Critique 088: Higher levels of alcohol intake may slightly increase risk of age-related macular degeneration, with no effect from moderate drinking — 22 August 2012
Adams MKM, Chong EW, Williamson E, Aung KZ, Makeyeva GA, Giles GG, English DR, Hopper J, Guymer RH, Baird PN, Robman LD, Simpson JA. 20/20—Alcohol and age-related macular degeneration: The Melbourne Collaborative Cohort Study. Am J Epidemiol 2012;176:289-298.
Little evidence exists regarding associations between age-related macular degeneration (AMD) and moderate alcohol consumption, patterns of consumption, or different types of alcoholic beverage. The authors examined associations between AMD prevalence and alcohol intake using 20,963 participants from the Melbourne Collaborative Cohort Study aged 40–69 years at baseline (1990–1994). Participants’ alcohol consumption was determined from a structured interview at baseline. At follow-up from 2003 to 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs.
Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline, having adjusted for sex, age, smoking, country of birth, education, physical activity, and energy from food. This positive association was apparent for wine, beer, and spirits. The estimates were similar for both sexes. The odds ratio for those drinking more than 20 g of alcohol per day for late AMD was 1.44 (95% confidence interval: 0.85, 2.45; P = 0.17). These results show a modest association between alcohol consumption and increased AMD risk.
Background: Age-related macular degeneration (AMD) is the single most important cause of irreversible visual loss in elderly populations of the developed world. It is considered to be a complex disease affected by both genetics and environmental factors. Of the latter, smoking is the most established modifiable risk factor for developing AMD.
Previous research has suggested that alcohol might be a risk factor for AMD, although associations in most epidemiologic studies have not shown a significant correlation. In their summary of risk factors for AMD, Lambrou and Dessouki1 state that “The Blue Mountain Eye Study,2 the Framingham Eye Study,3 and the Physician Health Study4 showed no appreciable increased risk for AMD with alcohol consumption. The Beaver Dam Eye Study showed a slight correlation between consumption of beer and neovascular AMD, as well as beer drinking and the appearance of retinal drusen.5 This same study showed no association with wine consumption. However, the First National Health Nutrition and Examination Survey showed that moderate consumption of wine could decrease the odds of developing AMD.6” Lower risk of AMD associated with alcohol consumption has also been noted by others.7,8
A meta-analysis by Chong et al9 concluded that “heavy alcohol consumption (more than three standard drinks per day) is associated with an increased risk of early AMD.” These authors added: “Although this association seems to be independent of smoking, residual confounding effects from smoking cannot be excluded completely.9”
The present analyses are based on the follow up of more than 20,000 participants recruited in 1990-1994 for the Melbourne Collaborative Cohort Study in Australia. At follow up between 2003 and 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs among about one-half of the original participants. There were 2,663 cases of early AMD and 121 cases of late AMD identified.
Specific comments on study: Stated one Forum reviewer: “The Melbourne Collaborative Cohort Study is a large and well done study. The results are credible and adjustments (including sex, age, smoking, country of birth, education, physical activity and energy from food) seem to be state-of-the art.” There are some concerns about this study, however, especially in that while it is “population-based,” only about one-half of the original participants came for the follow-up eye examination. Subjects who died during follow up (which occurred more commonly among non-drinkers than among drinkers in this cohort) did not survive until the evaluations for AMD were carried out. “The loss to follow up is substantial (49%) and the differential loss to follow up according to smoking is worrying.” Further, there were no data on potential changes in alcohol intake during follow up; hence, all estimates were based on the reported alcohol intake at baseline
The main results suggest no effect of alcohol on AMD risk for never smokers, but an increase in risk for former smokers, especially those consuming 20 or more grams of alcohol per day. However, the study did not demonstrate a dose-response curve (increasing risk of AMD for increasing levels of alcohol intake). When the effects of alcohol by frequency of intake were assessed (based on one week of diet records in the week prior to the baseline examination), there was an increase in risk of AMD seen only for subjects reporting ≥280 g/week. For subjects consuming less, there was no difference between those consuming alcohol on 1-3 days/week and 4-6 days/week.
The discussion of possible biological pathways for the harmful effect of alcohol is weak, and the pathophysiology of AMD remains poorly understood. Stated one reviewer: “I get the impression that the authors are downplaying the results of other studies that had indicated reduced risk of age-related macular degeneration associated with moderate drinking. In particular, the work of Obisesan et al6,7 supports a decrease in risk of AMD for moderate wine drinkers.”
Smoking and alcohol consumption: Stated another reviewer: “A few results seem surprising: Never smokers seem to have negligible increased risk at all levels of alcohol consumption, even >20g/day. Also, former smokers are a very large group and have a very high risk. These results seem to suggest that the disease may be caused by some sort of interaction between smoking and drinking, a possibility the authors do not discuss.” The authors do not point out in their discussion that never smokers show no increase in risk with alcohol. For unexplained reasons, spirits drinkers >20g/day have the lowest risk, 0.72, but with very wide confidence intervals; this is not commented upon in the discussion.
In any case, the present study is generally consistent with earlier studies suggesting a slightly increased risk of AMD for heavier consumers of alcohol. In this study, while there was no increase in risk for light-to-moderate drinkers, there was no suggestion of reduced risk, as had been shown in some earlier sutdies. This study stuggests that smoking may be a much more important environmental factor affecting AMD than alcohol, as there was no increase in risk for alcohol consumers who were never smokers.
Net effects of moderate alcohol consumption on health: Forum reviewer Goldfinger had an interesting comment on the net health effects of alcohol: “We appropriately report a greater longevity associated with moderate alcohol consumption, thereby exposing people to a greater likelihood of some age-related diseases as they enjoy longer life. Whereas presesrvation of vision is a key factor in quality of life in the aged, getting there (to older age) is more likely because of the cardioprotective effect of moderate drinking.”
1. Lambrou Jr FH, Dessouki A. Risk factors and prevention of age related macular degeneration. Available at
2. Smith W, Mitchell P. Alcohol intake and age-related maculopathy. Am J Ophthalmol. 1996; 122:743-745.
3. Kahn HA, Leibowitz HM, Ganley JP, et al. The Framingham Eye Study II. Association of ophthalmic pathology with single variables previously measured in the Framingham Health Study. Am J Epidemiol. 1977; 106: 33-41.
4. Ajani UA, Christen WG, Manson JE, et al. A prospective study of alcohol consumption and the risk of age-related macular degeneration. Ann Epidemiol 1999;9:172-177.
5. Moss SE, Klein R, Klein BEK, et al. Alcohol consumption and the 5-year incidence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmol 1998;105:789-794.
6. Obisesan TO, Hirsch R, Kosoko O, et al. Moderate wine consumption is associated with decreased odds of developing age-related macular degeneration in NHANES-1. JAGS 1998; 46:1-7.
7. Obisesan TO. Wine: protective in macular degeneration. In: Sandler M, Pinder R, eds. Wine: A Scientific Exploration. London: Taylor & Francis 2003:285-298.
8. Arnarsson A, Sverrisson T, Stefánsson E, et al. Risk factors for five-year incident age-related macular degeneration: the Reykjavik Eye Study. Am J Ophthalmol 2006;142:419–428.
An analysis based on the follow up of more than 20,000 participants recruited in 1990-1994 for the Melbourne Collaborative Cohort Study in Australia related alcohol consumption at baseline to the subsequent development of age-related macular degeneration (AMD), a common cause of blindness in the elderly. At a follow-up examination between 2003 and 2007, digital macula photographs of both eyes were taken and evaluated for early and late AMD signs; there were 2,663 cases of early AMD and 121 cases of late AMD identified.
The authors report: “Drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD (odds ratio = 1.21, 95% confidence interval: 1.06, 1.38; P = 0.004) when compared with those who reported no alcohol intake at baseline.” (An average of 20 grams/day of alcohol is the equivalent of about 2 daily drinks by British standards or 1 ½ drinks by US standards.) The analyses show that the increased risk was almost exclusively among smokers, with no significant effect among non-smokers who consumed any amount of alcohol.
Forum reviewers had some concern that approximately one-half of this “population-based” study did not have measurements for AMD; these included those who had died during the follow-up period (and deaths were more common among non-drinkers than among drinkers). Further, the authors focus only on the slight increase in risk of AMD seen for heavier drinkers, but do not emphasize that among never smokers there was no increase in risk for consumers of any amount of alcohol. Their results suggest a possible interaction between smoking and alcohol consumption in the etiology of this disease.
The findings of no effect (either positive or negative) from drinking < 20 g/day of alcohol in this study does not support some earlier reports of reduced risk of AMD among moderate wine drinkers. In the present study, there were no detectable differences in effect between the consumption of wine or of beer. A key point of this study may be that never-smokers do not show increased risk of AMD with alcohol consumption.
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The following members of the International Scientific Forum on Alcohol Research provided comments for this critique:
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis; Davis, CA, USA
Yuqing Zhang, MD, DSc, Epidemiology, Boston University School of Medicine, Boston, MA, USA
Creina Stockley, PhD, MBA, Clinical Pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia
Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA