Split-spectrum amplitude decorrelation optoretinography for functional imaging of mouse photoreceptors

Optoretinography (ORG) encompasses a diverse group of innovative ophthalmic imaging techniques that can detect and quantify light-evoked morphological and optical property changes within the photoreceptors, the light-sensing cells on the back of the eye. It promises noninvasive and objective measures of photoreceptor-mediated visual function. However, many current ORG approaches rely on complex optical configurations or have small measurement fields, which have limited applications to research settings and small-scale validations. In this work, we present optical coherence tomography (OCT) based split-spectrum amplitude-decorrelation optoretinography (SSADOR), which can detect and quantify photoreceptor responses to light without resolving and tracking single photoreceptor cells. Therefore, it allows rapid mapping of photoreceptor functions over a relatively large retinal area, with high spatial resolution and using an OCT instrument comparable to existing clinical and commercial devices. SSADOR was used to measure photoreceptor light responses in the living mouse retina following a green flash. Significantly greater SSADOR decorrelation was observed in the photoreceptor inner and outer segments than in the inner retina or retinal pigment epithelium, confirming the origin of the observed contrast. The SSADOR response size correlated with the intensity of the light stimulus. Furthermore, we showed that retinas of a mouse model of retinal degeneration had significantly lower SSADOR responses than age-matched wild-type controls. The results demonstrate the utility of SSADOR for characterizing photoreceptor-dependent responses to light stimuli in the mouse retina and may offer researchers an accessible and reliable new method to study retinal dynamics in vivo.