Quantitative measures of corneal transparency, derived from objective analysis of depth-resolved corneal images, demonstrated with full-field optical coherence tomographic microscopy.

Romain Bocheux,Kristina Irsch,Pascal Pernot,Karsten Plamann,Vincent Borderie,Ireneusz Grulkowski

doi:10.1371/journal.pone.0221707

Abstract

Loss of corneal transparency, as occurs with various pathologies, infections, immune reactions, trauma, aging, and surgery, is a major cause of visual handicap worldwide. However, current means to assess corneal transparency are extremely limited and clinical and eye-bank practice usually involve a subjective and qualitative observation of opacities, sometimes with comparison against an arbitrary grading scale, by means of slit-lamp biomicroscopy. Here, we describe a novel objective optical data analysis-based method that enables quantifiable and standardized characterization of corneal transparency from depth-resolved corneal images, addressing the demand for such a means in both the laboratory and clinical ophthalmology setting. Our approach is based on a mathematical analysis of the acquired optical data with respect to the light attenuation from scattering processes in the corneal stroma. Applicable to any depth-resolved corneal imaging modality, it has been validated by means of full-field optical coherence tomographic microscopy (FF-OCT or FF-OCM). Specifically, our results on ex-vivo corneal specimens illustrate that 1) in homogeneous tissues, characterized by an exponential light attenuation with stromal depth (z), the computation of the scattering mean-free path (ls) from the rate of exponential decay allows quantification of the degree of transparency; 2) in heterogeneous tissues, identified by significant deviations from the normal exponential z -profile, a measure of exponential-decay model inadequacy (e.g., by computation of the Birge ratio) allows the estimation of severity of stromal heterogeneity, and the associated depth-dependent variations around the average ls enables precise localization of the pathology.

Highlights

Vision is dependent upon the transparency of the cornea, which largely relates directly to stromal structure, more precisely the regular microstructure of the lamellae and the nanostructure of the closely packed collagen fibrils that are embedded in an optically homogeneous ground substance [1,2]
Corneal transparency can be compromised by various pathologies, infections, immune reactions, trauma, aging, and surgery, all of which result in increased light scattering
Applicable to any depth-resolved corneal imaging modality, we demonstrate the feasibility of our optical data analysis-based method by means of full-field optical coherence tomographic microscopy (FF-optical coherence tomography (OCT) or FF-OCM)

Summary

Introduction

Vision is dependent upon the transparency of the cornea, which largely relates directly to stromal structure, more precisely the regular microstructure of the lamellae and the nanostructure of the closely packed collagen fibrils that are embedded in an optically homogeneous ground substance [1,2]. Surgical intervention, involving the replacement of the affected cornea by donated tissue (the so-called graft that is taken from a recently deceased individual), becomes the only treatment option. Over 10 million people worldwide suffer severe visual handicap due to loss of corneal transparency. Over 1.5 million go blind every year, often due to poor suitability for corneal transplantation, or due to a shortage of available grafts [3]. For those in whom grafting may be possible, success rates range from 60% to 90% [4]

Methods

Results

Conclusion