Is Drusen Area Really So Important? An Assessment of Risk of Conversion to Neovascular AMD Based on Computerized Measurements of Drusen

PURPOSE. To assess the relative risk of an eye's conversion to wet age-related macular degeneration (AMD) based primarily on drusen measurements obtained from analysis of digitized images. METHODS. Four hundred forty-four subjects (820 eyes) enrolled in the Age-Related Eye Disease Study (AREDS I) and 78 subjects (129 eyes) from the Prophylactic Treatment of AMD trial (PTAMD) were studied retrospectively. Drusen size, distribution, drusen area, and hyperpigmentation in two central macular regions on baseline fundus images were determined using an image analysis algorithm. The relative risk for choroidal neovascularization (CNV) based on drusen area, presence of one or five large drusen, hyperpigmentation, and fellow eye status was calculated. RESULTS. Odds ratios (ORs) for measured drusen area within the 1000- and 3000-mu m regions were 1.644* (1.251-2.162) and 1.278 (0.927-1.762) for AREDS eyes and 0.832 (0.345-2.005) and 1.094 (0.524-2.283) for PTAMD eyes (*P < 0.05). In the 1000-mu m region, respective ORs for the presence of a large druse, hyperpigmentation, and fellow eye affected were 2.60, 1.71, and 6.44* for AREDS eyes and 8.24, 1.37, and 17.56* for PTAMD eyes; for the 3000-mu m region, ORs were 3.45*, 3.40*, and 4.59* for AREDS and nonsignificant, 6.58, and 11.62* for PTAMD eyes, respectively. CONCLUSIONS. Total drusen area, presence of large drusen, and the presence of hyperpigmentation were not consistent risk factors for an eye's development of CNV. Risk depended on study cohort as well as location. Having an affected fellow eye was the strongest and most consistent risk factor across all models. A larger drusen area does not necessarily increase an eye's risk of conversion to CNV. (Invest Ophthalmol Vis Sci. 2012;53:1742-1751) DOI:10.1167/iovs.11-9338