Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration
NCT00000145 (AREDS) NCT00345176 (AREDS2) | AREDS and AREDS2 | Keenan TDL et al. (2024)
Keenan, T. D. L., Agrón, E., Keane, P. A., Domalpally, A., Chew, E. Y. Oral Antioxidant and Lutein/Zeaxanthin Supplements Slow Geographic Atrophy Progression to the Fovea in Age-Related Macular Degeneration. Ophthalmology, 2024; -:1-16.
Locations
93 centers across the United States
Study Period
• AREDS: 1992-2001 • AREDS2: 2006-2012
Study Design
Post hoc analysis of two multicenter randomized, placebo-controlled trials (AREDS and AREDS2)
Study Population
Experimental Group
Control Group
Follow-up Time: 3.0 years
Outcomes
Durability
Not reported
Vision
BCVA Decline Over Time
AREDS:
• No significant difference (p > 0.05)
AREDS2:
• Lutein/Zeaxanthin slowed BCVA decline in noncentral GA (-2.1 letters/year [95% CI: -3.4 to -0.8] vs. -4.2 letters/year [95% CI: -5.7 to -2.7]
• Difference = 2.1 letters/year [95% CI: 0.4 to 3.8], p = 0.007).
Other
Primary Outcome: GA Progression Toward Central Macula
AREDS:
• Antioxidants slowed GA progression: 50.7 µm/year (95% CI: 38.0–63.4) vs. placebo: 72.9 µm/year (95% CI: 61.3–84.5)
• Difference: -22.2 µm/year (95% CI: -30.5 to -13.9, p = 0.012).
AREDS2:
• Lutein/Zeaxanthin slowed GA progression: 80.1 µm/year (95% CI: 60.9–99.3) vs. placebo: 114.4 µm/year (95% CI: 96.2–132.7)
• Difference: -34.3 µm/year (95% CI: -46.2 to -22.4, p = 0.011).
GA Area Progression AREDS:
• No significant difference in area-based GA progression (95% CI: -0.08 to 0.04, p = 0.63).
AREDS2:
• No significant difference for Lutein/Zeaxanthin (95% CI: -0.07 to 0.03, p = 0.64)
• Significant for Beta-carotene (0.264 mm²/year [95% CI: 0.23 to 0.29] vs. 0.301 mm²/year [95% CI: 0.26 to 0.34] with difference = -0.037 mm²/year [95% CI: -0.05 to -0.02], p = 0.009).
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Safety
Not reported
Conclusion
Oral antioxidant and lutein/zeaxanthin supplementation slowed GA progression toward the fovea in noncentral GA, likely augmenting the natural phenomenon of foveal sparing. No significant effect on GA area progression. Further trials are warranted to confirm findings.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: “A random block design was implemented using the AREDS2 Advantage Electronic Data Capture system (AdvantageEDCSM) by the AREDS2 Coordinating Center (The EMMES Corporation, Rockville, Maryland) and stratified by clinical center and AMD status (large drusen both eyes or large drusen in one eye and advanced AMD in the fellow eye) to assure approximate balance across centers over time.” As this is a post hoc analysis, there was concerns about the baseline characteristics balanced among the groups.
Missing Outcome Data
Some concerns
Note: Due to this is a post hoc analysis.
Selection of the Reported Results
Low risk Note: Due to this is a post hoc analysis, the primary outcome of this study was not the one listed in the protocol.
Deviations from Intended Observations
Some concerns Note: Both of them are double blinded studies. As this is a post hoc analysis, there are concerns of the potential impact of the deviations on the outcome.
Measurement of the Outcome
Low risk Note: masked and consistent.
Overall
High risk
Categories: Dry AMD Geographic Atrophy