Age-Related Macular Degeneration and Mortality: A Systematic Review and Meta-Analysis

ABSTRACT

Purpose: Age-related macular degeneration (AMD) is the leading cause of severe, irreversible vision loss in older adults. Evidence for an association between AMD and mortality remains inconclusive despite evidence for an association with cardiovascular and inflammatory diseases. We aim to compare all-cause, cardiovascular and cancer mortality between those with early or late AMD and control study participants.

Methods: A protocol was registered at PROSPERO (CRD42015020622). A systematic search of Medline (Ovid), PubMed, and Embase (Ovid) was conducted on 6 June 2015. Reference lists from identified studies and four clinical trial registries were searched for additional studies. Participants were required to be over the age of 40 years, and AMD status must have been objectively assessed. The Risk Of Bias In Non-Randomized Studies – of Interventions (ROBINS-I) tool was used to assess the risk of bias. Random-effects meta-analyses were performed.

Results: A total of 12 reports from 10 studies were included in the meta-analysis. Late AMD was associated with elevated rates of all-cause (nine studies, hazard ratio (HR) 1.20, 95% confidence interval, CI, 1.02–1.41) and cardiovascular mortality (six studies, HR 1.46, 95% CI 1.13–1.98), but early AMD was not (all-cause mortality, 10 studies, HR 1.06, 95% CI 0.98–1.14; cardiovascular mortality, five studies, HR 1.12, 95% CI 0.96–1.31). There was no evidence of an association between early or late AMD and cancer mortality (early AMD, three studies, HR 1.17, 95% CI 0.78–1.75; late AMD, three studies, HR 1.01, 95% CI 0.77–1.33).

Conclusion: Late AMD is associated with increased rates of all-cause and cardiovascular mortality, suggesting shared pathways between late AMD and systemic disease.

KEYWORDS:

• Age-related macular degeneration
• cancer
• cardiovascular disease
• meta-analysis
• mortality
• survival

Supplemental materials

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Acknowledgments

The authors are grateful to Professor Hugh Taylor for granting access to the Melbourne Vision Impairment Project data and to Dr Emily Chew and Ms Elvira Argon for providing additional data from the Age-related Eye Diseases Study group.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the writing and content of this article.

Funding

This work was supported by an Australian Postgraduate Award and a studentship courtesy of the Victorian Centre for Biostatistics (NHMRC: Centre of Research Excellence grant 1035261) to MBM; the Lloyd and Kathleen Ansell Ophthalmology Foundation and the Mankiewicz-Zelkin Fellowship of the University of Melbourne to RPF; and CERA receives operational infrastructure support from the Victorian government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Additional information

Funding

This work was supported by an Australian Postgraduate Award and a studentship courtesy of the Victorian Centre for Biostatistics (NHMRC: Centre of Research Excellence grant 1035261) to MBM; the Lloyd and Kathleen Ansell Ophthalmology Foundation and the Mankiewicz-Zelkin Fellowship of the University of Melbourne to RPF; and CERA receives operational infrastructure support from the Victorian government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.