SAN DIEGO — Nutritional supplements recommended to slow age-related macular degeneration might instead accelerate the condition in people with certain genotypes, a new study shows.
"There is a potentially huge public health impact," Carl Awh, MD, private practice ophthalmologist at Tennessee Retina in Nashville said here at the 32nd Annual Meeting of the American Society of Retina Specialists.
For their genotype study, Dr. Awh and his team analyzed data from the Age-Related Eye Disease Study (AREDS), a randomized controlled trial in which nutritional supplements were shown to slow age-related macular degeneration (Arch Ophthalmol. 2001;119:1417-1413). That study led the National Eye Institute to recommend the formulation for people in the moderate stage of the disease.
Researchers have long known that people with certain genes have a higher risk for macular degeneration. For their analysis, Dr. Awh's team evaluated DNA samples that had been collected from AREDS participants.
In a previous analysis of the AREDS data, Dr. Awh and his team found that people with certain genotypes were likely to derive more benefit from the supplements (Ophthalmology. 2013;120:2317-2323). That analysis stimulated controversy.
Recently, an analysis funded by the National Eye Institute found no difference in the effects of the AREDS formulation of supplements by genotype (Ophthalmology. Published online June 26, 2014).
Dr. Awh said that the recent study was flawed because it divided about 1200 patients into 27 genetic groups. With each group so tiny, the sample sizes were too small to show statistical significance, he explained.
In their current analysis, Dr. Awh and his colleagues did the opposite. They divided patients with 9 genotypes into just 4 groups on the basis of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk: high CFH and high ARMS2 risk; high CFH and low ARMS2; low CFH and high ARMS2; and low CFH and low ARMS2.
Identifying Those At Risk
With larger groups, the team was able to show statistical significance. For patients with high CFH and low ARMS2 risk, who made up 13% of the study cohort, the risk for progression to advanced macular degeneration within 7 years was 135% higher if they were in the supplement group than if they were in the placebo group.
For patients with low CFH and high ARMS2 risk, who made up 35% of the study cohort, the risk for progression within 7 years was 37% lower in the supplement group than in the placebo group.
In patients with high CFH and high ARMS2 risk and with low CFH and low ARMS2 risk, there was no strong benefit or harm with the supplements.
"It's something to keep in mind as we recommend nutritional therapy for people with macular degeneration," said Dr. Awh. "We don't want to give a therapy to an identifiable subgroup of people that more than doubles their risk of disease progression."
Dr. Awh said he often tests the genes of his patients with moderate age-related macular degeneration before prescribing nutritional supplements.
The presentation attracted a lot of attention, noted session moderator Eugene de Juan, MD, distinguished professor in the Department of Ophthalmology at the University of California, San Francisco, who was not involved in the study.
"There has been quite a bit of interest and controversy over these results because they are pretty impactful if they are correct," Dr. de Juan told Medscape Medical News. "I think it's important. I think it's reasonable. I think there needs to be more research in this area."
He said that if he had age-related macular degeneration, "I would undergo the test."
But Dr. de Juan added that more research is needed before clinical guidelines are changed. "Other datasets are available and could be analyzed," he said.
He also called for more public discussion. Most retina specialists "don't fully understand the complexity" of genetics, he explained.
Dr. Awh reports a financial relationship with Arctic DX, a Toronto-based company that makes a test for genetics associated with age-related macular degeneration, but he emphasized that the testing in this study was done by an independent laboratory, not a commercial test. Dr. de Juan has disclosed no relevant financial relationships.
32nd Annual Meeting of the American Society of Retina Specialists (ASRS). Presented August 10, 2014