Intrinsic signal optoretinography of rod photoreceptor dysfunction due to retinal degeneration

Early detection of photoreceptor dysfunction is essential for preventing vision loss due to retinal degenerative diseases, such as age-related macular degeneration (AMD) and inherited retinal degenerations (IRDs). Functional intrinsic optical signal (IOS) imaging promises a high-resolution method for objective optoretinography (ORG). Stimulus-evoked photoreceptor-IOS has been recently demonstrated in healthy animal and human retinas. The fast photoreceptor-IOS response was found to occur at the photoreceptor outer segment (OS) right after the onset of retinal stimulation. However, in vivo IOS response of photoreceptor dysfunctions is not yet validated, which is essential to measure the clinical usability of ORG measurement. In this study, we report in vivo IOS imaging of rod photoreceptor dysfunction in retinal degeneration 10 (rd10) mice. A custom-designed optical coherence tomography (OCT) was used for photoreceptor-IOS imaging. A significant attenuation of the photoreceptor-IOS was found in rd10 mice due to disorganized ultrastructure of the photoreceptor OSs, which appeared ahead of progressive rod cell death. Our experiments demonstrate that fast photoreceptor-IOS is highly sensitive to ultrastructural integrity of the photoreceptor OSs. We anticipate that quantitative imaging of fast photoreceptor-IOS will provide objective ORG measurement to advance the study and diagnosis of AMD, IRDs, and other retinal diseases that can cause photoreceptor dysfunctions.