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Study of geographic atrophy in 3 siblings
One way to advance the current understanding of GA is to study how disease progression varies among related individuals.
(Image Credit: AdobeStock/Diego Cervo)
Researchers from Johns Hopkins in Baltimore, and the Bascom Palmer Eye Institute in Miami, joined together to conduct clinical imaging and histopathologic studies to gain a better understanding of geographic atrophy (GA) in 3 siblings who had been followed for 18 to 20 years.
“Age-related macular degeneration (AMD) is a highly complex disease that involves many different cell types. One way to advance the current understanding of GA is to study how disease progression varies among related individuals,” according to lead author Malia M. Edwards, PhD, assistant professor, Wilmer Eye Institute, Johns Hopkins Hospital, underscoring the importance of a sibling study.
In this study,1 2 of the 3 brothers underwent clinical imaging in 2016, 2 years before death. Immunohistochemistry of both flat-mounts and cross-sections, histology, and transmission electron microscopy images were used to compare the choroid and retina in eyes with GA to those of age-matched controls.
The authors reported the following findings. Staining of the choroid with Ulex europaeus agglutinin lectin showed a significant reduction in the percent vascular area and vessel diameter. In one donor, histopathology showed 2 separate areas with choroidal neovascularization (CNV). Reevaluation of swept-source optical coherence tomography angiography (SS-OCTA) images showed the presence of CNV in 2 of the brothers.
Staining also identified a significant reduction in the retinal vasculature in the atrophic area. A subretinal glial membrane comprised of processes positive for glial fibrillary acidic protein and/or vimentin occupied areas identical to those of the retinal pigment epithelium (RPE) and choroidal atrophy in all 3 brothers. SS-OCTA also visualized presumed calcific drusen in the 2 donors who underwent imaging in 2016. Immunohistochemical analysis and alizarin red S staining verified calcium within the drusen, which was ensheathed by glial processes, the investigators reported.
In commenting on the findings, they said, “This study demonstrates the importance of clinicopathologic correlations to increasing our understanding of AMD. This study confirmed previous studies showing that choriocapillaris atrophy is associated with RPE loss while also identifying isolated nonexudative CNV in eyes with GA. It also demonstrated that subretinal glial cells create a membrane with junctions and a collagen component anterior to the region of RPE atrophy and choriocapillaris loss in GA. This membrane could create a barrier to treatments, including stem cell–derived therapy. This study also confirmed the presence of calcium in presumed calcified drusen seen on OCT imaging in 2 of the 3 three brothers.”
