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The Blue Mountains Eye Study is a cross-sectional population based study of common eye diseases carried out among urban residents in a specific area of Australia in the early 1990's. As part of this study retinal photos were obtained on at least one eye in 2900 subjects who had completed usable Food Frequency Questionnaires (FFQ). The Wisconsin grading system (Dr. Ronald Klein, Univ. of Wisconsin) was used to stage AMD lesions. In general the study compared diet factors comparing those with late AMD (classified as neovascular or geographic atrophy), early AMD or no AMD (1). In this sample, 47 subjects were graded as having late AMD; 181 were graded as having early AMD. The antioxidants evaluated were beta-carotene, zinc, vitamin C and vitamin A.

Odd's ratios (highest quintile vs lowest quintile intake)

* Relative risk of AMD

The authors reported that no significant associations were found between current intake level of any antioxidant evaluated and presence of early or late AMD. The risk of early AMD among subjects in the highest quintile intake-level of beta-carotene relative to that among subjects in the lowest quintile intake level (odd's ratio) was 0.66 (95 % CI 0.39 - 1.1) which numerically suggests a 30-35% decrease in risk. However this odd's ratio was not statistically significant.

Comments:

The authors did evaluate statistical power and determined that the odd's ratio computed for any evaluation would have to indicate an increased risk of 70% (odd's ratio=1.7, low intake relative to high intake) to be detected with 80% power. The small numbers of subjects with late AMD generally resulted in only about 8-10 cases in the highest and lowest intake quintiles of the nutrients evaluated. It really doesn't seem surprising that no statistical significance was achieved.

It is believed that AMD may develop due to cumulative oxidative damage in the aging eye. This etiology is consistent with epidemiological findings identifying some of the risk factors for AMD: age, smoking, increased sunlight exposure, low ocular melanin, and light-colored iris (2). There is evidence that increased serum levels of and dietary intake of specific carotenoids and other antioxidants are inversely related to risk of AMD .

Investigators in the NEI-funded Eye Disease Case-Control Study reported in 1993 that among the 1000-plus participants, those with high serum levels (upper quintile) of the antioxidant dietary carotenoids lutein/zeaxanthin, and beta-carotene, had a 70% decreased risk of neovascular AMD compared with those in the lowest quintile (3). High serum levels of cryptoxanthin and lycopene were associated with 40-50% decreases in risk. The Blue Mountain Study did not evaluate these carotenoids.

Vitamin C and vitamin E had numeric decreases in risk in the case-control study (30% and 40% respectively) but the odd's ratios did not reach statistical significance. Seddon and colleagues studied over 300 patients and reported a 57% decrease in risk of AMD in patients with increased dietary intake of lutein and zeaxanthin (4).

In a smaller case control study within the Beaver Dam Cohort, Mares-Perlman and colleagues found significant decreases in risk of AMD with higher serum levels of alpha-tocopherol and lycopene (5). On the whole the case-control design studies have provided better statistical power for detection of associations between nutrient intake and risk of AMD - especially late AMD .

References

1. Smith W, Mitchell P, Webb K and Leeder SR. Dietary Antioxidants and Age-Related Maculopathy. Ophthalmology 1999;106:4;761-767.
2. Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr. 1995; 62(suppl): 1448s-1461s.
3. Eye Disease Case Control Study Group. Antioxidant Status and Neovascular Age-Related Macular Degeneration. Arch Ophthalmol. 1993; 111:104-109.
4. Seddon JM, Ajani UA, Sperduto RD et al. Dietary Carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. JAMA 1994; 272: 1413-1420.
5. Mares-Perlman JA, Brady WE, Klein R et. al. Serum Antioxidants and Age-Related Macular Degeneration in a Population-Based Case-Control Study. Arch Ophthalmol 1995;113:1518-1523.