Oxygen extraction in the retina of healthy and diabetic subjects

Diabetic retinopathy (DR) is one of the main causes of blindness in the Western World and a severe complication of diabetes. The most important risk factors for DR include duration of diabetes, poor glycemic control and high blood pressure. Over the past years a strong association between the retinal vessel diameter and the incidence and progression of DR was found. However, no technique is currently available to quantify the ischemic and hypoxic processes that lead to retinal neovascularisation. Hypoxia is, however, considered the major trigger for neovascularization of the retina in DR. One way to gain insight into degree of hypoxia in DR is to measure oxygen extraction. In present grant proposal we propose a technique, which allows to measure the oxygen extraction in the whole human retina in vivo. For this it is necessary to measure oxygen saturation as well as retinal blood flow in retinal vessels. The evaluation of the blood flow values will be done with bi-directional Doppler Fourier Domain Optical Coherence Tomography (OCT), a device which was recently developed in our laboratory. The Retinal Vessel Analyzer will be used for measurements of the retinal oxygen saturation and the diameter of the vessels. In addition, alternative techniques for the measurement of retinal saturation including spectroscopic OCT and a combination of Swept Source OCT and photoacoustic will be evaluated. The parameters obtained with these devices allow us to calculate the total retinal oxygen extraction, a parameter that has not been assessed before. This calculation is based on a model of oxygen transport in the retina outlined in the grant proposal. In the current grant proposal the hypotheses that retinal oxygen extraction is reduced in patients with diabetes will be tested. This technique may become an important clinical test in diabetes, as hypoxia is considered a major trigger for the development and progression of DR

In the present project the question of retinal oxygen extraction in patients with diabetes was investigated. For this purpose we used a novel technique for the measurement of total retinal oxygen extraction. This approach is based on the measurement of total retinal blood flow using Doppler optical coherence tomography and spectroscopic measurement of oxygen extraction. The study shows that retinal blood flow is increased in patients with diabetes. Retinal arterio-venous oxygen difference and total retinal oxygen extraction are, however, significantly decreased. These changes indicate that retinal hypoxia is an early mechanism in patients with diabetes, which is an attractive novel treatment target.