Deep Capillary Nonperfusion on OCT Angiography Predicts Complications in Eyes with Referable Nonproliferative Diabetic Retinopathy

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.

Keywords: Deep capillary plexus; Diabetic retinopathy; Nonproliferative diabetic retinopathy; OCT angiography; Retina.

Figure 1.. Determination of geometric perfusion deficits (GPD) from OCTA images.

Columns from left to right represent superficial (SCP), middle (MCP), and deep capillary plexuses (DCP). GPDs (red areas) were determined as areas greater than 30 μm away from the center of the nearest blood vessel, excluding the foveal avascular zone as it represents a physiologic area of nonperfusion.

Figure 2.. Cumulative frequency plots of deep capillary plexus (DCP) geometric perfusion deficits (GPDs) and vessel densities (VD) in patients with and without clinically significant outcomes at 1 year.

Gray dots indicate patients with clinically significant outcomes (“Complications”); black dots are those without (“No complications”). Each point corresponds to the percentile rank for the OCTA parameter value in the specified population. Red lines indicate the cutoff values for the OCTA parameters that maximized sensitivity and specificity, based on Youden’s index. (A) Plot for DCP GPD. (B) Plot for DCP VD.

Figure 3.. OCTA vessel parameters in middle (MCP) and deep capillary plexuses (DCP) are more predictive of 1-year clinically significant outcomes than superficial (SCP) parameters.

ROC curves for each parameter are presented in the top row, with corresponding precision-recall (PR) curves in the bottom row. (A and C) ROC and PR curves for geometric perfusion deficits in superficial (SCP; red), middle (MCP; blue), and deep capillary plexuses (DCP; black). (B and D) ROC and PR curves for vessel densities in SCP (red), MCP (blue), and DCP (black). Reference lines assuming random assignment are indicated as gray dashed lines. P-values indicate pairwise comparisons of ROC curves with Bonferroni correction for multiple comparisons. AUC = area under ROC curve; AUPRC = area under PR curve; SN = sensitivity; SP = specificity.

Figure 4.. After adjusting significant OCTA parameters for sex, baseline corrected VA, and baseline NPDR severity, models show improved accuracy in predicting clinically significant outcomes.

ROC curves for each parameter are presented in the top row, with corresponding precision-recall (PR) curves in the bottom row. Columns correspond to each OCTA parameter, with middle capillary plexus (MCP) geometric perfusion deficits (GPD), deep capillary plexus (DCP) GPD, MCP vessel density (VD), and DCP VD from left to right. AUC = area under ROC curve; AUPRC = area under PR curve; SN = sensitivity; SP = specificity.