Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium

Abstract

Purpose: To describe methods to harmonize the classification of age-related macular degeneration (AMD) phenotypes across four population-based cohort studies: the Beaver Dam Eye Study (BDES), the Blue Mountains Eye Study (BMES), the Los Angeles Latino Eye Study (LALES), and the Rotterdam Study (RS).

Methods: AMD grading protocols, definitions of categories, and grading forms from each study were compared to determine whether there were systematic differences in AMD severity definitions and lesion categorization among the three grading centers. Each center graded the same set of 60 images using their respective systems to determine presence and severity of AMD lesions. A common 5-step AMD severity scale and definitions of lesion measurement cutpoints and early and late AMD were developed from this exercise.

Results: Applying this severity scale changed the age-sex adjusted prevalence of early AMD from 18.7% to 20.3% in BDES, from 4.7% to 14.4% in BMES, from 14.1% to 15.8% in LALES, and from 7.5% to 17.1% in RS. Age-sex adjusted prevalences of late AMD remained unchanged. Comparison of each center's grades of the 60 images converted to the consortium scale showed that exact agreement of AMD severity among centers varied from 61.0-81.4%, and one-step agreement varied from 84.7-98.3%.

Conclusion: Harmonization of AMD classification reduced categorical differences in phenotypic definitions across the studies, resulted in a new 5-step AMD severity scale, and enhanced similarity of AMD prevalence among the four cohorts. Despite harmonization it may still be difficult to remove systematic differences in grading, if present.

Figure 1

A. Grids defining the 9 macular subfields (not to scale). B. Measuring tools for lesion size and area of involvement (not to scale). Circles represent fractions of the total area of the center (C), inner (I), and outer (O) subfields of the grid in part A, and the 3 crossed lines each measure 1000 μm in length. CC, center circle; II, inner inferior; IN, inner nasal; IS, inner superior; IT, inner temporal; OI, outer inferior; ON, outer nasal; OS, outer superior; OT, outer temporal.

Figure 1

A. Grids defining the 9 macular subfields (not to scale). B. Measuring tools for lesion size and area of involvement (not to scale). Circles represent fractions of the total area of the center (C), inner (I), and outer (O) subfields of the grid in part A, and the 3 crossed lines each measure 1000 μm in length. CC, center circle; II, inner inferior; IN, inner nasal; IS, inner superior; IT, inner temporal; OI, outer inferior; ON, outer nasal; OS, outer superior; OT, outer temporal.

Figure 2

Agreement between each pair of grading centers for grading of age-related macular degeneration using the Three Continent AMD Consortium Age-Related Macular Degeneration Severity Scale after harmonization. A. Beaver Dam Eye Study (BDES) vs. Blue Mountains Eye Study (BMES); B. BDES vs. Rotterdam Study (RS); C. BMES vs. RS; D. BDES vs. Los Angeles Latino Eye Study (LALES); E. BMES vs. LALES; F. RS vs. LALES. CG, cannot grade; CI, confidence interval.