Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging

Ke Wang, Murray A. Johnstone, Chen Xin, Shaozhen Song, Steven Padilla, Janice Vranka, Ted Acott, Kai Zhou, Stephen A. Schwaner, Ruikang K. Wang, Todd Sulchek, C. Ross Ethier

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

PURPOSE. The purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements. METHODS. Postmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm’s canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward. RESULTS. The elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018). CONCLUSIONS. TM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

Original languageEnglish (US)
Pages (from-to)4809-4817
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number11
DOIs
StatePublished - Sep 1 2017

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Trabecular Meshwork
Optical Coherence Tomography
Atomic Force Microscopy
Elastic Modulus
Glaucoma
Pressure

Keywords

  • AFM
  • Finite element modeling
  • Glaucoma
  • Ocular biomechanics
  • Stiffness
  • Trabecular meshwork

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging. / Wang, Ke; Johnstone, Murray A.; Xin, Chen; Song, Shaozhen; Padilla, Steven; Vranka, Janice; Acott, Ted; Zhou, Kai; Schwaner, Stephen A.; Wang, Ruikang K.; Sulchek, Todd; Ethier, C. Ross.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 11, 01.09.2017, p. 4809-4817.

Research output: Contribution to journalArticle

Wang, K, Johnstone, MA, Xin, C, Song, S, Padilla, S, Vranka, J, Acott, T, Zhou, K, Schwaner, SA, Wang, RK, Sulchek, T & Ethier, CR 2017, 'Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging', Investigative Ophthalmology and Visual Science, vol. 58, no. 11, pp. 4809-4817. https://doi.org/10.1167/iovs.17-22175
Wang, Ke ; Johnstone, Murray A. ; Xin, Chen ; Song, Shaozhen ; Padilla, Steven ; Vranka, Janice ; Acott, Ted ; Zhou, Kai ; Schwaner, Stephen A. ; Wang, Ruikang K. ; Sulchek, Todd ; Ethier, C. Ross. / Estimating human trabecular meshwork stiffness by numerical modeling and advanced OCT imaging. In: Investigative Ophthalmology and Visual Science. 2017 ; Vol. 58, No. 11. pp. 4809-4817.
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AU - Johnstone, Murray A.

AU - Xin, Chen

AU - Song, Shaozhen

AU - Padilla, Steven

AU - Vranka, Janice

AU - Acott, Ted

AU - Zhou, Kai

AU - Schwaner, Stephen A.

AU - Wang, Ruikang K.

AU - Sulchek, Todd

AU - Ethier, C. Ross

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N2 - PURPOSE. The purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements. METHODS. Postmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm’s canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward. RESULTS. The elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018). CONCLUSIONS. TM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

AB - PURPOSE. The purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements. METHODS. Postmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm’s canal luminal pressure was directly manipulated. TM stiffness was deduced by an inverse finite element modeling (FEM) approach. A series of AFM forcemaps was acquired along a line traversing the anterior angle on a radially cut flat-mount corneoscleral wedge with TM facing upward. RESULTS. The elastic modulus of normal hTM estimated by inverse FEM was 70 ± 20 kPa (mean ± SD), whereas glaucomatous hTM was slightly stiffer (98 ± 19 kPa). This trend was consistent with TM stiffnesses measured by AFM: normal hTM stiffness = 1.37 ± 0.56 kPa, which was lower than glaucomatous hTM stiffness (2.75 ± 1.19 kPa). None of these differences were statistically significant. TM in HF wedges was softer than that in LF wedges for both normal and glaucomatous eyes based on the inverse FEM approach but not by AFM. Outflow facility was significantly correlated with TM stiffness estimated by FEM in six human eyes (P = 0.018). CONCLUSIONS. TM stiffness is higher, but only modestly so, in glaucomatous patients. Outflow facility in both normal and glaucomatous human eyes appears to associate with TM stiffness. This evidence motivates further studies to investigate factors underlying TM biomechanical property regulation.

KW - AFM

KW - Finite element modeling

KW - Glaucoma

KW - Ocular biomechanics

KW - Stiffness

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