Nanosensitive optical coherence tomography to monitor corneal burn and treatment response in vivo.

Chemical burns account for 10-22% of ocular injuries, with alkali burns being the most frequent and severe. There is a significant need for treatment of these injuries, as well as an effective imaging method to monitor both the injury and treatment progression. Currently, there are limited options for monitoring the burn and treatment response of the sub-micron structures within the corneal tissue in vivo and non-destructively, due to factors such as the resolution limit of optical imaging systems. Optical coherence tomography (OCT) is a non-invasive imaging technique that provides high-resolution, cross-sectional imaging of biological tissue at good imaging depths. Due to the diffraction limit, OCT resolution is limited to the micron scale, preventing monitoring of nanoscale changes. Nanosensitive optical coherence tomography (nsOCT) overcomes this limitation by recovering high spatial frequency information through spectral encoding, enabling assessment of sub-micron tissue features. Here, we present variations of nsOCT with improved sensitivity for detecting nanoscale tissue changes. These methods were applied to a corneal alkali burn model and a treatment model using mesenchymal stromal cell-derived extracellular vesicles. Correlation of axial spatial frequency profiles (ASFP) and mapping of ASFP differences enabled sensitive detection of nanoscale structural changes post-injury and during treatment progression. A statistically significant disruption of the sub-micron structure was observed after injury, followed by partial restoration during the reparative phase. The proposed methods provide improved sensitivity to nanoscale tissue changes and may support monitoring of cell therapy and other medical applications for diagnostic purposes.