Abstract
Abstract: :
Purpose: The development of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) represents the most common cause of vision loss in patients over the age of 60 years old. Recent clinical observations that reperfusion of the subretinal neovascular complex is usually seen following treatment of the superficial capillary component by photodynamic therapy suggest that deep intrachoroidal new vessels may also be present in this disease. The following study was undertaken to examine this possibility using choroidal imaging in patients with CNV and AMD and by examining choroidal architectural changes in a rodent model of CNV. Methods: Brown Norway (BN) rats were subretinally injected with a low dose of an E-1 deleted adenoviral vector encoding vascular endothelial growth factor 165 (Ad.VEGF165) to induce CNV. Histologic sections were examined at 2 and 4 weeks after injection to determine changes in choroidal vascularity and cellularity. Formation of new intrachoroidal vessels was detected by flat mount and cross-sectional lectin staining and FITC-dextran injection. Intrachoroidal changes in patients with CNV and AMD was detected by high-speed indocyanine green angiography (HS-ICG) and verified by computer registration with standard fluorescein angiograms (FA). Results: Animals studies at both 2 and 4 weeks after Ad.VEGF injected revealed a progressive increase in choroidal cellularity, as seen by histology, and the formation of larger diameter intrachoroidal vessels, as detected by flat mount lectin staining and FITC-dextran injections, with connections to a smaller complex of subretinal new capillaries. HS-ICG detected extensive intrachoroidal new vessel formation in ≷90% of patients with CNV in AMD which appear to connect to areas of CNV as detected by FA. Conclusion: These studies indicate that the formation of neovascularization in CNV may consist of 2 distinct processes; one of larger intrachoroidal new vessel formation and the other of smaller subretinal capillary growth. This observation raises the possibility of developing newer therapies for and exploring alternative pathogenic mechanisms of CNV in AMD.
Keywords: 346 choroid: neovascularization • 308 age-related macular degeneration • 345 choroid