UC Berkeley

Ophthalmic technologies have evolved over the past ten years to not only resolve every photoreceptor within the densely packed fovea, but also to reveal hidden structures within the translucent retinal layers. Although structurally intact, patches of seemingly healthy photoreceptors could have a decreased sensitivity indicating signs of pathology with no structural discrepancies visible. To better understand the health of the retina we have further developed both structural and functional retinal imaging to shed light on the photoreceptors as a more precise indicator of health by probing the sensitivity and physical elongation of these neurons upon stimulation. With a cellular-scale tool which can quantify both the neuron’s structure and function, the health of the retina can be precisely monitored and probed to bring new insights into pathophysiology and diagnostics of retinal diseases.Adaptive optics scanning laser ophthalmoscopy (AOSLO) is a powerful tool for imaging the retina at high spatial and temporal resolution. In this dissertation, four developments are documented based on AOSLO technology for imaging the structure and function of the retina. Firstly, a wide-vergence, multi-spectral AOSLO was designed, constructed, and experimentally verified by measuring the point spread function (PSF) of the illumination and collection paths for each spectral channel via a phase retrieval technique. The system’s optical quality was then demonstrated by resolving the foveal cone mosaic in all three imaging channels from human volunteers and comparing against expected performance. Secondly, a multi-detector scheme for AOSLO with two main detection configurations was developed: pixel reassignment and offset aperture imaging. In the multi-detector scheme, the single element detector of the standard AOSLO was replaced by a fiber bundle which couples the detected light into multiple detectors. The pixel reassignment configuration enabled high resolution imaging with an increased light collection efficiency. The offset aperture imaging configuration enhanced the detection of multiply scattered light, which improves the contrast of retinal vasculature and inner retinal layers. Thirdly, an additional system was built with active eye motion correction for an optical coherence tomography (OCT). The AOSLO was an integral part for driving the aberration correction and tracking the eye motion to guide the AOOCT. An independent focus adjustment was implemented into the AOOCT path for imaging the nerve fiber layers and ganglion cells with optimal lateral resolution while maintaining high fidelity photoreceptor mosaic for AOSLO tracking. Lastly, by using the complex field from measured AOOCT interferogram, the phase information was acquired to measure the physiological response of the photoreceptors with nm scale accuracy and record the elongation of the cone outer segment in response to a stimulus. This system successfully characterized the optoretinogram of photoreceptors which has potential to be further utilized as an optical biomarker for the function of the neuron allowing both the classification of the cone type and the assessment of the photoreceptor’s health.