Retinal Risk Factors and Progression to Geographic Atrophy in Age–Related Macular Degeneration

Abstract

Abstract: : Purpose: To determine the predisposing anatomic features and the sequence of events leading to the formation of geographic atrophy (GA) in age–related macular degeneration (AMD). Methods: In the Age–Related Eye Disease Study (AREDS), we reviewed film–based color fundus photography of all patients from two clinical centers (University of Wisconsin and Devers Eye Institute) in whom geographic atrophy first appeared in the macula of one or both eyes a minimum of 4 years after baseline evaluation. We determined the location of the initial appearance of GA, and then reviewed fundus photographs from all previous yearly visits. For each yearly visit, at the site of future GA we recorded the presence of anatomic features including presence of drusen, largest drusen size, drusen confluence, hyperpigmentation, hypopigmentation, drusenoid PED, calcification, and other lesions. Results: There were a total of 95 eyes of 77 patients in whom geographic atrophy developed at least 4 years after their initial study evaluation (range = 4–11 years; average = 6.5 years). The following lesions were determined to have been present at the site of future GA formation: drusen = 95/95 eyes (100%), large drusen (>125 microns) = 91/95 eyes (95.8%), focal hyperpigmentation = 91/95 eyes (95.8%), drusen confluence = 89/95 eyes (93.7%), very large drusen (>250 microns) 79/95 eyes (83.2%), hypopigmentation = 77/95 eyes (81%), and calcification = 20/57 eyes (35%). The average interval from the time of appearance of these lesions to the development of GA was: drusen and drusen confluence = >6.5 years, hyperpigmentation = 4.0 years, hypopigmentation = 2.3 years, and calcification = 1.5 years. Conclusions: In eyes with AMD, GA usually originates from an accumulation of large, confluent drusen, often associated with focal hyperpigmentation. The subsequent sequence of events leading to GA is characterized by: development of hyperpigmentation in those eyes in which it was not initially present; fading of drusen; loss of hyperpigmentation; development of hypopigmentation; and formation of GA.

Keywords: age-related macular degeneration • clinical (human) or epidemiologic studies: natural history • clinical (human) or epidemiologic studies: risk factor assessment