Retinal blood flow measurement using bi-directional FDODT

Fourier domain optical coherence tomography (FDOCT) has become a standard tool in retinal imaging. In the recent years much focus was directed towards extension of this technique to gain insight into functional aspects of the retina. In our laboratory we investigated the possibility of combining FDOCT with the principles of laser Doppler velocimetry to gain insight into retinal perfusion. Based on a previous FWF grant we have built a bi- directional Fourier domain optical Doppler tomograph (FDODT) capable of measuring absolute blood velocities in retinal arteries and veins. In the present grant proposal we aim to extend this approach in order to develop a technology capable of measuring total retinal blood flow with high reproducibility and sensitivity. For this purpose the bi-directional FDODT technology will be coupled into a commercially available Retinal Vessel Analyzer (RVA) providing high resolution data of retinal vessel diameters. Combining FDODT with RVA analysis will allow for the measurement of total retinal blood flow. In addition, information on retinal velocity profiles will be available providing information on flow abnormalities in retinal vascular disease and on sheer stress. The clinical feasibility of the system will be tested in several studies in healthy subjects. This will include a thorough investigation of the short-term, day-to-day and interobserver variability. In addition, a flicker stimulation system will be included to allow for the study of neurovascular coupling in the retina. Finally, we will perform measurements in patients with systemic hypertension and in different stages of diabetic retinopathy. The present grant application is considered a major step towards the clinical routine measurement of retinal blood flow, which may be feasible in patients suffering from ocular vascular disease including those who suffer from vascular occlusions, diabetic retinopathy or glaucoma.

In the present project a procedure for the measurement of retinal blood flow based on Doppler Optical Coherence Tomography (OCT) was realized. The key point of this technique is the used of two laser beams. With this approach the problem that the Doppler angle is unknown is overcome. Quantification of total retinal blood flow is possible as long as the angle between the two beams is known. Another key feature of the system is that it is coupled to a fundus camera. This allows for the extraction of vessel diameters and an accurate measurement of perfusion. One focus of the present project was directed towards the validity of the measurements. It was shown that there is a pronounced reduction in retinal blood flow during 100% oxygen breathing. In addition, a number of experiments was scheduled in order to proof that the technique is capable of assessing correct values for retinal perfusion. This includes that Murrays law is fulfilled, that there is a high degree of correlation with measurements using laser Doppler velocimetry, and that the law of continuity is fulfilled at bifurcations. For the measurement of total retinal blood flow several scanning pattern were realized. Data for total retinal blood flow are in good agreement as obtained with laser Doppler velocimetry. The technique offers good validity and reproducibility and has significant potential for future clinical applications.