A few good responses: which mechanical effects of IOP on the ONH to study?

PURPOSE The biomechanical effects of IOP on the optic nerve head (ONH) are believed to play a role in glaucomatous neuropathy. There is, however, no consensus on which effects of IOP should be prioritized for investigation. Our goal was to identify a small set of variables capturing the majority of the effects of acute IOP on the ONH. METHODS We produced 4646 finite element models of the human ONH representing a wide range of tissue anatomies and mechanical properties. The effects of IOP were quantified through a set of 25 responses including stress, strain, and geometric deformation of the lamina cribrosa (LC) and peripapillary sclera. The correlations between the responses were analyzed and principal component analysis (PCA) was used to identify uncorrelated variables capturing the largest possible variance in the responses. RESULTS The responses formed groups with strong correlations. The top five principal components (PCs) accounted for 72.8%, 13.0%, 7.1%, 3.1%, and 2.0% of the variance, respectively. CONCLUSIONS Few PCs capture the majority of the mechanical effects of acute changes in IOP on the ONH, which previously required 25 measures. The PCs represented four key effects of IOP: lateral deformation associated with canal expansion (PC1), anterior-posterior deformation of the LC and the forces through it determined by either the mechanical properties of the LC (PC2) or of the neural tissue (PC4), rotation of the peripapillary sclera (PC5), and forces through the peripapillary sclera (PC3). A small set of uncorrelated variables will simplify describing and understanding the effects of IOP on the ONH.