In vivo elastography of the human retina using light-evoked intrinsic actuation

Abstract

The biomechanical properties of the retina govern its function, structural integrity, and susceptibility to disease, yet remain difficult to measure in vivo due to the lack of safe, spatially localized mechanical actuation. Here, we introduce a framework for probing retinal biomechanics in the living human eye by leveraging intrinsic optical actuation driven by phototransduction. Using phase-resolved optical coherence tomography with a local phase-referencing approach, we resolved signed, nanometer-scale displacements of the major outer retinal interfaces evoked by light. The resulting deformation field, originating in the photoreceptor outer segment, was distributed across retinal compartments in an eccentricity-dependent manner, with efficient axial transfer in the fovea and attenuated propagation in the parafovea. A hybrid analytical and finite-element framework was developed that retrieved the biomechanical properties of the retinal compartments based on their coordinated deformation and the anatomical variation in retinal structure versus eccentricity. In retinitis pigmentosa, the paradigm enabled the detection of light-evoked deformation in the transition zone despite the loss of native lamination, enabling a functional readout of the vulnerable photoreceptors at the leading edge of degeneration. Together, these results establish intrinsic optical stimulation as a basis for in vivo retinal elastography and enable the non-invasive, quantitative imaging of retinal biomechanics and function in the living human retina.