Spatially-resolved Brillouin spectroscopy reveals biomechanical abnormalities in mild to advanced keratoconus in vivo

Peng Shao,Amira M Eltony,Seok-Hyun Yun,Tobias Koller,Roberto Pineda,Behrouz Tavakol,Theo G Seiler

doi:10.1038/s41598-019-43811-5

Abstract

Mounting evidence connects the biomechanical properties of tissues to the development of eye diseases such as keratoconus, a disease in which the cornea thins and bulges into a conical shape. However, measuring biomechanical changes in vivo with sufficient sensitivity for disease detection has proven challenging. Here, we demonstrate the diagnostic potential of Brillouin light-scattering microscopy, a modality that measures longitudinal mechanical modulus in tissues with high measurement sensitivity and spatial resolution. We have performed a study of 85 human subjects (93 eyes), consisting of 47 healthy volunteers and 38 keratoconus patients at differing stages of disease, ranging from stage I to stage IV. The Brillouin data in vivo reveal increasing biomechanical inhomogeneity in the cornea with keratoconus progression and biomechanical asymmetry between the left and right eyes at the onset of keratoconus. The receiver operating characteristic analysis of the stage-I patient data indicates that mean Brillouin shift of the cone performs better than corneal thickness and maximum curvature respectively. In conjunction with morphological patterns, Brillouin microscopy may add value for diagnosis of keratoconus and potentially for screening subjects at risk of complications prior to laser eye surgeries.

Highlights

Growing evidence indicates that the biomechanical properties of ocular tissues can be diagnostic targets due to their association with various eye diseases and refractive errors[1]
The other rackmounted system was built at Massachusetts General Hospital (MGH) and shipped to Zürich for studies at Institute for Refractive and Ophthalmic Surgery (IROC) (Fig. 1B)
The optical power on the cornea is 3–5 mW (Fig. 1D), which is several times lower than the maximum permissible exposure level according to American National Standard Institutes (ANSI) guidelines (Supplementary Information)

Summary

Introduction

Growing evidence indicates that the biomechanical properties of ocular tissues can be diagnostic targets due to their association with various eye diseases and refractive errors[1]. The mechanical properties of the cornea stem from the intricate lattice of macromolecules, including collagen fibers and proteoglycans, making up the corneal stroma[3,4]. Disintegration of this structure alters the biomechanical properties of the stroma and shifts the overall mechanical homeostasis, potentially leading to vision-impairing morphological changes[5,6]. Advances in pachymetry and topography have greatly improved the diagnosis and treatment monitoring of KC These morphological changes are thought to be secondary to biomechanical degeneration. Www.nature.com/scientificreports motivated the development of increasingly sophisticated morphology-based metrics, specific genetic and molecular markers, and other diagnostic approaches such as measuring corneal biomechanics[1,14]

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