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Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

Usha Chakravarthy1*, Tien Y Wong23, Astrid Fletcher4, Elisabeth Piault5, Christopher Evans5, Gergana Zlateva6, Ronald Buggage7, Andreas Pleil6 and Paul Mitchell8

Author Affiliations

1 Centre for Vision Science, Queen's University Belfast, Northern Ireland, UK

2 Singapore Eye Research Institute, National University of Singapore, Singapore

3 Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia

4 Dept of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK

5 Mapi Values, Boston, Massachusetts, USA

6 Pfizer Inc, New York, New York, USA

7 Novartis, East Hanover, New Jersey, USA

8 Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, Australia

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BMC Ophthalmology 2010, 10:31  doi:10.1186/1471-2415-10-31

Published: 13 December 2010



Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours.


A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR) and/or relative risk (RR) outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI) were calculated.


Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels.


Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.