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.Population-based studies conducted in Russia, China, and India and histological examination of enucleated human globes.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.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.Presence of RPE loss and of subretinal proliferations.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.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.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.© 2025 by the American Academy of Ophthalmologyé.