Optical Assessment of Photoreceptor Function and Integrity

Oregon Health & Science University, Portland OR

Investigators

Abstract

Photoreceptors are specialized sensory cells that convert light stimuli to neuronal signal. Diminished responses to light suggest cell damage and death, which lead to poor vision and blindness. Preserving and restoring photoreceptors are meaningful therapeutic targets for retinal degeneration. Diagnosing, managing, and drug development require accurate and reliable assessment of visual function. This multidisciplinary program will develop innovative ophthalmic imaging technologies and novel objective, quantifiable functional biomarkers for cone photoreceptors. The prospect of a sensitive tool for detecting early vision changes and over a short period of time represents a paradigm shift in ophthalmic tests and trial design. Aim 1. We will develop next generation optical coherence tomography (OCT) technologies to enable functional photoreceptor imaging over a wide retinal area and at high topographical resolution. OCT split-spectrum amplitude-decorrelation optoretinography (SSADOR) is an integrated hardware-software approach that can measure photoreceptor light response without the need for electrode contact, subjective feedback, or highly complex instruments. OCT SSADOR enables co- registered analysis of photoreceptor function and retina morphology, which can help understand disease mechanisms and to facilitate longitudinal observations. Innovations in ultrahigh speed OCT and SSADOR will lead to a clinically accessible tool for assessing photoreceptor function over the macula, which is responsible for fine central vision and associated with quality of life. Aim 2. We will develop novel objective, sensitive, and reliable biomarkers of cone mediated visual function. Advanced software algorithms can reduce SSADOR measurement variability. We will use parallel computing technique to reduce processing time and enable real time feedback to guide clinical imaging, further reduce variations and improving yield. Highly accurate and sensitive SSADOR cone functional measurements can identify subtler impairments and detect changes early in disease progression. This study will characterize the measurement repeatability of SSADOR biomarkers. Additionally, we will establish a normative reference database to allow for inter-subject comparison and facilitate clinical interpretation. Aim 3. We will investigate cone photoreceptor impairment and loss associated with inherited retinal disease (IRD), a heterogenous family of vision threatening conditions. This pilot clinical study will compare SSADOR functional biomarkers in two independent cohorts of IRD patients and age-matched normal controls in global, regional, and local scales. Measurements will be correlated with clinical diagnoses of disease severity and visual function (e.g., best corrected visual acuity, retinal sensitivity, and electroretinogram). We will follow IRD patients longitudinally to monitor disease progression and identify fast progressors. If successful, this program will develop imaging biomarkers of visual function that can be practically used in the clinics for a wide range of retinal diseases. This will save vision by guiding medical intervention through active progression monitoring, and by facilitating therapeutic trials with sensitive and reliable visual outcome endpoints.