Objective: To assess the prevalences of subfoveal retinal pigment epithelium (RPE) loss versus subfoveal tissue proliferation as causes of vision loss in patients with late-stage age-related macular degeneration (AMD) or myopic macular atrophy. Design: Population-based studies conducted in Russia, China, and India and histological examination of enucleated human globes. Participants: The Russian Ural Eye and Medical Study (n = 5899 participants; age: ≥40 years), Ural Very Old Study (n = 1526; age: 85+ years), Beijing Eye Study (n = 3468; age: ≥40 years), and Central India Eye and Medical Study (n = 4711) were conducted in rural and urban regions in Bashkortostan/Russia, Beijing/China, and Nagpur/India, respectively. The histological study part included human eyes enucleated because of reasons like malignant melanomas, or were post mortem enucleated. Methods: The participants underwent a series of general medical and ophthalmological examinations including OCT of the macula. In the histological study part, the enucleated globes were histomorphometrically examined. Main Outcome Measures: Presence of RPE loss and of subretinal proliferations. Results: In all 4 population-based studies combined, late-stage AMD and myopic macular atrophy were detected in 291 eyes and 46 eyes, respectively. Retinal pigment epithelium cell loss was dominant in 136 (94%) out of 145 eyes with geographic atrophy and in 35 (76%) out of 46 eyes with myopic macular atrophy, whereas subretinal proliferations were predominantly present in 127 (87%) out of 146 eyes with neovascular AMD. Among all 337 eyes with late AMD or myopic macular atrophy, RPE loss was the main cause for vision loss in 190 (56%) eyes and subretinal proliferations in 147 (44%) eyes, with no significant difference (P > 0.05) between the study cohorts. In the histological specimen, subretinal proliferations included melanin-bearing cells in contact with a periodic acid—Schiff-positive membrane, resembling RPE cells. Conclusions: Subretinal proliferations in the foveal region were the main reason for central visual acuity loss in 44% of all eyes with late AMD or myopic macular atrophy in 4 population-based studies. Subretinal foveal RPE cell proliferation and RPE loss are roughly equally important as a cause of vision loss in AMD and myopic macular atrophy.