title: Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey.
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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laser Research Laboratory, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Reinke
authors.forename: C
authors.initials: C
authors.lastname: Canakis
authors.forename: D
authors.initials: D
authors.lastname: Husain
authors.forename: N
authors.initials: N
authors.lastname: Michaud
authors.forename: T J
authors.initials: TJ
authors.lastname: Flotte
authors.forename: E S
authors.initials: ES
authors.lastname: Gragoudas
authors.forename: J W
authors.initials: JW
authors.lastname: Miller
mesh_terms: D000818:Animals; D002829:Choroid / Q000187:drug effects* / Q000473:pathology; D015862:Choroid Diseases / Q000139:chemically induced / Q000473:pathology; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008252:Macaca fascicularis; D009898:Optic Disk / Q000187:drug effects / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000473:pathology; D009901:Optic Nerve Diseases / Q000139:chemically induced / Q000473:pathology; D010778:Photochemotherapy / Q000009:adverse effects*; D010781:Photography; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*; D011166:Porphyrins / Q000008:administration & dosage / Q000009:adverse effects*; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced / Q000473:pathology; D019233:Retreatment; D012449:Safety; D000077362:Verteporfin
chemical_list: D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin