Abstract
Purpose:
To determine whether combining quantitative optical coherence tomography angiography (OCTA) parameters can achieve high sensitivity and specificity to distinguish eyes with nonproliferative diabetic retinopathy (NPDR) from those with proliferative diabetic retinopathy (PDR) as well as eyes with diabetes and no DR (NoDR) from those with clinical DR (any DR).
Methods:
This cross-sectional study included 28 eyes (17 patients) with NoDR, 54 eyes (34 patients) with NPDR, and 56 eyes (36 patients) with PDR. OCTA images were processed to quantify the foveal avascular zone (FAZ) area, acircularity, vessel density, skeletonized vessel density, fractal dimension, and intersections and average vessel diameter for the superficial (SCP) and the deep capillary plexus (DCP). Binary logistic regression models were used to identify the OCTA parameters that best distinguished DR severity groups. The area (AUC) under the receiver operating characteristic (ROC) curves, and sensitivity and specificity were calculated for each model.
Results:
The regression model identified the SCP FAZ area, DCP vessel density, and acircularity as parameters that best distinguished between DR severity groups. ROC curves for NPDR versus PDR had an AUC of 0.845 (P < 0.001) and sensitivity and specificity of 86% and 70%, respectively. ROC curves for NoDR versus any DR showed an AUC of 0.946 (P < 0.001) with sensitivity of 89% and specificity of 96%, with comparable results when explored in males and females separately.
Conclusions:
We identified a set of OCTA parameters with high sensitivity and specificity for distinguishing between groups based on DR severity, suggesting potential clinical application for OCTA as a screening tool for DR.
Optical coherence tomography angiography (OCTA) is a new, noninvasive modality that visualizes retinal capillary blood flow without the need for intravenous dye.
1 In contrast to fluorescein angiography, OCTA uniquely visualizes individual retinal capillary plexuses, including the superficial capillary plexus (SCP), deep capillary plexus (DCP), and more recently, the middle capillary plexus (MCP).
2
Several studies have explored the relationship between individual OCTA parameters and the stage of diabetic retinopathy (DR).
3–9 Of these studies, some have looked at the SCP and DCP separately,
4,9,10 while others have examined the full-thickness slab of the retina.
6,7 These studies explored a variety of OCTA parameters, including vessel density,
9–11 skeletonized vessel density,
9,10 vessel tortuosity,
12 fractal dimensions,
4,13 adjusted flow index,
11 foveal avascular zone (FAZ) parameters,
8,14–16 and intercapillary spaces.
6 However, discrepancies exist as to which parameter and/or vascular layer is most representative of changes across DR severity levels. Bhanushali et al.,
5 using fractal analysis, explored the spacing between vessels and found that parameters in the SCP (not the DCP) were significantly different between grades of DR. In contrast, Samara et al.
9 used different parameters (vessel density and skeletonized vessel density) and found that the DCP showed a statistically significant difference between eyes with any stage of nonproliferative DR (NPDR) compared to those with proliferative DR (PDR). Furthermore, using full-thickness slabs, Salz et al.
7 showed that the perifoveal intercapillary area was significantly different when comparing healthy controls to eyes with any stage of DR, and these same parameters also showed significant differences when comparing eyes with PDR to those with NPDR.
While OCTA parameters have been studied individually, only one study has attempted to combine these parameters to differentiate eyes with and without DR.
17 Furthermore, no study has examined whether combining OCTA parameters can differentiate eyes with NPDR from those with PDR. Therefore, the aim of the present study was to narrow down the complex array of previously studied parameters to a feasible set of parameters that, combined, could differentiate eyes with NoDR from those with any DR as well as differentiate eyes with NPDR from those with PDR. The overall goal was to identify a minimal set of OCTA parameters that would have high impact in a clinical setting.
Statistical analysis was performed using a commercially available statistical software program (SPSS for Windows, version 23; IBM/SPSS, Chicago, IL, USA). One-way ANOVA was used to study each OCTA variable across the three DR severity groups (NoDR, NPDR, and PDR). Bonferroni post hoc analysis was conducted to examine the statistically significant differences. Variables that were statistically significant in the univariate analysis were included in a multivariable binary logistic regression model comparing eyes with NPDR versus PDR, using backward elimination for stepwise elimination of the nonsignificant variables from the final model. The same model was used to compare eyes with NoDR to eyes with any DR (NPDR and PDR combined). Generalized estimating equation (GEE) was used to correct for the correlation between the two eyes. We also corrected for age and sex. The receiver operating characteristic (ROC) curves were generated based on the binary logistic regression models, and summary statistics, including area under the curve (AUC), sensitivity, and specificity were calculated from the ROC curve. A value of P < 0.05 was considered statistically significant.
Supported by National Institutes of Health 1DP3DK108248 (AAF) and research instrument and software support by OptoVue, Inc., Fremont, California, United States. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Disclosure: M. Ashraf, None; P.L. Nesper, None; L.M. Jampol, None; F. Yu, None; A.A. Fawzi, None