Liposomal benzoporphyrin derivative verteporfin photodynamic therapy. Selective treatment of choroidal neovascularization in monkeys.
OBJECTIVE
The authors have previously shown that photodynamic therapy (PDT) using lipoprotein-delivered benzoporphyrin derivative mono-acid (BPD) effectively closed experimental choroidal neovascularization (CNV). In the current study, the authors used a clinical preparation, liposomal BPD verteporfin in the same model, with experiments designed to establish optimal dye and light doses, and the timing of laser light irradiation after dye injection, for effective and selective closure of CNV.


METHODS
Experimental CNV was induced in the maculae of cynomolgus monkeys. Liposomal BPD verteporfin was injected intravenously at doses of 1.0, 0.5, 0.375, and 0.25 mg/kg. Laser light at 692 nm then was applied to CNV, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2, at various times after dye injection, ranging from 5 to 120 minutes. Treatment effect was assessed by fundus photography and fluorescein angiography and confirmed by light and electron microscopy. The PDT of experimental CNV was studied to assess efficacy; PDT performance on normal eyes was studied to investigate selectivity.


RESULTS
The CNV closure was demonstrated by fluorescein angiography and histopathologic findings at all tested dye doses. A dye dose of 0.375 mg/kg, with laser light irradiation applied 20 to 50 minutes after dye injection, optimized CNV closure with minimal retinal and choroidal damage. No major local adverse effects were noted, and the drug was well tolerated systematically.


CONCLUSIONS
Liposomal BPD verteporfin is a potent photosensitizer, and PDT using this dye is a potentially effective and selective treatment for CNV.
Kramer
M
M
Laser Research Laboratory, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, 02114, USA.
Miller
J W
JW
Michaud
N
N
Moulton
R S
RS
Hasan
T
T
Flotte
T J
TJ
Gragoudas
E S
ES
D000818:Animals; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D004337:Drug Carriers; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D008081:Liposomes; D008252:Macaca fascicularis; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011166:Porphyrins / Q000008:administration & dosage*; D012160:Retina / Q000187:drug effects / Q000648:ultrastructure; D000077362:Verteporfin
D004337:Drug Carriers; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin