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Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction



To evaluate whether intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (nAMD) patients with prior stroke or acute myocardial infarction (AMI) are associated with increased mortality.


From 2005 to 2013, nAMD patients in the Taiwan National Health Insurance Research Database who received IVI of anti-VEGF and had a diagnosis of stroke/AMI prior to their first injections were defined as the IVI group. The mortality of the IVI group during the study period was compared to that of the non-IVI group, which consisted of nAMD patients who had prior stroke/AMI but were never exposed to anti-VEGF. The IVI group and the non-IVI group were 1–4 matched according to propensity score (PS), which was derived from age, sex, date of stroke/AMI and comorbidities. PS-adjusted Cox regression analyses were used to estimate the hazard ratio (HR) for mortality associated with IVI of anti-VEGF. Subgroup analyses were also performed according to the interval between stroke/AMI and IVI (≤6 months, 6 months to 1 year, 1–2 years, >2 years).


There were 3384 individuals in the IVI group and 13,536 individuals in the non-IVI group. The IVI group had a significantly higher mortality risk (adjusted HR = 2.37; 95% confidence interval (CI), 2.14–2.62) than the non-IVI group. Subgroup analyses revealed that elevated mortality was significant when anti-VEGF was injected within 1 year after stroke/AMI.


We found an increased mortality risk associated with IVI of anti-VEGF in nAMD patients with prior stroke/AMI compared to the mortality risk of nAMD patients with prior stroke/AMD but without exposure to anti-VEGF.

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Fig. 1: Risk of mortal according to interval between stroke/AMI and IVI of anti-VEGF.

Data availability

Data are available from the National Health Insurance Research Database (NHIRD) published by Taiwan National Health Insurance (NHI) Bureau. The data utilized in this study cannot be made available in the manuscript, the supplemental files, or in a public repository due to the ‘Personal Information Protection Act’ executed by Taiwan’s government, starting from 2012. Requests for data can be sent as a formal proposal to the NHIRD ( or by email to wt.gro.irhn@drihn.


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This work was supported by the Taichung Veterans General Hospital (Grant number TCVGH-1106901B).

Author information




Y-YC, Y-JL and Y-FY were involved in research design. Y-YC, Y-FY and PC were responsible for data collection. Y-YC, Y-JL and PC were involved in analysis and interpretation. Y-YC was responsible for manuscript preparation.

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Correspondence to Yu-Yen Chen.

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The authors declare that they have no conflict of interest.

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This study was approved by the ethical committee of National Yang-Ming University Hospital (2015A018).

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Chen, YY., Lai, YJ., Yen, YF. et al. Increased mortality after intravitreal injections of anti-VEGF for neovascular AMD among patients with prior stroke or acute myocardial infarction. Eye (2021).

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