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S. Bressler, N.M. Bressler, S.R. Chandra, E.Y. Chew, T.E. Clemons, R. Klein, J.M. Seddon, AREDS Research Group; Mortality in the Age-Related Eye Disease Study: Associations With Age-Related Macular Degeneration (AMD) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2056.
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Purpose: To assess retrospectively whether advanced AMD is associated with mortality among participants in the Age-Related Eye Disease Study (AREDS), a randomized clinical trial of AMD and lens opacity. Methods: Stereoscopic color fundus photographs taken at baseline and graded at a reading center were used to enroll AREDS participants into one of four AMD categories. Category 1 - Few if any small drusen; Category 2 - Extensive small drusen or at least 1 medium size druse; Category 3 - Extensive medium size drusen or at least 1 large druse; and Category 4 - Advanced AMD in one eye. Median follow-up was 6.5 years. The primary outcome for this report was all-cause mortality. Analyses of cause-specific mortality, based on ICD-9 codes, were also performed. Covariate-adjusted (i.e., age, gender, race, education, smoking, BMI, diabetes, angina, cancer and hypertension) Cox-proportional hazards models were created with AMD category at baseline as the independent variable. Results: Between 1993 and 2001, 507 (11%) of the 4,753 participants (age 55 to 81 years [mean 69 years]) with follow-up data died. All-cause mortality increased with worsening macular pathology. Participants with late AMD in one eye (Category 4) compared to participants with few if any drusen (Category 1) had a significantly increased risk of mortality (RR 1.41; 95% CI: 1.06, 1.86). Significant associations were not found for AMD Category 2 (RR=1.06) or AMD Category 3 (RR=1.11). Advanced AMD remained a significant predictor of mortality in models accounting for lens opacities or cataract surgery. In analyses of cause-specific mortality, advanced AMD in one eye (RR 1.87; 95% CI: 1.13, 3.08) was associated with an increased risk of cardiovascular deaths. Results from analyses considering potential AREDS treatment effect remain consistent. Conclusions: All-cause mortality was increased among AREDS participants who had advanced AMD in one eye. No associations with all-cause mortality were noted for persons with less severe age-related macular abnormalities (Categories 2 or 3). Persons with advanced AMD were at increased risk of death from cardiovascular disease. The relation of these statistical associations to cause and effect is unknown.
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