Computational aberration correction enables full-thickness retinal imaging with adaptive optics optical coherence...

Biomedical optical imaging has become a key tool for noninvasive evaluation of the human eye, offering a unique window into both ocular and systemic diseases. Among these techniques, adaptive optics optical coherence tomography (AO-OCT) stands out for its ability to achieve volumetric, in vivo cellular-level imaging of the retina. However, the high numerical aperture associated with AO-OCT restricts the depth of focus (DOF) to tens of micrometers, making it challenging to obtain sharply resolved features across the full retinal thickness within a single volume. A common solution is to acquire multiple volumes at different focal depths and digitally register and average them to extend the DOF. Here, we demonstrate that this hardware-intensive approach can be simplified through post-processing computational defocus correction, applied within a computational aberration correction (CAC) framework. By applying CAC to AO-OCT volumes acquired with the system focus placed at a single mid-retinal plane, we correct depth-dependent defocus and restore cellular sharpness throughout the entire retinal thickness, effectively extending the DOF without the need for sequential refocusing. We further show that CAC enhances en face AO-OCT images even at 1.5° temporal to the fovea, underscoring the benefits of combining hardware AO-OCT with computational defocus correction to reduce imaging complexity, decrease session duration, and improve clinical viability. Finally, we demonstrate improved rendering of cellular structures in eyes with retinal pathology, highlighting the translational potential of this hybrid AO-OCT + CAC approach.