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

Martin H. Reinke, Christina Canakis, Deeba Husain, Norman Michaud, Thomas J. Flotte, Evangelos S. Gragoudas, Joan W. Miller

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

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/m2, 12 mg/m2, or 18 mg/m2. 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/m2 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/m2 and 18-mg/m2 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/m2, and both optic nerves became atrophic in the 18-mg/m2 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/m2 verteporfin with light doses and the timing of irradiation kept constant. However, PDT using higher dye doses of 12 mg/m2 and 18 mg/m2 led to significant chronic damage to the normal retina, choroid, and optic nerve.

Original languageEnglish (US)
Pages (from-to)1915-1923
Number of pages9
JournalOphthalmology
Volume106
Issue number10
DOIs
StatePublished - Oct 1 1999

ASJC Scopus subject areas

  • Ophthalmology

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    Reinke, M. H., Canakis, C., Husain, D., Michaud, N., Flotte, T. J., Gragoudas, E. S., & Miller, J. W. (1999). Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey. Ophthalmology, 106(10), 1915-1923. https://doi.org/10.1016/S0161-6420(99)90401-3