Correlation of Quantitative Measurements with Diabetic Disease Severity Utilizing Multiple En-Face OCTA Image Averaging

Purpose: To evaluate the effect of averaging en-face optical coherence tomography angiography (OCTA) images on quantitative measurements of the retinal microvasculature and their correlation to diabetic retinopathy (DR) disease severity. Design: Cross-sectional cohort study PARTICIPANTS: 105 eyes (65 patients) with 28 eyes from 19 healthy, aged-matched controls, 14 eyes from 9 diabetics without DR and 63 eyes from 37 diabetics with varying levels of DR. Methods: Spectral-domain OCTA images with uniform illumination, good foveal centration, and no macular edema or significant motion artifact were acquired 5 times with the 3x3 mm scan pattern on the CIRRUSTM 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec, Dublin, CA) software. En-face images of the superficial retinal layer (SRL) and deep retinal layer (DRL) were registered and averaged. Included eyes had a signal strength ≥7. Vessel length density (VLD), perfusion density (PD) and foveal avascular zone (FAZ) parameters were measured on averaged versus single OCTA images. Pearson correlation coefficient compared the two groups. Univariate and multivariate linear regression correlated quantitative metrics to DR severity and best corrected visual acuity (BCVA). Results: 84 eyes (55 patients) met the inclusion criteria. Almost uniformly, lower VLD and PD parameters were significantly associated with worse DR severity and BCVA. Multivariable linear regression for DR severity resulted in an R2 value of 0.82 and 0.77 for single and averaged groups, respectively. No variables remained significantly associated with DR severity in multivariate analysis with single images but in averaged images, increased superior SRL PD significantly predicted worse DR severity (coefficient 52.7, p=0.026). Multivariate linear regression for BCVA had an R2 value of 0.42 and 0.47 for single and averaged groups, respectively. FAZ size was not associated with DR severity when single OCTA images (p=0.98) were considered, but was highly associated when using averaged images (coefficient 6.18, p<0.001). FAZ size was predictive for logMAR BCVA with averaged images (0.21, p=0.004), but not with single images (p=0.31). Conclusions: Averaging of en-face OCTA images improves the visualization of capillaries, particularly increasing the clarity of the FAZ borders, and therefore improves the correlation of vessel density and FAZ-specific parameters to DR severity and BCVA.