COVID-19 and subsequent risk of coded diabetic retinopathy in patients with type 2 diabetes: a multicenter propensity score-matched cohort study

Abstract

Background Evidence remains limited regarding whether coronavirus disease 2019 (COVID-19) is associated with the subsequent risk of EHR-recorded diabetic retinopathy (DR) during available follow-up in patients with type 2 diabetes mellitus (T2DM). We evaluated the risk of EHR-recorded DR and clinically relevant DR subtypes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during follow-up within a maximum 5-year analytic window. Methods This retrospective multicenter cohort study used the TriNetX Global Collaborative Network. Adults with T2DM were classified into COVID-19 and control groups between January 1, 2020, and June 30, 2022. A 6-month landmark design was applied to reduce early outcome misclassification. After 1:1 propensity score matching, 773,768 patients were included in each group. The primary outcome was electronic health record (EHR)-recorded incident DR. Secondary outcomes included EHR-recorded DR subtypes (non-proliferative DR, proliferative DR, and diabetic macular edema) and glycemic events, including hyperglycemia (glucose ≥180 mg/dL), poor glycemic control (HbA1c ≥9%), and hypoglycemia (glucose <70 mg/dL). Secondary and supportive analyses were exploratory and were not adjusted for multiplicity. Results Median follow-up was 1,487 days in the COVID-19 group and 1,634 days in controls. EHR-recorded incident DR occurred more frequently in the COVID-19 group than in the control group (2.17% vs. 1.64%; absolute risk difference, 0.53 percentage points; hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.48–1.55; p<0.001). COVID-19 was also associated with higher risks of non-proliferative DR (HR, 1.53; 95% CI, 1.49–1.58), proliferative DR (HR, 1.67; 95% CI, 1.57–1.78), and diabetic macular edema (HR, 1.75; 95% CI, 1.67–1.83). In addition, COVID-19 was associated with increased risks of glycemic events. The associations remained consistent across sensitivity analyses, including survivor-only, healthcare-visit-restricted, eye-care-visit-restricted, 1-year landmark, and 2-year landmark models. Exploratory severe-COVID analysis showed a similar direction of association. Conclusions Among adults with T2DM, COVID-19 was associated with an increased risk of EHR-recorded incident DR, including coded vision-threatening subtypes (proliferative DR and diabetic macular edema), during follow-up. These findings suggest a possible association between COVID-19 and subsequent EHR-recorded DR during available follow-up, although residual confounding and differential ophthalmic surveillance cannot be excluded.