Histology and clinical lifecycle of acquired vitelliform lesion, a pathway to atrophy in age-related macular degeneration

Abstract

Purpose : Acquired vitelliform lesions (AVL) are a CAM5 optical coherence tomography (OCT) feature in age-related macular degeneration (AMD; PMID 33348085) and may be a distinct pathway leading to complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA; PMID 29103793). This study aimed to correlate OCT to histology in eyes with AMD, evaluate AVL content, identify clinical and diagnostic biomarkers, and to generate hypotheses about the AVL lifecycle.

Methods : Donor eyes (n=2) underwent multimodal ex vivo imaging prior to histologic processing. Light microscopy was corresponded to OCT B-scans. Transmission electron microscopy was used for qualitative and quantitative analysis of AVL content via point-counting stereology. AMD eyes exhibiting AVL by OCT (and if available, color fundus photography and fundus autofluorescence) were selected retrospectively from two 3°clinics. In vivo OCT from 41 eyes followed up to 12 years was evaluated.

Results : Histology confirmed characteristic AMD deposits, photoreceptor (PR) degeneration, and AVL material located foveally between the PR and RPE. Light and transmission electron microscopy revealed an inhomogeneous AVL composition including RPE organelles (3–22 % of volume), outer segments (OS, 2–10 %), lipid droplets (0.2–12 %), and a flocculent material (57–59 %). Clinical cases showed high prevalence of subretinal drusenoid deposit (SDD), subfoveal predilection and AVL growth / regression phases. Most resorbing / collapsing AVL disappeared within 1 year after maximum AVL expansion (max. exp.). Hyperreflective foci and ellipsoid zone dis-integrity were rarely observed before AVL formation and frequently at max. exp. Hyperreflective thickening of the RPE-basal lamina-Bruch’s membrane (RPE-BL-BrM) band was always observed at max. exp. and not before AVL formation.

Conclusions : AVL includes an extracellular deposit with varying amounts of RPE granules, some OS, and a major component remaining to be identified. Histologic composition and clinical appearance of AVL content and adjacent RPE-BL-BrM band indicate that RPE granules translocate from the RPE layer and are a transitory part of the AVL. Subfoveal predilection, autofluorescence, association with SDD, and growth / regression phases raise the possibility that AVL formation includes dysregulation of PR-specific molecular pathways, as suggested for SDD and drusen (PMID 23266879).

This is a 2021 ARVO Annual Meeting abstract.