The Strain Response to Intraocular Pressure Decrease in the Lamina Cribrosa of Patients with Glaucoma

Czerpak, Cameron A.; Kashaf, Michael Saheb; Zimmerman, Brandon; Quigley, Harry A.; Nguyen, Thao D.

doi:10.1016/j.ogla.2022.07.005

Cited by 13 publications

(47 citation statements)

References 85 publications

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“…Indeed, mildly damaged glaucoma eyes have lower strains than more severely damaged eyes. 87 This is consistent with our postmortem strain data that showed greater strain in glaucoma eyes with worse damage compared to less damaged eyes. 45 The fact that LC beams were found to be thinner in more advanced OAG eyes in our data supports the conclusion that strains would be greater.…”

Section: Discussionsupporting

confidence: 91%

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Guan

Pease

Quillen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To measure quantitatively changes in lamina cribrosa (LC) cell and connective tissue structure in human glaucoma eyes. Methods We studied 27 glaucoma and 19 age-matched non-glaucoma postmortem eyes. In 25 eyes, LC cross-sections were examined by confocal and multiphoton microscopy to quantify structures identified by anti-glial fibrillary acidic protein (GFAP), phalloidin-labeled F-actin, nuclear 4′,6-diamidino-2-phenylindole (DAPI), and by second harmonic generation imaging of LC beams. Additional light and transmission electron microscopy were performed in 21 eyes to confirm features of LC remodeling, including immunolabeling by anti-SOX9 and anti-collagen IV. All glaucoma eyes had detailed clinical histories of open-angle glaucoma status, and degree of axon loss was quantified in retrolaminar optic nerve cross-sections. Results Within LC pores, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes than in controls ( P = 0.01). Nuclei were rounder (lower median aspect ratio) in glaucoma specimens ( P = 0.02). In models assessing degree of glaucoma damage, F-actin process width was significantly wider in glaucoma eyes with more damage ( P = 0.024), average LC beam width decreased with worse glaucoma damage ( P = 0.042), and nuclear count per square millimeter rose with worse damage ( P = 0.019). The greater cell count in LC pores represented 92.3% astrocytes by SOX9 labeling. The results are consistent with replacement of axons in LC pores by basement membrane labeled by anti-collagen IV and in-migrating astrocytes. Conclusions Alteration in LC structure in glaucoma involves migration of astrocytes into axonal bundles, change in astrocyte orientation and processes, production of basement membrane material, and thinning of connective tissue beams.

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Section: Discussionsupporting

confidence: 91%

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Guan

Pease

Quillen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Most importantly, our data and those of Girard et al 11 indicate that eyes with greater loss of retinal ganglion cells have greater LC strain. 14 , 15 These data suggest that short-term LC strain measurements may provide biomarkers for glaucoma susceptibility.…”

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confidence: 79%

“…Eyes were imaged by OCT (Spectralis, Heidelberg Engineering) before and 7.3 ± 1.4 days after IOP change, using methods previously described. 14 Before the first imaging session, all eyes underwent a standard glaucoma examination to assess disease progression, which measured their average retinal nerve fiber layer (RNFL) thickness and visual field (VF) status (Zeiss Humphrey Field Analyzer [HFA2i or 3] 24-2 Swedish Interactive Threshold Algorithm [SITA Standard] field tests; Zeiss HFA2i) with the indices mean deviation (MD) and VF index (VFI) within 3 months of imaging. Retinal nerve fiber layer thickness was measured using Cirrus OCT (Zeiss).…”

Section: Methodsmentioning

confidence: 99%

“… 9 , 10 , 11 , 12 , 13 With modest IOP lowering, biomechanical strains are regularly obtainable and fit with the expected deformation of the LC tissue, undergoing expansion in the anterior–posterior direction and contraction in diameter. 14 Artificial elevation of IOP produced corresponding compression of the lamina. Most importantly, our data and those of Girard et al 11 indicate that eyes with greater loss of retinal ganglion cells have greater LC strain.…”

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confidence: 99%

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A Noninvasive Clinical Method to Measure in Vivo Mechanical Strains of the Lamina Cribrosa by OCT

Hannay,

Czerpak,

Quigley

et al. 2024

Ophthalmology Science

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“…Optical coherence tomography (OCT) combined with DVC is also a promising technique to investigate soft tissues. OCT-based DVC applications include measurement of displacement/strain fields in porcine aortic tissues ( Acosta Santamaría et al, 2018 ) and biomechanical strains in human ocular tissue of patients affected by glaucoma ( Czerpak et al, 2022 ). Its further implementation in musculoskeletal tissues such as articular cartilage and tendon/ligament would surely contribute to advance understanding of their biomechanics.…”

Section: Open Challenges and Current/future Developmentsmentioning

confidence: 99%

Digital volume correlation for the characterization of musculoskeletal tissues: Current challenges and future developments

Dall’Ara

Tozzi

2022

Front. Bioeng. Biotechnol.

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Biological tissues are complex hierarchical materials, difficult to characterise due to the challenges associated to the separation of scale and heterogeneity of the mechanical properties at different dimensional levels.The Digital Volume Correlation approach is the only image-based experimental approach that can accurately measure internal strain field within biological tissues under complex loading scenarios. In this minireview examples of DVC applications to study the deformation of musculoskeletal tissues at different dimensional scales are reported, highlighting the potential and challenges of this relatively new technique.The manuscript aims at reporting the wide breath of DVC applications in the past 2 decades and discuss future perspective for this unique technique, including fast analysis, applications on soft tissues, high precision approaches, and clinical applications.

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The Strain Response to Intraocular Pressure Decrease in the Lamina Cribrosa of Patients with Glaucoma

Cited by 13 publications

References 85 publications

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

A Noninvasive Clinical Method to Measure in Vivo Mechanical Strains of the Lamina Cribrosa by OCT

Digital volume correlation for the characterization of musculoskeletal tissues: Current challenges and future developments

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