Alcohol Consumption and the Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis ELAINE W.-T. CHONG, ANDREAS J. KREIS, TIEN Y. WONG, JULIE A. SIMPSON, AND ROBYN H. GUYMER ● PURPOSE: To review systematically the evidence cur- rently available on alcohol consumption and the risk of age-related macular degeneration (AMD). ● DESIGN: Systematic review and meta-analysis of obser- vational studies. ● METHODS: Seven databases were searched systematically with no limits on the year or language of publication for prospective cohort studies. References identified from per- tinent reviews and articles also were retrieved. Two review- ers independently searched the above databases and selected the studies using prespecified standardized criteria. These criteria included appropriate adjustment for age and smok- ing in the analysis. Of the 441 studies identified initially, five cohort studies met the selection criteria. Data extrac- tion and study quality evaluation were performed indepen- dently by two reviewers and results were pooled quantitatively using meta-analytic methods. ● RESULTS: The five cohort studies included 136,946 people, among whom AMD developed in 1923 (1,513 early and 410 late). Pooled results showed that heavy alcohol consumption was associated with an increased risk of early AMD (pooled odds ratio, 1.47; 95% confidence interval, 1.10 to 1.95), whereas the association between heavy alcohol consumption and risk of late AMD was inconclu- sive. There were insufficient data to evaluate a dose- response association between alcohol consumption and AMD or the association between moderate alcohol con- sumption and AMD. ● CONCLUSIONS: Heavy alcohol consumption (more than three standard drinks per day) is associated with an increased risk of early AMD. Although this association seems to be independent of smoking, residual confound- ing effects from smoking cannot be excluded completely. (Am J Ophthalmol 2008;145:707–715. © 2008 by Elsevier Inc. All rights reserved.) A GE-RELATED MACULAR DEGENERATION (AMD) IS the leading cause of severe visual loss among people aged 50 years and older in the developed world. 1–6 Despite the recent progress in uncovering its underlying risk factors, the exact pathogenesis of AMD remains unresolved. 7 Increasing age and several genetic markers have been associated with the risk of AMD. 8,9 However, smoking remains the only consistently found modifiable risk factor for AMD. 10 –12 Although promising new treatments for AMD have emerged, these therapies are confined to exudative or wet AMD, 13–15 and there remains a vital interest in finding additional modifiable risk factors for early AMD. Alcohol consumption hypothetically may have both harmful and protective effects on AMD. This is based partly on observations that AMD and cardiovascular disease share several common risk factors 16 –18 and that the J-shaped association described for alcohol consumption and cardiovascular disease also may be present for AMD. 19 –21 Alcohol is a known neurotoxin that can result in oxidative brain damage, 22,23 and thus in heavy amounts may be expected to have an adverse effect on the retina. However, moderate consumption is associated with de- creased platelet aggregation, 24 lower serum fibrinogen levels, 25,26 lower C-reactive protein concentrations, 27,28 and higher high-density lipoprotein levels, 29,30 all of which may be protective for AMD. 31–34 Epidemiologic studies that have assessed this relation- ship, however, have not shown consistently that heavy alcohol consumption is associated with a higher risk of AMD, nor that moderate alcohol consumption is protec- tive. To address this uncertainty, we performed a system- atic review and meta-analysis of the literature to evaluate the associations between alcohol consumption and AMD. We considered for inclusion only prospective cohort stud- ies, because of the limitations with retrospective studies in assessing associations of alcohol consumption where recall bias is significant. METHODS ● DATA SOURCES: We conducted a systematic review of seven databases, including PubMed (1950 to June 8, 2007), Web of Science (1900 to June 8, 2007), EMBASE Accepted for publication Dec 5, 2007. From the Centre for Eye Research Australia, The University of Melbourne, Victoria, Australia (E.W.-T.C., A.J.K., T.Y.W., R.H.G.); and the Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore (T.Y.W.); the Centre for Molecular, Environmental, Genetic and Ana- lytic Epidemiology, The University of Melbourne, Victoria, Australia (J.A.S.); and the Cancer Epidemiology Centre, The Cancer Council of Victoria, Victoria, Australia (J.A.S.). Inquiries to Tien Y. Wong, Centre for Eye Research Australia, the University of Melbourne, 32 Gisborne Street, East Melbourne 3002, Victoria, Australia; e-mail: twong@unimelb.edu.au © 2008 BY ELSEVIER INC.ALL RIGHTS RESERVED. 0002-9394/08/$34.00 707 doi:10.1016/j.ajo.2007.12.005