Abstract
OBJECTIVE: To evaluate the ability of capillary nonperfusion parameters on OCT angiography (OCTA) to predict the development of clinically significant outcomes in eyes with referable nonproliferative diabetic retinopathy (NPDR). DESIGN: Prospective longitudinal observational study. SUBJECTS: In total, 59 patients (74 eyes) with treatment-naive moderate and severe (referable) NPDR. METHODS: Patients were imaged with OCTA at baseline and then followed-up for 1 year. We evaluated 2 OCTA capillary nonperfusion metrics, vessel density (VD) and geometric perfusion deficits (GPDs), in the superficial capillary plexus, middle capillary plexus (MCP), and deep capillary plexus (DCP). We compared the predictive accuracy of baseline OCTA metrics for clinically significant diabetic retinopathy (DR) outcomes at 1 year. MAIN OUTCOME MEASURES: Significant clinical outcomes at 1 year, defined as 1 or more of the following-vitreous hemorrhage, center-involving diabetic macular edema, and initiation of treatment with pan-retinal photocoagulation or anti-VEGF injections. RESULTS: Overall, 49 patients (61 eyes) returned for the 1-year follow-up. Geometric perfusion deficits and VD in the MCP and DCP correlated with clinically significant outcomes at 1 year (P < 0.001). Eyes with these outcomes had lower VD and higher GPD, indicating worse nonperfusion of the deeper retinal layers than those that remained free from complication. These differences remained significant (P = 0.046 to < 0.001) when OCTA parameters were incorporated into models that also considered sex, baseline corrected visual acuity, and baseline DR severity. Adjusted receiver operating characteristic curve for DCP GPD achieved an area under the curve (AUC) of 0.929, with sensitivity of 89% and specificity of 98%. In a separate analysis focusing on high-risk proliferative diabetic retinopathy outcomes, MCP and DCP GPD and VD remained significantly predictive with comparable AUC and sensitivities to the pooled analysis. CONCLUSIONS: Evidence of deep capillary nonperfusion at baseline in eyes with clinically referable NPDR can predict short-term DR complications with high accuracy, suggesting that deep retinal ischemia has an important pathophysiologic role in DR progression. Our results suggest that OCTA may provide additional prognostic benefit to clinical DR staging in eyes with high risk.