The cornea

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber and has an optical and protective function.



Corneal stiffness plays a critical role in shaping the cornea with respect to intraocular pressure and physical interventions. However, it remains difficult to measure mechanical properties non-invasively. Here, we report the first measurement of the shear modulus in human corneas in vivo using surface elastic wave-based optical coherence elastography (OCE). In a pilot study of 12 healthy subjects between the ages of 25 and 67, the Rayleigh wave velocity was 7.86 ± 0.75 m / s, corresponding to a shear modulus of 72 ± 14 kPa.
The shear modulus is an elastic constant that characterizes the change in shape that an elastic material experiences when shear stresses are applied to it.
Our data reveal two unexpected trends: no correlation was found between wave velocity and intraocular pressure between 13-18 mmHg, and the shear modulus decreased with age (- 0.32 ± 0.17 m / s per decade). We propose that shear stiffness is governed by the interfibrillar matrix, while tensile strength is dominated by collagen fibrils. Rayleigh wave ECO can be useful for clinical diagnosis, refractive surgery, and treatment follow-up.

The cornea plays an important role in human vision by providing approximately two-thirds of the refractive power of the eye. The meniscus shape of the cornea is the result of a mechanical balance of the cornea with respect to intraocular pressure (IOP). A change in mechanical homeostasis can alter the shape of the cornea and thus affect visual acuity. This relationship is also the basis of refractive surgeries that improve vision, such as laser-assisted in situ keratomileusis (LASIK) and limbal relaxing incision (LRI), in which refractive errors are corrected by means of the combination of tissue ablation and the resulting stress - and stiffness - driven remodeling. Corneal tissues are believed to lose stiffness in degenerative corneal disorders, such as keratoconus, leading to conical ectasia with impaired vision. An accepted treatment for ectasia, corneal reticulation (CXL), is intended to mechanically stabilize the cornea. Therefore, the measurement of the mechanical parameters of the cornea is useful in assessing the health of the cornea, improving refractive treatments, and diagnosing degenerative disorders.

While the measurement of intraocular pressure by tonometry is well established and performed routinely as part of standard care, it remains a challenge to quantitatively characterize the physical integrity of the cornea in a clinical setting. Standard mechanical characterization techniques, such as uniaxial strip (corneal), compression and inflation testing, have provided a basic understanding of corneal biomechanics ex vivo, but these invasive methods are not applicable for clinical use. .

Elastography

For in vivo measurement, elastography holds promise, and several specific approaches have been devised with different advantages. Strain-imaging ultrasound elastography and shear wave elasticity imaging (SWEI) have been used to examine sclerosis and liver cancers, but their spatial resolution and required acoustic energy are not suitable for routine corneal applications. Surface wave elastometry using a pair of ultrasound transducers was proposed for corneal applications, but the two-point approach did not offer spatial resolution or the ability to distinguish different types of elastic waves. Ocular response analyzers and optical elastography using air stimuli provide empirical indices related to the viscoelastic properties of the cornea. However, these approaches do not provide a quantitative reading of the elastic modulus and require complex numerical analysis for spatial resolution measurements. Brillouin microscopy can measure the longitudinal modulus of the cornea with high spatial resolution, but it is the shear and Young's moduli that are directly related to the stiffness of the cornea with respect to external force.

Optical coherence elastography

Optical coherence elastography (OCE) has emerged as a promising technique with high spatial resolution and great sensitivity to mechanical tissue deformation. Recently, a compression-based ECO technique has been tested in humans, but the ability to measure elasticity remains to be developed quantitatively. Quantitative approaches based on elastic wave excitation have been widely studied with ex vivo tissues and living animals.

The article reports, for the first time to our knowledge, on the quantitative in vivo measurement of the shear modulus of the human cornea. This measurement was made possible by using an OCE system with a miniature contact probe that safely excites low-energy elastic waves in the human cornea in a frequency range centered around 10 kHz. This relatively high excitation frequency induces Rayleigh-like elastic waves in the human cornea, allowing measurements with great precision and spatial resolution. We also demonstrate in vivo measurement of the human sclera.

A pilot study of 12 healthy subjects yielded interesting conclusions that were not expected from previous ex vivo results, such as the dependence of the shear modulus on age and physiological IOP levels.
We provide possible explanations for our observation based on a constitutive mechanical model of the cornea.

The work is a collaboration between the Institute of Optics (Visual Optics and Biophotonics Lab) and the Wellman Center for Photomedicine and Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.

Link to the paper