Wide-field OCTA Quantified Peripheral Nonperfusion Areas Predict the Risk of Subclinical Neovascularization

Purpose: To demonstrate the capabilities of single-shot widefield swept-source OCT angiography (SS-OCTA) in detecting subclinical retinal neovascularization (RNV), quantifying nonperfusion areas (NPAs), and exploring the relations between NPA and subclinical RNV in eyes graded as nonproliferative diabetic retinopathy (NPDR). Methods: Eyes clinically graded as moderate to severe NPDR underwent SS-OCTA imaging. Expert graders identified subclinical RNV, defined as vessels with flow signal above the internal limiting membrane on OCTA that are not visible on dilated fundus examination. This identification was based on a combination of en face OCT, en face OCTA, and cross-sectional OCTA overlaid on OCT. NPA index was calculated as a percentage of automatically quantified NPA over area in the posterior pole, the mid-periphery, and the total imaged area. Results: Totally 37 eyes including 21 had severe NPDR and 16 had moderate NPDR. Subclinical RNV was present in 14 eyes (37.8%). The eyes with RNV had significantly higher mid-peripheral and total NPA indices but not in the posterior region (mid-peripheral NPA: 31.97% ± 7.02% vs. 24.80% ± 6.60%, p =0.041; total NPA: 27.96% ± 6.36% vs. 21.61% ± 5.65%, p =0.046). The total NPA index showed the highest diagnostic accuracy for subclinical RNV detection (AUC: 0.761, with a sensitivity of 64.3% and a specificity of 87% at a cutoff value of 28.84%). Conclusion: Widefield SS-OCTA can detect subclinical RNV. The eyes with higher mid-peripheral NPA indices are more likely to have subclinical RNV, indicating that the NPA index may be a useful biomarker for identifying eyes at risk of RNV.