Evaluating Human Rod Photoreceptor Function Using Pixelwise Intensity-Based Optoretinography.

Purpose: More than 50 inherited retinal diseases are known, with rod photoreceptor functional loss serving as an early indicator in nearly half of them. The "optoretinogram" is a relatively new assay that detects optical changes in cells in response to stimuli. This tool has excellent potential for providing insights into the earliest functional changes of rod photoreceptors, with the potential to assist in the early detection, monitoring, and treatment of retinal diseases. Methods: In this work, we obtained intensity-based optoretinograms (iORGs) from rod photoreceptors using an adaptive optics scanning laser ophthalmoscope. We explore the necessity of both individual rod identification for extracting these waveforms and discuss rod iORG root mean square (RMS) morphology in the context of previously reported cone iORGs. Results: We found that human rod iORG RMS waveforms have slower implicit times and lower amplitudes than cone iORG RMS waveforms. Additionally, we determined that we obtain very similar iORG RMS metrics using either only rod locations or all pixels where rods reside. Conclusions: The ability to obtain rod optoretinograms without counting individual rods greatly simplifies the functional evaluation of rods and makes the approach more practical and scalable for larger populations and diseased retina. Translational Relevance: This work indicates that obtaining rod optoretinograms is feasible even in devices or participants in which rod photoreceptors are not fully resolved, enabling their use in a much broader clinically relevant population.