CLINICAL TRIAL SPOTLIGHT

AREDS2 Completes Enrollment

One of the most-watched AMD trials has completed enrollment. What's next?

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

The Age-Related Eye Disease Study 2 (AREDS2) was launched in September 2006 and enrollment of over 4200 patients was completed in September 2008 at 82 sites nationwide. Like the original AREDS study, AREDS2 is a trial to evaluate the efficacy of vitamin supplements in patients with intermediate risk of age-related macular degeneration (AMD) and also advanced AMD in 1 eye. The original AREDS study garnered some of the largest attention that any AMD trial has ever received, and AREDS2 promises to be as pivotal a study. Retinal Physician spoke with Emily Y. Chew, MD, of the National Eye Institute, who is the AREDS2 study chair, about the current status of the AREDS2 trial.

Asked how the AREDS2 study differed from the original study, Dr. Chew said, "AREDS2 is evaluating different oral supplements than AREDS. The observational data from AREDS suggested that persons who eat lutein/zeaxanthin containing vegetables (spinach, collard greens, kale, etc.) had a decreased risk of having neovascular AMD or geographic AMD. An intake of 2 servings of fish reduced the risk of neovascular AMD by about 40%."

Dr. Chew continued, "AREDS2 will examine the roles of lutein/zeaxanthin and/or omega-3 long chain polyunsaturated fatty acids (LCPUFAs, specifically, DHA and EPA in preventing the progression to advanced AMD, defined as neovascular AMD or geographic atrophy involving the center of fovea. The subjects enrolled have intermediate to high risk of having AMD and they have bilateral large drusen or advanced AMD in 1 eye. AREDS compared patients with no, mild, and intermediate AMD to those with advanced AMD in 1 eye."

THE ROLES OF BETA-CAROTENE AND ZINC

Another key difference between AREDS2 and AREDS is the refining of current AREDS supplements. "Beta-carotene is known to increase the risk of lung cancer in smokers," Dr. Chew said. "Zinc given as 80 mg zinc oxide is a high dose and the participants in AREDS taking zinc reported a higher incidence of hospitalizations for genitourinary conditions, particularly hyperplasia of the prostate in men. AREDS2 participants will be offered an opportunity to be further randomized to receive either the full AREDS formulation, AREDS formulation minus the beta-carotene, AREDS formulation with reduced zinc, or a combination of beta-carotene elimination and reduced zinc."

WHAT'S NEXT?

So what direction is the AREDS2 study taking now that it is fully enrolled? "We will follow all participants for 5 years through their progression to advanced AMD, based upon annual stereoscopic fundus photography," Dr. Chew said. "We will evaluate cataract surgery as well as progression of cataract both on red reflex fundus photos and clinical examination. The rate of moderate vision loss (15 letters or more on the logMAR scale) will be assessed."

She continued, "We will also evaluate the progression of AMD along the scale that was developed based upon the AREDS study, in part to validate this scale. Additional outcomes include the effect of the therapy, especially, omega-3 fatty acids for the treatment of cognitive function, which is evaluated at baseline and during the course of the study. The effect of therapy on cardiovascular disease is a secondary outcome of interest."

RESULTS TO BE SEEN

In the meantime, Dr. Chew and colleagues have published 2 papers on phase 1 AREDS2 studies focusing on serum levels of lutein/zeaxanthin and omega-3 fatty acids and adverse effects, as well as macular pigment measurements. These data from AREDS2 will be evaluated regularly by the Data and Safety Monitoring Committee. The trial is expected to be complete in September 2013. RP