Predicting vision-threatening diabetic retinopathy in patients with type 2 diabetes mellitus: Systematic review, meta-analysis, and prospective validation study.

Background: Delayed diagnosis and treatment of vision-threatening diabetic retinopathy (VTDR) is a common cause of visual impairment in individuals with type 2 diabetes mellitus (T2DM). Identification of VTDR predictors is the key to early prevention and intervention, but the predictors from previous studies are inconsistent. This study aims to conduct a systematic review and meta-analysis of the existing evidence for VTDR predictors, then to develop a risk prediction model after quantitatively summarising the predictors across studies, and finally to validate the model with two Chinese cohorts. Methods: We systematically retrieved cohort studies that reported predictors of VTDR in T2DM patients from PubMed, Ovid, Embase, Scopus, Cochrane Library, Web of Science, and ProQuest from their inception to December 2023. We extracted predictors reported in two or more studies and combined their corresponding relative risk (RRs) using meta-analysis to obtain pooled RRs. We only selected predictors with statistically significant pooled RRs to develop the prediction model. We also prospectively collected two Chinese cohorts of T2DM patients as the validation set and assessed the discrimination and calibration performance of the prediction model by the time-dependent ROC curve and calibration curve. Results: Twenty-one cohort studies involving 622 490 patients with T2DM and 57 107 patients with VTDR were included in the meta-analysis. Age of diabetes onset, duration of diabetes, glycosylated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), hypertension, high albuminuria and diabetic treatment were used to construct the prediction model. We validated the model externally in a prospective multicentre cohort of 555 patients with a median follow-up of 52 months (interquartile range = 39-77). The area under the curve (AUC) of the prediction model was all above 0.8 for 3- to 10-year follow-up periods and different cut-off value of each year provided the optimal balance between sensitivity and specificity. The data points of the calibration curves for each year closely surround the corresponding dashed line. Conclusions: The risk prediction model of VTDR has high discrimination and calibration performance based on validation cohorts. Given its demonstrated effectiveness, there is significant potential to expand the utilisation of this model within clinical settings to enhance the detection and management of individuals at high risk of VTDR.