TY - JOUR
T1 - Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey
AU - Reinke, Martin H.
AU - Canakis, Christina
AU - Husain, Deeba
AU - Michaud, Norman
AU - Flotte, Thomas J.
AU - Gragoudas, Evangelos S.
AU - Miller, Joan W.
N1 - Funding Information:
Supported in part by QLT Phototherapeutics, Inc., Vancouver, British Columbia, Canada; the Massachusetts Lions Eye Research Fund (J.W.M.); and Research to Prevent Blindness (J.W.M.).
PY - 1999/10/1
Y1 - 1999/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0161-6420(99)90401-3
DO - 10.1016/S0161-6420(99)90401-3
M3 - Article
C2 - 10519585
AN - SCOPUS:0033208744
SN - 0161-6420
VL - 106
SP - 1915
EP - 1923
JO - Ophthalmology
JF - Ophthalmology
IS - 10
ER -