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In a prospective study with a 5-year follow-up, we assessed the effect of a single series of low-dose radiation on the distance visual acuity in eyes with angiographically confirmed subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). The posterior pole of 12 eyes was treated with 5 Gy (4 x 1.25 Gy), and 34 eyes treated with 8 Gy (4 x 2 Gy). The best corrected distance visual acuity was measured at the time of treatment, and annually thereafter for 5 years. The study obtained complete follow-up for 11 patients in the 5-Gy group (nine classic, two occult CNVs), and 29 patients in the 8-Gy group (12 classic, 17 occult CNVs). At baseline, the mean distance visual acuity of the treated eyes was 0.16 (20/125) in the 5-Gy group, and 0.2 (20/100) in the 8-Gy group. Five years later, an average loss of 3.2 lines was present in the 5-Gy group, and 4 lines in the 8-Gy group. After 5 years, an average loss of 2 lines was found in a control group consisting of 18 second eyes with low stage dry ARMD, with a mean distance visual acuity of 0.5 (20/40) at baseline. Statistical analyses with Wilcoxon and Mann-Whitney U-tests showed that a single series of low dose radiation with either 5 Gy or 8 Gy was not able to stabilize the distance visual acuity of eyes with subfoveal CNV in ARMD during a 5-year follow-up.