Laser-induced Choroidal Neovascularization(CNV) in Drug Development – Experiences with the Monkey Model

Abstract

Abstract: : Introduction: Age-related macular degeneration (AMD) is the most common cause of vision loss in individuals over the age of sixty. Among the models used for AMD, non-human primates are the only laboratory mammals having a macula. This laboratory has conducted studies using the non-human primate CNV model. This study evaluated the potential for repeated laser treatment in primates that did not develop CNV following initial laser treatment. Methods: Laser lesions were placed in the left eye of Monkey 1 (perimacular) and Monkey 2 (non-macular) during the initial session. No lesions were placed in the right eye during the initial session. Approximately 12 months after the initial session, a second set of lesions was placed. Monkey 1 received three macular lesions in the right eye and no additional lesions in the left eye. Monkey 2 received non-macular lesions in the left eye and one macular lesion in the right eye. A green laser (532 nm) was used, with parameters of 75-100 µm spot size, 450-900 mW and 0.1-0.2 second exposure for both sessions. CNV development was evaluated via fluorescein angiography. Safety was evaluated via ophthalmologic examinations and electroretinography (ERG). At the end of the study, the animals were returned to the colony. Results: Fluorescein angiograms after the first laser session did not reveal evidence of CNV. Ophthalmologic changes were limited to those attributed to the laser treatment – evidence of laser lesions and depigmentation/repigmentation as the lesions resolved. ERGs after the initial laser session did not indicate any retinal functional impairment. Placement of a second set of lesions did not result in confirmed CNV. Monkey 1 had mild decreases in ERG responses in both eyes. Monkey 2 did not have decreases in ERG responses. There were no ophthalmologic abnormalities other than those that were related to laser treatment. Fundus photographs taken approximately 3 months after the second laser session showed evidence of lesions from both laser sessions in both animals. Conclusions: While it is difficult to draw conclusions from only two animals, it does not appear that reuse of animals subjected to laser treatment is feasible. The development of CNV, or lack thereof, may be due to individual animal differences in the healing process. Evidence of laser lesions persists long after the lesions have been placed.

Keywords: age-related macular degeneration • animal model • choroid: neovascularization