IVCM image analysis for limbal stem cell deficiency: quantitative diagnostics of the corneal epithelium...

Limbal stem cell deficiency (LSCD), a sight-threatening condition, is caused by dysfunction of the limbal stem cells (LSCs) which maintain the corneal epithelium. An effective treatment of LSCD is the transplantation of ex-vivo cultured LSCs from the patient's healthy other eye (in unilateral cases) or a donor eye (in bilateral cases) to the affected eye. Here we identify and quantify diagnostic and monitoring criteria for the recovery of the corneal epithelium post-LSC transplant using cellular images.

We consider the in-vivo confocal microscopy (IVCM) images from 10 patients with total unilateral LSCD caused by chemical burns, taken before and after LSC transplant. Images encompass the entire thickness of the corneal epithelium in the central and four peripheral regions. Approximately 1500 images were segmented using a bespoke algorithm to extract morphological data for analysis.

The probability density of cell areas is shown to be a sensitive monitoring tool of corneal epithelial status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the distribution narrows with high statistical confidence and approaches that of the healthy cornea. We find a strong patient-to-patient variability in the epithelial cell area distribution and its variation with corneal depth. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells are roughly hexagonal.

Cell area is a sensitive and easily accessible marker of corneal epithelial recovery in LSCD patients post-LSC transplant.