Abstract
Purpose:
In keratoconus, corneal mechanical stability is gradually compromised which contributes to progressive morphological changes. In particular, the spatial distribution of elastic modulus within the cornea may lead to a mechanical imbalance within the cornea, which is expected to be a major driver of corneal shape changes. Here we use novel Brillouin microscopy to observe, for the first time, that keratoconic corneas present regions of localized decrease in stromal strength.
Methods:
We recruited six healthy volunteers (Age=37±15) and five patients with advanced keratoconus (Age=43±7). All participants signed an informed consent form approved by the Institutional Review Board of Partners Healthcare, in accordance with the principles embodied in the Declaration of Helsinki. Using a clinically-viable confocal Brillouin microscope we measured the Brillouin shift in the anterior stroma, which we have previously shown to correlate to the stromal elastic modulus. To compare the spatial distributions, we mapped the Brillouin shift in areas of typical size of 5mm x 5mm.
Results:
Keratoconic corneas showed strong spatial variations of Brillouin shift across the cornea; on the other hand, normal subjects presented a uniform distribution. In keratoconus corneas, Brillouin shift was markedly lower than normal in the cone region (within a 1mm radius from thinnest point) while it was comparable to normal values outside the cone region (> 3mm away from the cone). From the Brillouin shift values, we estimated that the decrease in elastic modulus in the cone area is very significant (~ 70%) compared to normal values. All these observation are consistent with our ex vivo investigation of normal vs advanced keratoconus cornea tissue samples.
Conclusions:
Brillouin microscopy allowed identifying and quantifying a notable biomechanical feature of keratoconus progression, i.e. a marked and localized loss of strength in the cone area. This suggests that elasticity-based metrics may be highly relevant for keratoconus diagnosis and management as well as for therapy monitoring. Our results clearly demonstrate the need of performing spatially-resolved measurements when characterizing corneal biomechanics.