Photodynamic therapy of experimental choroidal neovascularization in the mouse

Purpose: To evaluate the qualitative and quantitative effects of verteporfin photodynamic therapy (PDT) on laser-induced choroidal neovascularization (CNV) in the mouse. Methods: PDT was applied to the normal mouse fundus using light doses of 32, 64, and 83 s, and histological analysis of the treated areas was performed. CNV was induced using krypton laser photocoagulation of the fundus, and the CNV lesions were subsequently treated with PDT using light doses of 32, 64, and 83 s. Enucleated eyes were analyzed with light and transmission electron microscopies, and measurements of CNV size were done on histologic sections and on isolectin B4-stained choroidal flat mounts. Results: PDT induced a light dose-dependent damage to the surrounding neural retina in normal eyes. At a light dose of 32 s, minimal damage was detected in the neural retina, whereas higher light doses caused distortion and disruption of the outer and inner nuclear layers and of the retinal pigment epithelium. When PDT was applied over laser-induced CNV lesions, the relative height of the lesions was significantly reduced (p < 0.05) using all light doses. Transmission electron microscopy 1 day after PDT treatment revealed occlusion of many of the CNV vessels. One week after PDT treatment, the CNV lesions contained patent vessels irrespective of light dose applied. Accordingly, PDT treatment inhibited (p < 0.05) but did not halt CNV lesion growth. Conclusions: PDT treatment of laser-induced CNV may create an acute occlusion of neovessels and an inhibition of CNV lesion growth without apparent injury to the surrounding neural retina. However, PDT-treated areas will remain vascularized with continued growth of the CNV lesion, which in turn may explain the often limited effect of PDT in patients with neovascular age-related macular degeneration. Elevating the PDT light dose will not increase the treatment effect substantially but may lead to increased collateral injury.