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T. E. Clemons, E. Y. Chew, R. C. Milton, AREDS Research Group; Association of Mortality With AMD, Cataract and High-Dose Antioxidants and Zinc After Long-Term Follow-Up in the Age-Related Eye Disease Study. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2458.
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To assess retrospectively the association of late age-related macular degeneration (AMD), lens opacity, cataract surgery, visual acuity or high-doses of antioxidants and zinc with mortality in the Age-Related Eye Disease Study (AREDS) after a median 10.5 years of follow-up.
Color fundus photographs taken at baseline were used to classify participants into one of four AMD categories: Category 1 - Few if any drusen; Category 2 - Extensive small drusen or at least 1 intermediate size druse; Category 3 - Extensive intermediate drusen or at least 1 large druse; and Category 4 - Advanced AMD (AAMD) in one eye. Lens photographs were taken at baseline to assess the presence and severity of nuclear, cortical and posterior subcapsular lens opacities using the AREDS Cataract Classification. A history of cataract surgery at baseline was also collected. Baseline refraction and measurement of visual acuity were performed and each participant was classified into 1 of 2 visual acuity groups: 20/40 or better in both eyes versus worse than 20/40 in one eye. AREDS included a randomized clinical trial that evaluated the effect of high doses of selected supplements (vitamin C, 500 mg; vitamin E, 400 IU; beta-carotene, 15 mg; zinc-oxide, 80 mg; and cupric oxide, 2 mg) on the incidence and progression of the AAMD and cataract. The primary outcome was all cause mortality. Cause-specific mortality was based on ICD9 or ICD10 codes. Age- and gender-adjusted Cox-proportional hazards models were created with AMD category at baseline as the independent variable. Significant health status indicators were added to models that examined the effect of the ocular characteristics on mortality.
During a median follow-up of 10.5 years, 1057 (22%) of 4753 AREDS participants died. After adjusting for age, gender, and factors associated with mortality, poorer survival was associated with AAMD (risk ratio [RR], 1.27; 95% confidence interval [CI], 1.05 - 1.54), visual acuity worse than 20/40 in at least one eye (RR, 1.27; 95% CI, 1.10 - 1.47), nuclear cataract (RR, 1.29, 95% CI, 1.10 - 1.52), and cataract surgery (RR, 1.30, 95% CI 1.05 - 1.61). Participants randomly assigned to zinc at baseline had lower mortality compared to those not randomized to zinc (RR, 0.83, 95% CI 0.73 - 0.95).
Long-term follow-up of AREDS participants confirm that AMD, cataract and visual acuity is related to decreased survival. The study provides additional evidence of improved survival in individuals randomly assigned to zinc.
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