Geometric Perfusion Deficits: A Novel OCT Angiography Biomarker for Diabetic Retinopathy Based on Oxygen Diffusion

Abstract

Purpose: To develop geometric perfusion deficits (GPD), an optical coherence tomography angiography (OCTA) biomarker based on oxygen diffusion, and to evaluate its utility in a pilot study of healthy subjects and patients with diabetic retinopathy (DR).

Design: Retrospective cross-sectional study.

Methods: Commercial spectral-domain optical coherence tomography angiography (OCTA) instruments were used to acquire repeated 3 × 3-mm² and 6 × 6-mm² motion-corrected macular OCTA volumes. En face OCTA images corresponding to the superficial capillary plexus (SCP), deep capillary plexus (DCP), and full retinal projections were obtained using automatic segmentation. For each projection, the GPD percentage and the vessel density percentage, the control metric, were computed, and their values were compared between the normal and DR eyes. The repeated OCTA acquisitions were used to assess the test-retest repeatability of the GPD and vessel density percentages.

Results: Repeated OCTA scans of 15 normal eyes and 12 DR eyes were obtained. For all en face projections, GPD percentages were significantly higher in DR eyes than in normal eyes; vessel density percentages were significantly lower in all but 1 projection (DCP). Large GPD areas were used to identify focal perfusion deficits. Test-retest analysis showed that the GPD percentage had superior repeatability than the vessel density percentage in most cases. A strong negative correlation between the GPD percentage and the vessel density percentage was also found.

Conclusions: Geometric perfusion deficits, an OCTA biomarker based on oxygen diffusion, provides a quantitative metric of macular microvascular remodeling with a strong physiological underpinning. The GPD percentage may serve as a useful biomarker for detecting and monitoring DR.

FIGURE 1.

Schematic of a skeletonized capillary network. (Top row) Ground truth network. (Middle row) The same network but with an artifactual discontinuity (white circle). In the intercapillary area analysis (left column), the discontinuity leads to the merging of 2 adjacent regions into a single, markedly enlarged intercapillary area. In contrast, the effect of this discontinuity is insignificant in the perfusion distance map (middle plot). (Bottom row) Hypothetical focal lesion characterized by displaced vessels. The vessel density analysis will not detect this hypothetical lesion, as the linear or area vessel density remains mostly unchanged for the region (right column); however, the capillary perfusion distance analysis proportionately detects these focal lesions (center-bottom plot).

FIGURE 2.

Representative capillary perfusion distance and vessel density maps of 4 representative subjects, generated by using SCP, DCP, and full retinal OCTA projections from 3 × 3-mm² macular scans, respectively. (Rows 1, 3, and 5) Perfusion distance maps. GPD areas (where capillary perfusion distance d was > 30 μm) and FAZ are highlighted using pseudocolor based on capillary perfusion distance. (Rows 2, 4, and 6) Vessel density maps retrieved from Optovue software. DCP = deep capillary plexus; FAZ = foveal avascular zone; GPD = geometric perfusion deficit; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.

FIGURE 3.

Scatter plots show repeated measurements of GPD percentages and vessel density percentages for each subject by using SCP, DCP, and full retinal OCTA projections from 3 × 3-mm² macular scans. Filled circles = normal eyes; open circles = eyes diagnosed with diabetic retinopathy. DCP = deep capillary plexus; GPD = geometric perfusion deficit; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.

FIGURE 4.

Bar plot shows GPD percentage and vessel density percentage calculated using SCP, DCP, and full retinal OCTA projections, respectively. Eyes are subdivided into 3 groups: normal, NPDR, and PDR. All 3 × 3-mm² macular OCTA scans are included. DCP = deep capillary plexus; GPD = geometric perfusion deficit; NPDR = nonproliferative diabetic retinopathy; PDR proliferative diabetic retinopathy; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.

FIGURE 5.

Bar plot show GPD percentages and vessel density percentages calculated using SCP, DCP, and full retinal OCTA projections, respectively. Eyes are subdivided into 3 groups: normal, NPDR, and PDR. Only 3 × 3 mm² macular OCTA scans with quality index, Q ≥ 5, are included. DCP = deep capillary plexus; GPD = geometric perfusion deficit; NPDR = nonproliferative diabetic retinopathy; PDR proliferative diabetic retinopathy; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.

FIGURE 6.

Focal changes are represented by the sum of the largest GPD areas, calculated using all 3 × 3-mm² macular OCTA scans. Shaded area indicates sum of 10 largest GPD areas. Full height indicates sum of 20 largest GPD areas. DCP = deep capillary plexus; GPD = geometric perfusion deficit; NPDR = nonproliferative diabetic retinopathy; OCTA = optical coherence tomography angiography; PDR = proliverative diabetic retinopathy; SCP = superficial capillary plexus

FIGURE 7.

Correlation between the GPD percentages and vessel density percentages, calculated using all 3 × 3-mm² macular OCTA scans. Dashed line indicates linear regression; ρ = Pearson correlation coefficient; DCP = deep capillary plexus; GPD = geometric perfusion deficit; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.

FIGURE 8.

Scatter plots show repeated measurements of GPD percentages and vessel density percentages for each subject using the SCP OCTA projection from 6 × 6-mm² macular scans. The GPD and vessel density percentages were calculated, respectively, on 3 subregions: the parafovea, that is, between the 1- and 3-mm-diameter ETDRS circle; the perifoveal, that is, between the 3- and 6-mm-diameter ETDRS circle; and the combined para- and perifovea, that is, between the 1- and 6-mm ETDRS circle. Vessel density percentages in the combined para- and perifoveal regions were not available in the Optovue software and are not shown. Filled circles = normal eyes; open circles = eyes diagnosed with diabetic retinopathy. ETDRS = Early Treatment Diabetic Retinopathy Study; GPD = geometric perfusion deficit; OCTA = optical coherence tomography angiography; SCP = superficial capillary plexus.