Choriocapillaris Vascular Dropout Related to Density of Drusen in Human Eyes with Early Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is a common, potentially blinding disease characterized by the presence of extracellular deposits beneath the retinal pigment epithelium (RPE). Choroidal vascular changes have also been noted in AMD. This study examined the relationship between the choroidal vasculature and extent of drusen and other sub-RPE deposits, the key pathologic landmarks of AMD. Sections of the maculas of 45 human eyes (21 early AMD and 24 age-matched control) were evaluated morphometrically. The cross-sectional area of sub-RPE deposits, vascular density, number of CD45+ leukocytes, and number of "ghost vessels" were determined in a masked fashion and evaluated by regression analysis. In addition, the extramacular vascular density either directly beneath drusen or adjacent to drusen was evaluated in a separate set of donor eyes. The vascular density of the choriocapillaris showed a trend toward decreasing in association with AMD status. By linear regression analysis, vascular density was inversely associated with sub-RPE deposit density (r(2) = 0.22, P < 0.01). The number of ghost vessels was negatively correlated with vascular density (r(2) = 0.55, P < 0.001) and positively correlated with sub-RPE deposit density (r(2) = 0.57, P < 0.001). In morphologic studies of extramacular solitary drusen, vascular density beneath drusen was found to be 45% lower than adjacent to drusen (P < 0.01). These findings support the concept that microvascular changes are related to the pathogenesis of AMD and suggest that vascular endothelial cell loss occurs in association with sub-RPE deposit formation. Whether microvascular events are a cause or consequence of drusen or other deposit formation remains to be determined.