Brillouin Spectroscopy of Normal and Keratoconus Corneas

Am J Ophthalmol. 2019 Jun;202:118-125. doi: 10.1016/j.ajo.2019.02.010. Epub 2019 Feb 15.


Purpose: To investigate the age dependence of Brillouin spectroscopy of the cornea and to compare normal and keratoconus corneas.

Design: Retrospective case-control study.

Methods: Study Population: Healthy patients and patients suffering from keratoconus seen at the Institut für Refraktive und Ophthalmo-Chirurgie (IROC) between December 2016 and March 2017. Brillouin frequency shifts of patients of 2 different groups were examined with Brillouin spectroscopy perpendicular to the corneal surface. Group 1 consisted of 47 healthy eyes, whereas Group 2 included 36 eyes with keratoconus of unclear progression. Besides Brillouin examinations, corneal tomographies were acquired so that correlations and comparisons between geometric parameters and Brillouin frequency shifts could be evaluated.

Main outcome measures: Corneal Brillouin frequency shifts averaged over full corneal thickness.

Results: A significant correlation between age and central Brillouin frequency shift was identified (P = .011) with an increase in Brillouin frequency shift of 4 MHz per decade in normal corneas. Keratoconus corneas have a significantly reduced Brillouin frequency shift at the thinnest point compared to normal corneas (5.7072 ± 0.0214 vs 5.7236 ± 0.0146 GHz, P < .001). The Brillouin frequency shift at the point of maximum posterior elevation showed best correlation with geometry-derived keratoconus indices. The receiver operating characteristic curve analysis of Brillouin frequency shift showed substantially worse sensitivity and specificity compared to Kmax and thinnest pachymetry for keratoconus detection.

Conclusion: Noninvasive Brillouin spectroscopy adds clinical information about the biomechanical state of the cornea perpendicular to the surface. An age-dependent stiffening of the cornea has been found and keratoconus corneas are statistically significantly different from normal corneas, but for precise differentiating of keratoconus stages (including normal corneas) the method is currently neither specific nor sensitive enough. Further development including standardized mapping and establishment of new indices may increase the potential of Brillouin spectroscopy substantially.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cornea / diagnostic imaging*
  • Corneal Pachymetry
  • Corneal Topography / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Keratoconus / diagnosis*
  • Male
  • Middle Aged
  • ROC Curve
  • Retrospective Studies
  • Spectrum Analysis / methods*
  • Young Adult