Time to Progression to Proliferative Diabetic Retinopathy in Patients With Type 2 Diabetes

Abstract

Importance: Risk stratification of patients at risk of progression to proliferative diabetic retinopathy (PDR) enables earlier detection and more efficient allocation of health care resources.

Objective: To develop survival models to predict progression to PDR in patients with type 2 diabetes.

Design, setting, and participants: This prognostic study used deidentified electronic health record data from the University of California (UC) Health Data Warehouse (UCHDW) from March 1, 2012, to July 3, 2024. The UCHDW consists of data on 10 million patients receiving care from the UC Health system. Patients aged 18 years or older with nonproliferative diabetic retinopathy (NPDR) or diabetic macular edema (DME) and type 2 diabetes were included. Patients who had a diagnosis of PDR before the index date or failed to meet the look-back criterion (≥1 outpatient visit at least 1 year before index date) were excluded. The cohort was divided into a development set and an external test set by UC Health site. The development set was split into an internal training set (75%) and test set (25%). The 3 survival models used (Cox proportional hazards regression, Cox with least absolute shrinkage and selection operator [LASSO] regression, and random survival forest [RSF]) were trained on the internal training set and validated on the internal and external test sets.

Exposures: Risk factors included demographics, eye-related diagnoses, systemic comorbidities, laboratory data, vital signs, medications, and procedures.

Main outcomes and measures: The primary outcome was time from the index date (first diagnosis of diabetic retinopathy recorded in the UCHDW) to the first PDR diagnosis or the last in-person visit. Harrell concordance index (C index) was used to assess the model's predictive performance.

Results: Among 7739 participants (mean [SD] age, 66.7 [11.4] years; 4116 males [53.2%]; 1548 Asian [20.0%], 744 Black or African American [9.6%], 1665 Hispanic or Latino [21.5%]; 3278 White [42.4%], 1286 other [16.6%] individuals) were included. Of these patients, 723 (9.3%) had PDR progression with a mean (SD) progression time of 1.89 (2.09) years. All survival models had good predictive discrimination (C index, 0.73-0.75) for the internal and external test sets. The Cox proportional hazards regression and RSF models had good calibration for up to 2 years. Key independent risk factors summarized across all models were baseline age, race, ethnicity, DME, NPDR severity, mean hemoglobin A1c level, and diabetic nephropathy.

Conclusions and relevance: The survival models developed and validated in this study demonstrated good discrimination across internal and external test sets and good calibration up to 2 years. These models have the potential to enable earlier identification, personalized follow-up, and targeted resource allocation for high-risk patients.