Association of Mortality with Ocular Diseases and Visual Impairment in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 13

Ophthalmology. 2018 Apr;125(4):512-521. doi: 10.1016/j.ophtha.2017.10.028. Epub 2017 Nov 16.


Purpose: To evaluate the association of mortality with visual acuity (VA) impairment, age-related macular degeneration (AMD), and cataract surgery.

Design: Cohort study.

Participants: Participants with at least intermediate AMD enrolled in a randomized controlled clinical trial of lutein/zeaxanthin and/or omega-3 fatty acids, the Age-Related Eye Disease Study 2 (AREDS2), for treatment of AMD and cataract.

Methods: Baseline and annual eye examinations included best-corrected visual acuity (BCVA) assessments, slit-lamp examinations, and stereoscopic fundus photographs that were centrally graded for development of late AMD (central geographic atrophy or neovascular AMD) or pseudophakia. Cause-specific mortality was determined on the basis of the International Classification of Diseases 9th or 10th Revision codes. Risk of all-cause and cause-specific mortality was assessed with Cox proportional hazards models adjusted for age, sex, AMD severity, VA, history of cataract surgery, and assigned AREDS2 study treatment. Analyses included baseline covariates: race, education, smoking status, diabetes, and cardiovascular disease.

Results: During follow-up (median 5 years), 368 (9%) of the 4203 AREDS2 participants died. Participants with neovascular AMD in 1 eye at baseline had a statistically significant increased risk for mortality compared with participants with no or few drusen (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.21-2.01; P < 0.001). Poorer survival was associated with bilateral cataract surgery before enrollment compared with baseline bilateral phakia (HR, 1.63; 95% CI, 1.29-2.07; P < 0.001) and with BCVA of less than 20/40 compared with participants with 20/40 or better (HR, 1.56; 95% CI, 1.06-2.30; P = 0.024), adjusted for age, sex, and statistically significant covariates. Participants who received antivascular endothelial growth factor therapies for neovascular AMD had decreased mortality compared with those who did not (HR, 0.71; 95% CI, 0.57-0.88; P = 0.002). The association between all-cause mortality and AREDS2 treatment whether assessing the main or individual treatment effect was not significantly different (omega-3 fatty acids main effect HR, 1.18; 95% CI, 0.96-1.45; P = 0.12; lutein/zeaxanthin main effect HR, 1.04; 95% CI, 0.85-1.28; P = 0.71).

Conclusions: In AREDS2, the presence of late AMD, bilateral cataract surgery, and VA less than 20/40 was associated with decreased survival. However, oral supplementation with omega-3 fatty acids, lutein plus zeaxanthin, zinc, or beta-carotene had no statistically significant impact on mortality.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use
  • Cataract Extraction / mortality*
  • Cause of Death
  • Cohort Studies
  • Dietary Supplements
  • Double-Blind Method
  • Fatty Acids, Omega-3 / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Lutein / therapeutic use
  • Macular Degeneration / drug therapy
  • Macular Degeneration / mortality*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Slit Lamp Microscopy
  • Survival Rate
  • United States / epidemiology
  • Visual Acuity / physiology*
  • Visually Impaired Persons / statistics & numerical data*
  • Zeaxanthins / therapeutic use


  • Angiogenesis Inhibitors
  • Fatty Acids, Omega-3
  • Zeaxanthins
  • Lutein