Extravascular Motion Signal Detected by OCT Angiography Indicates Altered Vascular-Tissue Biomechanical Interactions in Glaucoma

Purpose: To report and characterize a novel extravascular motion (EVM) signal detected by optical coherence tomography angiography (OCTA) and test the hypothesis that it can be used to quantify physiologic changes in glaucomatous eyes. Methods: We used existing data from ongoing studies of unilateral experimental glaucoma (EG) in rhesus macaques (n = 47; 41 females, six males; ages 6-18 years). OCTA scans centered on the ONH (768 × 768 × 496 voxels over 15° × 15°) were manually segmented to quantify the number and length of EVM lines and classify major blood vessels in en face angiographs. Two-way ANOVA with Šídák's multiple comparisons post hoc tests and linear regression were applied for statistical analysis and hypothesis testing. Results: EVM signals manifest as isolated line segments along the fast-scanning axis (i.e., along individual B-scan lines). Their inter-B-scan spacing produced an estimate of heart rate that accurately predicts actual heart rate. EVM lines were more common adjacent to arteries compared to veins, and uncommon in non-vascular areas (P < 0.0001). They were more numerous at higher intraocular pressure (IOP) and in EG compared to fellow control eyes (P < 0.0001), even after accounting for IOP at the time of scan acquisition (P < 0.01). EVM count or length was not correlated with EG severity or age at the time of the scan, but EVM timing did correlate with heart rate (P < 0.0001). Conclusions: We report a novel OCTA EVM signal representing pulsatile tissue displacement caused by the cardiac cycle, most commonly adjacent to arteries, more prominent in EG eyes, and strongly influenced by IOP, which may be indicative of altered biomechanical properties of the vasculature and/or paravascular retinal parenchyma.