AREDS2: Perspectives, Recommendations, and Questions

Abstract and Introduction

Abstract

Purpose of review: This review provides a perspective on the Age-related Eye Disease Study 2 (AREDS2) including a summary of the goals and rationale of the study, major findings, subsequent management recommendations, and questions that remain to be answered.

Recent findings: The primary goal of the AREDS2 was to evaluate the efficacy and safety of lutein plus zeaxanthin and/or omega-3 long-chain polyunsaturated acid supplementation in reducing the risk of developing advanced age-related macular degeneration (AMD). AREDS2 also investigated the effects of omitting β-carotene and reducing the concentration of zinc from the original AREDS formulation. Although primary analysis from the AREDS2 did not reveal a benefit of daily supplementation with lutein/zeaxanthin on AMD progression, secondary exploratory analyses suggested that lutein/zeaxanthin were helpful in reducing this risk. Comparison of low-dose to higher-dose zinc showed no significant benefit.

Summary: The overall evidence on the beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than β-carotene in AREDS-type supplements. Questions remain regarding the AREDS2 study results such as: whether the findings are generalizable to the population as a whole, what is the long-term safety profile of lutein/zeaxanthin supplementation, should other carotenoids be included in AREDS-type supplements, and at what optimal doses?

Introduction

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries.^[1,2] An estimated 21 million individuals are affected worldwide, and as the population ages, these numbers are projected to increase significantly.^[3] The introduction of intravitreal therapies targeted at inhibition of vascular endothelial growth factor (VEGF) has provided effective treatment for the neovascular form of AMD.^[4] At present, no such therapy exists for the atrophic form of AMD.^[5] In the original Age-related Eye Disease Study (AREDS), supplements containing vitamin C, vitamin E, β-carotene, and zinc were shown to reduce the 5-year likelihood of developing advanced AMD by an estimated 25% in at-risk individuals.^[6] Furthermore, this treatment effect persisted in those who continued to be monitored at the 5 year time point following cessation of this controlled, randomized, clinical trial.^[7] The Age-related Eye Disease Study 2 (AREDS2) was designed to further investigate whether inclusion of lutein/zeaxanthin and/or omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) to the original AREDS formulation would additionally reduce the risk for progression to advanced AMD. The present review summarizes the goals and rationale for undertaking the AREDS2, significant findings, treatment recommendations, and questions that remain to be answered.