Patients in the late stage of age-related macular degeneration (AMD) who took oral antioxidants showed slower progression of geographic atrophy (GA) toward the central macula, according to a new analysis of data from the Age-related Eye Diseases Study (AREDS) and the follow-up study AREDS2. The post hoc analysis was published in the journal Ophthalmology.¹

Between 1992 and 2012, the National Institutes of Health conducted AREDS and AREDS2 as multicenter randomized placebo-controlled trials. The original AREDS trial found that a supplement formula containing antioxidants (vitamin C, E, and β-carotene), along with zinc and copper, could slow progression of intermediate to late-stage AMD. The AREDS2 trial, which began in 2006, found that substituting the antioxidants lutein and zeaxanthin for beta-carotene improved the efficacy of the supplement formula and eliminated certain risks. However, at the time, neither trial detected any benefit to vitamin supplementation once participants had developed late-stage AMD.

In the new study, which also was supported by the NIH, researchers reviewed the original color fundus photographs, taken at annual visits, of 318 patients (392 eyes) with GA who participated in AREDS and 891 patients (1,210 eyes) with GA from AREDS2. These images were used to measure changes in GA proximity to the central macula, or fovea, as well as total GA area growth over time.

Researchers found that once GA encroached on the foveal area, which provides the highest acuity central vision, the supplements had little benefit. However, because most patients initially develop GA outside the fovea — a phenomenon known as “foveal sparing” — the supplements slowed the rate of GA expansion toward the fovea by approximately 55% over an average of 3 years. The researchers found that in AREDS eyes with noncentral GA (n=208), proximity-based progression towards the central macula was significantly slower with randomization to antioxidants versus none, at 50.7 μm/year (95% CI 38.0-63.4 μm/year) versus 72.9 μm/year (95% CI 61.3-84.5 μm/year; p=0.012), respectively. In AREDS2 eyes with noncentral GA, in participants assigned to AREDS antioxidants without β-carotene (n=325 eyes), proximity-based progression was significantly slower with randomization to lutein/zeaxanthin versus none, at 80.1 μm/year (95% CI 60.9-99.3 μm/year) versus 114.4 μm/year (95% CI 96.2-132.7 μm/year; p=0.011), respectively.

“We’ve known for a long time that AREDS2 supplements help slow the progression from intermediate to late AMD. Our analysis shows that taking AREDS2 supplements can also slow disease progression in people with late dry AMD,” said Tiarnan Keenan, MD, PhD, of NIH’s National Eye Institute (NEI) and lead author of the study. “These findings support the continued use of AREDS2 supplements by people with late dry AMD.”²

The researchers hypothesized that the antioxidants or lutein/zeaxanthin supplements likely augmented the natural phenomenon of foveal sparing. “Our high acuity central vision is essential for tasks like reading and driving,” said Dr. Keenan. “Given that there are few therapeutic options for people with late-stage dry AMD to retain or restore their vision, antioxidant supplementation is a simple step that may slow central vision loss, even for those with late disease. We plan to confirm these findings in a dedicated clinical trial in the near future.”

References

1. Keenan TDL, Agrón E, Keane PA, Domalpally A, Chew EY; AREDS and AREDS2 Research Groups. Oral antioxidant and lutein/zeaxanthin supplements slow geographic atrophy progression to the fovea in age-related macular degeneration. Ophthalmology. Published online July 16, 2024. 

2. National Institutes of Health. Supplements slow disease progression during late stage of “dry” age-related macular degeneration. July 16, 2024. Accessed July 23, 2024. https://www.nih.gov/news-events/news-releases/supplements-slow-disease-progression-during-late-stage-dry-age-related-macular-degeneration.