The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

This was a 2-year head-to-head randomized clinical trial in adults with nonadvanced age-related macular degeneration conducted in Waterford, Ireland. The active intervention groups were the Macushield Gold regimen (60 randomized) and an AREDS2-based regimen without mesozeaxanthin (61 randomized), with outcomes assessed in the study eye.

Adults with nonadvanced age-related macular degeneration received one of two oral antioxidant/carotenoid regimens daily for 24 months. The macular carotenoid arm received 10 mg/day mesozeaxanthin, 10 mg/day lutein, 2 mg/day zeaxanthin, plus vitamin C 500 mg/day, vitamin E 400 IU/day, zinc 25 mg/day, and copper 2 mg/day (Macushield Gold); the comparison arm received an AREDS2-based formula with lutein 10 mg/day, zeaxanthin 2 mg/day, vitamin C 500 mg/day, vitamin E 400 IU/day, zinc 25 mg/day, and copper 2 mg/day, without mesozeaxanthin.

Both antioxidant/carotenoid regimens improved macular pigment and several measures of visual function over 24 months, but adding mesozeaxanthin did not confer extra benefit over the AREDS2-based formulation. For the primary outcome, letter contrast sensitivity at 6 cycles per degree increased slightly in both groups (1.53 to 1.57 and 1.58 to 1.61), with a significant time effect (P = 0.013) and no between-group difference (time-by-group P = 0.881). Several secondary outcomes also improved over time, including contrast sensitivity at other frequencies, mesopic and photopic measures, photostress recovery, retinal straylight, and reading speed, again with no meaningful differences between interventions; macular pigment increased at all eccentricities, serum lutein and zeaxanthin rose, and serum mesozeaxanthin increased only in the mesozeaxanthin arm. Vision-related quality of life changed little, adverse events were comparable (15 of 57 vs 10 of 61; P = 0.187), and no serious safety concerns were reported.

The active-arm sample sizes were modest and the trial was single-center, which limits precision and generalizability. Because this was a head-to-head active comparison, it does not isolate effects against placebo or usual care, and some subgroup interactions were not robust in intention-to-treat analysis. Vision-related quality of life showed limited change, and one case of progression to advanced AMD occurred in the AREDS2-based arm.