Abstract
OBJECTIVE: To characterize the performance of 56 parameters from electroretinography (ERG)/pupillometry, color fundus photography (FP), OCT angiography (OCTA), and ultra-widefield fluorescein angiography (UWF-FA) for predicting which subjects with nonproliferative diabetic retinopathy (NPDR) will progress to vision-threating complications (VTCs) within 48 weeks. DESIGN: A longitudinal prospective study from 44 trial sites in the United States. PARTICIPANTS: Subjects had moderate-to-severe NPDR and no center-involved diabetic macular edema. Among the 162 subjects, the mean age was 57 years and 58% were male. INTERVENTION: Although this study tested an experimental drug, there was no indication of a treatment effect. Results are analyzed over all subjects regardless of study treatment. MAIN OUTCOME MEASURES: Specialized reading centers measured 56 parameters from 4 testing modalities (ERG/pupillometry, FP, OCTA, and UWF-FA) to evaluate diabetic retinopathy (DR) status. Kaplan-Meier analysis and a Cox proportional hazards model were applied to each parameter to identify significant predictors of progression to VTC, defined as progression to proliferative DR, diabetic macular edema, or treatment thereof. RESULTS: Of the 56 parameters, the strongest predictor of progression in the following 48 weeks was the RETeval DR score, which combines ERG and pupil response. A DR score ≥26.9 had a relative risk (RR) of 5.6 (P < 0.0001). The most predictive parameter from the other modalities were UWF-FA's total ischemia index ≥0.125 with an RR of 5.3 (P < 0.0001), OCTA's foveal avascular zone area ≥0.295 mm(2) with an RR of 3.6 (P < 0.05), and FP's diabetic retinopathy severity scale ≥47 (moderate NPDR) with an RR of 2.1 (P < 0.05). CONCLUSIONS: Both functional (ERG, pupil response) and structural (FP, OCTA, UWF-FA) testing can predict progression to VTC from DR, with the DR score having the best predictive capability. These results suggest it is possible to improve the DR staging system which in turn may enable better allocation of health care resources. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.