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R. A. Adelman, F. Lu, Z. Hu, J. Sinard, A. Garen; Histopathology of Tissue Factor-Targeted Photodynamic Therapy for the Treatment of Choroidal Neovascularization in a Laser Induced Rat Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1966.
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To study the histopathology of Tissue Factor-Targeted Photodynamic Therapy (TFPT) for the treatment of choroidal neovascularization (CNV) in a rat model.
Multiple CNV lesions were induced by laser photocoagulation of the retina in Norway-Brown rats. After 4 weeks, 6 rats were divided into two groups and received intravitreal or intravenous injection of verteporfin conjugated with Factor VII, the natural ligand for TF. Lesions in one eye were treated with 689nm laser (50 J/cm2) after 30 or 60 minutes, while the other eye left as control. Fluorescein angiogram was performed. Histological and immunohistochemical examinations were performed on day 1,3 and 7 after treatment to assess the efficacy and safety of TFPT.
In the 6 control eyes, a chorioretinal scar was found in new vessels and hemosiderin laden macrophages. The scar progressed over time to become more fibrotic and hypocellular, with limited inflammatory response. In the 3 rats treated by TFPT intravitreally, the eyes showed a diffuse inflammation, which was not seen in the control eyes. In addition, the scars from the initial laser injury were more cellular, with lymphocytes and macrophages. The rats treated intravenously by TFPT followed by laser activation did not show the diffuse inflammation but showed the same increased cellularity and decreased fibrosis seen in the intravitreally treated eyes. Fluorescein angiogram suggest that intravenous and intravitreal injections of verteporfin targeted to TF by Factor VII result in regression of laser-induced CNV.
Intravitreal treatment followed by laser activation induces a diffuse inflammation, which is not seen in intravenous treatment. The treated eyes show less fibrotic scars compared to the control eyes.
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