To evaluate iris color, change of iris color, and iris pigment epithelial defects as risk factors in age-related macular degeneration, we compared 101 patients with age-related macular changes with 102 control subjects in a case-control study. Three of 101 patients (3%) and four of 102 control subjects (4%) had epithelial iris defects. Light iris color during youth was reported by 51 of 101 patients (50.5%) and 42 of 102 control subjects (41.2%) (odds ratio, 1.46; P = .184). Of the 101 patients, 26 (25.7%) noticed their iris color to have become lighter during life compared with six of 102 control subjects (5.9%) (odds ratio, 5.5; P = .0001). At present examination, 63 of 101 patients (62.4%) had light irides compared with 43 of 102 control subjects (42.2%) (odds ratio, 2.27; P = .004). These results suggest that initial light iris color and iris pigment epithelial defects are not associated with an increased risk of age-related macular degeneration, whereas decreased stromal iris pigmentation may indicate a higher risk.