Extramacular Drusen and Progression of Age-Related Macular Degeneration: Age Related Eye Disease Study 2 Report 30

Abstract

Purpose: To identify the prevalence of extramacular drusen and their role in the progression of age-related macular degeneration (AMD).

Design: Retrospective analysis of a prospective cohort study.

Participants: The study was conducted in 4168 eyes (2998 participants) with intermediate AMD in one or both eyes enrolled in the Age-Related Eye Disease Study 2 (AREDS2), a 5-year multicenter study of nutritional supplements.

Methods: Baseline 3-field 30-degree color photographs were evaluated for drusen characteristics outside the macular grid, including size, area, and location. The characteristics of extramacular drusen were compared with those of drusen within the macula.

Main outcome measures: Progression rates to late AMD.

Results: Although extramacular drusen were observed in 3624 (86.9%) eyes, they represented a small area (< 0.5 mm²) in 50.3% of eyes, with only 17.5% exhibiting an area of > 1 disc area. Eyes with extramacular drusen exhibited larger macular drusen size and area than eyes without extramacular drusen (P < 0.001). Extramacular drusen were not associated with progression to late AMD. The hazard ratio adjusted for baseline age, sex, smoking, AMD severity level, and reticular pseudodrusen for 4043 eyes at risk of developing late AMD over 5 years was 1.17 (95% confidence interval [CI], 0.88-1.54; P = 0.27) for geographic atrophy and 0.96 (95% CI, 0.76-1.2; P = 0.7) for neovascular AMD.

Conclusions: Extramacular drusen are commonly observed in eyes with AMD and are more frequent with an increasing drusen burden within the macula. In eyes with intermediate AMD, extramacular drusen do not confer additional risk to previously identified risk factors in progression to late AMD.

Keywords: AMD; ARMD; Drusen; Extramacular drusen; Geographic atrophy; Late AMD; Midperipheral drusen; Neovascular AMD.

Figure 1:

Field 2 macula centered fundus photograph with macular grid overlay. Extramacular drusen were assessed in the region outside the grid using temporal and nasal fields shown on the right.

Figure 2:

Forest plot showing the hazard ratio and 95% confidence limits of the association between known age-related macular degeneration (AMD) risk factors and progression to late AMD. Extramacular drusen were not associated with risk of progression to late AMD. Age-Related Eye Disease Study (AREDS)