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PURPOSE: To describe fundus autofluorescence (AF) patterns and their change over time in patients with age-related macular degeneration (AMD) and high risk of visual loss participating in the drusen laser study (DLS). DESIGN: Randomized clinical trial. METHODS: The study population consisted of 29 patients (35 eyes) participating in the DLS, which is a prospective, randomized, controlled clinical trial of prophylactic laser therapy in patients with AMD and high risk of neovascular complications. The intervention consisted of 16 eyes having prophylactic laser and 19 receiving no treatment. The main outcome measures were changes in the distribution of drusen and AF. Patients were reviewed for a median follow-up or 24 months (range 12-36 months). RESULTS: At baseline, four patterns of fundus AF were recognized: focal increased AF (n = 18), reticular AF (n = 3), combined focal and reticular AF (n = 2), and homogeneous AF (n = 12). At last follow-up, fundus AF remained unchanged in 15 untreated (78%) and in seven treated (43%) eyes. In only one untreated eye, focal areas of increased AF returned to background levels and were no longer detectable at last follow-up, compared with six treated eyes. This difference was statistically significant (P = .03). Only large foveal soft drusen (drusenoid pigment epithelium detachments) consistently corresponded with focal changes in AF, whereas no obvious correspondence was found between small soft drusen located elsewhere and changes in AF. CONCLUSION: The lack of obvious correspondence between the distribution of drusen and of AF found in this study appears to indicate that drusen and AF represent independent measures of aging in the posterior pole. © 2002 Elsevier Science Inc. All rights reserved.