Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma

Gerberich, Brandon G.; Hannon, Bailey G.; Brown, Dillon; Read, A. Thomas; Ritch, Matthew D.; Echeverri, Elisa Schrader; Nichols, Lauren M.; Potnis, Cahil; Sridhar, Sreesh; Toothman, Maya G; Schwaner, Stephen A.; Winger, Erin J; Huang, Hannah G.; Gershon, G.S.; Feola, Andrew; Pardue, Machelle T.; Prausnitz, Mark R.; Ethier, C. Ross

doi:10.1167/tvst.11.5.7

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…In vivo rodent models of experimentally induced glaucoma did not show a protective effect of PPS stiffening against glaucoma damage, despite reduced in-plane strains. 49 , 50 These results, along with the findings in the present study, indicated that the ONH and PPS radial compression may be potentially a more important driver in IOP-related glaucomatous damage and warrants further study.…”

Section: Discussionsupporting

confidence: 63%

Three-Dimensional Ultrasound Elastography Detects Age-Related Increase in Anterior Peripapillary Sclera and Optic Nerve Head Compression During IOP Elevation

Kwok

Pan

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose High-frequency ultrasound elastography offers a tool to resolve the complex and heterogeneous deformation through the full thickness of the optic nerve head (ONH) and peripapillary sclera (PPS). Using this tool, we quantified the three-dimensional deformation of the ONH and PPS in human donor eyes and evaluated age-associated changes. Methods The ONH and PPS in 15 human donor globes were imaged with a 50-MHz ultrasound probe while increasing intraocular pressure (IOP) from 15 to 30 mm Hg. Tissue displacements were obtained using correlation-based ultrasound speckle tracking. Three-dimensional spherical strains (radial, circumferential, meridional, and respective shear strains) were calculated for the ONH and PPS volumes segmented from three-dimensional ultrasound images. Age-related trends of different strains in each region of interest were explored. Results The dominant form of IOP-induced deformation in the ONH and PPS was radial compression. High-magnitude localized out-of-plane shear strains were also observed in both regions. Most strains were concentrated in the anterior one-half of the ONH and PPS. The magnitude of radial and volumetric strains increased with age in the anterior ONH and anterior PPS, indicating greater radial compression and volume loss during IOP elevation in older age. Conclusions The age-associated increase of radial compression, the predominant form of IOP-induced deformation in anterior ONH and PPS, may underlie age-associated glaucoma risk. High-frequency ultrasound elastography offers a useful tool to quantify all types of deformation comprehensively in all regions of ONH and PPS, which may improve our understanding of the biomechanical factors contributing to glaucoma risk.

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Section: Discussionsupporting

confidence: 63%

Three-Dimensional Ultrasound Elastography Detects Age-Related Increase in Anterior Peripapillary Sclera and Optic Nerve Head Compression During IOP Elevation

Kwok

Pan

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…Additional studies could correlate the number of crosslinks needed for minipig and human eyes to achieve the same increase in scleral mechanical strength as seen in rat. It is unknown if a similar extent of crosslinking is required in minipig or human sclera to achieve similar treatment outcomes that were achieved in rat [ 10 ] or if those levels of scleral stiffening will be effective to treat glaucoma [ 17 ]. Additionally, experiments should be done to determine if spatial crosslinking distribution in minipig and human being in the centre of the sclera gives different biomechanical outcomes than in rat, which has crosslinking in the posterior sclera.…”

Section: Discussionmentioning

confidence: 99%

“…Scleral crosslinking for glaucoma treatment is proposed to be targeted to a region of sclera that rings the optic disc [ 10 , 17 ]. We calculated the volume ( V ) of a hollow spherical frustum comprising the peripapillary tissue targeted for selective photocrosslinking by assuming the eye to be a perfect sphere in all species (electronic supplementary material, §S1).…”

Section: Methodsmentioning

confidence: 99%

“…Selective peripapillary scleral crosslinking is of interest for glaucoma treatment since this tissue undergoes more strain compared to anterior scleral tissue during IOP increase in glaucomatous patients [ 16 , 17 ]. It is our hypothesis that decreasing strain around the optic nerve by selective peripapillary scleral crosslinking could help prevent glaucomatous damage [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Computational modelling of scleral photocrosslinking: from rat to minipig to human

Wood-Yang,

Gerberich,

Prausnitz

2024

J. R. Soc. Interface.

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Selective scleral crosslinking has been proposed as a novel treatment to increase scleral stiffness to counteract biomechanical changes associated with glaucoma and high myopia. Scleral stiffening has been shown by transpupillary peripapillary scleral photocrosslinking in rats, where the photosensitizer, methylene blue (MB), was injected retrobulbarly and red light initiated crosslinking reactions with collagen. Here, we adapted a computational model previously developed to model this treatment in rat eyes to additionally model MB photocrosslinking in minipigs and humans. Increased tissue length and subsequent diffusion and light penetration limitations were found to be barriers to achieving the same extent of crosslinking as in rats. Per cent inspired O 2 , injected MB concentration and laser fluence were simultaneously varied to overcome these limitations and used to determine optimal combinations of treatment parameters in rats, minipigs and humans. Increasing these three treatment parameters simultaneously resulted in maximum crosslinking, except in rats, where the highest MB concentrations decreased crosslinking. Additionally, the kinetics and diffusion of photocrosslinking reaction intermediates and unproductive side products were modelled across space and time. The model provides a mechanistic understanding of MB photocrosslinking in scleral tissue and a basis for adapting and screening treatment parameters in larger animal models and, eventually, human eyes.

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The Morphology of Normal, Aging, and Glaucomatous Optic Nerves

Jakobs

2024

Reference Module in Neuroscience and Biobehavioral Psychology

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Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma

Cited by 5 publications

References 69 publications

Three-Dimensional Ultrasound Elastography Detects Age-Related Increase in Anterior Peripapillary Sclera and Optic Nerve Head Compression During IOP Elevation

Three-Dimensional Ultrasound Elastography Detects Age-Related Increase in Anterior Peripapillary Sclera and Optic Nerve Head Compression During IOP Elevation

Computational modelling of scleral photocrosslinking: from rat to minipig to human

The Morphology of Normal, Aging, and Glaucomatous Optic Nerves

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