Absolute retinal blood flow in healthy eyes and in eyes with retinal vein occlusion.

PURPOSE: To measure non-invasively retinal venous blood flow (RBF) in healthy subjects and patients with retinal venous occlusion (RVO). METHODS: The prototype named AO-LDV (Adaptive Optics Laser Doppler Velocimeter), which combines a new absolute laser Doppler velocimeter with an adaptive optics fundus camera (rtx1, Imagine Eyes®, Orsay, France), was studied for the measurement of absolute RBF as a function of retinal vessel diameters and simultaneous measurement of red blood cell velocity. RBF was measured in healthy subjects (n = 15) and patients with retinal venous occlusion (RVO, n = 6). We also evaluated two softwares for the measurement of retinal vessel diameters: software 1 (automatic vessel detection, profile analysis) and software 2 (based on the use of deep neural networks for semantic segmentation of vessels, using a M2u-Net architecture). RESULTS: Software 2 provided a higher rate of automatic retinal vessel measurement (99.5 % of 12,320 AO images) than software 1 (64.9 %) and wider measurements (75.5 ± 15.7 µm vs 70.9 ± 19.8 µm, p < 0.001). For healthy subjects (n = 15), all the retinal veins in one eye were measured to obtain the total RBF. In healthy subjects, the total RBF was 37.8 ± 6.8 µl/min. There was a significant linear correlation between retinal vessel diameter and maximal velocity (slope = 0.1016; p < 0.001; r2 = 0.8597) and a significant power curve correlation between retinal vessel diameter and blood flow (3.63 × 10-5 × D2.54; p < 0.001; r2 = 0.7287). No significant relationship was found between total RBF and systolic and diastolic blood pressure, ocular perfusion pressure, heart rate, or hematocrit. For RVO patients (n = 6), a significant decrease in RBF was noted in occluded veins (3.51 ± 2.25 µl/min) compared with the contralateral healthy eye (11.07 ± 4.53 µl/min). For occluded vessels, the slope between diameter and velocity was 0.0195 (p < 0.001; r2 = 0.6068) and the relation between diameter and flow was Q = 9.91 × 10-6 × D2.41 (p < 0.01; r2 = 0.2526). CONCLUSION: This AO-LDV prototype offers new opportunity to study RBF in humans and to evaluate treatment in retinal vein diseases.

Absolute retinal blood flowmeter using a laser Doppler velocimeter combined with adaptive optics.

SIGNIFICANCE: The development of a technique allowing for non-invasive measurement of retinal blood flow (RBF) in humans is needed to understand many retinal vascular diseases (pathophysiology) and evaluate treatment with potential improvement of blood flow. AIM: We developed and validated an absolute laser Doppler velocimeter (LDV) based on an adaptive optical fundus camera that provides simultaneously high-definition images of the fundus vessels and absolute maximal red blood cells (RBCs) velocity to calculate the absolute RBF. APPROACH: This new absolute LDV is combined with the adaptive optics (AO) fundus camera (rtx1, Imagine Eyes©, Orsay, France) outside its optical wavefront correction path. A 4-s recording includes 40 images, each synchronized with two Doppler shift power spectra. Image analysis provides a vessel diameter close to the probing beam, and the velocity of the RBCs in the vessels are extracted from the Doppler spectral analysis. A combination of these values gives an average of the absolute RBF. RESULTS: An in vitro experiment consisting of latex microspheres flowing in water through a glass capillary to simulate a blood vessel and in vivo measurements on six healthy humans was done to assess the device. In the in vitro experiment, the calculated flow varied between 1.75 and 25.9 µL / min and was highly correlated (r2 = 0.995) with the flow imposed by a syringe pump. In the in vivo experiment, the error between the flow in the parent vessel and the sum of the flow in the daughter vessels was between -11 % and 36% (mean ± sd, 5.7 ± 18.5 % ). RBF in the main temporal retinal veins of healthy subjects varied between 0.9 and 13.2 µL / min. CONCLUSIONS: The AO LDV prototype allows for the real-time measurement of absolute RBF derived from the retinal vessel diameter and the maximum RBCs velocity in that vessel.