Cited by 854Retinal Diseases and TreatmentsRetinal Imaging and AnalysisOphthalmology and Visual Impairment Studies

The DOI matches its Crossref record; 83 of the 85 references it cites were found in a registry or an index; none of the 31 sources its claims cite is checked for support yet.

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

Open access

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis found increasing age, current smoking, previous cataract surgery, and family history of AMD were strong and consistent risk factors for late AMD, with cardiovascular/metabolic factors showing moderate associations. It synthesizes 45 retained articles to identify risk factors that can be assessed by primary care physicians and general ophthalmologists.

Key findings

  • Strong and consistent associations with late AMD were reported for increasing age, current cigarette smoking, previous cataract surgery, and family history of AMD. Smoking: prospective RR 1.86 (95% CI 1.27–2.73), cross-sectional OR 3.58 (2.68–4.79), case-control OR 1.78 (1.52–2.09). Cataract surgery: prospective RR 3.05 (2.05–4.55), cross-sectional OR 1.59 (1.08–2.34), case-control OR 1.54 (1.24–1.91). Family history: cross-sectional OR 3.95 (1.35–11.54); case-control OR 6.18 (0.98–38.90) in Table 3.
  • Moderate and consistent associations were reported for higher BMI (case-control OR 1.52, 1.15–2.00; prospective RR 1.28, 0.98–1.67), history of cardiovascular disease (case-control OR 2.20, 1.49–3.26), hypertension (case-control OR 1.48, 1.22–1.78), and higher plasma fibrinogen (cross-sectional OR 1.45, 1.22–1.73).
  • Weaker and inconsistent associations were reported for gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Diabetes was significant in prospective studies (RR 1.66, 1.05–2.63) but not in cross-sectional or case-control analyses.
  • Increasing age was strongly associated with late AMD in all studies; prevalence rose with age, e.g. 12.0% in the ≥80-year Blue Mountains white cohort (Table 4).

Methods

  • Systematic review and meta-analysis of 16 pre-selected risk factors considered readily measured in nonspecialist settings; ocular, genetic, and nutritional factors were excluded. Searches were conducted in Medline and Cochrane, completed 28 February 2007 and repeated November 2008; 295 references were initially yielded, 147 articles were assessed, 70 fulfilled eligibility criteria, and 45 articles were retained.
  • Included prospective cohort, cross-sectional, and case-control studies reporting an OR or RR between late AMD and at least one risk factor; adjusted estimates were selected. Fixed-effects meta-analyses were used unless heterogeneity was present (I² p<0.10), in which case random-effects models were used; funnel plots explored publication bias.
  • The abstract reports 18 prospective and cross-sectional studies and 6 case-control studies involving 113,780 persons with 17,236 late AMD cases; the Results section reports 18 prospective/cross-sectional and 8 case-control studies contributing 94,058 patients and 3,178 late AMD cases.

Limitations

  • The paper states that appropriateness or completeness of adjustment could not be ascertained; some data were crude and subject to measurement error (e.g. “history of cardiovascular disease” spanning asymptomatic angina to myocardial infarction), likely diluting effects. It excluded ocular factors, dietary factors, and genetic factors; included only English-language articles; searched only Medline and Cochrane (not EMBASE); and notes that prognostic use requires further research, with generally small observed odds ratios and limited preventive interventions.
  • Evident from the text: study counts and sample sizes are inconsistent between the abstract and Results (113,780 persons/17,236 cases and 6 case-control studies vs 94,058 patients/3,178 cases and 8 case-control studies), and the family-history confidence interval in the narrative (1.94–6.61) differs from Table 3 (0.98–38.90).

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Integrity signals

Registry

Crossref · 10.1186/1471-2415-10-31

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Study selection process.
Figure 1 Study selection process.CC BY · PubMed Central
Figure 2 Prevalence of late AMD by age (adapted from Varma et al[61]and Kawasaki et al[19]).
Figure 2 Prevalence of late AMD by age (adapted from Varma et al[61]and Kawasaki et al[19]).CC BY · PubMed Central
Figure 3 Pooled odds ratio for late AMD by gender (female vs. male).
Figure 3 Pooled odds ratio for late AMD by gender (female vs. male).CC BY · PubMed Central
Figure 4 Pooled odds ratio for late AMD and by race/ethnicity (whites vs. other races/ethnicities).
Figure 4 Pooled odds ratio for late AMD and by race/ethnicity (whites vs. other races/ethnicities).CC BY · PubMed Central
Figure 5 Pooled odds ratio for late AMD by family history (presence or absence).
Figure 5 Pooled odds ratio for late AMD by family history (presence or absence).CC BY · PubMed Central
Figure 6 Pooled odds ratio for late AMD by history of previous cataract surgery.
Figure 6 Pooled odds ratio for late AMD by history of previous cataract surgery.CC BY · PubMed Central
Figure 7 Pooled odds ratio for late AMD by smoking status (current vs. never).
Figure 7 Pooled odds ratio for late AMD by smoking status (current vs. never).CC BY · PubMed Central
Figure 8 Pooled odds ratio for late AMD by iris color (brown vs. blue eyes).
Figure 8 Pooled odds ratio for late AMD by iris color (brown vs. blue eyes).CC BY · PubMed Central
Figure 9 Pooled odds ratio for late AMD by body mass index (obese vs. non-obese).
Figure 9 Pooled odds ratio for late AMD by body mass index (obese vs. non-obese).CC BY · PubMed Central
Figure 10 Pooled odds ratio for late AMD by hypertension (presence or absence).
Figure 10 Pooled odds ratio for late AMD by hypertension (presence or absence).CC BY · PubMed Central
Figure 11 Pooled odds ratio for late AMD by diabetes (presence or absence).
Figure 11 Pooled odds ratio for late AMD by diabetes (presence or absence).CC BY · PubMed Central
Figure 12 Pooled odds ratio for late AMD by cardiovascular disease (presence or absence).
Figure 12 Pooled odds ratio for late AMD by cardiovascular disease (presence or absence).CC BY · PubMed Central
Figure 13 Pooled odds ratio for late AMD by cerebrovascular disease (presence or absence).
Figure 13 Pooled odds ratio for late AMD by cerebrovascular disease (presence or absence).CC BY · PubMed Central
Figure 14 Pooled odds ratio for late AMD by plasma fibrinogen.
Figure 14 Pooled odds ratio for late AMD by plasma fibrinogen.CC BY · PubMed Central

Verification

Claims the paper makes

30 Own result · 15 Own method · 10 Not checked yet · 9 Own interpretation · 1 No basis given

Verify all 31 references — free account

Show all 41 claims

  • It may state two separate claims as one. 13
  • Probably not a substantial claim. 13
24 of 24
  • The paper relies on this without support.

    The 16 selected risk factors are readily measured in nonspecialist settings.

    “Following review by an expert panel (UC, AF, PM, TYW), 16 factors that were considered to be readily measured in nonspecialist settings were selected for the full systematic review.”
  • The paper relies on this without support.

    The risk factors identified as associated with cardiovascular disease are also likely to be measured and monitored in the primary care setting.

    “All of these factors are associated with cardiovascular disease and are also likely to be measured and monitored in the primary care setting.”
  • The paper relies on this without support.

    The risk factors are easily assessed through discussions with patients and do not entail a lengthy medical history taking or laboratory evaluations.

    “All of these are easily assessed through discussions with patients and do not entail a lengthy medical history taking or laboratory evaluations.”
  • The paper relies on this without support.

    Vascular diseases, including myocardial infarction, stroke, angina, and hypertension, are pathogenic factors for the development of late AMD.

    “Vascular diseases, including myocardial infarction, stroke, angina, and hypertension are thought to be pathogenic factors for the development of late AMD.”
  • The paper relies on this without support.

    Genetic testing is not readily available in general clinical practice.

    “we felt that genetic testing was not readily available in general clinical practice”
  • The paper relies on this without support.

    Ocular factors (e.g., presence of large drusen) cannot be easily ascertained by family physicians.

    “we felt they could not be easily ascertained by family physicians”
  • The paper relies on this without support.

    There are limited interventions to prevent AMD.

    “there are limited interventions to prevent AMD”
7 of 7

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

5 of 5

Citations

Cites

Show all 85 references

Research works printed but not linked: 13

  1. Despriet DD, Klaver CC, Witteman JC, Bergen AA, Kardys I, de Maat MP, et al: Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration. JAMA. 2006, 296: 301-9. 10.1001/jama.296.3.301. · DOI · Paper page
  2. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD: Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies.[see comment]. American Journal of Ophthalmology. 2003, 135 (6): 849-56. 10.1016/S0002-9394(02)02253-5. · DOI
  3. Van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, De Jong PT: The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study.[erratum appears in Arch Ophthalmol. 2003 Jul;121(7):955]. Archives of Ophthalmology. 2003, 121 (4): 519-26. 10.1001/archopht.121.4.519. · DOI · Paper page
  4. Van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, De Jong PT: The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study.[erratum appears in Arch Ophthalmol. 2003 Jul;121(7):955]. Archives of Ophthalmology. 2003, 121 (4): 519-26. 10.1001/archopht.121.4.519. · DOI · Paper page
  5. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD: Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies.[see comment]. American Journal of Ophthalmology. 2003, 135 (6): 849-56. 10.1016/S0002-9394(02)02253-5. · DOI
  6. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD: Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies.[see comment]. American Journal of Ophthalmology. 2003, 135 (6): 849-56. 10.1016/S0002-9394(02)02253-5. · DOI
  7. Klein R, Klein BE, Franke T: The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study.[see comment]. Ophthalmology. 1993, 100 (3): 406-14. · DOI
  8. Klein R, Klein BE, Franke T: The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study.[see comment]. Ophthalmology. 1993, 100 (3): 406-14. · DOI
  9. Seddon JM, Francis PJ, George S, Schultz DW, Rosner B, Klein ML: Association of CFH Y402H and LOC387715 A69S with progression of age-related macular degeneration. JAMA. 2007, 297: 1793-800. 10.1001/jama.297.16.1793. · DOI · Paper page
  10. Haines JL, Pericak-Vance MA: Rapid dissection of the genetic risk of age-related macular degeneration: achieving the promise of the genomic era. JAMA. 2007, 297: 401-2. 10.1001/jama.297.4.401. · DOI · Paper page
  11. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD: Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies.[see comment]. American Journal of Ophthalmology. 2003, 135 (6): 849-56. 10.1016/S0002-9394(02)02253-5. · DOI
  12. Klein R, Klein BE, Franke T: The relationship of cardiovascular disease and its risk factors to age-related maculopathy. The Beaver Dam Eye Study.[see comment]. Ophthalmology. 1993, 100 (3): 406-14. · DOI
  13. Van Leeuwen R, Klaver CC, Vingerling JR, Hofman A, De Jong PT: The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study.[erratum appears in Arch Ophthalmol. 2003 Jul;121(7):955]. Archives of Ophthalmology. 2003, 121 (4): 519-26. 10.1001/archopht.121.4.519. · DOI · Paper page

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Metadata

Authors
Chakravarthy, U., Wong, T. Y., Fletcher, A., Piault, E., Evans, C., Zlateva, G., Buggage, R., Pleil, A., & Mitchell, P.
Affiliations
  • Queen's University Belfast (GB)
  • The University of Melbourne (AU)
  • London School of Hygiene & Tropical Medicine (GB)
  • Pfizer (United States) (US)
  • Novartis (United States) (US)
  • The University of Sydney (AU)
Corresponding author
Chakravarthy, Usha
Venue
BMC Ophthalmology
Published
2010-12
Volume
10
Issue
1
Pages
31-31
ISSN
1471-2415 (ISSN-L)
OpenAlex
W2147322584
Cited by
842
References
85
Citations by year
2026: 44 · 2025: 60 · 2024: 53 · 2023: 74 · 2022: 67 · 2021: 70 · 2020: 52 · 2019: 42 · 2018: 56 · 2017: 61 · 2016: 38 · 2015: 50 · 2014: 69 · 2013: 43 · 2012: 48
FWCI
6.20
Type
journal article
Language
en
Open access
Locations
  • BMC Ophthalmology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • National University of Singapore (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Research Portal (Queen's University Belfast) (submittedVersion)
Funders
Pfizer
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 › Ophthalmology and Visual Impairment Studies
Keywords
age-related macular degeneration, late AMD, risk factors, cigarette smoking, cataract surgery, family history (medicine), body mass index, cardiovascular disease, hypertension, fibrinogen, age
MeSH terms
Aging, Cardiovascular Diseases, Cataract Extraction, Eye Color, Fibrinogen, Humans, Macular Degeneration, Obesity, Risk, Risk Factors, Sex Factors, Smoking, Odds Ratio, Evidence-Based Medicine, Genetic Predisposition to Disease, Racial Groups, Diabetes Complications

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