Brillouin microscopy for focal biomechanical measurements in normal and keratoconic corneas: A narrative review.

Corneal mechanical weakness is widely recognized as the root cause of keratoconus and a primary driver for undesirable refractive surgery outcomes. Theory, finite element modeling, and initial data predict that focal rather than generalized weakening precipitates corneal mechanical decompensation. Direct, 3-dimensionally (3-D) localized in vivo corneal mechanical measurements thus have the potential to revolutionize keratoconus management and the surgical correction of myopia. Collagen microarchitecture and mechanical profiles in normal and keratoconic corneas have been evaluated ex vivo, but significant gaps remain in our understanding of the earliest subclinical manifestations that can eventually lead to clinical disease. Nonperturbative Brillouin microscopy has emerged as a novel approach for measuring corneal mechanics by analyzing Brillouin light scattering, which encodes the corneal elastic modulus (longitudinal modulus). Early ex vivo works demonstrated the technique's ability to identify depth-dependent (axial) anisotropy in the normal cornea, focal weakening in the keratoconic cornea, and stiffening after corneal cross-linking. Recent advances using motion-tracking Brillouin imaging, which employs optical coherence tomography and eye tracking to facilitate 3-D signal localization, have provided novel insights into keratoconus at the subclinical stage. Locally reduced Brillouin shift values in the anterior cornea have differentiated subclinical keratoconic cornea from normal controls and outperformed current clinical standard morphologic evaluation using Scheimpflug technology. Herein, we highlight the development of Brillouin microscopy for in vivo corneal analysis, current imaging advances and technological limitations, and future directions for in vivo analysis of subclinical keratoconus to advance our understanding of keratoconus diagnosis, disease evolution, and management.