Association of Age-Related Macular Degeneration With Risk of All-Cause and Specific-Cause Mortality in the National Health and Nutrition Examination Survey, 2005 to 2008

IMPORTANCE: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness in the United States if subretinal neovascularization is left untreated. Knowledge of the association between AMD and survival is informative for underlying mechanisms of AMD. OBJECTIVE: To examine the association between AMD and risk of all-cause and specific-cause mortality in a representative US sample. DESIGN, SETTING, AND PARTICIPANTS: This population-based prospective cohort study included 5603 participants 40 years or older who responded to the National Health and Nutrition Examination Survey (NHANES) in the 2005-2008 phase. Retinal photographs were graded as early, late, or no AMD. All analyses accounted for the complex and stratified design of NHANES with weighted data. Risks of all-cause mortality were assessed with Cox proportional hazards regression models; risks of specific-cause mortality, with Fine and Gray competing risks regression models. Time to death was counted from baseline to date of death or December 31, 2011, whichever came first. Data analysis was conducted from April 1 through 30, 2018. EXPOSURES: Age-related macular degeneration status as determined by digital fundus images. MAIN OUTCOMES AND MEASURES: Mortality resulting from all causes and specific causes until December 31, 2011. RESULTS: Among the 5603 participants (52.6% female [n = 2793] and 77.1% white [n = 3017]; mean [SE] age, 56.4 [0.4] years), weighted prevalence of any AMD was 6.6%, with 386 (5.8%) having early AMD and 55 (0.8%) having late AMD. After a median follow-up of 4.5 years (interquartile range, 3.6-5.6 years), 433 (5.3%) died of all causes, of whom 361 (83.1%) had no AMD, 54 (11.5%) had signs of early AMD, 18 (5.4%) had signs of late AMD, and 72 (16.9%) had any AMD at baseline. Overall, unadjusted all-cause and specific-cause mortality rates were higher for those participants who had early, late, or any AMD compared with no AMD. However, after adjusting confounding factors, only late AMD was associated with more than a doubling of all-cause mortality (hazard ratio [HR], 2.01; 95% CI, 1.00-4.03) and more than a 3-fold higher risk of mortality due to causes other than cardiovascular disease and cancer (HR, 3.42; 95% CI, 1.38-8.49). No association was identified between AMD presence or early AMD and all-cause or specific-cause mortality. CONCLUSIONS AND RELEVANCE: In this study’s findings, only late AMD was independently associated with all-cause mortality and mortality due to causes other than cardiovascular disease and cancer, indicating that late AMD may be a marker of biological aging. Alternatively, this association may be due to unmeasured or inadequately assessed confounding factors for late AMD.