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Originally published In Press as doi:10.1167/iovs.08-2833 on April 8, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3890-3896.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2833
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Factor VII–Verteporfin for Targeted Photodynamic Therapy in a Rat Model of Choroidal Neovascularization

Fang Lu,1,2 Zhiwei Hu,*,3,4 John Sinard,1,5 Alan Garen,4 and Ron A. Adelman*,1

1From the Departments of Ophthalmology and Visual Science, 3Obstetrics, Gynecology and Reproductive Sciences, 4Molecular Biophysics and Biochemistry, and 5Pathology, Yale University School of Medicine, New Haven, Connecticut; and the 2Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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/m2) or Visudyne (6.0 mg/ m2; 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/m2 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/m2 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.






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