Choroidal vascular changes in early and advanced AMD: relationship with ARMS2 genotype

Abstract

Purpose : There is considerable evidence that early age-related macular degeneration (AMD) is characterized by degeneration of the choriocapillaris, the vascular supply for the RPE and photoreceptor cells. We sought to quantify the extent to which vascular loss is associated with disease progression to GA and the impact of ARMS2 A69S genotype on these features.

Methods : Human donor maculas from a previously unpublished cohort included 99 unaffected controls and 35 maculas with early AMD. In addition 7 maculas with clinically diagnosed geographic atrophy (collected from outside the zone of RPE degeneration) were studied. Morphometric analyses of choriocapillaris density, vascular lumen-to-stroma ratio in the outer choroid, and choroidal thickness were performed. Eyes were also genotyped for the A69S polymorphism in the ARMS2 gene.

Results : Choriocapillaris loss was observed in early AMD (Bonferroni corrected p=0.028) with greater loss in GA, observed outside of the areas of central RPE degeneration (pcorr <0.001). In contrast, choroidal thickness and lumen-to-stroma ratio in the outer choroid was not found to differ between controls and AMD eyes (p >0.05), suggesting that AMD-related changes in the choriocapillaris occur earlier and are more prevalent than those in the outer choroid. High-risk homozygous and heterozygous genotypes for ARMS2 A69S were associated with significantly thinner choroids (pcorr<0.01) but not with other vascular parameters.

Conclusions : These findings support the concept that choroidal vascular degeneration contributes to dry AMD and GA, with the most predominant damage in the choriocapillaris microvasculature. The AMD-associated risk variant in ARMS2 was associated with thin choroids but not with vascular degeneration. Addressing the capillary loss in AMD remains an important translational target.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.