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. 2023 Jul 1;141(7):658-666.
doi: 10.1001/jamaophthalmol.2023.2098.

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections

Sidra Zafar  1 , Annette Walder  2 , Salim Virani  2   3 , Kristin Biggerstaff  4   5 , Silvia Orengo-Nania  4   5 , Jonathan Chang  6 , Roomasa Channa  6
Affiliations

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections

Sidra Zafar et al. JAMA Ophthalmol. .

Abstract

Importance: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups.

Objective: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes.

Design, setting, and participants: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and December 31, 2012, were identified. Data were then extracted on incident systemic adverse events among this patient cohort from January 1, 2013, to December 31, 2017. All individuals with diabetes who did and did not receive anti-VEGF injections were included. Patients with a history of prior systemic adverse events and those who received an intravitreal injection between January 1, 2011, and December 31, 2012, were excluded. Data were analyzed from October 2019 to March 2023.

Exposure: Anti-VEGF injection.

Main outcomes and measures: Proportion of patients with any incident systemic adverse event, acute myocardial infarction, cardiovascular disease, or kidney disease at 1-, 3-, and 5-year follow-up.

Results: A total of 1 731 782 patients (mean [SD] age, 63.8 [12.3] years; 1 656 589 [95.7%] male) with type 2 diabetes were included. DR was present in 476 013 (27.5%), and 14 022 (0.8%) received anti-VEGF injections. Of the total number of patients with type 2 diabetes, 321 940 (18.6%) developed systemic adverse events between 2013 and 2017. The 5-year cumulative incidence of any systemic adverse event was 37.0% (5187/14 022) in the injection group vs 18.4% (316 753/1 717 760) in the noninjection group (P < .001). Anti-VEGF injections were independently associated with a higher likelihood of developing any systemic adverse event (odds ratio, 1.8; 95% CI, 1.7-1.9) when controlling for age, race, sex, ethnicity, tobacco use, severity of DR, Deyo-Charlson Comorbidity Index score, mean hemoglobin A1c, total number of injections, and statin use.

Conclusion and relevance: In this study, intravitreal anti-VEGF injections were independently associated with a higher likelihood of systemic adverse events among patients with diabetes.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Virani reported grants from Department of Veterans Affairs, National Institutes of Health, and Tahir and Jooma Family Research grant as well as honoraria from the American College of Cardiology for serving as Associate Editor for Innovations outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Proportion of Patients Who Developed Systemic Adverse Events at Years 1, 3, and 5 of Follow-up in the Whole Cohort
See this image and copyright information in PMC

Comment in

References

    1. Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;3(1):1. doi:10.1186/s40842-016-0039-3 - DOI - PMC - PubMed
    1. US Centers for Disease Control and Prevention . National diabetes statistics report 2020. Accessed February 23, 2023. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-stat...
    1. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17. doi:10.1186/s40662-015-0026-2 - DOI - PMC - PubMed
    1. Lazarus A, Keshet E. Vascular endothelial growth factor and vascular homeostasis. Proc Am Thorac Soc. 2011;8(6):508-511. doi:10.1513/pats.201102-021MW - DOI - PubMed
    1. Scappaticci FA, Skillings JR, Holden SN, et al. . Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. 2007;99(16):1232-1239. doi:10.1093/jnci/djm086 - DOI - PubMed

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