What is the Age-Related Eye Disease Study 2 (AREDS 2)?

From the Guidelines

AREDS2 is a recommended vitamin supplement for individuals with intermediate or advanced age-related macular degeneration (AMD) to slow disease progression, as evidenced by the most recent study 1. The formula contains vitamin C (500 mg), vitamin E (400 IU), zinc (80 mg), copper (2 mg), lutein (10 mg), and zeaxanthin (2 mg). Key points to consider:

• Take one pill twice daily with meals
• This formulation is an improvement over the original AREDS formula as it removed beta-carotene, which was linked to increased lung cancer risk in smokers, as noted in 1
• The nutrients in AREDS2 work by providing antioxidant protection to the retina, reducing oxidative stress and inflammation that contribute to AMD progression
• Zinc helps maintain retinal health, while lutein and zeaxanthin are carotenoids that naturally concentrate in the macula and filter harmful blue light
• Clinical studies show AREDS2 supplements can reduce the risk of progression to advanced AMD by about 25% over five years in at-risk individuals, as reported in 1
• These supplements are not preventative for those without AMD and should be taken under physician guidance It is essential to identify patients at higher risk because the AREDS2 supplement formulation has been shown to have preventive efficacy in this higher-risk group, with an estimated 8 million persons at least 55 years old in the United States having monocular or binocular intermediate AMD or monocular advanced AMD, as stated in 1. Cigarette smoking has been consistently identified in numerous studies as a risk factor for progression of AMD, and the risk increases relative to the number of pack-years smoked, highlighting the importance of smoking-cessation counseling, as mentioned in 1 and 1. Early treatment of AMD is associated with a more favorable prognosis, and anti-vascular endothelial growth factor (VEGF) treatment given within 2 years after diagnosis of neovascular AMD in non-Hispanic white patients has been shown to reduce legal blindness and visual impairment, as noted in 1.

From the Research

Overview of AREDS 2

• The Age-Related Eye Disease Study 2 (AREDS2) was a multicenter, randomized, controlled clinical trial that evaluated the efficacy and safety of lutein plus zeaxanthin (L+Z) and/or ω-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation in reducing the risk of developing advanced age-related macular degeneration (AMD) 2, 3.
• The study also assessed the reduction in zinc and the omission of β-carotene from the original AREDS formulation 2, 3.

Study Design and Participants

• The study enrolled 4203 participants at 82 clinical centers located in the United States, with a mean age of 74 years and 57% female 2.
• Participants were randomly assigned to receive L+Z, ω-3 LCPUFAs, or the combination of L+Z and ω-3 LCPUFAs, as well as a secondary randomization to 4 variations of the original AREDS formulation 2, 3.

Results and Implications

• The study found that adding L+Z, DHA + EPA, or both to the AREDS formulation did not further reduce the risk of progression to advanced AMD 3.
• However, the study suggested that L+Z could be an appropriate carotenoid substitute in the AREDS formulation, particularly for former smokers 3.
• The results of the AREDS2 study have implications for the clinical care of nonexudative AMD patients, and highlight the importance of nutritional supplements in reducing the risk of progression to advanced forms of AMD 4.

Adherence to AREDS 2 Supplements

• A recent study found that only 60% of patients with AMD were taking AREDS 2 supplements, with 83% of non-compliant patients not recalling being advised of their benefit 5.
• The study highlights the need for ophthalmologists to promote patient compliance with AREDS supplements and to actively promote the cessation of smoking to prevent vision loss in patients with AMD 5.