Phenotypic heterogeneity in families with age-related macular degeneration

Purpose. Age-related macular degeneration (ARMD) is the most common cause of blindness among the elderly in the western world. Genetic factors have been proposed to be involved in the pathogenesis. The purpose of this project was to evaluate the phenotypic appearance of macular changes in families with multiple affected individuals. Methods. Eight families with multiple individuals previously diagnosed with ARMD were identified in Massachusetts and North Carolina. Affected individuals were examined by the authors or fundus photographs were obtained for review. The macular findings were graded (1 through 5) according to a modification of the grading system used in the Age-Related Eye Disease Study (AREDS) as follows: Stage 1 no drusen or a few small hard drusen Stage 2 extensive small drusen or non-extensive intermediate drusen, or pigment abnormalities Stage 3 extensive intermediate drusen or any large drusen Stage 4 geographic atrophy Stage 5 exudative maculopathy including retinal pigment epithelial detachments, choroidal neovascular membranes, or disciform scars Reaults. All families had at least 3 individuals with stage 3 or higher maculopathy in at least one eye. Six of the families had at least 2 individuals with stages 4 or 5. In addition, the finding of individuals with stages 2 or 3 was observed in families with individuals found to have higher stages of maculopathy (5 families). Individuals with stages 4 and 5 were of similar age compared to those with stage 3; however, they tended to be older than those with stage 2. Conclusion. The phenotypic appearance of the macula in families with multiple affected individuals is heterogeneous and representative of the spectrum of macular findings typically associated with ARMD.