Histology and Clinical Lifecycle of Acquired Vitelliform Lesion, a Pathway to Advanced Age-Related Macular Degeneration

Purpose: To evaluate hypotheses about the role of acquired vitelliform lesion (AVL) in age-related macular degeneration pathophysiology. Design: Laboratory histology study; retrospective, observational case series. Methods: Two donor eyes in a research archive with AVL and age-related macular degeneration were analyzed with light and electron microscopy for AVL content at locations matched to ex vivo B-scans. A retrospective, observational clinical cohort study of 42 eyes of 30 patients at 2 referral clinics determined the frequency of optical coherence tomography features stratified by AVL fate. Results: Histologic and clinical cases showed subretinal drusenoid deposit and drusen. Ultrastructural AVL components in 2 donor eyes included retinal pigment epithelium (RPE) organelles (3%-22% of volume), outer segments (2%-10%), lipid droplets (0.2%-12%), and a flocculent material (57%-59%). Of 48 AVLs (mean follow-up 46 ± 39 months), 50% collapsed to complete RPE and outer retinal atrophy, 38% were stable, 10% resorbed, and 2% developed neovascularization. The Early Treatment Diabetic Retinopathy Study grid central subfield contained 77% of AVLs. Hyperreflective foci, ellipsoid zone disruption, and hyperreflective thickening of the RPE-basal lamina-Bruch membrane band were common at maximum AVL expansion. Collapsing and noncollapsing AVLs had different growth rates (rapid vs slow, respectively). Conclusions: AVL deposits contain unexpectedly low levels of RPE organelles and outer segments. Subfoveal predilection, reflectivity on optical coherence tomography, hyperautofluorescence, yellow color, and growth-regression phases suggest dysregulation of lipid transfer pathways specific to cone photoreceptors and supporting cells in formation of AVL deposit, analogous to drusen and subretinal drusenoid deposit. Prediction of AVL outcomes via growth rates should be confirmed in larger clinical studies.