Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey

Objective: This study evaluated the effect of repeated photodynamic therapy (PDT) applications on normal primate retina and choroid using an intravenous infusion of liposomal benzoporphyrin derivative (verteporfin). Design: This was an experimental study in a primate model. Animals/Controls: Six cynomolgus monkeys were used as experimental subjects and one monkey was used as a control subject. Intervention: Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea or the optic nerve of each eye. Verteporfin was delivered by intravenous infusion at a dose of 6 mg/m(2), 12 mg/m(2), or 18 mg/m(2). Laser irradiation was then applied using a diode laser (689 nm) with light doses and spot sizes kept constant. Main Outcome Measures: Findings were documented by fundus photography, fluorescein angiography, and light and electron microscopy. Results: A cumulative dose response was seen angiographically and histologically with more severe damage to the retina and choroid noted at higher dye doses. Photodynamic therapy applied to the macula using the 6-mg/m(2) verteporfin dose showed recovery of choriocapillaris, with mild retinal pigment epithelium and outer photoreceptor damage at 6 weeks. At this dose, the optic nerve showed few focal sites of axon atrophy and capillary loss. Treatments over the macula using the 12-mg/m(2) and 18-mg/m(2) doses led to chronic absence of choriocapillaris and photoreceptors at 6 weeks. One of two optic nerves became atrophic after PDT applications using dye doses of 12 mg/m(2), and both optic nerves became atrophic in the 18-mg/m(2) dye dose group. Conclusion: Limited damage to the retina, choroid, and optic nerve was present in primates treated with multiple PDT sessions using 6 mg/m(2) verteporfin with light doses and the timing of irradiation kept constant. However, PDT using higher dye doses of 12 mg/m(2) and 18 mg/m(2) led to significant chronic damage to the normal retina, choroid, and optic nerve.