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

Ing, Eliesa; Ivers, Kevin M.; Yang, Hongli; Gardiner, Stuart K.; Reynaud, Juan; Cull, Grant; Wang, Lin; Burgoyne, Claude F.

doi:10.1167/iovs.15-18975

Cited by 21 publications

(21 citation statements)

References 56 publications

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“…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. In line with our results, in an experimental animal study, Ing et al 36 showed that while RNFL thickness demonstrated profound thinning, ALD was not displaced posteriorly approximately 50 days following optic nerve transection. As these findings are in contrast to OCT detection of significant laminar deformation after chronic IOP elevation, 33 the authors proposed that posterior laminar deformation following connective tissue damage should be included in the definitions used to distinguish glaucomatous and nonglaucomatous optic neuropathy in the monkey eye.…”

Section: Discussionsupporting

confidence: 92%

“…Lee et al 24 also found that prelaminar thickness was less in glaucomatous patients than in NAION patients. Similarly, Ing et al 36 found prelaminar tissue thinning following experimental optic nerve transaction. Lack of optic disc excavation and changes in optic rim in atrophic optic nerve due to NAION have been described in previous studies.…”

Section: Discussionmentioning

confidence: 80%

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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: 92%

Section: Discussionmentioning

confidence: 80%

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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“…Prelaminar thinning results from thinning of the prelaminar tissues due to physical compression and/or loss of retinal ganglion cell axons without important laminar or ONH connective tissue involvement. Ing et al 17 reported anterior rather than posterior laminar deformation postoptic nerve transection in a monkey model due to profound thinning of the RNFL and prelaminar rim tissue, which shows ‘prelaminar’ or ‘shallow’ forms of ‘cupping’ in ‘non-glaucomatous’ optic neuropathies that are not accompanied by laminar deformation. In our study, both glaucomatous and non-glaucomatous cupping groups had similar thinning in PLT than control eyes.…”

Section: Discussionmentioning

confidence: 99%

Optic nerve head cupping in glaucomatous and non-glaucomatous optic neuropathy

et al. 2018

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“…However, we also emphasize that, to date, selectively killing RGC soma or axons alone, by whatever mechanism, has not been shown to create a glaucomatous optic neuropathy (i.e. glaucomatous ONH cupping) (Brooks et al, 2004; Chauhan et al, 2004; Ing et al, 2016; Joachim et al, 2013; Wax et al, 2008; Yang et al, 2014a). …”

Section: 0 Introductionmentioning

confidence: 85%

“…In addition, they confirm that early glaucomatous damage to the monkey ONH includes both neural and connective tissue components (Yang et al, 2007a; Yang et al, 2009a). This finding is important because it identifies OCT-detectable ONH connective tissue endpoints for other monkey experimental optic neuropathy models including chronic experimental CSFp lowering (Yang et al, 2014a), endothelin (Brooks et al, 2004), optic nerve transection (Ing et al, 2016) and anterior ischemic optic neuropathy (AION) (Miller et al, 2014) which are discussed in Section 4.0, below.…”

Section: 0 Experimental Evidence Of Onh Connective Tissue Deformatimentioning

confidence: 99%

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

Yang

Reynaud

Lockwood

et al. 2017

Progress in Retinal and Eye Research

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In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon and laminar beam and retrolaminar capillary homeostasis that may initially be “protective” but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect.

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

Cited by 21 publications

References 56 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

Optic nerve head cupping in glaucomatous and non-glaucomatous optic neuropathy

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

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