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–3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study^1,2,3,4

¹ From the National Eye Institute, Bethesda, MD (JPS, EA, GFR, RDS, and EYC); the EMMES Corporation, Rockville, MD (TEC); and the Department of Ophthalmology, George Washington University, Washington, DC (ADM).

² JPS and EA contributed equally to this work.

³ Supported by the National Eye Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.

⁴ Address correspondence to JP SanGiovanni, National Eye Institute, Clinical Trials Branch, National Institutes of Health 10 Center Drive, MSC-1204, Building 10, CRC, Room 3-2521, Bethesda, MD 20892-1204. E-mail: jpsangio{at}post.harvard.edu.

Background: –3 (n–3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD).

Objective: We investigated whether –3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD.

Design: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on –3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit.

Results: Participants who reported the highest –3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P 0.02) and 0.68 (95% CI: 0.49, 0.94; P 0.02).

Conclusions: The 12-y incidence of CGA and NV AMD in participants at moderate-to-high risk of these outcomes was lowest for those reporting the highest consumption of –3 LCPUFAs. If these results are generalizable, they may guide the development of low-cost and easily implemented preventive interventions for progression to advanced AMD. This trial was registered at clinicaltrials.gov as NCT00594672.