The contribution of the sclera and lamina cribrosa to the pathogenesis of glaucoma

Quigley, Harry A.

doi:10.1016/bs.pbr.2015.04.003

Cited by 58 publications

(38 citation statements)

References 121 publications

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“…Normal lamina cribrosa structure is remodeled in glaucoma eyes, becoming deeper and wider 8 under the influence of a variety of factors, notably the stress of IOP as delivered through the sclera. 9 The regional differences in connective tissue density and pore size within the lamina cribrosa and greater regional strains suggest that the upper and lower poles of the ONH are weaker at resisting the stress of IOP in both human 10-14 and nonhuman primate eyes. 15 Indeed, these regions contain the axons of the RGCs most susceptible to glaucoma injury.…”

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confidence: 99%

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

Quigley

Arora

Idrees

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to measure change in anterior lamina cribrosa depth (ALD) globally and regionally in glaucoma eyes at different intraocular pressures (IOP).METHODS. Twenty-seven glaucoma patients were imaged before and after IOP-lowering procedures using optical coherence tomography. The anterior lamina was marked in approximately 25 locations in each of six radial scans to obtain global and regional estimates of ALD. ALD and its change with IOP were compared with optic disc damage, nerve fiber layer thickness, and visual field loss. RESULTS.Variables associated with deeper baseline ALD included larger cup/disc ratio, thinner rim area, larger cup volume, thinner central corneal thickness, and male sex (all P 0.02). When IOP was lowered, ALD position became more anterior, more posterior, or was unchanged. The mean ALD change after lowering was 27 6 142 lm (P ¼ 0.3). The mean absolute value of ALD change was 112 6 90 lm (P ¼ 0.002). Change in ALD was greater in eyes with lower IOP in paired comparisons (P ¼ 0.006) but was not associated with the magnitude of IOP lowering between imaging sessions (P ¼ 0.94). Eyes with no significant change in ALD tended to have more visual field loss than those with significant anterior ALD displacement (P ¼ 0.07). Areas within each optic nerve head that corresponded to zones with thicker nerve fiber layer had greater ALD positional change (P ¼ 0.0007).CONCLUSIONS. The lamina can move either anteriorly or posteriorly with IOP decrease, with greater displacement at lower IOP. Glaucoma eyes and regions within glaucoma eyes associated with greater glaucoma damage exhibited smaller responses.Keywords: glaucoma, lamina cribrosa, optic nerve head, optical coherence tomography, intraocular pressure, biomechanics, stress A major site of damage to retinal ganglion cell (RGC) axons in glaucoma is the optic nerve head (ONH), within the lamina cribrosa.1-3 The biomechanical transmission of stress from intraocular pressure (IOP) produces strain in both the sclera and the ONH, 4-6 generating detrimental effects on RGC axons, ONH astrocytes, and nutritional blood flow in the nerve head. 7 The IOP level that produces RGC loss can be variable among individuals; some eyes suffer damage at IOPs that would be considered normal based on population studies, whereas many eyes with elevated IOP suffer no detectable damage. This suggests that the short-and long-term responses of scleral and ONH connective tissues to changes in IOP represent possible biomarkers for glaucoma incidence and progression. Normal lamina cribrosa structure is remodeled in glaucoma eyes, becoming deeper and wider 8 under the influence of a variety of factors, notably the stress of IOP as delivered through the sclera. 9 The regional differences in connective tissue density and pore size within the lamina cribrosa and greater regional strains suggest that the upper and lower poles of the ONH are weaker at resisting the stress of IOP in both human 10-14 and nonhuman primate eyes. 15 Indeed, these regions contain...

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confidence: 99%

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

Quigley

Arora

Idrees

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…While proof still needs to be provided that tissue properties are linked to IOP susceptibility in dogs, initial biomechanical studies in ADAMTS10 ‐mutant beagles showed that their posterior sclera is weaker with reduced fibrous collagen density . Similarly, some genetically altered mice are resistant to glaucoma damage, while treatment of the sclera with cross‐linking agents worsens IOP‐related damage to the RGC axons . Once we define advantageous biomechanical properties of the fibrous layer of the eye, therapeutic tools can be developed to modify these properties in order to achieve a protective effect.…”

Section: Novel Treatment Strategies For the Futurementioning

confidence: 99%

“…The biomechanical properties of the eye, most importantly its fibrous layer (cornea, sclera, and lamina cribrosa), determine the susceptibility to various levels of IOP. 98 Even physiologic IOP can damage RGC axons as they pass through the lamina cribrosa if the surrounding connective tissue does not provide the necessary protective support. This may contribute to the disease process in nearly half of human patients with open-angle glaucoma who are normotensive with IOP measurements consistently lower than 21mmHg.…”

Section: Modification Of the Eye's Biomechanical Propertiesmentioning

confidence: 99%

“…[104][105][106] Similarly, some genetically altered mice are resistant to glaucoma damage, while treatment of the sclera with cross-linking agents worsens IOP-related damage to the RGC axons. 98 Once we define advantageous biomechanical properties of the fibrous layer of the eye, therapeutic tools can be developed to modify these properties in order to achieve a protective effect.…”

Section: Modification Of the Eye's Biomechanical Propertiesmentioning

confidence: 99%

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The future of canine glaucoma therapy

Komàromy

Bras²,

Esson

et al. 2019

Veterinary Ophthalmology

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Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO‐VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP‐lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.

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“…1,2 The biomechanical response of ONH tissue is recognized as an important risk factor in glaucoma damage. [3][4][5] OCT imaging of this response has sequentially improved with better resolution of the position of the surface of the ONH and the anterior border of the lamina cribrosa (LC). In OCT images taken at two levels of IOP, the anterior LC moves relative to reference positions, such as Bruch's membrane opening (BMO) or the choroidal-scleral interface (CSI).…”

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confidence: 99%

Evaluation of Automated Segmentation Algorithms for Optic Nerve Head Structures in Optical Coherence Tomography Images

Duan

Jefferys

Quigley

2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To compare the identification of optic nerve head (ONH) structures in optical coherence tomography images by observers and automated algorithms.METHODS. ONH images in 24 radial scan sets by optical coherence tomography were obtained in 51 eyes of 29 glaucoma patients and suspects. Masked intraobserver and interobserver comparisons were made of marked endpoints of Bruch's membrane opening (BMO) and the anterior lamina cribrosa (LC). BMO and LC positional markings were compared between observer and automated algorithm. Repeated analysis on 20 eyes by the algorithm was compared. Regional ONH data were derived from the algorithms. RESULTS.Intraobserver difference in BMO width was not significantly different from zero (P ‡ 0.32) and the difference in LC position was less than 1% different (P ¼ 0.04). Interobserver were slightly larger than intraobserver differences, but interobserver BMO width difference was 0.36% (P ¼ 0.63). Mean interobserver difference in LC position was 14.74 lm (P ¼ 0.004), 3% of the typical anterior lamina depth (ALD). Between observer and algorithm, BMO width differed by 1.85% (P ¼ 0.23) and mean LC position was not significantly different (3.77 lm, P ¼ 0.77). Repeat algorithmic analysis had a mean difference in BMO area of 0.38% (P ¼ 0.47) and mean ALD difference of 0.54 6 0.72%. Regional ALD had greater variability in the horizontal ONH regions. Some individual outlier images were not validly marked by either observers or algorithm.CONCLUSIONS. Automated identification of ONH structures is comparable to observer markings for BMO and anterior LC position, making BMO a practical reference plane for algorithmic analysis.

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The contribution of the sclera and lamina cribrosa to the pathogenesis of glaucoma

Cited by 58 publications

References 121 publications

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

Biomechanical Responses of Lamina Cribrosa to Intraocular Pressure Change Assessed by Optical Coherence Tomography in Glaucoma Eyes

The future of canine glaucoma therapy

Evaluation of Automated Segmentation Algorithms for Optic Nerve Head Structures in Optical Coherence Tomography Images

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