Brillouin microscopy: assessing ocular tissue biomechanics

Abstract

Purpose of review: Assessment of corneal biomechanics has been an unmet clinical need in ophthalmology for many years. Many researchers and clinicians have identified corneal biomechanics as source of variability in refractive procedures and one of the main factors in keratoconus. However, it has been difficult to accurately characterize corneal biomechanics in patients. The recent development of Brillouin light scattering microscopy heightens the promise of bringing biomechanics into the clinic. The aim of this review is to overview the progress and discuss prospective applications of this new technology.

Recent findings: Brillouin microscopy uses a low-power near-infrared laser beam to determine longitudinal modulus or mechanical compressibility of tissue by analyzing the return signal spectrum. Human clinical studies have demonstrated significant difference in the elastic properties of normal corneas versus corneas diagnosed with mild and severe keratoconus. Clinical data have also shown biomechanical changes after corneal cross-linking treatment of keratoconus patients. Brillouin measurements of the crystalline lens and sclera have also been demonstrated.

Summary: Brillouin microscopy is a promising technology under commercial development at present. The technique enables physicians to characterize the biomechanical properties of ocular tissues.

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FIGURE 1

The principle of Brillouin microscopy. A low-power, narrowband NIR laser light is focused into the corneal tissue, and the Doppler Brillouin frequency shift of scattered light from the focus is analyzed by a confocal spectrometer. Spontaneous Brillouin scattering originates from thermodynamically induced pressure (acoustic) waves. The magnitude of Brillouin frequency is proportional to the acoustic propagation speed of tissue at the focus and provides a direct measurement of local longitudinal modulus of the tissue. NIR, near-infrared.

FIGURE 2

Brillouin measurements of normal population. (a) Central cornea Brillouin frequency values of normal individuals in an age range of 15–70. (b) Diurnal change of a healthy volunteer. Within 1 h after wake-up, the hydration level of corneal stroma is stabilized, so are the central corneal thickness (CCT) and Brillouin frequency. The magnitude of frequency variation during day time is less than the instrument's sensitivity of ±10 MHz.

FIGURE 3

Brillouin measurement of keratoconus patients. (a) Brillouin maps and corresponding pachymetry maps by Pentacam (Oculus Gmbh) of patients diagnosed with mild KC (stage 1; middle) and severe KC (right), in comparison to a normal subject (left). (b) The difference in Brillouin frequency between left and right eyes. The bilateral asymmetry is significantly higher in early-stage keratoconus.

FIGURE 4

Brillouin axial profiles of the crystalline lens in two healthy volunteers with different ages.