Three-Dimensional Histomorphometry of the Normal and Early Glaucomatous Monkey Optic Nerve Head: Neural Canal and Subarachnoid Space Architecture

Downs, J. Crawford; Yang, Hongli; Girkin, Christopher A.; Sakata, Lisandro M.; Bellezza, Anthony J.; Thompson, Hilary W.; Burgoyne, Claude F.

doi:10.1167/iovs.07-0021

Cited by 158 publications

(202 citation statements)

References 64 publications

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“…22,[37][38][39][40][41] While this may be correct in a slowly progressive condition like glaucoma, our findings in papilledema shows substantial deformations of the peripapillary RPE/BM, in some cases over short time intervals, relative to other surface and subsurface regions of the optic disc. There may be limits to the use of the RPE/BM as a reference plane in patients with intracranial hypertension.…”

Section: Discussionmentioning

confidence: 56%

Optical Coherence Tomography of the Swollen Optic Nerve Head: Deformation of the Peripapillary Retinal Pigment Epithelium Layer in Papilledema

Kupersmith

Sibony

Mandel

et al. 2011

Invest. Ophthalmol. Vis. Sci.

128

100

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PURPOSE.To examine the biomechanical deformation of load bearing structures of the optic nerve head (ONH) resulting from raised intracranial pressure, using high definition optical coherence tomography (HD-OCT). The authors postulate that elevated intracranial pressure induces forces in the retrolaminar subarachnoid space that can deform ONH structures, particularly the peripapillary Bruch's membrane (BM) and RPE layers. METHODS.The authors compared HD-OCT optic nerve and peripapillary retinal nerve fiber layer (RNFL) findings in eyes with papilledema caused by raised intracranial pressure to findings in eyes with optic disc swelling caused by optic neuritis and nonarteritic anterior ischemic optic neuropathy (NAION), conditions without intracranial hypertension. The authors measured average thickness of the RNFL and the angle of the RPE/BM at the temporal and nasal borders of the neural canal opening. The angle was measured as positive with inward (toward the vitreous) angulation and as negative with outward angulation. RESULTS. Of 30 eyes with papilledema, 20 eyes (67%) had positive RPE/BM rim angles. One of eight optic neuritis (12%) eyes and 1 of 12 NAION (8%) eyes had positive angulation. In five eyes with papilledema, RNFL thickening increased, three of which developed positive RPE/BM angles. On follow-up, 22 papilledema eyes had a reduction of RNFL swelling, and 17 of these eyes had less positive RPE/BM angulation. CONCLUSIONS. In papilledema, the RPE/BM is commonly deflected inward, in contrast to eyes with NAION or optic neuritis. The RPE/BM angulation is presumed to be caused by elevated pressure in the subarachnoid space, does not correlate with the amount of RNFL swelling, and resolves as papilledema subsides. (Invest Ophthalmol Vis Sci. 2011;52: 6558 -6564) DOI:10.1167/iovs.10-6782 P apilledema is caused by increased intracranial pressure. Histopathologic studies in animal models have shown that elevated pressure within the optic nerve sheath causes stasis of axoplasmic flow and decreased blood flow to axons in the neural canal.1-3 The ensuing optic disc swelling (papilledema) is a consequence of axonal distension of the prelaminar and peripapillary nerve fibers. Vascular congestion, leakage, and ischemia follow the acute axoplasmic flow stasis and are associated with interstitial edema. Although the proximate cause of early edema is stagnant axonal transport, there still remains some uncertainty about the relative effects of compression and ischemia. 1-3Burgoyne et al. 4 and others 5-11 have proposed a conceptual approach that analyzes the optic nerve head (ONH) as a biomechanical structure. They hypothesize that stress (force/ cross-sectional area) and strain (local deformation) on the ONH may be key determinants of axonal, glial, and vascular dysfunction in the pathogenesis and progression of glaucoma. Although the forces acting on the nerve head in papilledema differ from those in glaucoma, the application of biomechanical principles may provide insights about the clinical effects of intracrania...

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Section: Discussionmentioning

confidence: 56%

Optical Coherence Tomography of the Swollen Optic Nerve Head: Deformation of the Peripapillary Retinal Pigment Epithelium Layer in Papilledema

Kupersmith

Sibony

Mandel

et al. 2011

Invest. Ophthalmol. Vis. Sci.

128

100

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“…Hayreh, et al 96,97 has argued that primary ischemia to the retrolaminar optic nerve could cause a fibrotic response that pulls the lamina posteriorly into a form that is indistinguishable from glaucomatous cupping. However, we see no evidence for this in early experimental glaucoma monkeys (16 -30% axon loss) that demonstrate profound posterior deformation of the lamina and expansion of the scleral portion of the neural canal 45,46,[48][49][50] . These deformations occur after four to eight weeks of minimal to moderate IOP elevations.…”

contrasting

confidence: 58%

“…"Laminar deformation" is that portion of cup enlargement that results from lamina cribrosa and peripapillary scleral connective tissue damage followed by permanent, IOP-induced deformation 45,46,48,49,64 . Laminar deformation results in a clinically deeper form of cupping that occurs only in those optic neuropathies in which the ONH connective tissues have been damaged and have become susceptible to permanent, IOP-induced deformation.…”

Section: Onh Biomechanics and Onh Cuppingmentioning

confidence: 99%

“…"Prelaminar thinning" is that portion of cup enlargement that results from net thinning of the prelaminar tissues due to physical compression and/or loss of RGC axons even in the presence of gliosis [90][91][92][93] . In this paradigm, prelaminar thinning results in a clinically shallow form of cupping 94,95 (being limited to the prelaminar tissues) that occurs in all forms of RGC axon loss (including aging) and is therefore nonspecific."Laminar deformation" is that portion of cup enlargement that results from lamina cribrosa and peripapillary scleral connective tissue damage followed by permanent, IOP-induced deformation 45,46,48,49,64 . Laminar deformation results in a clinically deeper form of cupping that occurs only in those optic neuropathies in which the ONH connective tissues have been damaged and have become susceptible to permanent, IOP-induced deformation.…”

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confidence: 99%

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Premise and Prediction???How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

Burgoyne¹,

Downs²

2008

Journal of Glaucoma

Self Cite

192

169

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We propose that age-related alterations in optic nerve head (ONH) biomechanics underlie the clinical behavior and increased susceptibility of the aged ONH to glaucomatous damage. The literature which suggests that the aged ONH is more susceptible to glaucomatous damage at all levels of intraocular pressure is reviewed. The relevant biomechanics of the aged ONH are discussed and a biomechanical explanation for why, on average, the stiffened peripapillary scleral and lamina cribrosa connective tissues of the aged eye should lead to a shallow (senile sclerotic) form of cupping is proposed. A logic for why age-related axon loss and the optic neuropathy of glaucoma in the aged eye may overlap is discussed. Finally, we argue for a need to characterize all forms of clinical cupping into prelaminar and laminar components so as to add precision to the discussion of clinical cupping which does not currently exist. Such characterization may lead to the early detection of ONH axonal and connective tissue pathology in ocular hypertension and eventually aid in the assessment of etiology in all forms of optic neuropathy including those that may be purely age-related. The Susceptibility of the Aged Optic Nerve Head (ONH)A variety of data suggest that the ONH becomes more susceptible to progressive glaucomatous damage as it ages, though this concept remains unproven through direct experimentation, and may not be true for every aged eye. These data can be summarized as follows. First, in most [1][2][3][4][5] , but not all 6,7 , population based studies, intraocular pressure (IOP) either does not increase with age or if it does, the magnitude of increase is not likely to be clinically important. Thus, the fact that the prevalence of the neuropathy increases with age 8 is likely explained by a greater susceptibility to IOP and other non-IOP-related risk factors, rather than a higher prevalence of IOP elevation, with increasing age. Second, in an extensive review of the literature, we can find only a few reports of the onset and progression of normal tension glaucoma (NTG) in infants, children and young adults 9 . While we acknowledge that accurate NTG prevalence estimates require long-term telemetric characterization of untreated IOP and rigorous population based ONH and visual field examinations, all existing studies suggest that NTG is most commonly a disease of the elderly [10][11][12][13][14][15] in the young 9 . Third, age is an independent risk factor for both the prevalence 16 and progression of the neuropathy at all stages of damage [17][18][19] . The Clinical Behavior of the Aged ONHApart from the issue of ONH susceptibility, we predict that if all aspects of insult are equal (alterations in IOP, the volume flow of blood and nutrient transfer from the laminar capillary to the ONH astrocyte are all of the same magnitude, duration and fluctuation), the aged eye will demonstrate clinical cupping that is on average shallow and pale (at all stages of field loss) compared to the eye of a child or young adult. This clini...

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“…On the other hand, the optic disc boundary, also called Bruch's membrane opening (BMO) showed in ONH-centered OCT image is a stability landmark, as it is unaffected by glaucomatous cupping [15]. The BMO can be used for computing ONH parameters, and tracking the glaucomatous changing [16][17][18]. Therefore, a reliable SD-OCT image analysis method for optic disc boundary detection and retinal layer segmentation in the ONH region is urgently needed for glaucoma disease evaluation and treatment planning.…”

Section: Introductionmentioning

confidence: 99%

Shared-hole graph search with adaptive constraints for 3D optic nerve head optical coherence tomography image segmentation

Shi

Gao

et al. 2018

Biomed. Opt. Express

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Optic nerve head (ONH) is a crucial region for glaucoma detection and tracking based on spectral domain optical coherence tomography (SD-OCT) images. In this region, the existence of a "hole" structure makes retinal layer segmentation and analysis very challenging. To improve retinal layer segmentation, we propose a 3D method for ONH centered SD-OCT image segmentation, which is based on a modified graph search algorithm with a shared-hole and locally adaptive constraints. With the proposed method, both the optic disc boundary and nine retinal surfaces can be accurately segmented in SD-OCT images. An overall mean unsigned border positioning error of 7.27 ± 5.40 µm was achieved for layer segmentation, and a mean Dice coefficient of 0.925 ± 0.03 was achieved for optic disc region detection. "Automated boundary detection of the optic disc and layer segmentation of the peripapillary retina in volumetric structural and angiographic optical coherence tomography," Biomed.

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Three-Dimensional Histomorphometry of the Normal and Early Glaucomatous Monkey Optic Nerve Head: Neural Canal and Subarachnoid Space Architecture

Abstract: Profound deformation of the neural canal and ASAS architecture are present in young adult monkey eyes at the onset of ONH surface change in early experimental glaucoma.

Cited by 158 publications

References 64 publications

Optical Coherence Tomography of the Swollen Optic Nerve Head: Deformation of the Peripapillary Retinal Pigment Epithelium Layer in Papilledema

Optical Coherence Tomography of the Swollen Optic Nerve Head: Deformation of the Peripapillary Retinal Pigment Epithelium Layer in Papilledema

Premise and Prediction???How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

Shared-hole graph search with adaptive constraints for 3D optic nerve head optical coherence tomography image segmentation

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