title: What is a typical optic nerve head?
abstract: Whereas it is known that elevated intraocular pressure (IOP) increases the risk of glaucoma, it is not known why optic nerve heads (ONHs) vary so much in sensitivity to IOP and how this sensitivity depends on the characteristics of the ONH such as tissue mechanical properties and geometry. It is often assumed that ONHs with uncommon or atypical sensitivity to IOP, high sensitivity in normal tension glaucoma or high robustness in ocular hypertension, also have atypical ONH characteristics. Here we address two specific questions quantitatively: Do atypical ONH characteristics necessarily lead to atypical biomechanical responses to elevated IOP? And, do typical biomechanical responses necessarily come from ONHs with typical characteristics. We generated 100,000 ONH numerical models with randomly selected values for the characteristics, all falling within literature ranges of normal ONHs. The models were solved to predict their biomechanical response to an increase in IOP. We classified ONH characteristics and biomechanical responses into typical or atypical using a percentile-based threshold, and calculated the fraction of ONHs for which the answers to the two questions were true and/or false. We then studied the effects of varying the percentile threshold. We found that when we classified the extreme 5% of individual ONH characteristics or responses as atypical, only 28% of ONHs with an atypical characteristic had an atypical response. Further, almost 29% of typical responses came from ONHs with at least one atypical characteristic. Thus, the answer to both questions is no. This answer held irrespective of the threshold for classifying typical or atypical. Our results challenge the assumption that ONHs with atypical sensitivity to IOP must have atypical characteristics. This finding suggests that the traditional approach of identifying risk factors by comparing characteristics between patient groups (e.g. ocular hypertensive vs. primary open angle glaucoma) may not be a sound strategy.
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Voorhees
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Grimm
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Bilonick
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kagemann
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Fox Center for Vision Restoration of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Schuman
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wollstein
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; McGowan Institute for Regenerative Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: Ian@ocularbiomechanics.com.
authors.forename: I A
authors.initials: IA
authors.lastname: Sigal
mesh_terms: D001696:Biomechanical Phenomena; D003198:Computer Simulation; D020342:Finite Element Analysis; D005901:Glaucoma / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008962:Models, Theoretical; D009898:Optic Disk / Q000503:physiopathology*
keywords: Biomechanics; Glaucoma; IOP; Lamina cribrosa; Optic nerve head; Sensitivity; Stochastic modeling