Factor VII-verteporfin for targeted photodynamic therapy in a rat model of choroidal neovascularization.

Author(s): Lu F, Hu Z, Sinard J, Garen A, Adelman RA

Affiliation(s): Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA.

Publication date & source: 2009-08, Invest Ophthalmol Vis Sci., 50(8):3890-6. Epub 2009 Apr 8.

Publication type: Research Support, Non-U.S. Gov't

PURPOSE: To study the efficacy and safety of factor VII (fVII)-verteporfin for targeted photodynamic therapy (TPT) compared with nontargeted photodynamic therapy (PDT) in a rat model of choroidal neovascularization (CNV). fVII-verteporfin binds tightly and specifically to tissue factor, which is expressed on endothelial cells of CNV but not normal vasculature. METHODS: Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, the rats were injected intravenously with fVII-verteporfin (0.5 and 1.0 mg/m(2)) or Visudyne (6.0 mg/ m(2); QLT Inc., Vancouver, BC, Canada). Randomly selected lesions were treated with a 689-nm laser 30 or 60 minutes later. The lesions were evaluated by fluorescein angiography and histopathology. RESULTS: The rats treated with Visudyne PDT showed leakage in 75% of the CNV lesions on day 7 and 100% of lesions on day 14. The rats treated with fVII-verteporfin TPT at a dose of 0.5 mg/m(2) showed leakage in 33% and 36% of the CNV lesions on days 7 and 14, respectively. When the dose was increased to 1.0 mg/m(2) for TPT, leakage was detected in 25% and 23% of the CNV lesions on days 7 and 14, respectively. No ocular side effect was detected by histopathologic evaluation. CONCLUSIONS: The frequency of leakage in CNV lesions was significantly reduced using fVII-verteporfin TPT compared with PDT. The efficacious dose with fVII-verteporfin was approximately 10% of the dose usually used in nontargeted Visudyne PDT. Using fVII-verteporfin for TPT may improve the efficacy and safety of PDT for treating choroidal neovascularization.