Optoretinography for the Functional Assessment of the Human Retina in Health and Disease

Abstract

Imaging retinal structure and function is crucial for detecting and diagnosing disease, guiding treatment strategies, and ultimately improving patient outcomes. Optoretinography (ORG) is an emerging paradigm capable of quantifying the light-evoked, nanometer-scale deformations of photoreceptors and offers a powerful, objective biomarker for retinal function. This dissertation introduces coarse-scale ORG (CoORG), an extended-field, line-scan OCT platform with high speed and phase sensitivity suitable for imaging retinal structure and function in a range of diseases. Normative data from healthy eyes reveal that cone ORG amplitude increases with retinal photon density and scales linearly with cone outer segment length. In healthy aging, ORG amplitudes decline, and the structure-function correction weakens compared to younger controls. Additionally, novel multi-layer ORG analyses extend the paradigm beyond photoreceptors and provide deeper physiological insight into outer retinal function. In patients with inherited retinal dystrophies (IRDs), ORG detects cone dysfunction even in areas with normal retinal structure and enables significantly greater sensitivity in monitoring longitudinal progression over conventional clinical imaging. Overall, this dissertation demonstrates the potential of ORG as a rapid, sensitive, patient-friendly biomarker for disease progression and outcome measure for clinical trials.