AREDS II tests refined formulation

Chicago-The Age-Related Eye Disease Study II (AREDS II) will begin soon after the initial AREDS concludes next month.

Emily Y. Chew, MD, deputy director of the division of ep-idemiology and clinical research, National Eye Institute, National Institutes of Health, Bethesda, MD, explained the study design of AREDS II during retina subspecialty day at the American Academy of Ophthalmology annual meeting.

"AREDS is an important study because, while this supplementation is not a cure, reducing vision loss by 25% has a very important public health impact," Dr. Chew added. "If all 8 million people at high risk of developing AMD were to take the AREDS supplements, we could save 300,000 patients from vision loss over the next 5 years."

AREDS II aims to improve on this by revisiting the micronutrients xanthophylls (lutein and zeaxanthin) and omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]).

Dr. Chew explained that the AREDS data and epidemiologic studies have reported evidence that patients with lower dietary intake of omega 3 and lutein have an increased risk of developing AMD. AREDS II will test this by evaluating oral supplements that contain lutein (10 mg/ dl), zeaxanthin (2 mg/dl) and/or omega-3 long-chain polyunsaturated fatty acids (DHA and EPA) (1 g/dl) compared with placebo.

"There is compelling evidence that these micronutrients might be important for reducing the risk of AMD," Dr. Chew said. "However, this is observational and there are no data to suggest that we can actually reduce the risk of AMD by taking large amounts of the micronutrients."

To address this unanswered question, patients with AREDS AMD categories 3 (patients with large drusen) and 4 (patients with advanced AMD in one eye) will be included in AREDS II and will receive placebo (n = 1,000), lutein and zeaxanthin (n = 1,000), omega 3 (n = 1,000), or all three micronutrients (n = 1,000), assigned in a randomized fashion, according to Dr. Chew, for an approximate study size of 4,000 patients.

The study will be multicentered (20 to 60 centers) and be conducted in academic centers as well as in private practices. Patients will undergo annual fundus photographs. Patients will be evaluated for moderate vision loss, progression to AMD, and cataract development.

Refining formulation

In addition, AREDS II will refine the AREDS formulation by including a second randomization in patients choosing to take the AREDS formulation.

Some may choose not to receive AREDS supplements and approximately 3,000 or more patients will receive one of the following: the AREDS supplements; the supplement with no beta-carotene; the supplement with a low dose of zinc; or the supplement with no beta-carotene and a low dose of zinc.

Dr. Chew noted that beta carotene was found to have a detrimental effect in patients who are smokers with an increase in lung cancers. In addition, a high dose of zinc (80 mg) was originally included because a 1988 study indicated that it had a protective effect; however, that dose resulted in adverse effects of increased hospitalizations for genitourinary problems in AREDS patients.