To describe the system for grading age-related macular degeneration from fundus photographs
in the Age-Related Eye Disease Study. This is a prospective multicenter cohort study
of the course of age-related macular degeneration and a placebo-controlled clinical
trial of the effect of high-dose vitamin and mineral supplements on development of
advanced age-related macular degeneration.
Standardized stereoscopic 30-degree color fundus photographs are taken at 11 clinical
centers and evaluated by graders at a reading center for quality and age-related macular
degeneration abnormalities. Macular subfields are defined by a grid, and presence
and severity of various age-related macular degeneration abnormalities are graded
using standard/example photographs and measuring circles. Advanced age-related macular
degeneration abnormalities (presence/absence) include retinal pigment epithelial detachment,
serous (or hemorrhagic) sensory retinal detachment, hard exudates, subretinal/subretinal
pigment epithelial hemorrhage, subretinal fibrous tissue, and photocoagulation scars.
Other abnormalities (multistep scales) include retinal pigment epithelial abnormalities
(geographic atrophy, depigmentation, and increased pigment), and drusen (size, type
[hard versus soft distinct or indistinct], and total area). Contemporaneous variability
is tested by having different graders evaluate samples of photographs, and temporal
variability by annual regrading of a dedicated subset.
In a cumulative sample of 1230 eyes for contemporaneous reproducibility, agreement
on advanced age-related macular degeneration was 96% (kappa = 0.88) and for four-step
age-related macular degeneration level was 83% (kappa = 0.77). Agreement was moderate
for pigment epithelial detachment (kappa = 0.54) and substantial for serous sensory
retinal detachment, hard exudates, subretinal/subretinal pigment epithelial hemorrhage,
subretinal fibrous tissue, and central geographic atrophy (kappa = 0.73-0.82). For
pigment abnormalities, agreement was substantial for geographic atrophy (kappa = 0.63;
kappa(weighted) = 0.71, 0.75 weight for one-step disagreements), and moderate for
depigmentation (kappa = 0.41, kappa(weighted) = 0.51) and increased pigment (kappa
= 0.54, kappa(weighted) = 0.71). For drusen, agreement was moderate to substantial
for presence/maximum size (kappa = 0.50, kappa(weighted) = 0.68), type (kappa = 0.61,
kappa(weighted) = 0.69), and area (kappa = 0.56, kappa(weighted) = 0.77). Six annual
regrades of 119 eyes showed little temporal drift in grading of various age-related
macular degeneration abnormalities, except for drusen type.
The Age-Related Eye Disease Study has demonstrated satisfactory reliability for detecting
onset of advanced age-related macular degeneration in a cohort, and moderate to substantial
agreement on various abnormalities across the age-related macular degeneration spectrum.
The Age-Related Eye Disease Study system for classification of age-related macular
degeneration is suitable for longitudinal multicenter studies.