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Supplementation with antioxidants, zinc may delay AMD progression
Patients at risk of developing AMD should have yearly eye exams; those without contraindications should consider supplements.
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WASHINGTON — People over 55 years old who are at risk for developing age-related macular degeneration may benefit from supplementation with antioxidants and zinc, according to a large multicenter study.
Commenting on the Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, director Paul A. Sieving, MD, PhD, said, “This is an exciting discovery because for people at high risk for developing advanced AMD, these dietary supplements are the first effective treatment to slow the progression of the disease.”
AREDS was conducted at 11 nationwide retinal specialty clinics. The study enrolled 4,757 patients, aged 55 to 80 years, from November 13, 1992 through January 15, 1998. Patients were followed until April 16, 2001. All patients had a best-corrected visual acuity of 20/32 or better in at least one eye, reported Aaron Kassoff, MD, and AREDS investigators in Archives of Ophthalmology.
Four AMD categories
Patients were divided into four AMD categories, based on the size and extent of drusen and retinal pigment epithelial abnormalities in each eye, the presence of advanced AMD and visual acuity.
Patients in category 1 were virtually free of age-related macular abnormalities, had a total drusen area of less than five small drusen (<63 µm) and had a visual acuity of 20/32 or better in both eyes.
Category 2 patients had mild or borderline age-related macular features, multiple small drusen, single or nonextensive intermediate drusen (63 µm to 124 µm), pigment abnormalities or any combination of these in one or both eyes, and visual acuity of 20/32 or better in both eyes.
Patients in category 3 had no advanced AMD in both eyes and at least one eye with visual acuity of 20/32 or better with at least one large drusen (125 µm), extensive intermediate drusen, geographic atrophy not involving the center of the macula or any combination of these.
Category 4 patients had visual acuity of 20/32 or better and no advanced AMD in the study eye; the other eye had either lesions of advanced AMD or visual acuity less than 20/32 and AMD abnormalities that would account for reduced visual acuity.
“This randomized clinical trial was designed to evaluate the effect of high doses of zinc and selected antioxidant vitamins … on the development of advanced AMD in a cohort of older [patients],” said Dr. Kassoff of The Eye Center at Memorial in Albany, N.Y.
The AREDS consisted of two clinical trials — one for AMD and one for cataract — that generally shared the same participants. In the cataract trial, use of a high-dose formulation of vitamin C, vitamin E and beta carotene had no significant effect on the development or progression of age-related lens opacities or visual acuity loss, according to the study.
Because 1,117 participants in category 1 did not have at least early stages of AMD, the AMD portion of the trial included the 3,640 participants who had at least early AMD (categories 2 through 4), according to investigators.
Study design
Study participants were randomly assigned in a double-masked fashion to receive one of four treatments: antioxidants (500 mg of vitamin C, 400 IU of vitamin E and 15 mg of beta carotene), zinc (80 mg of zinc as zinc oxide and 2 mg of copper as cupric oxide to prevent potential anemia), a combination of antioxidants and zinc or placebo. The supplements were provided by Bausch & Lomb.
Investigators performed general physical and ophthalmic examinations at baseline and at annual intervals. Exams included height and weight measurement, blood pressure, manifest refraction, best-corrected visual acuity and intraocular pressure. Slit-lamp biomicroscopy and ophthalmoscopy were performed at each examination. Stereoscopic fundus photographs of the macula were taken at baseline and annually beginning two years after randomization, investigators wrote. Demographic information, smoking history, sunlight exposure, medical history, prescription drug history, history of nonprescription medication use and history of vitamin and mineral use were obtained at baseline.
Results
Researchers found that patients at high risk of developing advanced stages of AMD lowered their risk by approximately 25% when treated with a high-dose combination of antioxidants and zinc. Risk of vision loss caused by advanced AMD was reduced by about 19% in the same high-risk group, the study showed.
After an average of 6.3 years of follow-up, researchers found a statistically significant odds reduction for the development of advanced AMD in patients assigned antioxidants plus zinc versus those assigned placebo (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52 to 0.98). The OR for patients assigned zinc only was 0.75 (99% CI, 0.55 to 1.03); 0.80 (99% CI, 0.59 to 1.09) for antioxidants-alone patients.
“Patients with extensive small drusen, nonextensive intermediate size drusen or pigment abnormalities had only a 1.3% 5-year probability of progressing to advanced AMD,” Dr. Kassoff and colleagues wrote.
When these 1,063 patients were excluded, odds reduction estimates increased (antioxidants plus zinc: OR, 0.66; 99% CI, 0.47 to 0.91; zinc: OR, 0.71; 99% CI, 0.52 to 0.99; antioxidants: OR, 0.76; 99% CI, 0.55 to 1.05). Both zinc and zinc/antioxidant combination significantly reduced the odds of developing advanced AMD in this group. The only statistically significant reduction in rates of at least moderate visual acuity loss occurred in patients assigned to receive antioxidants plus zinc (OR, 0.73; 99% CI, 0.54 to 0.99). There were no statistically significant serious adverse effects associated with any of the formulations, according to researchers.
Stephen Bartels, PhD, director of RD&E research for Bausch & Lomb, told Ocular Surgery News, “The AREDS investigators are recommending that people have an eye exam to determine their risk of developing advanced AMD. After the evaluation is made, if the patient is determined to be in that high-risk category, he or she should consider supplementing with the antioxidant plus zinc formulation that was used in the trial.”
The supplements are not a cure for AMD, according to Dr. Sieving.
“Nor will they restore vision already lost from the disease. But they will play a key role in helping people at high risk for developing advanced AMD keep their vision,” he said.
For Your Information:Reference:
- The Age-Related Eye Disease Study Group can be reached at AREDS Coordinating Center, The EMMES Corp., 401 N. Washington St., Suite 700, Rockville, MD 20850-1707; e-mail: aredspub@emmes.com.
- Stephen Bartels, PhD is director of RD&E research for Bausch & Lomb. He can be reached at (716) 338-6524.
- Age-Related Eye Disease Study Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene and zinc for age-related macular degeneration and vision loss. Arch Ophthalmol. 2001;119:1417-1436.