Glaucomatous cupping of the human optic disk

Vrabec, F

doi:10.1007/bf00410715

Cited by 50 publications

(20 citation statements)

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“…We categorized the patients into three groups of equal size (nine eyes each) based on the direction that the lamina moved with IOP change: (1) those that moved in a negative direction (ALD was deeper at lower IOP), (2) those that had no defined ALD change, and (3) those that moved in a positive direction (ALD was deeper at higher IOP) ( Table 1). The no change group had ALD difference values within intrasubject reproducibility ( 50-lm mean difference in either direction).…”

Section: Change In Ald Grouped By Direction Of Movementmentioning

confidence: 99%

“…[1][2][3] The biomechanical transmission of stress from intraocular pressure (IOP) produces strain in both the sclera and the ONH, [4][5][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.…”

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confidence: 99%

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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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Section: Change In Ald Grouped By Direction Of Movementmentioning

confidence: 99%

mentioning

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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“…The results suggest further that ONH structural deformation is an “upstream” event in the pathophysiology of glaucoma, at least in this model. The hypothesis that axons are injured within the ONH by glaucomatous deformation has been proposed and evaluated before [1,2,5,42,43], and extended more recently to rodent models [44,45] (c.f. Chauhan et al [46]), so the results of this study can be considered confirmatory and to have extended the evidence provided by earlier studies.…”

Section: Discussionmentioning

confidence: 99%

Does Optic Nerve Head Surface Topography Change Prior to Loss of Retinal Nerve Fiber Layer Thickness: A Test of the Site of Injury Hypothesis in Experimental Glaucoma

et al. 2013

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PurposeTo test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG).Methods68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an ‘endpoint’ occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT.ResultsRegardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d’) was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone.ConclusionsThis study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma.

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“…(Quigley, 1999, 2011; Quigley et al, 1981; Weinreb and Khaw, 2004) The initiating injury to RGCs and their axons is thought to occur within the optic nerve head (ONH). (Anderson and Hendrickson, 1974; Emery et al, 1974; Howell et al, 2012; Nickells et al, 2012; Quigley, 1999; Quigley et al, 1981; Vrabec, 1976) Indeed, chronic progressive deformation of the ONH tissues (traditionally referred to as “cupping” and/or “excavation”) is considered the hallmark of glaucoma, a clinical sign used to distinguish it from other optic neuropathies. (Danesh-Meyer et al, 2009; Quigley, 1993, 2011; Van Buskirk and Cioffi, 1992; Weinreb and Khaw, 2004) Thus clinical diagnosis and management of glaucoma depend not only on assessment of vision function, such as by measuring sensitivity across the visual field using automated perimetry, but also on assessment of structural integrity of the ONH and RGC axons within the retinal nerve fiber layer (RNFL).…”

Section: Introductionmentioning

confidence: 99%

In vivo imaging methods to assess glaucomatous optic neuropathy

Fortune

2015

Experimental Eye Research

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The goal of this review is to summarize the most common imaging methods currently applied for in vivo assessment of ocular structure in animal models of experimental glaucoma with an emphasis on translational relevance to clinical studies of the human disease. The most common techniques in current use include optical coherence tomography and scanning laser ophthalmoscopy. In reviewing the application of these and other imaging modalities to study glaucomatous optic neuropathy, this article is organized into three major sections: 1) imaging the optic nerve head, 2) imaging the retinal nerve fiber layer and 3) imaging retinal ganglion cell soma and dendrites. The article concludes with a brief section on possible future directions.

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Glaucomatous cupping of the human optic disk

Cited by 50 publications

References 15 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

Does Optic Nerve Head Surface Topography Change Prior to Loss of Retinal Nerve Fiber Layer Thickness: A Test of the Site of Injury Hypothesis in Experimental Glaucoma

In vivo imaging methods to assess glaucomatous optic neuropathy

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