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Purpose Previous studies have reported alterations in total retinal blood flow (TRBF), oxygen delivery (DO2), oxygen metabolism (MO2), and oxygen extraction fraction (OEF) due to retinal diseases. The purposes of the current study were to determine variabilities and establish normal confidence intervals (CIs) for these metrics. Methods A total of 22 healthy and 14 diabetic subjects participated in the study. Retinal vascular oxygen saturation (SO2) and TRBF were measured by oximetry and Doppler optical coherence tomography, respectively. DO2, MO2, and OEF were calculated from SO2 and TRBF measurements. Means, standard deviations (SDs), and CIs of metrics were determined in healthy subjects. Intra-visit variability was determined by the mean SDs of repeated measurements. Inter-visit variability was determined by the difference of measurements between two visits. Results TRBF was 44 ± 15 µL/min (95% CI, 37–51) in healthy subjects. Intra-visit variabilities of TRBF were 5 µL/min and 6 µL/min in healthy and diabetic subjects, respectively. Inter-visit variability of TRBF was 3 µL/min in diabetic subjects. DO2, MO2, and OEF were 8.3 ± 2.9 µLO2/min (95% CI, 7.0–9.6), 3.2 ± 0.9 µLO2/min (95% CI, 2.8–3.6), and 0.40 ± 0.08 (95% CI, 0.36–0.43), respectively, in healthy subjects. Inter-visit variabilities of DO2, MO2, and OEF were 0.6 µLO2/min, 0.1 µLO2/min, and 0.03, respectively, in diabetic subjects. Conclusions The findings established variabilities and normal baselines for TRBF, DO2, MO2, and OEF measurements in a small cohort of subjects. Translational Relevance The variability and normal baselines of retinal oxygen metrics may be useful for diagnosing and monitoring patients with retinal diseases.

Phase wrapping is a crucial issue in Doppler optical coherence tomography (OCT) and restricts its automatic implementation for clinical applications that quantify total retinal blood flow. We propose an automated phase-unwrapping technique that takes advantage of the parabolic profile of blood flow velocity in vessels. Instead of inspecting the phase shift manually, the algorithm calculates the gradient magnitude of the phase shift on the cross-sectional image and automatically detects the presence of phase wrapping. The voxels affected by phase wrapping are corrected according to the determined flow direction adjacent to the vessel walls. We validated this technique in the rodent retina using a prototype visible-light OCT and in the human retina with a commercial infrared OCT system. We believe this signal processing method may well accelerate clinical applications of Doppler OCT in ophthalmology.

PURPOSE To use multiplane en face Doppler optical coherence tomography (OCT) to measure the change in total retinal blood flow (TRBF) in response to hyperoxia. METHODS One eye of each healthy human participant (n = 8) was scanned with a commercial high-speed (70-kHz) spectral OCT system. Three repeated scans were captured at baseline and after 10 minutes of oxygen (hyperoxia) by open nasal mask. The procedure was performed twice on day 1 and once more on day 2. Blood flow of each vein was estimated using Doppler OCT at an optimized en face plane. The TRBF was summed from all veins at the optic disc. The TRBF hyperoxic response was calculated as the TRBF percent change from baseline. RESULTS Participants experienced a 23.6% ± 10.7% (mean ± standard deviation [SD]) decrease (P < 0.001, paired t-test) in TRBF during hyperoxia. The within-day repeatability of baseline TRBF was 4.1% and the between-day reproducibility was 10.9% coefficient of variation (CV). Between-grader reproducibility was 3.9% CV. The repeatability and reproducibility (pooled SD) of hyperoxic response were 6.1% and 6.4%, respectively. CONCLUSIONS The multiplane en face Doppler OCT algorithm was able to detect, in all participants, a decreased TRBF in response to hyperoxia. The response magnitude for each participant varied among repeated trials, and the averaging of multiple trials was helpful in establishing the individual response. This technique shows good potential for the clinical investigation of vascular autoregulation.