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

Design Cohort, longitudinal study.

Participants Five non-syndromic RP patients and eight 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 healthy, unaffected 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.

Vimal Pandiyan and Ramkumar Sabesan have filed a patent on the line-scan OCT technology used here for optoretinography (PCT/US2020/029984).

This study was funded by: NIH grant U01EY032055, EY029710, Unrestricted grant from the Research to Prevent Blindness, Dawn's Light Foundation, George and Martina Kren Professorship in Vision Research.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The institutional review board of the University of Washington (IRB#STUDY00002923) gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.