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

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.

The Role of Corneal Biomechanics for the Evaluation of Ectasia Patients

“…Considering the "focal" nature of KC and ectatic diseases, this biomechanical corneal "mapping" might be relevant for allowing earlier detection of the disease. Interestingly, mild KC was discriminated from normal and clinically ectatic corneas comparing the Brillouin frequency between eyes, with biomechanical asymmetry being an efficient and accurate metric [38,39].…”

An interferometric ex vivo study of corneal biomechanics under physiologically representative loading, highlighting the role of the limbus in pressure compensation

“…Acknowledging the limitations of strip testing, a variety of methods have now been investigated to probe the biomechanics of intact corneal tissue under physiologically relevant loading conditions, these methods include; Brillouin spectroscopy (BrS), optical coherence elastography (OCE), high frequency ultrasound (HFU), digital image correlation (DIC) and interferometry. Of these, BrS and OCE have demonstrated potential to acquire data in a clinical setting [11,12]. BrS evaluates longitudinal modulus, which is related to compressibility (bulk modulus) in isotropic materials.…”

In vivo measurement of shear modulus of the human cornea using optical coherence elastography

“…However, these approaches do not offer a quantitative readout of elastic modulus and require complex numerical analysis for spatially-resolved measurements 14 . Brillouin microscopy can measure longitudinal modulus with high spatial resolution 15,16 , but it is shear and Young's moduli that are directly related to corneal stiffness with respect to external force. Optical coherence elastography (OCE) has emerged as a promising technique with high spatial resolution and high sensitivity to mechanical deformation of tissue 17,18 .…”