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The purpose of this study was to investigate changes in total retinal blood flow (RBF) using Doppler Fourier Domain Optical Coherence Tomography (Doppler FD-OCT) in response to the manipulation of systemic partial pressure of CO2 (PETCO2). Double circular Doppler blood flow scans were captured in nine healthy individuals (mean age ± standard deviation: 27.1 ± 4.1, six males) using the RTVue(™) FD-OCT (Optovue). PETCO2 was manipulated using a custom-designed computer-controlled gas blender (RespirAct(™)) connected to a sequential gas delivery rebreathing circuit. Doppler FD-OCT measurements were captured at baseline, during stages of hypercapnia (+5/+10/+15 mmHg PETCO2), return to baseline and during stages of hypocapnia (-5/-10/-15 mmHg PETCO2). Repeated measures analysis of variance (reANOVA) and Tukeys post hoc analysis were used to compare Doppler FD-OCT measurements between the various PETCO2 levels relative to baseline. The effect of PETCO2 on TRBF was also investigated using linear regression models. The average RBF significantly increased by 15% (P < 0.0001) with an increase in PETCO2 and decreased significantly by 10% with a decrease in PETCO2 (P = 0.001). Venous velocity significantly increased by 3.11% from baseline to extreme hypercapnia (P < 0.001) and reduced significantly by 2.01% at extreme hypocapnia (P = 0.012). No significant changes were found in the average venous area measurements under hypercapnia (P = 0.36) or hypocapnia (P = 0.40). Overall, increased and decreased PETCO2 values had a significant effect on RBF outcomes (P < 0.002). In healthy individuals, altered end-tidal CO2 levels significantly changed RBF as measured by Doppler FD-OCT.

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 phaseunwrapping 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 visiblelight 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. [ABSTRACT FROM AUTHOR]

An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2 x 2 mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4 ± 6.7 µl/min for healthy control and 34.7 ± 7.6 µl/min for glaucomatous participants (p-value µ 0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement. [ABSTRACT FROM AUTHOR]

Purpose: To investigate grader learning effect and to quantify intergrader reproducibility of Doppler Spectral-Domain Optical Coherence Tomography (SD-OCT) derived retinal blood flow measurements. Methods: Fifteen healthy young subjects (mean age 28.44; SD 3 years) underwent Doppler SD-OCT scans of one eye using the circumpapillary double circular scan protocol of the Optovue RTVue by one of two experienced operators. One trained (i.e. having undergone certification) and one novice (i.e. preliminary training comprising five standard practice data sets) individual then graded a standardized set of scans, consisting of 15 data sets (session 1) using custom Doppler Optical Coherence Tomography of Retinal Circulation (DOCTORC) software. One week later (session 2), the novice grader underwent further training by grading an additional 15 practice data sets and then both graders subsequently regraded the original 15 data sets. Results: Measurements achieved by a novice grader during session 1 showed a trend to be higher in terms of total retinal venous blood flow (TRBF) and also to be significantly (p = 0.03) higher for venous area, compared with a trained grader. Session 2 results were not significantly different for either grader. The mean TRBF for session 2 for the trained and novice grader was 45.29 ± 9.28 (il/min and 44.39 ± 7.36 (il/min, respectively. The coefficient of repeatability (COR) of session 2 TRBF values between the trained and novice grader was 8.09 μl/min. Conclusions: There is a grader learning effect which impacts the venous area measurements. Reproducible and repeatable retinal blood flow measurements were achieved among trained graders using DOCTORC software. [ABSTRACT FROM AUTHOR]

Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. However, the role of IOP in glaucoma progression, as well as retinal physiology in general, remains incompletely understood. We demonstrate the use of visible light optical coherence tomography to measure retinal responses to acute IOP elevation in Brown Norway rats. We monitored retinal responses in reflectivity, angiography, blood flow, oxygen saturation ( sO 2 ), and oxygen metabolism over a range of IOP from 10 to 100 mmHg. As IOP was elevated, nerve fiber layer reflectivity was found to decrease. Vascular perfusion in the three retinal capillary plexuses remained steady until IOP exceeded 70 mmHg and arterial flow was noted to reverse periodically at high IOPs. However, a significant drop in total retinal blood flow was observed first at 40 mmHg. As IOP increased, the venous sO 2 demonstrated a gradual decrease despite steady arterial sO 2 , which is consistent with increased arterial-venous oxygen extraction across the retinal capillary beds. Calculated total retinal oxygen metabolism was steady, reflecting balanced responses of blood flow and oxygen extraction, until IOP exceeded 40 mmHg, and fell to 0 at 70 and 80 mmHg. Above this, measurements were unattainable. All measurements reverted to baseline when the IOP was returned to 10 mmHg, indicating good recovery following acute pressure challenge. These results demonstrate the ability of this system to monitor retinal oxygen metabolism noninvasively and how it can help us understand retinal responses to elevated IOP.

Purpose: The purpose of this study was to determine the within-session variability and between-session repeatability of spectral Fourier-domain optical coherence tomography (Doppler FD-OCT) Doppler retinal blood flow measurements in young and elderly subjects., Methods: Doppler FD-OCT blood flow was measured using the RTVue system. One eye of each of 20 healthy young (24.7 ± 2.7 years) and 16 healthy elderly (64.6 ± 5.1 years) subjects was randomly selected, and the pupil was dilated. The double circular scanning pattern of the RTVue was employed. Six Doppler FD-OCT measurements (i.e., each separate measurement comprising an upper and a lower nasal pupil scan) were acquired at each session. Measurements were repeated approximately 2 weeks later. Total retinal blood flow was calculated by summing flow from all detectable venules surrounding the optic nerve head. The coefficient of variation (COV) and coefficient of repeatability (COR) were calculated for each individual., Results: The individual COVs for retinal blood flow for young subjects ranged from 0.4% to 20.4% (median 7.5%) and for the elderly subjects ranged from 0.6% to 34.6% (median 9.2%). The group mean CORs for retinal blood flow for young participants were 6.4 μL/min (median 5.91 μL/min, relative to a mean effect 39.8 μL/min) and for elderly subjects were 10.5 μL/min (median 9.2 μL/min, relative to a mean effect 46.4 μL/min)., Conclusions: Doppler FD-OCT gave consistent and repeatable blood flow measurements within retinal venules in normal subjects. Considering the individual variation in blood flow measurements, confidence limits for retinal hemodynamics need to be determined on an individual basis., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)