AREDS Micronutrients Show No Benefit in Geographic Atrophy, with Paul Hahn, MD, PhD

AREDS micronutrients exhibited no benefit on geographic atrophy (GA) progression towards the fovea nor overall GA growth in a recent sham-controlled, randomized prospective phase 3 study presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA.1

Micronutrient supplementation has been a divisive topic in ophthalmology since the Age-Related Eye Diseases Study (AREDS) and AREDS2. Evidence exists on both sides of the line, both suggesting and denying varying degrees of benefit to patients with diabetic macular edema (DME). A study conducted in 2009 suggested that intake of omega-3 long-chain polyunsaturated fatty acids could reduce incidence of central GA, while a 2020 study found no benefit of alpha lipoic acid in reducing risk of geographic atrophy.2,3

This study was conducted in response to a recent post-hoc analysis of AREDS and AREDS2, which indicated the potential for oral supplementation to reduce the progression of nonsubfoveal (NSF) GA toward the fovea. Using color fundus photography, the post-hoc analysis also noted no decrease in overall GA area growth.1

Presented by Paul Hahn, MD, PhD, NJ Retina, this particular study investigated the effect of AREDS and AREDS2 oral micronutrient supplementation on GA growth towards the fovea and overall area growth, analyzing the OAKS and DERBY study populations. These trials were 2 prospective phase 3 trials demonstrating a reduction in GA growth following treatment with pegcetacoplan.1

The team included untreated sham and fellow eyes with NSF GA from subjects in the modified intent-to-treat population, grouping them by AREDS micronutrient usage at baseline (AREDS/AREDS2 versus none). Investigators then compared changes in GA distance to the foveal centerpoint from baseline and changes in square root transformed total lesion size between the two groups.1

A collective 1259 untreated eyes with GA were identified; 518 were on AREDS/AREDS2 micronutrient supplementation and 741 were not. Patients taking supplements at baseline continued taking supplements for an average of 95% of the study duration.1

Hahn sat down with HCPLive to discuss the findings of his study and its juxtaposition against prior studies that seemingly confirm the efficacy of AREDS micronutrients.

“Unfortunately, we did not find any effect of AREDS on any of our metrics or endpoints,” Hahn told HCPLive. “In particular, the endpoint that was positive in the initial AREDS2 post hoc analysis, which was reduction of growth towards the fovea, was not seen in OAKS and DERBY.”

Among NSF GA, Hahn and colleagues found no significant difference between eyes on and eyes not on oral supplements (.667 mm versus .633 mm, respectively; P = .12). After comparing individual micronutrient formulations for both endpoints and when analyzing overall GA growth by lesion location, investigators noted similar findings. Eyes treated with pegcetacoplan also exhibited no significant difference between those on and not on AREDS/AREDS2 micronutrients.1

Hahn went on to discuss the value of continuing to test similar potential treatments, particularly given the distinctly negative results of AREDS testing.

“I do think that our treatments need to be optimized,” Hahn said. “Personalized treatments, development of new or existing modalities, I think all of those are important. I think the most important thing is to recognize that all these analyses that we hear about, these post-hoc analyses, should be hypothesis-generating and need validation in either further studies or, ideally, prospective studies.”

Editor's Note: Hahn reports disclosures with Apellis, Genentech, Eyepoint, Alexion, OcuTerra, Regeneron, and others.

References

1. Hahn P, Guymer R, Holz F, et al. Impact of AREDS Oral Micronutrient Supplementation on Geographic Atrophy Progression: Insights from the Phase 3 OAKS and DERBY Trials. Abstract presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, July 30-August 2, 2025.

2. Sangiovanni JP, Agrón E, Meleth AD, et al. {omega}-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study. Am J Clin Nutr. 2009;90(6):1601-1607. doi:10.3945/ajcn.2009.27594

3. Kim BJ, Hunter A, Brucker AJ, et al. Orally Administered Alpha Lipoic Acid as a Treatment for Geographic Atrophy: A Randomized Clinical Trial. Ophthalmol Retina. 2020;4(9):889-898. doi:10.1016/j.oret.2020.03.019