Choriocapillaris dropout in early age-related macular degeneration

Abstract

Purpose : We have previously demonstrated a loss of choriocapillaris (CC) in advanced AMD. In this study, we examined postmortem eyes from donors with clinically documented early AMD (> 10 small drusen or <15 intermediate drusen, or pigment abnormalities associated with AMD) in choroidal whole mounts to determine the area, pattern and severity of vascular changes.

Methods : Postmortem aged human eyes were acquired from NDRI and Johanna Seddon at Tufts University School of Medicine. Choroids without AMD (n=7) and from eyes with a Grade 2 CARMS classification of early AMD (n=7) (Seddon et al,, Ophthalmol. 2006) were immunolabeled with Ulex Europaeus Agglutinin (UEA) lectin to stain blood vessels as previously reported (Seddon et al, JAMA Ophthalmol. 2016). Whole mounts were imaged using confocal microscopy and image analysis was performed to determine the area of vascular changes and density of vasculature (percent vascular area, %VA).

Results : In aged control eyes, the CC had a homogenous pattern of freely interconnecting capillaries with broad diameter lumen. The %VA in submacula was 78.1 +/- 3.25 %. In eyes with early AMD, CC dropout was observed in the submacular choroid as evidenced by a loss of interconnecting capillaries and a decrease in %VA to 60.1 +/- 10.4% which was significantly reduced compared to aged controls (p<0.0001). The paramacular %VA was not significantly different in eyes with or without AMD (79.7 +/- 3.25% in aged controls versus 79.2 +/-6.8% in early AMD). The area of submacular choroid affected by CC dropout was 0.04 +/- 0.09mm² in aged control eyes. In eyes with early AMD the area affected by CC dropout was 10.4 +/- 6.1mm² which was significantly increased compared to aged controls (p=0.00003). In some cases, incipient neovascular buds were observed at the border of regions with CC dropout in early AMD choroids.

Conclusions : Using lectin-labeled choroidal whole mounts from donors with clinically documented early AMD has provided a unique opportunity to examine regional changes in vascular pathology associated with small to intermediate drusen. No vascular pathology was observed outside the submacular region. While the affected area in some eyes was quite extensive histologically, these changes are probably not detectable clinically using standard in vivo imaging techniques.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.