Risk Alleles in CFH and ARMS2 and the Long-term Natural History of Age-Related Macular Degeneration:  The Beaver Dam Eye Study

Figure 1. Estimated cumulative incidence of early (height of light gray area) and late (height of dark gray area) age-related macular degeneration (AMD) by genetic risk and age (assuming no AMD at the starting age) in the Beaver Dam Eye Study, 1988-2010. Rows are ordered by increasing starting age (top, age 45 years; bottom, age 65 years), and columns are ordered by increasing genetic risk. A and D, Low risk. B and E, Intermediate risk. C and F, High risk. For example, A shows the cumulative incidence of AMD in individuals assuming no AMD at age 45 years and low genetic risk, and E shows the cumulative incidence of AMD in individuals assuming no AMD at age 65 years and intermediate genetic risk.

Figure 2. Estimated cumulative incidence of more severe age-related macular degeneration (AMD) in persons at age 45 years by increasing beginning AMD level (rows top [level 10] to bottom [level 40]) and increasing genetic risk (columns left [low] to right [high]) in the Beaver Dam Eye Study, 1988-2010. For example, A shows the cumulative incidence of AMD levels 20 to 50 (20 indicates height of light gray area; 30, height of medium gray area; 40, height of dark gray area; and 50, height of black area) for an individual whose AMD level is 10 at age 45 years and who has low genetic risk, and panel I shows the cumulative incidence of AMD levels 40 and 50 for an individual who had AMD level 30 at age 45 years and who has high genetic risk. Numbers to the right of lines indicate AMD severity level on the Beaver Dam Study AMD severity scale.

Figure 3. Estimated cumulative incidence of age-related macular degeneration (AMD) by increasing genetic risk level (from low [left] to intermediate [middle] to high [right]). A-C, Intermediate-sized and large drusen in individuals with no or small drusen at age 45 years. D-F, Hard distinct, soft distinct, and soft indistinct/reticular drusen in individuals with no or hard indistinct drusen at age 45 years. G-I, Increased retinal pigment, retinal pigment epithelial (RPE) depigmentation, pure geographic atrophy (GA), and exudative AMD in individuals with no pigmentary abnormalities at age 45 years.

Figure 4. Area under the receiver operating characteristic curves (AUC) for various models of progression from no or early age-related macular degeneration (AMD) to late AMD during a 5-year interval in the Beaver Dam Eye Study, 1988-2010. ARMS2 indicates age-related maculopathy susceptibility 2; CFH, complement factor H; and TR, traditional risk.