Longitudinal Changes in Optoretinography Provide an Early and Sensitive Biomarker of Outer Retinal Disease

Abstract

Objective: To examine whether optoretinography (ORG) can provide greater sensitivity for assessing the time-course of disease progression in Retinitis Pigmentosa (RP) compared to standard clinical imaging in a longitudinal study.

Design: Cohort study.

Participants: Five non-syndromic RP patients and 8 control subjects participated in the study.

Methods: Clinical examination, imaging sessions and data analysis were all conducted at the University of Washington. Five eyes of 5 patients diagnosed with RP, comparing standard clinical imaging to ORG, were collected over a 21-month span between August 2022 and May 2024.

Main outcome and measures: ORG response to visual stimuli, ellipsoid zone (EZ) width and outer segment length (OS length) were evaluated for longitudinal changes as markers of disease progression.

Results: The reduction in cone function with ORG over time exceeds that observed in standard clinical markers of photoreceptor structure - EZ width and OS length. EZ width and OSL decreased by 4.5% ± 5.9% and 6.5% ± 1.4%, respectively, approximately 9.9 and 6.9 times less than the reduction noted in ORG, respectively. The most notable degradation was noted at the borders of the transition zone, where ORG showed progressive and sub-clinical losses in photoreceptor function whereas standard OCT showed currently intact outer retinal structure.

Conclusions: Optoretinography detects sub-clinical disease and reliably identifies longitudinal markers of progression with greater sensitivity compared to standard clinical imaging. The ability to detect functional changes in the outer retina prior to standard clinical measures underscores its potential as a sensitive, accelerated and clinically-relevant outcome measure to guide patient selection and their therapeutic response in future clinical trials.