RT Journal Article SR Electronic T1 In vivo Modulation of Intraocular and Intracranial Pressures Causes Nonlinear and Non-monotonic Deformations of the Lamina Cribrosa and Scleral Canal JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.01.29.526113 DO 10.1101/2023.01.29.526113 A1 Zhu, Ziyi A1 Waxman, Susannah A1 Wang, Bo A1 Wallace, Jacob A1 Schmitt, Samantha E. A1 Tyler-Kabara, Elizabeth A1 Ishikawa, Hiroshi A1 Schuman, Joel S. A1 Smith, Matthew A. A1 Wollstein, Gadi A1 Sigal, Ian A. YR 2023 UL http://biorxiv.org/content/early/2023/01/31/2023.01.29.526113.abstract AB Purpose To evaluate changes in monkey optic nerve head (ONH) morphology under acutely controlled intraocular pressure (IOP) and intracranial pressure (ICP).Methods Seven ONHs from six monkeys were imaged via optical coherence tomography while IOP and ICP were maintained at one of 16 conditions. These conditions were defined by 4 levels for each pressure: low, baseline, high and very high. Images were processed to determine scleral canal area, aspect ratio, and planarity and anterior lamina cribrosa (ALC) shape index and curvature. Linear mixed effect models were utilized to investigate the effects of IOP, ICP and their interactions on ONH morphological features. The IOP-ICP interaction model was compared with one based on translaminar pressure difference (TLPD).Results We observed complex, eye-specific, non-linear patterns of ONH morphological changes with changes in IOP and ICP. For all ONH morphological features, linear mixed effects models demonstrated significant interactions between IOP and ICP that were unaccounted for by TLPD. Interactions indicate that the effects of IOP and ICP depend on the other pressure. The IOP-ICP interaction model was a higher quality predictor of ONH features than a TLPD model.Conclusions In vivo modulation of IOP and ICP causes nonlinear and non-monotonic changes in monkey ONH morphology that depend on both pressures and is not accounted for by a simplistic TLPD. These results support and extend prior findings.Translational Relevance: A better understanding of ICP’s influence on the effects of IOP can help inform the highly variable presentations of glaucoma and effective treatment strategies.Competing Interest StatementProprietary Interest: J.S. Schuman receives royalties for intellectual property licensed by Massachusetts Institute of Technology to Zeiss. All other authors: Nothing to disclose