Vision through photodynamic therapy of the eye

Abstract

Photodynamic therapy of conditions of the eye, especially those conditions characterized by unwanted neovasculature, such as age-related macular degeneration, results in enhanced visual acuity for treated subjects.

1 . A method to enhance visual acuity in a human subject, which method comprises: 
 irradiating target ocular tissue in said subject with light emitted from a laser,    wherein said subject has been administered a formulation of a photoactive compound coupled to a specific binding ligand which binds target ocular tissue;    wherein the wavelength of the light is absorbed by the photoactive compound; and    wherein said irradiation is conducted for a time and at an intensity sufficient to enhance visual acuity in said subject.    
     
     
         2 . The method of  claim 1  wherein said irradiation is administered beginning about 5-30 minutes after said subject has been administered said formulation.  
     
     
         3 . The method of  claim 1  wherein the eye of said subject contains unwanted neovasculature.  
     
     
         4 . The method of  claim 3  wherein the neovasculature is choroidal neovasculature.  
     
     
         5 . The method of  claim 1  wherein the photoactive compound is a polypyrrolic macrocycle.  
     
     
         6 . The method of  claim 5  wherein the photoactive compound is a green porphyrin, a hematoporphyrin derivative, a chlorin, or a phlorin.  
     
     
         7 . The method of  claim 6  wherein said photoactive compound is a green porphyrin.  
     
     
         8 . The method of  claim 7  wherein said green porphyrin is of the formula  
       
         
           
           
               
               
           
         
         wherein each of R 1  and R 2  is independently selected from the group consisting of carbalkoxyl (2-6C), alkyl (1-6C), arylsulfonyl (6-10C), cyano and —CONR 5 CO— wherein R 5  is aryl (6-10C) or alkyl (1-6C);  
         each R 3  is independently carboxyl, carboxyalkyl (2-6C) or a salt, amide, ester or acyl hydrazone thereof, or is alkyl (1-6C);  
         R 4  is CH═CH 2  or —CH(OR 4′ )CH 3  wherein R 4′  is H, or alkyl (1-6C) optionally substituted with a hydrophilic substituent.  
       
     
     
         9 . The method of  claim 8  wherein said green porphyrin is of the formula  
       
         
           
           
               
               
           
         
         wherein each of R 1  and R 2  is independently carbalkoxyl (2-6C);  
         one R 3  is carboxyalkyl (2-6C) and the other R 3  is the ester of a carboxyalkyl (2-6C) substituent; and  
         R 4  is CH═CH 2  or —CH(OH)CH 3 .  
       
     
     
         10 . The method of  claim 9  wherein said green porphyrin is of the formula  
       
         
           
           
               
               
           
         
       
       and 
 wherein R 1  and R 2  are methoxycarbonyl;  
 one R 3  is —CH 2 CH 2 COOCH 3  and the other R 3  is CH 2 CH 2 COOH; and  
 R 4  is CH═CH 2 ; i.e., BPD-MA.  
 
     
     
         11 . The method of  claim 1  wherein said formulation is a liposomal preparation.  
     
     
         12 . The method of  claim 1  wherein said subject has been diagnosed with age-related macular degeneration (AMD).  
     
     
         13 . The method of  claim 1  wherein the subject has been diagnosed with a condition selected from the group consisting of macular degeneration, ocular histoplasmosis syndrome, myopia, and inflammatory diseases.  
     
     
         14 . The method of  claim 1  wherein said irradiation is administered at an irradiance of about 600 mW/cm 2  to provide a total fluence of 50 J/cm 2 -150 J/cm 2  of said light.  
     
     
         15 . The method of  claim 1  wherein said irradiation is administered beginning about 5 minutes after said subject has been administered said formulation.