The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

Yang, Hongli; Ren, Ruojin; Lockwood, Howard; Williams, Galen; Libertiaux, Vincent; Downs, J. Crawford; Gardiner, Stuart K.; Burgoyne, Claude F.

doi:10.1167/iovs.15-17624

Cited by 45 publications

(49 citation statements)

References 61 publications

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“…He also proposed that profound laminar deformation and remodeling resulting from connective tissue changes are present in eyes with as little as 12% to 14% optic nerve axon loss. 18,21 Our finding that mild ischemic assault like NAION does not have a prominent effect on LC thickness and depth supports the theory of Burgoyne. In a recent study comparing eyes with compressive optic neuropathy and eyes with POAG, Hata et al 35 found that despite having the same cup-to-disc ratios in both groups, ALD was smaller in compressive optic neuropathy than in POAG eyes but similar to that in control healthy eyes.…”

Section: Discussionsupporting

confidence: 77%

“…17 Burgoyne 18 has proposed that only ''laminar'' or ''deep'' forms of ONH cupping are pathognomonic for glaucoma and that laminar deformation in nonglaucomatous optic neuropathy, such as that induced by experimentally reduced cerebrospinal fluid pressure in monkeys, might be minimal. [19][20][21] However, histologic studies may be prone to the effects of tissue swelling or shrinkage from fixation processes. Investigations in enucleated eyes suffer from postmortem changes in connective tissue and lack of vascular supply.…”

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confidence: 99%

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Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma

Fard

Afzali

Abdi

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Fard MA, Afzali M, Abdi P, et al. Optic nerve head morphology in nonarteritic anterior ischemic optic neuropathy compared to open-angle glaucoma. Invest Ophthalmol Vis Sci. 2016;57:4632-4640. DOI:10.1167/ iovs.16-19442 PURPOSE. To compare optic nerve head (ONH) morphology of optic nerve atrophy between eyes with primary open-angle glaucoma (POAG) and eyes with a history of nonarteritic anterior ischemic optic atrophy (NAION) using enhanced depth imaging (EDI) with spectraldomain optical coherence tomography (SD-OCT). METHODS.In this cross-sectional study, 121 eyes of 91 patients consisted of moderate to severe POAG (n ¼ 32 eyes), visual field mean deviation-matched NAION (n ¼ 30 eyes) and their fellow eyes (n ¼ 30 eyes), and healthy controls (n ¼ 29). The optic discs were scanned using SD-OCT and measurements were obtained using HEYEX software 6.0. Lamina cribrosa (LC) thickness and anterior lamina cribrosa depth (ALD) at three scans (midsuperior, central, and midinferior) were determined and compared. In addition, prelaminar tissue thickness was measured at three points of a single central scan.RESULTS. There was no significant difference in the visual field mean deviation (MD) between the NAION and POAG groups (P > 0.99), but both groups had a significantly worse MD than the healthy group (P < 0.001). The NAION and POAG groups had similar peripapillary retinal nerve fiber layer (pRNFL) thickness (P < 0.99). Eyes with POAG had greater ALD and thinner LC than control eyes and NAION eyes in all regions of the ONH (P < 0.001 for both). There was a marked prelaminar tissue thinning in POAG eyes compared to control and NAION eyes (P < 0.001). Lamina cribrosa thickness and ALD of NAION eyes were not different from their fellow eyes and control eyes. Although prelaminar thickness was thinner in NAION eyes compared to their fellow eyes (P ¼ 0.005), it was thicker than in control eyes (P < 0.001).CONCLUSIONS. Despite profound thinning and posterior displacement of LC in POAG, the thickness and position of LC in NAION eyes are similar to those seen in healthy control and their fellow eyes.Keywords: open-angle glaucoma, nonarteritic anterior ischemic optic atrophy, lamina cribrosa, optic nerve head, optic atrophy B oth open-angle glaucoma (OAG) as chronic progressive optic neuropathy and nonarteritic anterior ischemic optic neuropathy (NAION) as acute optic neuropathy with inflammation-associated axonal loss cause irreversible damage to the optic nerve.1-3 In contrast to NAION, which presents with disc pallor after an ischemic event, OAG results in the enlargement of the optic disc cup. Optic nerve head (ONH) morphologic features differ in NAION and OAG. While a small disc area and smaller cupping are predisposing risk factors for the development of NAION, [3][4][5]

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Section: Discussionsupporting

confidence: 77%

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confidence: 99%

Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma

Fard

Afzali

Abdi

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…6 We have also demonstrated early posterior deformation of the anterior lamina cribrosa surface (ALCS) that preceded the onset of detectable retinal nerve fiber layer thickness (RNFLT) thinning in a separate group of four young and four old monkeys with unilateral experimental glaucoma longitudinally followed with optical coherence tomography (OCT) imaging. 8 …”

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confidence: 94%

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

Ing

Ivers

Yang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo use optical coherence tomography (OCT) to test the hypothesis that optic nerve head (ONH) “cupping” in the monkey optic nerve transection (ONT) model does not include posterior laminar deformation.MethodsFive monkeys (aged 5.5–7.8 years) underwent ONH and retinal nerve fiber layer (RNFL) OCT imaging five times at baseline and biweekly following unilateral ONT until euthanization at ∼40% RNFL loss. Retinal nerve fiber layer thickness (RNFLT) and minimum rim width (MRW) were calculated from each pre- and post-ONT imaging session. The anterior lamina cribrosa surface (ALCS) was delineated within baseline and pre-euthanasia data sets. Significant ONT versus control eye pre-euthanasia change in prelaminar tissue thickness (PLTT), MRW, RNFLT, and ALCS depth (ALCSD) was determined using a linear mixed-effects model. Eye-specific change in each parameter exceeded the 95% confidence interval constructed from baseline measurements.ResultsAnimals were euthanized 49 to 51 days post ONT. Overall ONT eye change from baseline was significant for MRW (−26.2%, P = 0.0011), RNFLT (−43.8%, P < 0.0001), PLTT (−23.8%, P = 0.0013), and ALCSD (−20.8%, P = 0.033). All five ONT eyes demonstrated significant eye-specific decreases in MRW (−23.7% to −31.8%) and RNFLT (−39.6% to −49.7%). Four ONT eyes showed significant PLTT thinning (−23.0% to −28.2%). The ALCS was anteriorly displaced in three of the ONT eyes (−25.7% to −39.2%). No ONT eye demonstrated posterior laminar displacement.ConclusionsSeven weeks following surgical ONT in the monkey eye, ONH cupping involves prelaminar and rim tissue thinning without posterior deformation of the lamina cribrosa.

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“…In the area of biomechanics, important characterization of very early morphometric changes in the monkey ONH unilateral experimental glaucoma model has occurred (Yang et al, 2015). Briefly, the monkey ONH surface, LC, scleral canal and pp-sclera are compliant structures, demonstrating modest deformations that are reversible through an IOP range of 0 to 45mmHg.…”

Section: Recent Developmentsmentioning

confidence: 99%

Biomechanical aspects of axonal damage in glaucoma: A brief review

Tamm

Ethier

Dowling

et al. 2017

Experimental Eye Research

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The biomechanical environment within the optic nerve head (ONH) is complex and is likely directly involved in the loss of retinal ganglion cells (RGCs) in glaucoma. Unfortunately, our understanding of this process is poor. Here we describe factors that influence ONH biomechanics, including ONH connective tissue microarchitecture and anatomy; intraocular pressure (IOP); and cerebrospinal fluid pressure (CSFp). We note that connective tissue factors can vary significantly from one individual to the next, as well as regionally within an eye, and that the understanding of ONH biomechanics is hindered by anatomical differences between small-animal models of glaucoma (rats and mice) and humans. Other challenges of using animal models of glaucoma to study the role of biomechanics include the complexity of assessing the degree of glaucomatous progression; and inadequate tools for monitoring and consistently elevating IOP in animal models. We conclude with a consideration of important open research questions/challenges in this area, including: (i) Creating a systems biology description of the ONH; (ii) addressing the role of astrocyte connective tissue remodeling and reactivity in glaucoma; (iii) providing a better characterization of ONH astrocytes and non-astrocytic constituent cells; (iv) better understanding the role of ONH astrocyte phagocytosis, proliferation and death; (v) collecting gene expression and phenotype data on a larger, more coordinated scale; and (vi) developing an implantable IOP sensor.

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The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

Cited by 45 publications

References 61 publications

Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma

Optic Nerve Head Morphology in Nonarteritic Anterior Ischemic Optic Neuropathy Compared to Open-Angle Glaucoma

Cupping in the Monkey Optic Nerve Transection Model Consists of Prelaminar Tissue Thinning in the Absence of Posterior Laminar Deformation

Biomechanical aspects of axonal damage in glaucoma: A brief review

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