Nonperfusion Area and Other Vascular Metrics by Wider Field Swept-Source OCT Angiography as Biomarkers of Diabetic Retinopathy Severity

PURPOSE: To study the wider field (WF) swept-source OCT angiography (SS-OCTA) metrics, especially the nonperfusion area (NPA), in the diagnosing and staging of diabetic retinopathy (DR). DESIGN: Cross-sectional observational study (November 2018 to September 2020). PARTICIPANTS: A total of 473 eyes of 286 patients (69 eyes of 49 control patients and 404 eyes of 237 diabetic patients). METHODS: We imaged using 6 × 6 mm and 12 × 12 mm angiograms on WF SS-OCTA. Images were analyzed using the ARI Network and FIJI ImageJ. Mixed effects multiple regression models and receiver operating characteristic (ROC) analysis were used for statistical analyses. MAIN OUTCOME MEASURES: Quantitative metrics such as vessel density (VD); vessel skeletonized density (VSD); foveal avascular zone (FAZ) area, circularity, and perimeter; and NPA in DR and their relative performance for its diagnosis and grading. RESULTS: Among patients with diabetes (median age, 59 years), 51 eyes had no DR, 185 eyes (88 mild, 97 moderate-severe) had nonproliferative DR (NPDR), and 168 eyes had proliferative DR (PDR). Trend analysis revealed a progressive decline in superficial capillary plexus (SCP) VD and VSD, and increased NPA with increasing DR severity. Additionally, there was a significant reduction in deep capillary plexus (DCP) VD and VSD in early DR (mild NPDR), but the progressive reduction in advanced DR stages was not significant. The NPA was the best parameter to diagnose DR (area under the curve [AUC], 0.96), whereas all parameters combined on both angiograms efficiently diagnosed (AUC, 0.97) and differentiated between DR stages (AUC range, 0.83–0.97). The presence of diabetic macular edema was associated with reduced SCP and DCP VD and VSD within mild NPDR eyes, whereas increased VD and VSD in SCP were observed in the moderate-severe NPDR group. CONCLUSIONS: Our work highlights the importance of NPA, which can be measured more readily and easily with WF SS-OCTA compared with fluorescein angiography. It is quick and noninvasive, and thus can be an important adjunct for DR diagnosis and management. In our study, a combination of all OCTA metrics on both 6 × 6 mm and 12 × 12 mm angiograms had the best diagnostic accuracy for DR and its severity. Further longitudinal studies are needed to assess NPA as a biomarker for progression or regression of DR severity.