Earliest Evidence of Preclinical Diabetic Retinopathy Revealed Using Optical Coherence Tomography Angiography Perfused Capillary Density

Abstract

Purpose: To compare perfused capillary density (PCD) in diabetic patients and healthy controls using optical coherence tomography angiography (OCTA).

Methods: Forty controls, 36 diabetic subjects without clinical retinopathy (NoDR), 38 with nonproliferative retinopathy (NPDR), and 38 with proliferative retinopathy (PDR) were imaged using spectral-domain optical coherence tomography. A 3 × 3-mm full-thickness parafoveal OCTA scan was obtained from each participant. Following manual delineation of the foveal avascular zone (FAZ), FAZ area, perimeter, and acircularity index were determined. Seven consecutive equidistant 200-μm-wide annular segments were drawn at increasing eccentricities from the FAZ margin. Annular PCD (%) was defined as perfused capillary area divided by the corresponding annulus area after subtraction of noncapillary blood vessel areas. Nonparametric Kruskal-Wallis testing with Bonferroni correction was performed in pairwise comparisons of group PCD values.

Results: The NoDR group demonstrated consistently higher PCD compared to the control group in all 7 annuli, reaching statistical significance (36.6% ± 3.30% vs 33.6% ± 3.98%, P = .034) at the innermost annulus (FAZ margin to 200 μm out). The NPDR and PDR groups demonstrated progressively decreasing PCD. Differences in FAZ metrics between the NoDR and control groups did not reach statistical significance.

Conclusions: Relative to healthy controls, increased PCD values in the NoDR group likely represent an autoregulatory response to increased metabolic demand, while the decrease in PCD that follows in NPDR and PDR results largely from an incremental loss of capillary segments. These findings, consistent with previous studies, demonstrate the potential of OCTA as a clinical tool for earlier objective detection of preclinical diabetic retinopathy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Figure 1.

OCTA image processing procedure. A) Contrast-stretched full vascular slab OCTA. B) Manual segmentation of FAZ (in yellow) and automatic segmentation of noncapillary blood vessels using global thresholding (in white). C) Automatic segmentation of capillaries (in cyan) after the removal of noncapillary blood vessels. D) Overlay of PCD map with 7 consecutive 200-µm equidistant annuli starting from the FAZ margin going outward.

Figure 2.

Boxplots of FAZ metrics. A) FAZ area, B) FAZ perimeter, and C) FAZ acircularity index. Brackets indicate statistical significant differences between corresponding study groups.

Figure 3.

Group mean PCD and noncapillary blood vessel density values measured at each annulus. The NoDR group consistently showed higher PCD values compared to the other groups including the control group. Only the 200-µm annulus showed a statistically significant increase in perfused capillary density in the NoDR group compared to the control group (arrow, P=0.034).

Figure 4.

Boxplots of PCD (left column) and noncapillary blood vessel density (right column) measured at the A & B) 200-µm, C & D) 800-µm, and E &F) 1400-µm annuli. Brackets indicate statistically significant differences between corresponding study groups.

Figure 5.

Comparison of PCD maps in a healthy control and patients with various stages of diabetic retinopathy. Left column) Contrast-stretched full vascular slab OCTA. Middle column) Corresponding capillary segmentation highlighted in cyan. Right column) Corresponding PCD maps with noncapillary blood vessels indicated in white. The 200-µm annuli are delineated in all subjects for easier comparison.