The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17

Abstract

Objective: To develop a fundus photographic severity scale for age-related macular degeneration (AMD).

Methods: In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up.

Results: A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes.

Conclusions: The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

Figure 1

Grid and standard circles used in assessing size, area, and location of abnormalities. The radii of the grid circles are one-third, 1, and 2 disc diameters, respectively, and their areas are 4/9, 4, and 16 disc areas (DAs). When the diameter of the optic disc is assumed to be 1500 μm, the radius of the central circle of the grid is 500 μm, that of the middle (inner) circle is 1500 μm, and that of the outer circle is 3000 μm. The standard circles have the following diameters and areas: C-0, 63 μm and 0.0017 DA; C-1, 125 μm and 0.0069 DA; C-2, 250 μm and 0.028 DA; I-2, 354 μm and 0.056 DA; O-2, 650 μm and 0.19 DA; and 0.5 DA, 1061 μm and 0.50 DA. An additional circle, I-1 (diameter, 175 μm; not shown in the figure) is used to define the smallest area of depigmentation that can be classified as geographic atrophy.

Figure 2

Tree-structured analyses of progression to neovascular age-related macular degeneration or central geographic atrophy (CGA) within 5 years. A, Drusen area, increased pigment, and depigmentation–geographic atrophy (GA) as used in Table 2 and Table 4 were the only variables considered. B, To the variables in part A, drusen size and predominance of soft indistinct drusen were added and drusen area, increased pigment, and depigmentation were entered for each of the 3 nested zones. DA indicates disc area; C&I, central and inner circles; Neo, neovascular age-related macular degeneration.

Figure 3

Five-year progression rates in 6426 eyes of 3214 patients free of advanced age-related macular degeneration (AMD) in both eyes at baseline. The width of the bars is proportional to the number of eyes in the Age-Related Eye Disease Study (AREDS) scale step at baseline. A, Progression to scale steps 7 to 9 and to advanced AMD (neovascularAMD, central geographic atrophy [CGA], or both). Progression to steps 7 to 9 is shown as 100% for eyes in these steps at baseline. B, Progression to neovascular AMD alone or with CGA as well. C, Progression to CGA alone or with neovascular AMD as well.

Figure 4

Five-year rates of neovascular age-related macular degeneration (AMD) (with or without central geographic atrophy) in eyes with and without neovascular AMD in the fellow eye at baseline. The width of the bars is proportional to the number of eyes in the Age-Related Eye Disease Study (AREDS) scale step at baseline.