Velocity profiles in retinal arteries and veins

Retinal vascular occlusive disease can affect both arteries and veins and is a common cause of visual loss. Major branch vein occlusion (BRVO) has a prevalence of apprxoimately1% and occurs at arteriovenous crossings. The pathophysiological processes that lead to BRVO include three major processes: compression of the vein at the arteriovenous (A/V) crossing, degenerative changes of the vessel wall, and abnormal hematological factors. Although risk factors for the disease have been described, we do not have a method capable of identifying those patients who are at risk to develop the disease. In the recent years our research has focused on Optical Doppler Tomography (ODT), a functional extension of OCT, which allows for the measurement of blood velocities in retinal vessels. In preliminary experiments we have shown that this technique can also be used to study velocity profiles in retinal vessels. We were able to show deviations from parabolic velocity profiles at retinal venous bifurcations as well as at arterio-venous crossings. In the present grant proposal we propose to perform pilot studies investigating these phenomena in more detail. On the one hand we will characterize velocity profiles in healthy subjects at both arterial divergent and venous convergent bifurcations. Model calculations are planned to better understand blood flow regulation and deviations from parabolic velocity profiles. In addition, the experiments planned as part of this project will focus on velocity profiles at arterio-venous crossings. The hypothesis that velocity profiles show significant deviations from parabolic in fellow eyes of patients with BRVO as well as in patients with hypertensive retinopathy stage 3 and 4 will be tested. This is of interest, because both conditions have been shown to represent significant risk factors for the development of BRVO. This is done with the long-term aim to establish measurement of velocity profiles as a technique to identify patients at risk for developing BRVO. In addition, retinal blood flow will be quantified in the patients groups aiming to identify the degree of ischemia in patients with BRVO.

The objective of the research project Velocity profiles in retinal arteries and veins was the development of methods and algorithms for extraction of velocity profiles in human retinal vessels. To this end, measurements were performed via a dual-beam Doppler optical coherence tomography system, a noninvasive noncontact optical modality for measurement of both morphological structures and functional parameters in the eye. The algorithms were intended to be applied on OCT data yielded from healthy subjects as well as from patients with branch retinal vein occlusion (BRVO), systemic hypertension and hypertensive retinopathy. The methods and algorithms developed in course of the research project were published in an international top-journal in the field of biomedical optics and allow the simulation and modeling of velocity profiles in various vessel geometries. Furthermore they enable the reconstruction of true velocity profiles yielded from in vivo OCT measurements. In addition, methods for acquisition, registration and post-processing of Doppler OCT data that can be implemented in any OCT device and simplify the handling of the large data amount were developed. A principle conclusion that can be drawn from the experiments is the necessity of using at least two OCT detection arms to gain knowledge of the true velocity profile within the vessels under study. It could be shown that, when relying on only one detection arm, different phenomena can lead to false conclusions about the flow profiles. Measurement of retinal blood flow in patients with hypertension revealed a decrease in total flow as compared to a healthy control group. Furthermore, OCT measurements allowed for detection of a vessel wall thickening in these patients. The measurement of velocity profiles at locally very restricted vessel segments like bifurcations and arterio-venous crossings require a high degree of cooperation from side of the patient. Due to involuntary eye movements and problems of the patients in stabilizing their view onto a fixation target, the quality of the measurements was in some cases not adequate for extraction of the velocity profiles. As a result, also the detection of changes in the velocity profiles of the patients in comparison to a healthy control group was hampered. Due to the limitations given above, the research team directed its focus of research in parallel to a second field: The assessment of neurovascular coupling (NC) in the human retina based on the measurement of the total retinal blood flow at baseline condition and during stimulation of the retina with diffuse luminance flicker light. Using the methods developed in course of the research project, the researchers could show the potential of dual-beam Doppler OCT for quantifying NC and for monitoring its changes caused by various pathologies. The results gained from these experiments were very promising and led to an application of the established methods in studies investigating NC in neurodegenerative diseases like Alzheimers disease and diabetic retinopathy.