Evaluating the validity of the age-related eye disease study grading scale for age-related macular degeneration AREDS2 report 10

Abstract

IMPORTANCE To test potential treatments for age-related macular degeneration (AMD), clinical trials need standardized outcome measures that are valid for predicting AMD progression in different study populations. OBJECTIVE To evaluate the validity of the Age-Related Eye Disease Study (AREDS) detailed and simple AMD severity scales by comparing rates of development of late AMD (neovascular AMD and/or central geographic atrophy) between AREDS and AREDS2 participants. DESIGN, SETTING, AND PARTICIPANTS Both AREDS (1992-2001) and AREDS2 (2006-2012) enrolled patients from academic and community-based retinal practices across the United States. In AREDS (n = 4519), participants with varying severity of AMD-from no AMD to late AMD in 1 eye-were enrolled. In AREDS2 (n = 4203), participants with bilateral large drusen or large drusen in the study eye and late AMD in the fellow eye were enrolled. MAIN OUTCOMES AND MEASURES Five-year incidence of late AMD, assessed by annual masked centralized fundus photograph grading. RESULTS In AREDS, the mean (SD) age of the patients was 69.3 (5.7) years, and 2519 (55.7%) were female. In AREDS2, the mean (SD) age of the patients was 73.1 (7.7) years, and 2388 (56.8%) were female. The 5-year rates of late AMD did not differ between AREDS2 and AREDS participants within nearly all baseline AMD detailed severity scale levels: Levels 1 to 3: 2.4%vs 0.5%(difference, 1.9%; 95%CI, -0.2%to 4.0%; P < .001); level 4: 6.5%vs 4.9% (difference, 1.6%; 95%CI, -1.7%to 4.8%; P = .34); level 5: 8.0%vs 5.6%(difference, 2.4%; 95%CI, -1.2%to 5.9%; P = .22); level 6: 12.8%vs 13.7%(difference, -0.9%; 95%CI, -4.8% to 3.1%; P = .66); level 7: 26.2%vs 27.8%(difference, -1.5%; 95%CI, -6.6%to 3.5%; P = .54); and level 8: 46.4%vs 44.7%(difference, 1.7%; 95%CI, -7.5%to 10.9%; P = .72). Within simple scale levels, AREDS2 and AREDS 5-year rates did not differ significantly except for level 1 (9.4%vs 3.1%, P = .02; level 2: 12.8%vs 11.8%, P = .65; level 3: 26.3%vs 25.9%, P = .90; and level 4: 45.6%vs 47.3%, P = .57). CONCLUSIONS AND RELEVANCE The AREDS detailed and simple AMD severity scales were useful measures for assessing the risk of developing late AMD in the AREDS2 population; these data suggest that they should be useful tools for clinical trials of AMD treatments.