Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PURPOSE: To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). METHODS: PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. RESULTS: Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. CONCLUSION: PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

The squirrel monkey: characterization of a new-world primate model of experimental choroidal neovascularization and comparison with the macaque.

PURPOSE: To evaluate and characterize the New-World squirrel monkey as a primate model for experimental choroidal neovascularization (CNV) studies and to compare it with the current Old-World macaque monkey model. METHODS: Fibrovascular tissues (FVT) were elicited in 12 maculae of seven squirrel monkeys by laser photocoagulation using optimized laser parameters (532 nm, 0.05 second, 75 micro m, 650 mW). Follow-up fundus and fluorescein angiography (FA) examinations were conducted on postlaser days 30 and 35, followed by euthanasia and histologic analysis of tissues. For comparative evaluations, FVT development also was induced and analyzed in eight maculae of four macaque monkeys with laser parameters previously used in this species (514 nm, 0.1 second, 50 micro m, 390 and 455 mW). RESULTS: FVT developed in both primate species, consisting of fibrous tissue that contained vessels that ranged from sparse but identifiable capillaries to well-established neovascular networks. Overall, 65% of the photocoagulation sites in the squirrel monkey and 37% of sites in macaque monkey elicited development of FVT. Localized FVT ranged from modest to extensive thickenings of the choriocapillaris layer. Unexpectedly, 76% of the FVT sites in squirrel monkey eyes and 27% of the sites in macaque eyes showed diffuse FVT that expanded beyond the original photocoagulation sites, accompanied by neovascular infiltration of the retina. CONCLUSIONS: Like the macaque, the squirrel monkey can be considered a useful primate model for experimental CNV investigations, while additionally offering certain species-specific advantages. Diffuse FVT permit studies of antiangiogenic therapies in areas distant from laser photocoagulative trauma sites.