Methods for treating retinopathy with extended therapeutic effect

Abstract

Methods for treating and preventing retinopathic conditions by administering a glucocorticoid to the vitreous chamber of a patient at risk of, or suffering from, the retinopathy.

1 . A method for treating a retinopathy, the method comprising the steps of: 
 a) administering to the posterior chamber of an eye of a patient having a retinopathy a glucocorticoid capable of reducing the severity or progression of at least one symptom of the retinopathy;    b) permitting substantially all of the glucocorticoid to dissolve in the vitreous of the eye, and;    c) obtaining a continued reduction in the severity or progression of the at least one symptom at a time after a therapeutic amount of the glucocorticoid has ceased to be present in the posterior chamber.    
     
     
         2 . The method of  claim 1  wherein the at least one symptom is selected from the group consisting of increased anterior chamber flare, increased retinal vascular leakage, increased retinal vascular dilation, increased foveal thickness, a changed optic nerve cup volume, and a decreased electroretinography (ERG) value.  
     
     
         3 . The method of  claim 1  wherein the glucocorticoid is selected from the group consisting of dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide, beclomethasone, dipropionate, beclomethasone dipropionate monohydrate, flumethasone pivalate, diflorasone diacetate, fluocinolone acetonide, fluorometholone, fluorometholone acetate, clobetasol propionate, desoximethasone, fluoxymesterone, fluprednisolone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone cypionate, hydrocortisone probutate, hydrocortisone valerate, cortisone acetate, paramethasone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, clocortolone pivalate, flucinolone, dexamethasone 21-acetate, betamethasone 17-valerate, isoflupredone, 9-fluorocortisone, 6-hydroxydexamethasone, dichlorisone, meclorisone, flupredidene, doxibetasol, halopredone, halometasone, clobetasone, diflucortolone, isoflupredone acetate, fluorohydroxyandrostenedione, beclomethasone, flumethasone, diflorasone, clobetasol, cortisone, paramethasone, clocortolone, prednisolone 21-hemisuccinate free acid, prednisolone metasulphobenzoate, prednisolone terbutate, triamcinolone acetonide 21-palmitate, prednisolone, flurometholone, medrysone, loteprednol, fluazacort, betamethasone, prednisone, methylprednisolone, triamcinolone hexacatonide, paramethasone acetate, diflorasone, fluocinolone and fluocinonide, derivatives thereof, salts thereof, and mixtures thereof.  
     
     
         4 . The method of  claim 3  wherein said glucocorticoid is selected from the group consisting of dexamethasone and triamcinolone, derivatives thereof, salts thereof, and mixtures thereof.  
     
     
         5 . The method of  claim 1  wherein the glucocorticoid is administered in conjunction with a biodegradable implant comprising the glucocorticoid and a biodegradable polymer associated therewith.  
     
     
         6 . The method of  claim 5  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from the implant within 30 days following the administration.  
     
     
         7 . The method of  claim 5  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from the implant within 45 days following the administration.  
     
     
         8 . The method of  claim 5  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 60 days following the administration.  
     
     
         9 . The method of  claim 1  wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 45 days following the administration of the glucocorticoid.  
     
     
         10 . The method of  claim 1  wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 60 days following the administration of the glucocorticoid.  
     
     
         11 . The method of  claim 1  wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 90 days following the administration of the glucocorticoid.  
     
     
         12 . The method of  claim 1  wherein a continued reduction in the severity or progression of the at least one symptom continues for at least 120 days following the administration of the glucocorticoid.  
     
     
         13 . The method of  claim 1  wherein the glucocorticoid is injected directly into the vitreous chamber of the eye.  
     
     
         14 . The method of  claim 13  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 30 days following the administration.  
     
     
         15 . The method of  claim 13  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of said eye within 45 days following the administration.  
     
     
         16 . The method of  claim 13  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 60 days following the administration.  
     
     
         17 . A method of preventing the presentation of at least one symptom of a retinopathy comprising administering to the vitreous of a mammal at risk of such presentation a glucocorticoid at a dosage effective to reduce the severity of such symptom in a different patient suffering from the retinopathy, comprising administering the dosage to the vitreous of a patient's eye before the presentation of the at least one symptom.  
     
     
         18 . The method of  claim 17  wherein the at least one symptom is selected from the group consisting of increased anterior chamber flare, increased retinal vascular leakage, increased retinal vascular dilation, increased foveal thickness, an altered optic nerve cup volume, and decreased ERG values.  
     
     
         19 . The method of  claim 17  wherein the glucocorticoid is selected from the group consisting of dexamethasone, betamethasone, triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone hexacetonide, beclomethasone, dipropionate, beclomethasone dipropionate monohydrate, flumethasone pivalate, diflorasone diacetate, fluocinolone acetonide, fluorometholone, fluorometholone acetate, clobetasol propionate, desoximethasone, fluoxymesterone, fluprednisolone, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone cypionate, hydrocortisone probutate, hydrocortisone valerate, cortisone acetate, paramethasone acetate, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, prednisolone, prednisolone acetate, prednisolone sodium phosphate, prednisolone tebutate, clocortolone pivalate, flucinolone, dexamethasone 21-acetate, betamethasone 17-valerate, isoflupredone, 9-fluorocortisone, 6-hydroxydexamethasone, dichlorisone, meclorisone, flupredidene, doxibetasol, halopredone, halometasone, clobetasone, diflucortolone, isoflupredone acetate, fluorohydroxyandrostenedione, beclomethasone, flumethasone, diflorasone, clobetasol, cortisone, paramethasone, clocortolone, prednisolone 21-hemisuccinate free acid, prednisolone metasulphobenzoate, prednisolone terbutate, triamcinolone acetonide 21-palmitate, prednisolone, flurometholone, medrysone, loteprednol, fluazacort, betamethasone, prednisone, methylprednisolone, triamcinolone hexacatonide, paramethasone acetate, diflorasone, fluocinolone and fluocinonide, derivatives thereof, salts thereof, and mixtures thereof.  
     
     
         20 . The method of  claim 19  wherein the glucocorticoid is selected from the group consisting of dexamethasone and triamcinolone, derivatives thereof, salts thereof, and mixtures thereof.  
     
     
         21 . The method of  claim 17  wherein said glucocorticoid is administered in conjunction with a biodegradable implant comprising the glucocorticoid and a biodegradable polymer associated therewith.  
     
     
         22 . The method of  claim 21  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 30 days following the administration.  
     
     
         23 . The method of  claim 21  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 45 days following the administration.  
     
     
         25 . The method of  claim 21  wherein substantially all therapeutically effective amounts of the glucocorticoid are released from said implant within 60 days following the administration.  
     
     
         25 . The method of  claim 17  wherein a significant presentation of the at least one symptom does not occur for at least 45 days following the administration of the glucocorticoid.  
     
     
         26 . The method of  claim 17  wherein a significant presentation of the at least one symptom does not occur for at least 60 days following the administration of the glucocorticoid.  
     
     
         27 . The method of  claim 17  wherein a significant presentation of the at least one symptom does not occur for at least 90 days following the administration of the glucocorticoid.  
     
     
         28 . The method of  claim 17  wherein a significant presentation of the at least one symptom does not occur for at least 120 days following the administration of the glucocorticoid.  
     
     
         29 . The method of  claim 17  wherein the glucocorticoid is injected directly into the vitreous chamber of the eye.  
     
     
         30 . The method of  claim 29  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 30 days following the administration.  
     
     
         31 . The method of  claim 29  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 45 days following the administration.  
     
     
         32 . The method of  claim 29  wherein substantially all therapeutically effective amounts of the glucocorticoid are absent from the vitreous of the eye within 60 days following the administration.