Optical Coherence Tomography Angiography-Derived Flux As a Measure of Physiological Changes in Retinal Capillary Blood Flow

Abstract

Purpose: To compare optical coherence tomography angiography (OCTA)-derived flux with conventional OCTA measures of retinal vascular density in assessment of physiological changes in retinal blood flow.

Methods: Healthy subjects were recruited, and 3 × 3-mm2 fovea-centered scans were acquired using commercially available swept-source OCTA (SS-OCTA) while participants were breathing room air, 100% O2, or 5% CO2. Retinal perfusion was quantified using vessel area density (VAD) and vessel skeleton density (VSD), as well as novel measures of retinal perfusion, vessel area flux (VAF) and vessel skeleton flux (VSF). Flux is proportional to the number of red blood cells moving through a vessel segment per unit time. The percentage change in each measure was compared between the O2 and CO2 gas conditions for images of all vessels (arterioles, venules, and capillaries) and capillary-only images. Statistical significance was determined using paired t-tests and a linear mixed-effects model.

Results: Eighty-four OCTA scans from 29 subjects were included (age, 45.9 ± 19.5 years; 14 male, 48.3%). In capillary-only images, the change under the CO2 condition was 168% greater in VAF than in VAD (P = 0.002) and 124% greater in VSF than in VSD (P = 0.004). Similarly, under the O2 condition, the change was 94% greater in VAF than in VAD (P = 0.004) and 57% greater in VSF than in VSD (P = 0.01). Flux measures showed significantly greater change in capillary-only images compared with all-vessels images.

Conclusions: OCTA-derived flux measures quantify physiological changes in retinal blood flow at the capillary level with a greater effect size than conventional vessel density measures.

Translational relevance: OCTA-derived flux is a useful measure of subclinical changes in retinal capillary perfusion.

Figure 1.

(A) Original grayscale OCTA bitmap image. (B) All-vessels binarized image derived from previous panel. (C) All-vessels skeletonized image derived from previous panel. (D) Automatic detection of arterioles and venules (highlighted in yellow). (E) Capillary-only binary image (after removal of arterioles and venules). (F) Capillary-only skeletonized image. (G) To visually illustrate the calculation of OCTA-derived perfusion measures, we present a 9 × 9-pixel sample region that covers a larger vessel from A. (H) Binarized image derived from previous panel with raw decorrelation intensity pixel values overlaid. (I) Skeletonized image derived from previous panel with raw decorrelation intensity pixel values overlaid. For the 9 × 9-pixel image in G, VAD is the number of white pixels in H divided by the total number of pixels: 27/81 = 0.33. VSD is the number of white pixels in I divided by the total number of pixels: 9/81 = 0.11. VAF is the average of pixel values in H: 6667/27 = 246.92. VSF is the average of pixel values in I: 2277/9 = 253.

Figure 2.

OCTA scans of a representative subject under three breathing conditions. Arrows highlight the change in blood perfusion between scans. This change is most evident comparing the CO₂ and O₂ images. OCTA-derived retinal perfusion measures were calculated for each scan. The bottom plot illustrates the percentage change seen in each perfusion measure in response to the CO₂ and O₂ breathing conditions relative to the room-air breathing condition.

Figure 3.

Comparison of the change in OCTA-derived VAF in all-vessels (including arterioles and venules) versus capillary-only images. Means and 95% confidence intervals of the mean are shown.

Figure 4.

Comparison of the change in OCTA-derived VAD and VAF measures in capillary-only images. Means and 95% confidence intervals of the mean are shown.