The proposed design and construction of an optical coherence tomography (OCT) system, namely, a full-field (FF)-swept-source (SS)-OCT will allow rapid structural and functional measures of individual cone and rod photoreceptors (PRCs), the sub-retinal space (SRS) and retinal pigment epithelial (RPE) cells to an external light stimulus. Current OCT systems either have limited temporal resolution i.e. they are not fast enough to measure the neuronal response or lack the spatial resolution to resolve individual cells. Here, we will exploit the extremely high parallel image acquisition speed of FF-SS-OCT to study neuronal responses as short as a few milliseconds. Furthermore, as the system collects the whole back scattered electric field from the sample, numerical aberration correction (NAC) methods can be used allowing for the visualization of single cells without the need for techniques such as hardware based adaptive optics (AO). There are three stages to the proposed project: (i) the design and construction of FF-SS-OCT systems for both human and animal models (mice) of retinal disease - examining both species in parallel will speed up the clinical translation, (ii) testing the system performance in healthy retina of both humans and mice, (iii) measure the sensitivity of the system to detect microstructural functional changes by comparing age-matched controls to diseased cohorts. These will be early stage dry age-related macular degeneration (AMD) subjects and several AMD mouse models. Scientific rigor and reproducibility will be addressed by comparing FF-SS-OCT structural images to those obtained with our existing human and mice AO-OCT systems; functional measurements in human subjects will be compared to published data and also to clinical measures such as mfERG and visual fields. Functional measurements in mice will be compared to published data and also to the results from our first-generation mouse functional retinal imaging system and Ganzfeld ERG. Many potential therapies are under development for a range of ocular diseases, these systems fulfill a critical need for modalities that can not only determine whether the neurons are structurally intact but importantly are also exhibiting normal function.
A novel optical coherence tomography (OCT) system that allows very rapid structural and functional quantification of the outer retina including individual cone and rod photoreceptors (PRCs), sub-retinal space (SRS) and retinal pigment epithelial (RPE) cells will be designed and constructed. A particular strength of the proposed OCT system is that it can quantify functional changes in individual retinal cells in response to light stimulation. This is equivalent to testing retinal function at the level of a single neuron, far more sensitive than currently available clinical functional tests such as perimetry or electroretinography. The sensitivity of the proposed OCT system to these microscopic changes will be first demonstrated on both human and mouse controls before comparative measurement on a small cohort of subjects with dry age related macular degeneration (AMD) and the corresponding mouse AMD models.
