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Vitamin supplements known to potentially slow the progression of intermediate age-related macular degeneration do not seem to have a similar effect on geographic atrophy, an advanced form of the dry or non-neovascular form of the disease, according to an analysis of two pivotal trials.

The study looked at data from the phase 3 OAKS and DERBY trials of pegcetacoplan, which led the FDA in 2023 to approve the drug for geographic atrophy. Led by Robyn Guymer, MBBS, PhD, of The University of Melbourne in Melbourne, Australia, the researchers focused on the effect of a formulation of micronutrients, named for the Age-Related Eye Disease Study (AREDS), which have been shown to slow the progression from intermediate to advanced age-related macular degeneration and vision loss, most recently with the formulation known as AREDS2 which added lutein and zeaxanthin to the original.

“In the post hoc analysis looking at the AREDS vitamins in the robust dataset that was the OAKS and DERBY geographic atrophy studies, there’s no effect on growth toward the fovea, no effect on overall geographic atrophy growth, and no effect on the efficacy of pegcetacoplan or the incidence of exudative age-related macular degeneration,” Guymer said.

The growth of geographic atrophy lesions toward the fovea is a critical factor in evaluating potential vision loss because the fovea is the central part of the macula in the back of the eye that produces the sharpest vision and has the densest concentration of rods and cones. The AREDS2 study group earlier this year reported patients taking oral supplements had slower progression of geographic atrophy lesions toward the fovea, although it found no overall effect on geographic atrophy growth, Guymer said. Those researchers performed a post hoc analysis of both the original AREDS and AREDS2 studies.

Study Results

The new analysis included 1259 untreated eyes with geographic atrophy, 518 of which were on AREDS or AREDS2 supplementation and 741 were not on the nutrient therapy. The 24-month results in these untreated eyes were virtually the same, but the supplement eyes had a slightly greater (34 µm) overall growth of geographic atrophy (P = .1244).

In a subgroup of 226 untreated eyes in patients on the AREDS or AREDS2 formulations and 290 eyes without supplements, the analysis found a slightly increased growth — 13 µm growth toward the fovea with the supplement group (P = .04951) after 24 months.

In treated eyes, the analysis found supplements did not appear to alter the effectiveness of pegcetacoplan after 24 months: 18 µm slower growth in 169 eyes with supplements vs 234 eyes without (P = .4985) in the group on monthly pegcetacoplan, but a 34 µm greater growth in 179 eyes on supplements vs 227 eyes not on supplements in the group treated every other month (P = .2324).

Guymer said, the AREDS2 analysis and her group’s study were not identical. “The AREDS group had a cohort that were randomized regarding supplements; our study was not randomized regarding supplements, so we cannot be sure there are other confounders not considered in these data,” she told Medscape Medical News.

The AREDS2 group also used only color fundus photography to evaluate lesion growth, “where the center of the fovea would not be as easy to identify,” while the OAKS and DERBY trials used multimodal imaging consisting of optical coherence tomography and fluorescein autofluorescence. Two more differences: the AREDS studies used a single grader to evaluate imaging, while OAKS and DERBY used two graders, she added, and the AREDS studies used yearly evaluations compared with monthly evaluations in OAKS and DERBY.

“I think it shows in both studies no benefit to growth of geographic atrophy lesions, as everyone is showing this and this was what was in the original AREDS data as well,” Guymer said. “Whether it makes a difference in growth toward the fovea, people will have to weigh up this new evidence and decide the relative merits.”

‘Probably More Robust’

David Eichenbaum, MD, retina specialist with Retina Vitreous Associates of Florida in Tampa, Florida, said the more frequent image review, more graders, and the multimodal imaging used in OAKS and DERBY may explain the differences between the two studies’ findings.

“The data from OAKS and DERBY is probably more robust and certainly more modern than the data from AREDS and AREDS2,” Eichenbaum told Medscape Medical News. The first AREDS study was published in 2001; AREDS2 was published in 2013. “I would not definitively conclude that micronutrients have a significant effect on geographic atrophy growth,” he said.

A prospective study of how AREDS micronutrients affect geographic atrophy with modern imaging, frequent monitoring, and at least two masked graders would be needed to better answer this question, he said.

A limitation of Guymer group’s analysis is its post hoc nature, Eichenbaum said, but its strength compared with the AREDS analysis are the study population size, frequency of follow-up and data collection, and the addition of fluorescein autofluorescence imaging.

The OAKS and DERBY trials were funded by Apellis Pharmaceuticals. Guymer and Eichenbaum disclosed having relationships with Apellis Pharmaceuticals.

Richard Mark Kirkner is a medical journalist based in Philadelphia.