Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6)

Purpose: To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects. Design: Experimental animal study. Animals: Pigmented rabbits and Japanese monkeys were used in this study. Methods: Using a modified 664-nm diode laser, the fundi of pigmented rabbit s and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days a fter treatment. After enucleation 7 days after treatment, specimens were pr epared for light and electron microscopy. Main Outcome Measures: Angiographic evidence of occlusion and histopatholog ic evidence of retinal damage. Results: Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particul arly within the choriocapillaris, at low energy levels. Overlying neurosens ory retina was minimally affected, Fluorescein angiography of lesions treat ed with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm(2) showed a normal app earance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm( 2) showed marked hypofluorescence of choroidal lesions and occlusion of ret inal vessels 7 days after treatment, Conclusions: Effective occlusion of normal choroidal vessels was achieved a t 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 wi th minimal injury to overlying neurosensory retina.