Abstract
Purpose :
Dry AMD occurs when the retinal pigment epithelium (RPE) cells begin to thin and degenerate followed by photoreceptor loss. Geographic atrophy (GA) represents the atrophic late-stage of dry AMD. AMD pathology affects the RPE physiology and results in several noticeable morphological features in these cells. Visible light SLO autofluorescence (VAF-SLO) imaging visualizes the accumulation of the autofluorescent lipids composing lipofuscin at the level of the RPE cell monolayer in vivo in patients; whereas near-infrared SLO autofluorescence (IRAF-SLO) visualizes the distribution of melanin. Here, we characterized the GA from several donors eyes by VAF- and IRAF-SLO and correlated it to the morphology of RPE/photoreceptors.
Methods :
SLO, and fundus macrography (FM) were used to identify and measure the extent of GA lesions from 22 fixed donor eyes. Adjacent areas of the retina/RPE/choroid from the margins of the GA border were cut to generate two smaller fragments: one was processed for epon embedding while the other was processed for cryosectioning and immunofluorescence in the green-red and near-IR (NIR) channels that closely matched VAF- and IRAF-SLO ranges. DNA was obtained from blood samples or fixed eye tissue of the donors and genotyped for single nucleotide polymorphisms (SNPs) previously shown to be associated with the development and progression of AMD (rs800292 and rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3)).
Results :
The majority of the GA donors were homozygous for the risk alleles at the CFH I62V site. GA tissue displayed high and low levels of hyper-fluorescent rings that circumscribed the effected region. The cytoplasm of RPE cells at the GA margins contained fluorescent granules visible in both NIR and green-red channels. Very few NIR fluorescent melanin granules were still present in these RPE cells. Histologically, few photoreceptor nuclei were observed in the margin between GA abnormal and normal regions. Dissociated RPE cells lying on basal laminar deposit (BLamD), with or without dissociated RPE migrating towards the INL, were observed at the margins with high IRAF-SLO. Sloughed RPE was present at the lesion margins with low IRAF-SLO.
Conclusions :
GA can be sub-grouped based on the IRAF-SLO and RPE morphology.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.