, neurotrophic factors, or combinations thereof.  
   
   
       31 . The method of  claim 1 , wherein the sustained release delivery device of (A) comprises: 
 a nonlinear body member having a direction of extension, a longitudinal axis along the direction of extension, and a proximal end and a distal end,    wherein at least a portion of the body member deviates from the direction of extension,    and wherein the body member includes the one or more bioactive agents, and a polymer matrix.    
   
   
       32 . The method of  claim 31 , wherein the body member is coil-shaped.  
   
   
       33 . The method of  claim 31 , wherein a cap is positioned at the proximal end of the body member.  
   
   
       34 . The method of  claim 31 , wherein the body member includes a lumen.  
   
   
       35 . The method of  claim 31 , wherein the device is removable from the eye.  
   
   
       36 . The method of  claim 31 , wherein the polymer matrix comprises a first polymer and a second polymer wherein the first polymer is a poly(alkyl(meth)acrylate) or a poly(aromatic(meth)acrylate) and wherein the second polymer is poly(ethylene-co-vinyl acetate).  
   
   
       37 . The method of  claim 36 , wherein the first polymer comprises a poly(aromatic (meth)acrylate) selected from the group consisting of poly(aryl (meth)acrylate), poly(aralkyl(meth)acrylate), poly(alkaryl(meth)acrylate), poly(aryloxyalkyl (meth)acrylate), and poly (alkoxyaryl(meth)acrylate).  
   
   
       38 . The method of  claim 36 , wherein the first polymer comprises a poly(alkyl(meth)acrylate) selected from the group consisting of poly (n-butyl methacrylate), poly(n-butyl methacrylate-co-methyl methacrylate), poly(n-butyl methacrylate-co-isobutyl methacrylate), and poly(t-butyl methacrylate).  
   
   
       39 . The method of  claim 36 , wherein the first polymer is poly(butylmethacrylate) and the second polymer is poly(ethylene-co-vinyl acetate).  
   
   
       40 . The method of  claim 1 , wherein method (C) comprises injecting on or more bioactive agents into the vitreous humor.  
   
   
       41 . The method of  claim 1 , wherein method (C) comprises delivering on or more bioactive agents into the vitreous humor using iontophoresis.  
   
   
       42 . The method of  claim 41 , wherein the iontophoresis is transscleral iontophoresis.  
   
   
       43 . The method of  claim 1 , wherein the one or more bioactive agents are selected from antiproliferative agents, anti-inflammatory agents, inhibitors of angiogenesis, antibiotics, hormonal agents, neurotropic factors, or combinations thereof.  
   
   
       44 . The method of  claim 43 , wherein the antiproliferative agents are selected from taxol, sirolimus (rapamycin), analogues of rapamycin, tacrolimus, ABT-578, everolimus, paclitaxel, taxane, and vinorelbine.  
   
   
       45 . The method of  claim 43 , wherein the anti-inflammatory agents are selected from hydrocortisone, hydrocortisone acetate, dexamethasone 21-phosphate, fluocinolone, medrysone, methylprednisolone, prednisolone 21-phosphate, prednisolone acetate, fluoromethalone, betamethasone, triamcinolone, and triamcinolone acetonide.  
   
   
       46 . The method of  claim 43 , wherein the inhibitors of angiogensis are selected from angiostatin, anecortave acetate, thrombospondin, anti-VEGF antibody, and anti-VEGF fragment.  
   
   
       47 . The method of  claim 43 , wherein the hormonal agent is selected from estrogen, estradiol, progesterol, progesterone, insulin, calcitonin, parathyroid hormone, peptide, and vasopressin hypothalamus releasing factor.  
   
   
       48 . A method for instilling one or more bioactive agents into ocular tissue within an eye of a patient for the treatment of an ocular condition, the method comprising: (A) implanting a sustained release delivery device comprising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more bioactive agents into a vitreous humor; and (B) instilling one or more bioactive agents subretinally.