Corneal material nonlinearity and its effects on the comparative study of corneal biomechanics

Corneal biomechanical evaluation has become a research hotspot with wide clinical relevance in fields such as keratoconus, corneal cross-linking, refractive surgery, and glaucoma. Despite advances in in-vivo corneal biomechanical imaging, ex-vivo experiments remain essential for comparing biomechanical effects of diseases and treatment protocols. However, due to the nonlinear behaviour of corneal material, comparisons of biomechanical metrics obtained under different loading conditions can be difficult and misleading. Furthermore, biomechanical estimations conducted under unrealistic loads that exceed normal living conditions may have limited clinical relevance. The current study aims to evaluate this issue by assessing the biomechanical properties of the cornea under physiologic and extreme conditions. Stress-strain data were obtained for porcine corneal specimens subjected to widely different strain rates (0.8%, 25%, 83% and 420% /min). In all cases, the behaviour closely matched a two-stage pattern consisting of an initial nonlinear low-stress region followed by a linear region under higher stresses. Tangent moduli (Et) were calculated at physiologic stress levels (0.01, 0.015, and 0.02 MPa) and extreme ones (0.15, 1.0, and 2.0 MPa). While comparisons at physiologic stress levels showed similar increasing trends in Et with faster strain rates, at high/non-physiologic stress levels, Et values remained relatively unchanged across strain rates from 25% to 420% /min. These findings underscore the importance of testing corneal behaviour under physiologic loading levels and signal cautions when interpreting results under high loads that do not represent normal tissue conditions. • Corneal tissue is nonlinear at low stress and linear at high/non-physiologic stress • Tangent moduli comparisons made at different stress levels yield varied conclusions • Corneal material characterisation at high stress may have limited clinical value • Reporting corneal behaviour under physiologic loading levels is encouraged