Purpose:
To study the efficacy of targeted Photodynamic Therapy (PDT) using factor VII conjugated to verteporfin (fVII–verteporfin) for treating the choroidal neovasculature (CNV) in a rat model of macular degeneration.
Methods:
Multiple CNV lesions were induced by laser photocoagulation of the retina in Norway–Brown rats. After 4 weeks, 12 rats were injected intravenously with 0.5 and 1.0mg/m2 of fVII–verteporfin . Verteporfin was extracted from Visudyne and was covalently conjugated to fVII. Randomly selected lesions were irradiated with 689nm laser light (50 J/cm2) at 30 or 60 minutes after injection of fVII–verteporfin, while the other lesions were not irradiated. An additional 2 rats were injected with non–targeted free verteporfin. The lesions were evaluated by fluorescein angiography for CNV leakage on days 1, 7 and 14 to assess the efficacy of targeted and non–targeted PDT.
Results:
Among the CNV lesions treated by non–targeted PDT, leakage was detected in 75% of the lesions on day 7 and in all of the lesions on day 14. Among the CNV lesions treated by targeted PDT (1.0mg/m2), leakage was detected in 28% of the lesions on day 7 and in 34% of the lesions on day 14. These results are summarized in the Table below.
Conclusions:
Intravenous injection of verteporfin conjugated to factor VII for targeting to tissue factor enhanced the efficacy of verteporfin in stopping laser–induced leakage of the CNV. The optimal dose of fVII–targeted verteporfin was significantly less than the dose required for non–targeted verteporfin. These results suggest that factor VII–targeted verteporfin is a promising agent for PDT of macular degeneration.
Keywords: age-related macular degeneration • choroid: neovascularization • photodynamic therapy