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F. Lu, Z. Hu, A. Garan, R. Adelman; Targeted Photodynamic Therapy for Treatment of Choroidal Neovascularization in a Laser-Induced Rat Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3768.
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To study the efficacy of Targeted Photodynamic Therapy (TPT) using verteporfin conjugated to factor-VII for the treatment of choroidal neovascularization (CNV) in a rat model. Factor-VII binds specifically to tissue factor, which is expressed on endothelial cells of the CNV but not of normal vessels.
Multiple CNV lesions were induced by laser photocoagulation of the retina in Norway-Brown rats. After 4 weeks, 17 rats received verteporfin conjugated to factor-VII injected intravenously (i.v.). Randomly selected lesions were treated with 689nm laser (50 J/cm2) for 30 or 60 minutes after i.v. injection, while the other lesions in the same eyes were not treated as an internal control. Another 2 control rats were treated with non-targeted verteporfin (6.0 mg/m2). All the lesions were evaluated by fluorescein angiography on 1, 7 and 14 days after laser treatment to compare the efficacy of targeted and non-targeted photodynamic therapy (PDT). Histopathology was performed on day 14 on some of the rat eyes after PDT.
In the CNV lesions treated by non-targeted PDT, leakage stopped in 25% of the lesions on day 7, but started to leak again on day 14. In the CNV lesions treated by targeted PDT (0.5mg/m2, 30min ), 67% (24/36) of the lesions did not leak on day 7, and 64% (23/36) on day 14. In rats treated by targeted PDT at a higher dose (1.0mg/m2, 30min), 75% (40/53) and 77% (41/53) of the lesions did not leak on day 7 and day 14, respectively (p<0.05). Histopathological examination showed no toxicity of targeted PDT on the ocular tissues.
Verteporfin was conjugated to factor-VII and injected i.v. for targeting to Tissue Factor on the CNV in a rat model of laser-induced CNV. Using targeted verteporfin for PDT showed higher efficacy and safety than non-targeted verteporfin in stopping CNV leakage. Optimal efficacy for targeted verteporfin was achieved with 1/6 of the dose required for standard PDT.
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