Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer - Mono-L-aspartyl chlorin e6

Purpose: To demonstrate the selective localization of the hydrophilic photo sensitizer mono-L-aspartyl chlorin e6 (NPe6) in experimental choroidal neov ascularization in nonhuman primate eyes. Methods: Sixty-seven experimental choroidal neovascular lesions (CNV) were created in the fundi of Macaca monkeys using the modified Ryan's model and documented by fluorescein and indocyanine green angiography. To determine t he biodistribution of NPe6 and the optimal timing of laser irradiation afte r dye administration, NPe6 angiography and fluorescence microscopy with NPe 6 were performed. Photodynamic therapy (PDT) was performed at various dye d oses (0.5-10.0 mg/kg) and laser fluences (7.5-225.0 J/cm(2)) on the CNV and on 10 areas of normal retina and choroid. Treatment outcomes were assessed by fluorescein and indocyanine green angiography and confirmed by light an d electron microscopy. Results: NPe6 fluorescence microscopy demonstrated intense fluorescence of CNV and retinal pigment epithelial cells. Choroidal vessel walls and outer retina adjacent to CNV fluoresced moderately; retinal vessel walls and micr ocapillaries had trace fluorescence. The fluorescence of CNV lesions on flu orescein angiography became stronger than that of retinal vessels 20-60 min utes after dye injection. Choroidal neovascular lesion closure was achieved with NPe6 PDT without significant damage to the sensory retina. Histology demonstrated necrosis of CNV endothelial cells with minimal damage to surro unding tissues. Conclusions: NPe6 PDT selectively localizes to experimental CNV in nonhuman primates, resulting in occlusion of CNV with sparing of the neurosensory r etina.