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Am J Pathol. 2019 Apr 30. pii: S0002-9440(18)30884-8. doi: 10.1016/j.ajpath.2019.04.005. [Epub ahead of print]

Choriocapillaris Degeneration in Geographic Atrophy.

Author information

1
University of Iowa Institute for Vision Research; University of Iowa Department of Ophthalmology and Visual Sciences.
2
Cutaneous Biology Research Center, Massachusetts General Hospital and Department of Dermatology, Harvard Medical School.
3
University of Iowa Institute for Vision Research; University of Iowa Department of Biostatistics.
4
University of Iowa Institute for Vision Research; University of Iowa Department of Ophthalmology and Visual Sciences; Department of Electrical and Computer Engineering; University of Iowa Department of Biomedical Engineering.
5
University of Iowa Institute for Vision Research; University of Iowa Department of Ophthalmology and Visual Sciences. Electronic address: robert-mullins@uiowa.edu.

Abstract

Early age-related macular degeneration (AMD) is characterized by degeneration of the choriocapillaris, the vascular supply of retinal photoreceptor cells. We assessed vascular loss during disease progression in the choriocapillaris and larger vessels in the deeper choroid. Human donor maculas from controls (n=99), early AMD (n=35), or clinically diagnosed with geographic atrophy (GA; n=9, collected from outside the zone of retinal pigment epithelium degeneration) were evaluated using Ulex europaeus agglutinin-I labeling to discriminate between vessels with intact endothelial cells and ghost vessels. Morphometric analyses of choriocapillaris density (cross sectional area of capillary lumens divided by length) and of vascular lumen-to-stroma ratio in the outer choroid were performed. Choriocapillaris loss was observed in early AMD (Bonferroni corrected P (pcorr)=0.024) with greater loss in GA (pcorr <10-9) even in areas of intact retinal pigment epithelium. In contrast, changes in lumen-to-stroma ratio in the outer choroid were not found to differ between controls and AMD or GA eyes (P >0.05), suggesting that changes in the choriocapillaris are more prevalent in AMD than those in the outer choroid. In addition, vascular endothelial growth factor-A levels were negatively correlated with choriocapillaris vascular density. These findings support the concept that choroidal vascular degeneration contributes to dry AMD, and that these changes are predominant in the microvasculature. Addressing the capillary loss in AMD remains an important translational target.

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