Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression: AREDS2 Report 28.
Level 2 - randomized trial
Long-term post-trial cohort follow-up of randomized trial participants analyzed by original assignment
PubMed 35653117 · doi:10.1001/jamaophthalmol.2022.1640
What was done
A multicenter 5-year post-trial epidemiologic follow-up (total 10-year follow-up, 2012–2018) of 3,882 participants (6,351 eyes; mean baseline age 72.0 years; 57.7% women) with bilateral or unilateral intermediate age-related macular degeneration (AMD) from the AREDS2 randomized trial. During follow-up, all participants received AREDS2 supplements containing lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were collected via 6-month telephone calls and validated by medical records. Primary outcomes were 10-year risk of lung cancer (logistic regression) and progression to late AMD (proportional hazards regression), evaluated according to original trial randomization.
What was found
At 10 years, the odds ratio (OR) for lung cancer was 1.82 (95% CI, 1.06–3.12; P = .02) for those originally assigned to beta carotene and 1.15 (95% CI, 0.79–1.66; P = .46) for lutein/zeaxanthin. For progression to late AMD: - Lutein/zeaxanthin vs no lutein/zeaxanthin: hazard ratio (HR) 0.91 (95% CI, 0.84–0.99; P = .02). - Lutein/zeaxanthin main effect restricted to those assigned to beta carotene: HR 0.80 (95% CI, 0.68–0.92; P = .002). - Direct analysis of lutein/zeaxanthin vs beta carotene: HR 0.85 (95% CI, 0.73–0.98; P = .02). - ω-3 fatty acids vs no ω-3 fatty acids: HR 1.01 (95% CI, 0.93–1.09; P = .91). - Low vs high zinc: HR 1.04 (95% CI, 0.94–1.14; P = .49). - No beta carotene vs beta carotene: HR 1.04 (95% CI, 0.94–1.15; P = .48).
Why it matters
These 10-year findings support replacing beta carotene with lutein/zeaxanthin in AREDS supplements to reduce AMD progression without the persistent increased risk of lung cancer associated with beta carotene.
Limits
During the 5-year post-trial follow-up period, all participants were offered the AREDS2 formulation containing lutein/zeaxanthin, which could attenuate differences between original randomized arms. Follow-up outcome ascertainment relied on self-report via telephone interviews with subsequent medical record validation rather than standardized in-person protocol examinations.
Cited by
- context Randomized controlled trials show that lutein and zeaxanthin accumulate in the eye and can help prevent age-related macular degeneration.