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

Ophthalmology. 1999 Oct;106(10):1915-23. doi: 10.1016/S0161-6420(99)90401-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choroid / drug effects*
  • Choroid / pathology
  • Choroid Diseases / chemically induced
  • Choroid Diseases / pathology
  • Fluorescein Angiography
  • Fundus Oculi
  • Humans
  • Infusions, Intravenous
  • Liposomes
  • Macaca fascicularis
  • Optic Disk / drug effects
  • Optic Disk / pathology
  • Optic Nerve / drug effects
  • Optic Nerve / pathology
  • Optic Nerve Diseases / chemically induced
  • Optic Nerve Diseases / pathology
  • Photochemotherapy / adverse effects*
  • Photography
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / adverse effects*
  • Porphyrins / administration & dosage
  • Porphyrins / adverse effects*
  • Retina / drug effects*
  • Retina / pathology
  • Retinal Diseases / chemically induced
  • Retinal Diseases / pathology
  • Retreatment
  • Safety
  • Verteporfin


  • Liposomes
  • Photosensitizing Agents
  • Porphyrins
  • Verteporfin