title: Evaluating the Validity of the Age-Related Eye Disease Study Grading Scale for Age-Related Macular Degeneration: AREDS2 Report 10.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Susan
authors.initials: S
authors.lastname: Vitale
authors.affiliation: EMMES Corporation, Rockville, Maryland.
authors.forename: Traci E
authors.initials: TE
authors.lastname: Clemons
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Elvira
authors.initials: E
authors.lastname: Agrón
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ferris
authors.affiliation: Fundus Photograph Reading Center, University of Wisconsin, Madison.
authors.forename: Amitha
authors.initials: A
authors.lastname: Domalpally
authors.affiliation: Fundus Photograph Reading Center, University of Wisconsin, Madison.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Danis
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003941:Diagnostic Techniques, Ophthalmological; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008268:Macular Degeneration / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012720:Severity of Illness Index; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014792:Visual Acuity