Work

Quantitation of Stromal Distortion Across the Full Depth of Keratoconic Corneas

Year: 2026

Type: article

Abstract: Purpose: This study aimed at gaining new insights into the pathophysiology of keratoconus by providing a comprehensive and quantitative characterization of stromal structural alterations throughout the full thickness of keratoconic corneas and in regions both proximal to and distant from the cone. Methods: Complementary three-dimensional imaging techniques were combined in a pilot exploratory series of four keratoconic and four control human corneas: clinical spectral-domain optical coherence tomography, highly-resolved line-field confocal optical coherence tomography and second harmonic generation (SHG) microcopy. Several structural metrics were computed from SHG images using automatic image analysis pipelines. Results: Quantitative SHG imaging revealed striking structural shifts in keratoconic corneas compared to healthy controls. Most notably, we observed a significant rise in normalized striation Endpoints (P = 0.008) and End/Branch ratio (P = 0.015), consistent with the presence of wavy lamellae and the loss of the plywood-like structure found in control corneas. Importantly, these structural markers remained consistent in both the cone and outside the cone regions. Quantitative processing of collagen orientation revealed a single widely-spread orientation as opposed to two main orthogonal orientations in control corneas, and slight shifts in orientation between superimposed lamellae rather than the abrupt changes observed in control corneas. Conclusions: We provide new quantitative data on the structural alterations associated with keratoconus that could serve as useful biomarkers for earlier detection. Our findings are consistent with a decreased stromal stiffness and an increase in the corneal birefringence. They are also in favor of a global stromal disorder rather than a purely localized disorder.

Source: Investigative Ophthalmology & Visual Science

DOI: 10.1167/iovs.67.12.58