Towards an Era of Oculomics: The Relationship Between Baseline Severity of Diabetic Retinopathy and Risk of Mortality

PURPOSE: To assess whether baseline diabetic retinopathy (DR) severity is associated with mortality after accounting for sociodemographic and clinical factors. DESIGN: Retrospective cohort study. PARTICIPANTS: 524,687 patients with diabetes mellitus (DM) receiving care at health systems in the Sight Outcomes Research Collaborative (SOURCE) consortium, 2010-2023. METHODS: Clinical data from electronic health records of patients with DM were linked to mortality data from the National Death Index. Patients were categorized at their initial eyecare visit into six groups based on the level of DR in the more affected eye: DM without DR; non-proliferative DR (NPDR) without diabetic macular edema (DME); NPDR with DME; proliferative DR (PDR) without DME; PDR with DME; and unspecified DR severity. Cox regression modeling assessed the hazard of mortality associated with baseline DR severity, adjusting for sociodemographic and clinical factors, such as glycosylated hemoglobin. MAIN OUTCOME MEASURES: Hazard of mortality with 95% confidence intervals (CIs). RESULTS: The mean age was 59.1±16 years; 283,465 patients (54.0%) were female, 95,160 (18.1%) were Black, 66,547 (12.7%) were Latinx, and 306,104 (58.3%) were White. A total of 36,674 patients (7.0%) died over a mean 5.4±4.1 years of follow-up. After adjustment for potential confounders, compared to patients with DM without DR, those with NPDR without DME (HR:1.34; 95%CI:1.29-1.39) had a 34% increased hazard of death, those with NPDR with DME (HR:1.31; 95%CI:1.20-1.43) had a 31% increased hazard of death, those with PDR without DME (HR:2.28; 95%CI:2.17-2.39) had a 128% increased hazard of death, and those with PDR and DME (HR:1.87; 95%CI:1.72-2.05) had an 87% increased hazard of death. Older age, male sex, and residence in a less affluent community were also associated with increased hazard of death (p<0.01 for all). CONCLUSIONS: Patients with NPDR and PDR with or without DME are at higher risk of death over an average of 5 years of follow-up relative to diabetics without DR. These associations remain after adjusting for potential confounders. Eyecare professionals should be incentivized to communicate DR severity status to other medical professionals, as this may serve as an important opportunity to identify and address patients' medical comorbidities that may increase their mortality risk.