Multi-modal Imaging of Retinal Oxygenation

The retina is a light-sensitive tissue located at the back of the eye and plays a key role in vision. To maintain visual function, the amount of oxygen in the retina (retinal oxygenation) is highly regulated under normal physiological conditions. However, alteration of retinal oxygenation is implicated in common vision-threatening retinal diseases including diabetic retinopathy, glaucoma and macular degeneration. Additionally, retinal oxygenation can be perturbed and characterized by the physiological challenge of diffuse light flicker stimulation (DLFS). Therefore, research that characterizes retinal oxygenation and its response to DLFS in health and disease is essential. To date, available techniques for the direct assessment of retinal oxygenation are invasive and cannot be used in humans. Therefore, markers of retinal oxygenation in humans – retinal vessel diameter (D), retinal vessel oxygen saturation of hemoglobin (SO2) and the inner retinal oxygen extraction fraction (OEF) – are measured non-invasively instead. However, in animals, retinal oxygenation may be directly assessed by measurement of retinal tissue oxygen tension (tPO2). This thesis describes novel techniques to assess retinal oxygenation markers in humans and tPO2 in rats. An optical imaging system for the non-invasive measurement of retinal oxygenation markers in humans was developed and then applied to assess the effects of diabetic retinopathy disease stage and DLFS on markers. Additionally, the system was modified to measure and mathematically model the temporal dynamic responses of retinal oxygenation markers to DLFS. To address limitations in subjects’ fixation during the assessment of these temporal dynamics, a system for real-time image stabilization was developed. Finally, a technique for the three-dimensional assessment of retinal tPO2 in rats was developed, permitting the evaluation and assessment of multifocal retinal oxygenation abnormalities.