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        Ocular Disorders Associated with Increased Risk of Mortality, But Zinc Therapy Appears to Reduce Mortality

        Archives of Ophthalmology

        05/12/2004
        By Joene Hendry


        Individuals with advanced age-related macular degeneration (AMD) and with nuclear lens opacities or a history of cataract surgery show increased rates of all-cause mortality, but mortality appears to be reduced with zinc therapy, according to a report from the Age-Related Eye Disease Study (AREDS) Research Group.

        Study investigators assessed mortality as associated with ocular disorders and treatment characteristics in 4753 patients with AMD, who were a median age of 69 years at baseline. AMD severity was classified as category 1 with few if any small drusen; category 2 with extensive small drusen or nonextensive intermediate-sized drusen; category 3 with extensive intermediate-sized drusen, at least 1 large druse, or noncentral geographic atrophy; or category 4 with unilateral advanced AMD or unilateral vision loss to worse than 20/32 attributable to AMD.

        Overall, 10.4% of the patients were randomised to daily oral supplements of 80 mg zinc oxide with 2 mg cupric oxide alone, while 10.9% received zinc plus antioxidants including 500 mg vitamin C, 400 IU vitamin E, and 15 mg beta carotene, 14.8% received antioxidants alone, and 13.0% received placebo.

        During a median of 6.5 years, 11% of the study participants died. All-cause mortality rates were 6.2%, 7.3%, 9.3%, and 14.7% for AMD categories 1, 2, 3, and 4, respectively. Patients with category 4 AMD had an age and sex adjusted relative risk of all-cause mortality of 1.80 compared with those with category 1 AMD. The relative risk of mortality was 1.41 for category 4 AMD compared with category 1 AMD after additional adjustment for race, education, smoking status, body mass index, diabetes mellitus, angina, cancer, and hypertension.

        A similarly adjusted analysis showed that visual acuity worse than 20/40 in 1 eye had a relative risk of mortality of 1.36 compared with individuals with good acuity in both eyes. Also, nuclear opacity equal to or greater than 4 in at least 1 eye, compared with less than grade 4, had a relative risk of mortality of 1.40, while cataract surgery, compared with none, had a relative risk of 1.55.

        Additionally, patients randomly assigned to either zinc or zinc plus antioxidants had a relative risk of 0.73 compared with patients who did not receive zinc. "The positive association of zinc with decreased all-cause mortality did not seem to be due to reduction in deaths involving cardiovascular/circulatory disease or cancer," the authors note.

        While the ocular findings from this study are consistent with findings of other studies that show a potential link between ocular disorders and survival, reports the Writing Team for the AREDS Research Group, "This is the first large randomized trial to report a potential benefit of the use of high doses of zinc on survival."


        Arch Ophthalmol 2004;122:716-726

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