Carotenoids, Antioxidants Benefit Visual Acuity & Slow Progression in Early AMD

Carotenoids and Antioxidants in Early AMD

There is scientific support for the hypotheses that oxidative stress is involved in the pathogenesis of early age-related macular degeneration (AMD), and that a lack of lutein and zeaxanthin play a role in the development of AMD.

Based on the available evidence, a research team from Ireland undertook a randomized, controlled trial of supplementation with lutein, zeaxanthin and antioxidant vitamins and minerals in persons judged to be at highest risk of progression to advanced AMD.

Called the CARMA study, this trial enrolled participants who were followed for a minimum of 1 year. No difference was found between placebo and treatment groups for the primary endpoint of best-corrected visual acuity (BCVA) at the end of 12 months (data in press). However, a number of secondary outcomes were collected, including BCVA, for participants who had a longer than 12 month follow-up.

This paper (1) reports on those secondary outcomes, and the results suggest that long-term supplementation of carotenoids and antioxidant nutrients have functional and structural benefits in people with early AMD.

Methods

Participants included 433 adults, 55 years or older who were classified into two groups. Group 1 included those with early AMD in one eye and late-stage disease in the fellow eye. Group 2 consisted of those with early AMD in both eyes.

Participants received supplemental lutein and zeaxanthin (12.6 mg combined carotenoids), vitamins C (150 mg), E (15 mg), copper (.4 mg) and zinc (20 mg), or placebo daily.

Participants recruited in the early phases of the study were followed for up to 36 months (3 years). The main outcome measures included differences in BCVA at 24 and 36 months, contrast sensitivity, Raman spectroscopy (counts), serum antioxidant levels, and progression along the AMD severity scale at 12, 24 and 36 months.

Results

By 24 months, a steadily increasing difference was observed between groups in BCVA that favored the active group by 1.4 letters (p=0.04). Average BCVA in the active group was approximately 4.8 letters better compared to the placebo group for those who had 36 months of follow-up (p=0.04). (See Figure below).

Figure courtesy of Ophthalmology Journal

Point estimate showing the mean differential in the change in best-corrected visual acuity in the treatment and placebo groups (x-axis) at each study visit (y-axis), with the bars representing the 95% confidence limits.

In the longitudinal analysis, an increase in serum lutein levels correlated with improvements in BCVA. For a 1-log-unit increase in serum lutein, visual acuity was better by 1.4 letters (p=0.01; 95% CI, 0.03-2.5).

An increase in serum lutein was also associated with a slower progression on the AMD severity scale in the eyes of participants in the active group compared to the placebo group (p=0.014).

Macular pigment, as measured by Raman spectroscopy (Raman counts), demonstrated a small increase with time, while that of the placebo group showed a steady decline. Raman counts were recorded at 6-month intervals from baseline to 36 months. The difference in Raman counts over time between active and placebo groups was highly significant at all time points.

Changes in contrast sensitivity marginally favored the active group, but no statistically significant differences were seen.

Comments

One weakness of the CARMA study was a loss of follow-up of some 20% of participants in the first year of the trial. A number of the withdrawals were due to death or the development of late stage disease (neovascular or geographic atrophy) in the sole study eye, which was a pre-specified participant withdrawal requirement.

However, in this controlled, dual-site trial, supplementation with lutein, zeaxanthin and co-antioxidants benefited visual acuity at 2 years and beyond, and higher serum lutein values were associated with a slowing of AMD progression.

Reference