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

Abstract

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. K E Y W O R D Scorneal cross-linking, nanoscale alteration, nanoscale sensitivity, optical coherence tomography, spatial period

Characterization of nanosensitive multifractality in submicron scale tissue morphology and its alteration in tumor progression

“…In this regard, our research group actively engaged to develop nanosensitive optical coherence tomography (nsOCT) to detect depth-resolved submicron scale structure with few nanometer accuracy. [16][17][18] We have recently demonstrated label-free nsOCT-based imaging technique to visualize few nanometer structural changes 19,20 and its application in cornea crosslinking, 21 and wound healing study. 22 There is a recently demonstrated application of nsOCT for in vivo detection of nanosensitive changes of the human tympanic membrane in otitis media.…”

Accessing depth-resolved high spatial frequency content from the optical coherence tomography signal

“…One possible way to access information about high spatial frequencies is so called nano-sensitive OCT (nsOCT), (see “ Materials and methods ”). The nsOCT technique was invented to retain the high spatial frequency information and provide nano-sensitivity to structural changes 26 , 28 – 30 . Instead of using a conventional way to improve the resolution and sensitivity of the OCT by increasing the spectral bandwidth, nsOCT is a different approach, which permits the visualization of sub-wavelength structure from a single frame and provides nano-sensitivity to structural alteration at each volume of interest within a 3D biological object using the given spectral bandwidth.…”

Simple Characterization Scheme for Optical Coherence Tomography Systems With Application to a Commercial and a Near-Isometric Resolution Fibre-Based System

“…The improved image quality in conjunction to isometric image voxel geometry is of major interest for conventional OCT imaging [52], [53], [54], [55], [56], [57]. Our ongoing research to apply nano-sensitive OCT can benefit from the extended spectral bandwidth which permits access to a wider distribution of spatial frequencies and can improve the dynamic range, which is the subject of future research.…”