Total Retinal Blood Flow in a Nonhuman Primate Optic Nerve Transection Model Using Dual-Beam Bidirectional Doppler FD-OCT and Microsphere Method

Abstract

Citation: Told R, Wang L , Cull G, et al. Total retinal blood flow in a nonhuman primate optic nerve transection model using dual-beam bidirectional Doppler FD-OCT and microsphere method. Invest Ophthalmol Vis Sci. 2016;57:143257: -144057: . DOI:10.1167 PURPOSE. We validated noninvasive Doppler-optical coherence tomography (OCT) blood flow measurements against the terminal microsphere method in a surgical induced optic nerve transection nonhuman primate model. METHODS.In 6 nonhuman primates, total retinal blood flow (TRBF) was measured with a custom-built dual-beam bidirectional Doppler Fourier Domain (FD)-OCT. Peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by Spectralis spectral-domain (SD)-OCT. Measurements were performed every 10 to 15 days before and after unilateral optic nerve transection (ONT) until RNFLT was reduced by more than 40% from baseline. Before the animals were killed, TRBF was measured using the microsphere technique. RESULTS.A significant correlation between all arterial and venous Doppler OCT TRBF measurements was found in ONT and contralateral control eyes (both P < 0.01, n ¼ 6). The Bland-Altman analysis showed a bias of 0.57 in the ONT group and 0.02 in the contralateral control group. Also, excellent agreement was observed between Doppler OCT and microsphere measurements (P < 0.01, r ¼ 0.976, bias ¼ 0.54). After ONT, TRBF and RNFLT decreased by À51% 6 42% and À44% 6 2% (n ¼ 5), respectively. In the contralateral control eyes, TRBF and RNFLT were unchanged.CONCLUSIONS. Very good accordance was found between TRBF measurements, obtained with dual-beam bidirectional Doppler FD-OCT and the microsphere method. It also was possible to monitor changes over time in TRBF after ONT with Doppler OCT. These findings highlight the accuracy and potential of noninvasive Doppler OCT to provide valuable information for detecting early changes in ocular disease in future.

Effect of Diffuse Luminance Flicker Light Stimulation on Total Retinal Blood Flow Assessed With Dual-Beam Bidirectional Doppler OCT

“…These include in vitro experiments, 28,41 experiments at retinal vessel bifurcations, 41 as well as comparisons versus laser Doppler velocimetry 42 and invasive microsphere technology. 43 As such, it is interesting that the comparison of DOCT and DVA diameter changes in response to flicker stimulation as presented in the Appendix (Table A1) shows differences for FIGURE 6. Relative increase of CRAE and CRVE during flicker stimulation for each subject.…”

Age-Related Decline of Retinal Oxygen Extraction in Healthy Subjects

“…54,55 Finally, we need to consider the errors of Doppler OCT and spectroscopic reflectometry measurements. Doppler OCT has been validated against invasive microsphere technology in primates, 24 where eye motion can be eliminated. In humans, validation is difficult due to the absence of a gold standard technology, and the error of measurements is difficult to estimate.…”

“…20 We have developed a technique based on a two-beam approach 15,[21][22][23] that has been validated against invasive microsphere technology in nonhuman primates. 24 By combining this technique with spectroscopic measurement of oxygen saturation in retinal vessels, we were able to show that total retinal oxygen extraction (extO 2 ) can be calculated. 25,26 This provides an important step toward metabolic imaging in the retina by indicating how much oxygen is consumed in the inner retina.…”

Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy

“…Measurements were validated using in vitro experiments [17], and in vivo vs laser Doppler velocimetry [18] and invasive microsphere technology [19]. …”