Risk factors for incident age-related macular degeneration
Abstract
Objective To examine risk factors for incident age-related macular degeneration (AMD) after combining data from 3 population-based cohort studies.Design Population-based cohort study.Population A population of 9523 adults (age range, 43-95 years at baseline) living in Australia, The Netherlands, and the United States who participated in a baseline examination and a follow-up examination on average 5 or 6 years later.Methods Similar procedures were used at all study sites. Examinations included a standardized questionnaire, pupillary dilation, and stereoscopic color fundus photography. Fundus photographs were graded for lesions associated with AMD using the Wisconsin and International Age-Related Maculopathy Grading Systems. Senior investigators from each site adjudicated all photos graded as late AMD.Main outcomes measure Incidence of late AMD.Results Among studies, distributions for most risk factors differed, and overall incidence rates were similar. In the Beaver Dam Eye Study, total serum cholesterol was inversely associated with incident neovascular AMD. In the Blue Mountains Eye Study, current smoking (defined as smoking at the time of the baseline examination) was associated with an increased risk of incident geographic atrophy and late AMD; increased total serum cholesterol, having diabetes, and older age at menopause were positively associated with incident geographic atrophy; and an increase in high-density lipoprotein serum cholesterol was inversely related to incident geographic atrophy. In the Rotterdam Study, current smoking was associated with an increased risk of incident geographic atrophy, neovascular AMD, and late AMD; past smoking was associated with an increased risk of incident neovascular AMD and late AMD; and an increased number of years between menarche and menopause was directly related to incident geographic atrophy. After pooling data, the only statistically significant relationships found were between smoking and total serum cholesterol and incident AMD. Current smoking was associated with an increased incidence of geographic atrophy and late AMD (odds ratios [ORs] relative to nonsmokers: 2.83 and 2.35, respectively; ORs relative to past smokers: 2.80 and 1.82, respectively), and total serum cholesterol was associated directly with incident geographic atrophy (OR: 1.08 per 10 mg/dl) and inversely with incident neovascular AMD (OR: 0.94 per 10 mg/dl).Conclusions Pooled data support a growing body of evidence indicating that smoking is related to an increased risk of incident AMD. Current smokers were at higher risk of incident AMD than both past smokers and those who never smoked. The relationships found in this study between total serum cholesterol and incident geographic atrophy and neovascular AMD are not readily explained.
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The systematic review included 18 prospective and cross-sectional studies and 8 case control studies, contributing 94,058 patients and 3,178 late AMD cases.
“In total, data from 18 prospective, cross-sectional studies and 8 case control studies [12,24-26,28,30,31,33-47,49-54,57-73] were included in the final analysis, contributing a sample of some 94,058 patients (ranging from 261 to 22,071) including 3,178 (ranging from 8 to 776) late AMD cases.”
From Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis (2010) · cites this paper as [26]
The relationship of cataract surgery and late AMD was previously reported in a pooled analysis of 3 studies in different continents.
“The relationship of cataract surgery and late AMD was previously reported in a pooled analysis of 3 studies in different continents [26].”
From Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis (2010) · cites this paper as [26]
Smoking is a modifiable and consistently associated environmental factor, typically resulting in about two-fold increased risk of developing advanced AMD.
“Smoking is a modifiable and consistently associated environmental factor, typically resulting in about two-fold increased risk of developing advanced AMD (3, 112, 150, 155).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [150]
Some studies have shown a direct association between age-related macular degeneration and raised concentration of cholesterol, both in the serum and in the diet.
“Some studies have shown a direct association between age-related macular degeneration and raised concentration of cholesterol, both in the serum81 and in the diet.83”
From Age-related macular degeneration (2008) · cites this paper as [81]
Increased concentrations of HDL cholesterol have been shown to be associated with a reduced risk of age-related macular degeneration.
“Increased concentrations of HDL cholesterol—considered to be cardioprotective—have been shown to be associated with a reduced risk of age-related macular degeneration.80,81”
From Age-related macular degeneration (2008) · cites this paper as [81]
Control of modifiable risk factors such as smoking, hypertension, and body-mass index could reduce the risk of developing age-related macular degeneration by half.
“Control of modifiable risk factors such as smoking, hypertension, and body-mass index could reduce the risk of developing age-related macular degeneration by half.147”
From Age-related macular degeneration (2008) · cites this paper as [147]
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- Authors
- Tomany, S. C., Wang, J. J., van Leeuwen, R., Klein, R., Mitchell, P., Vingerling, J. R., Klein, B. E. K., Smith, W., & de Jong, P. T. V. M.
- Affiliations
- University of Wisconsin–Madison (US)
- The University of Sydney (AU)
- Erasmus MC (NL)
- University of Newcastle Australia (AU)
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 111
- Issue
- 7
- Pages
- 1280-1287
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W2104421727
- Cited by
- 621
- References
- 38
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 19 · 2023: 8 · 2022: 21 · 2021: 20 · 2020: 21 · 2019: 21 · 2018: 15 · 2017: 29 · 2016: 27 · 2015: 30 · 2014: 47 · 2013: 42 · 2012: 35
- FWCI
- 39.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Eye Institute (EY0-6594, U10EY006594)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, risk factors, smoking, total cholesterol, geographic atrophy, neovascular AMD, late AMD, menopause, diabetes mellitus, HDL cholesterol, pooled analysis, Beaver Dam Eye Study, Blue Mountains Eye Study, Rotterdam Study, fundus photography grading, incidence, pooled odds ratio
- MeSH terms
- Adult, Aged, Aged, 80 and over, Australia, Female, Humans, Hypercholesterolemia, Cholesterol, HDL, Macular Degeneration, Male, Middle Aged, Netherlands, Risk Factors, Smoking, United States, Cohort Studies, Incidence
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