Noninvasive detection of nanoscale structural changes in cornea associated with cross-linking treatment

Corneal cross-linking (CXL) using ultraviolet-A (UVA) irradiation with a riboflavin photosensitizer has grown from an interesting concept to a practical clinical treatment for corneal ectatic diseases globally, such as keratoconus. To characterize the corneal structural changes, existing methods such as X-ray microscopy, transmission electron microscopy, histology and optical coherence tomography (OCT) have been used. However, these methods have various drawbacks such as invasive detection, the impossibility for in vivo measurement, or limited resolution and sensitivity to structural alterations. Here, we report the application of oversampling nanosensitive OCT for probing the corneal structural alterations. The results indicate that the spatial period increases slightly after 30 minutes riboflavin instillation but decreases significantly after 30 minutes UVA irradiation following the Dresden protocol. The proposed noninvasive method can be implemented using existing OCT systems, without any additional components, for detecting nanoscale changes with the potential to assist diagnostic assessment during CXL treatment, and possibly to be a real-time monitoring tool in clinics.