Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study

Abstract

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials.

Keywords: Amish eye study; age-related macular degeneration; complete retinal pigment epithelial and outer retina atrophy; geographic atrophy; optical coherence tomography.

Figure 1

Representative examples of structural optical coherence tomography risk factors. (A) Drusenoid lesions with a hyporeflective core (white arrowheads)—note there is no evidence of any shadow artifact to explain the hyporeflectivity; (B) subretinal drusenoid deposits (white arrowheads); (C) intraretinal hyperreflective focus (white arrowhead)—here seen above the apex of the drusen; (D) drusen volume map from the Cirrus Advanced RPE analysis software—the algorithm segments the RPE band following the RPE contour and also estimates the original RPE position (termed the RPE fit) in the absence of an RPE elevation. The region between the RPE band and the RPE fit is then quantified as the drusen volume.

Figure 2

Illustration of the Beckman’s clinical classification of AMD based on color fundus photos. (A) No apparent aging changes; (B) Normal aging changes; (C) Early AMD; (D) Intermediate AMD; (E) Late AMD evidenced by geographic atrophy.

Figure 3

Bar plot showing the odds ratios from the univariate regression analysis (gray arrow indicates the direction of higher to lower risk for late AMD development).