Investigators wrote that anti-vascular endothelial growth factor agents are the mainstay of treatment for diabetic retinopathy. Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups. As such, they looked at the systemic safety of intravitreal anti-VEGF agents among patients with diabetes, as part of a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse database of patients within the U.S. Veteran Health Affairs. 

All patients 18 years and older with type 2 diabetes seen at any Veterans Affairs health-care facility in the between January 1, 2011, and December 31, 2012, were identified. Data were then extracted by incident systemic adverse events among the patient cohort from January 1, 2013, to December 31, 2017. All individuals with diabetes who did and didn’t 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.

The main outcomes and measures included the proportion of patients with any incident systemic adverse event, acute myocardial infarction, cardiovascular disease or kidney disease at one-, three- and five-year follow-up.

A total of 1,731,782 patients (mean [SD] age, 63.8 [12.3] years; 1,656,589 [95.7 percent] male) with type 2 diabetes were included. Here are some of the findings:

  • DR was present in 476,013 patients (27.5 percent), and 14,022 (0.8 percent) received injections. 
  • Of the type 2 diabetes patients, 321,940 (18.6 percent) developed systemic adverse events between 2013 and 2017. 
  • The five-year cumulative incidence of any systemic adverse event was 37 percent (5,187/14,022) in the injection group vs. 18.4 percent (316,753/1,717,760) in the non-injection group (p<0.001). 
  • Anti-VEGF injections were independently associated with a higher likelihood of developing any systemic adverse event (OR, 1.8; CI, 1.7 to 1.9) when controlling for age, race, sex, ethnicity, tobacco use, severity of DR, Deyo-Charlson Comorbidity Index score, mean hemoglobin A1c, number of injections and statin use.

Though investigators found that intravitreal anti-VEGF injections were independently associated with a higher likelihood of systemic adverse events among patients with diabetes, a commentary on the study indicates that further study is warranted before any definitive conclusion can be reached.


JAMA Ophthalmol 2023; Jun 1. [Epub ahead of print].
Zafar S, Walder A, Virani S, et al. 


Diabetes, Fuchs’ Associations

Scientists assessed risk for demographic variables and other health conditions associated with Fuchs’ endothelial corneal dystrophy.

They developed a case-control algorithm based on structured electronic health record data and confirmed accuracy by individual review of charts at three Veterans Affairs Medical Centers. This algorithm was applied to the Department of VA Million Veteran Program cohort from whom sex, genetic ancestry, comorbidities, diagnostic phecodes and laboratory values were extracted. Single-variable and multiple variable logistic regression models helped determine the association of these risk factors with FECD diagnosis.

Here are some of the findings:

  • Being a FECD case was associated with female sex, European genetic ancestry and a greater number of comorbidities. 
  • Of 1,417 diagnostic phecodes evaluated, 213 had a significant association with FECD and with ocular and non-ocular conditions, including diabetes mellitus. 
  • Five of 69 laboratory values were associated with FECD, with four being consistent with diabetes mellitus. 
  • Insulin dependency and type 1 diabetes mellitus raised risk to a greater degree than type 2 diabetes mellitus, like other microvascular diabetic complications.

Scientists concluded that female sex, European ancestry and multimorbidity increased Fuchs’ endothelial corneal dystrophy risk. Endocrine/metabolic clinic encounter codes and altered patterns of laboratory values supported diabetes mellitus increasing FECD risk, and a threshold model revealed that a FECD phenotype was intensified by diabetes mellitus and potentially other health conditions that alter corneal physiology. 


Cornea 2023; May 12. [Epub ahead of print].
Nealon CL, Halladay CW, Gorman BR, et al