June 10, 2008 — Eating fish and other foods high in omega-3 fatty acids is associated with reduced risk for age-related macular degeneration (AMD), according to the results of a study reported in the June issue of the Archives of Ophthalmology.

"Epidemiological studies have shown inverse associations, albeit not consistently, between dietary long-chain omega-3 fatty acid and fish intake and AMD risk, write Elaine W.-T. Chong, MBBS, from the University of Melbourne in Melbourne, Australia, and colleagues. "To evaluate these associations further, we performed a systematic review and meta-analysis on dietary omega-3 fatty acid and fish intake in the primary prevention of AMD."

Using standardized criteria and no limits on publication year or language, the reviewers systematically searched 7 databases for randomized controlled trials and prospective cohort, case-control, and cross-sectional studies. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met inclusion criteria. Meta-analytic methods allowed quantitative pooling of measures of associations.

Nine studies enrolled a total of 88,974 people, including 3203 cases of AMD. High dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk for late AMD (pooled odds ratio [OR], 0.62; 95% confidence interval [CI], 0.48 - 0.82). Eating fish at least twice weekly was associated with a decreased risk for both early AMD (pooled OR, 0.76; 95% CI, 0.64 - 0.90) and late AMD (pooled OR, 0.67; 95% CI, 0.53 - 0.85).

Limitations of this review include those inherent in included observational studies, such as possible recall bias and inability to infer temporal associations; possible publication bias; unknown confounders; lack of randomized controlled trials evaluating omega-3 fatty acid and fish intake in the primary prevention of AMD; study samples derived from populations in which participants are well nourished, reducing generalizability; assessment of AMD that varied between studies; and possible misclassification of dietary factors.

"Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention," the reviewers write.

A National Health and Medical Research Council Public Health Scholarship to Dr. Chong supported this study in part. Two other reviewers have disclosed various financial relationships with Pfizer and Novartis.

Arch Ophthalmol. 2008;126:826-833.

Clinical Context

Study Highlights

• Up to May 2007, the reviewers systematically searched 7 databases, with no limits on publication year or language and using standardized criteria. Randomized controlled trials and prospective cohort, case-control, and cross-sectional studies were included.
• Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met the criteria. Not all studies reported both omega-3 fatty acid and fish intake.
• No randomized controlled trials met the inclusion criteria.
• Measures of associations were pooled quantitatively with use of meta-analytic methods.
• 2 primary outcomes were evaluated: early AMD (defined as soft drusen or retinal pigmentary changes) and late AMD (exudative AMD or geographic atrophy).
• 9 studies provided data on a total sample of 88,974 people, including 3203 AMD cases (1847 early and 1356 late AMD cases).
• The results evaluating the association of omega-3 fatty acids and early AMD were not pooled; however, 2 prospective cohort studies, the Blue Mountains Eye Study and the Nurses' Health Study and the Health Professional Follow-Up Study, were consistent with a protective effect of omega-3 fatty acids against early AMD.
• A high dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk for late AMD (pooled OR, 0.62; 95% CI, 0.48 - 0.82).
• Fish intake at least twice a week was associated with a reduced risk for both early AMD (pooled OR, 0.76; 95% CI, 0.64 - 0.90) and late AMD (pooled OR, 0.67; 95% CI, 0.53 - 0.85).
• Limitations of this study included the following: no randomized controlled trials were included in evaluating omega-3 fatty acid and fish intake in the primary prevention of AMD; meta-analyses of observational data are known to have more biases than meta-analyses of randomized controlled trials, particularly prone to recall bias and temporal relationships between diet and disease; associations between AMD prevention and omega-3 fatty acid or fish intake may reflect other broader aspects of diet or lifestyle; the results could not be applied to all populations because the populations included in the studies were well nourished; the assessment of AMD varied between studies; and misclassification of dietary factors could have occurred.

Pearls for Practice

• Long-chain omega-3 fatty acids are believed to protect against oxygenic, inflammatory, and age-related retinal damage, which are key pathogenic processes in the development of AMD.
• This meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk for AMD; however, there was insufficient evidence with few prospective studies and no randomized clinical trials to support their routine consumption for the prevention of AMD.

CME Test