Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

Abstract

Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes.

Design: Prospective, cross-sectional, observational study.

Participants: One hundred and forty-four eyes of 114 patients with diabetes.

Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated.

Main outcome measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity.

Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 10⁷; 95% confidence interval, 6.529 × 10²-1.053 × 10¹³; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001-1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers.

Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs.

Financial disclosures: Proprietary or commercial disclosure may be found after the references.

Keywords: APD, areas with probabilistic differences; DR, diabetic retinopathy; Diabetic retinopathy; FA, fluorescein angiography; IQR, interquartile range; IRMA, intraretinal microvascular abnormality; NPA, nonperfusion area; NPDR, nonproliferative diabetic retinopathy; NPS, nonperfusion square; NV, neovascularization; NVD, neovascularization of the disc; NVE, retinal neovascularization; Neovascularization; Nonperfusion areas; OCTA, OCT angiography; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation; RPC, radial peripapillary capillary; Semiautomatic quantification; VA, visual acuity; Widefield OCT angiography.

Figure 1

Semiautomatic assessment of nonperfusion areas on OCT angiography in 2 representative diabetic eyes. The left eye of a 32-year-old patient with no apparent retinopathy (A, C, E, G), and the left eye of a 48-year-old patient with proliferative diabetic retinopathy (B, D, F, H). A, B, The montage image of 2 en face OCT angiography images. C, D, The binary image using the edge detection function of the ImageJ software plugin. E, F, The binary image is divided into squares of 10 × 10 pixels. Magnified images of the green rectangles in panels E and F are shown in panels G and H, respectively.

Figure 2

Ratios of the nonperfusion squares in each square based on diabetic retinopathy severity. The nonperfusion square ratios in each square in eyes with each diabetic retinopathy (DR) severity grade in pseudocolored maps. The nasal quadrant is on the right-hand side. NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy.

Figure 3

Probabilistic definition of clinically significant nonperfusion areas in diabetic retinopathy (DR). A, B, C, The differences in the ratios of nonperfusion squares (NPSs) in each square between eyes with no apparent retinopathy and those with DR (A), between eyes with no apparent retinopathy and those with nonproliferative diabetic retinopathy (NPDR) (B), and between eyes with NPDR and those with proliferative diabetic retinopathy (PDR) (C). The values are obtained by subtracting the NPS ratios of a milder group from those of a more severe group. D, E, F, After thresholding with the median, the areas with probabilistic differences (APDs) in panels A, B, and C were defined as the APD(DR), APD(NPDR), and APD(PDR), respectively. G, The merged image of APD(NPDR) and APD(PDR) shows unique distributions of APDs between the groups. The nasal quadrant is shown on the right-hand side.

Figure 4

Relationship between number of nonperfusion squares (NPSs) and clinically significant nonperfusion areas. A scatter plot of the number of NPSs and the P ratios (A) and N ratios (B). Eyes with proliferative diabetic retinopathy (PDR) have higher P ratios and lower N ratios, although the number of NPSs is not necessarily high in eyes with PDR. NPDR = nonproliferative diabetic retinopathy. $\mathrm{P}\text{ratio}=\frac{\text{The}\text{number}\text{of}\text{NPSs}\text{in}\text{APD}(\text{PDR})\text{but}\text{not}\text{in}\text{APD}(\text{NPDR})}{\text{The}\text{total}\text{number}\text{of}\text{NPSs}}$$\mathrm{N}\text{ratio}=\frac{\text{The}\text{number}\text{of}\text{NPSs}\text{in}\text{APD}(\text{NPDR})\text{but}\text{not}\text{in}\text{APD}(\text{PDR})}{\text{The}\text{total}\text{number}\text{of}\text{NPSs}}$

Figure 6

Association between retinal neovascularization (NVE) and areas with probabilistic differences (APD) between eyes with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) (APD[PDR]). A, The locations of APD(PDR) and neovascularization (NV) are shown. The nasal quadrant is shown on the right-hand side. B, The directions of NVs and their distances to the nearest square in the APD(PDR) are shown. Most NVEs are within or near the APD(PDR). C, The distances between the foveal center and NVs. The NVEs in the inferotemporal and superotemporal quadrants are nearest to the foveal center and those in the nasal quadrant are furthest. The white circle represents neovascularization of the disc. The black circle represents NVEs. I = inferior; N = nasal; S = superior; T = temporal.

Figure 5

Two major patterns of location of nonperfusion areas in eyes with nonproliferative diabetic retinopathy (NPDR). A, A dendrogram of hierarchical clustering by P ratios in eyes with NPDR is shown. Unsupervised clustering divides 73 eyes with NPDR into 2 major groups: a high-P-ratio group (n = 45 eyes) and a low-P-ratio group (n = 28 eyes). The threshold of the P ratios is 0.18. B, The P ratios in eyes with proliferative diabetic retinopathy (PDR) were similar to those of eyes with NPDR in the high-P-ratio group. C, D, E, Scatter plots of eyes with or without each 4-2-1 fundus finding. Hem = > 20 intraretinal hemorrhages in each of the 4 quadrants; VB in ≥ 2 quadrants; and intraretinal microvascular abnormalities in ≥ 1 quadrants. IRMA = intraretinal microvascular abnormalities; VB = venous beading. $\mathrm{P}\text{ratio}=\frac{\text{The}\text{number}\text{of}\text{NPSs}\text{in}\text{APD}(\text{PDR})\text{but}\text{not}\text{in}\text{APD}(\text{NPDR})}{\text{The}\text{total}\text{number}\text{of}\text{NPSs}}$$\mathrm{N}\text{ratio}=\frac{\text{The}\text{number}\text{of}\text{NPSs}\text{in}\text{APD}(\text{NPDR})\text{but}\text{not}\text{in}\text{APD}(\text{PDR})}{\text{The}\text{total}\text{number}\text{of}\text{NPSs}}$