Vol 59: MAY • MAI 2013 | Canadian Family Physician • Le Médecin de famille canadien 503 Download full-text
Vitamins for age-related macular degeneration
demonstrate minimal differences
Michael R. Kolber MD CCFP MSc Mathew Tennant MD FRCPS Tony Nickonchuk CDE
Does taking ocular vitamins (including antioxidants
and zinc) decrease the progression of age-related
macular degeneration (AMD)?
Ocular vitamins only slow visual loss in AMD patients
with intermediate and severe retinal findings (number
needed to treat [NNT] = 13). Progression to advanced
AMD is rare in patients with minimal AMD, and ocu-
lar vitamins do not prevent AMD in those without
AMD. Components of ocular vitamins are potentially
harmful and should be used only in selected patients.
The largest multicentre, double-blind, placebo-controlled
RCT of 4757 patients with AMD1 examined the effects of
antioxidants (500 mg of vitamin C, 400 IU of vitamin E, and
15 mg of beta-carotene); zinc (80 mg of zinc oxide); and
antioxidants in combination with zinc on AMD progression.
• Mean age 69 years; 56% females; 6.3 years follow-up.
• Baseline retinal photography classified patients in cat-
egories 1 (minimal) to 4 (advanced).
• For 15-letter visual acuity loss:
-Pooled together, category 2, 3, and 4 patients had no
significant improvement with any intervention.
-Category 3 and 4 patients had statistically significantly
reduced visual loss for antioxidants with zinc (23%)
versus placebo (29%); NNT = 17 (P = .008).
• For progression to advanced AMD (predominantly
-Category 3 and 4 patients had statistically significantly
reduced progression with zinc (NNT = 17, P = .008) and
antioxidants with zinc (NNT = 13, P = .001).
• Category 1 patients (23% of sample) were excluded,
reporting was selective, adjustments were made for base-
line characteristics, and the trial was industry supported.
• Inconsistent results seen in shorter, smaller studies.2
• In developed countries AMD is a common cause of
visual loss.3 Neovascular AMD accounts for more than
80% of AMD visual loss, but less than 15% develop
neovascular AMD (< 1% of category 1 or 2 patients).1,4
• Risk factors for AMD include being white, advanced
age, smoking, obesity, and family history.4-6
• For patients without AMD, vitamin E or beta-carotene
alone do not prevent AMD,7 and Canadian retina spe-
cialists recommend taking ocular vitamins.8
• Antioxidants increase adverse events including over-
all mortality (relative risk of 1.04, 95% CI 1.01 to 1.07).9
Visual impairment affects 23% of US patients older than
80 years,3 most commonly from cataracts, AMD, and glau-
coma.3 Ocular vitamins for AMD cost about $20 per month
and do not prevent or slow the progression of cataracts.10
Intravitreal injections of vascular endothelial growth fac-
tor inhibitors ranibizumab or bevacizumab decrease the
risk of further visual loss and might improve visual acu-
ity in AMD patients who progress to neovascularization.11
Bevacizumab (off-label use) has been shown to be clinically
noninferior to ranibizumab and is substantially cheaper.
Dr Kolber is Associate Professor in the Department of Family Medicine at the University
of Alberta in Edmonton. Dr Tennant is Associate Clinical Professor in the Department of
Ophthalmology at the University of Alberta and a retina specialist with an interest in treat-
ment of macular degeneration. Mr Nickonchuk is a pharmacist, a certified diabetic educa-
tor, and an advanced prescriber, and Pharmacy Manager at Walmart in Peace River, Alta.
The opinions expressed in Tools for Practice articles are those of the authors and do not
necessarily mirror the perspective and policy of the Alberta College of Family Physicians.
1. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clini-
cal 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(10):1417-36.
2. Evans JR. Antioxidant vitamin and mineral supplements for slowing the progression
of age-related macular degeneration. Cochrane Database Syst Rev 2006;(2):CD000254.
3. The Eye Diseases Prevalence Research Group. Causes and prevalence of visual
impairment among adults in the United States. Arch Ophthalmol 2004;122(4):477-85.
4. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med
5. Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL 3rd; Age-Related Eye Disease
Study Research Group. Risk factors for the incidence of advanced age-related macular
degeneration in the Age-Related Eye Disease Study. Ophthalmology 2005;112(4):533-9.
6. Ting AY, Lee TK, MacDonald IM. Genetics of age-related macular degeneration. Curr
Opin Ophthalmol 2009;20(5):369-76.
7. Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for preventing
age-related macular degeneration. Cochrane Database Syst Rev 2012;(6):CD000253.
8. Cruess AF, Berger A, Colleaux K, Greve M, Harvey P, Kertes PJ, et al. Canadian expert
consensus: optimal treatment of neovascular age-related macular degeneration. Can
J Ophthalmol 2012;47(3):227-35.
9. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements
for prevention of mortality in healthy participants and patients with various diseases.
Cochrane Database Syst Rev 2012;(3):CD007176.
10. Mathew MC, Ervin AM, Tao J, Davis RM. Antioxidant vitamin supplementation for
preventing and slowing the progression of age-related cataract. Cochrane Database
Syst Rev 2012;(6):CD004567.
11. Comparison of Age-related Macular Degeneration Treatments Trials (CATT)
Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-
related macular degeneration: two-year results. Ophthalmology 2012;119(7):1388-98.
Tools for Practice
Tools for Practice articles in Canadian Family Physician
(CFP) are adapted from articles published on the Alberta
College of Family Physicians (ACFP) website, summarizing
medical evidence with a focus on topical issues and
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Archived articles are available on the ACFP website: www.acfp.ca.