Microvascular Density Is Associated With Retinal Ganglion Cell Axonal Volume in the Laminar Compartments of the Human Optic Nerve Head

Kang, Min Sung; Suo, Mengchen; Balaratnasingam, Chandrakumar; Yu, Paula K.; Morgan, William H.; Yu, Dao‐Yi

doi:10.1167/iovs.17-23183

Cited by 7 publications

(6 citation statements)

References 44 publications

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“…3 Furthermore, a study utilizing a mathematical model suggested that the central area of the LC was more vulnerable to reduced blood supply following IOP elevation. 36 In addition, Kang et al 4 found that microvascular density correlates with retinal ganglion cell axonal volume in all regions of the ONH, but at a particularly greater ratio in the posterior LC, emphasizing the importance of this region for studies involving vascular parameters.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 In particular, microvascular perfusion is vital for the health of the optic nerve axons. 3,4 Alterations in the ophthalmic vasculature due to changes in perfusion pressure, vascular tone, local resistance, and even systemic dysregulation have been shown to increase the risk of glaucoma. 5–8 In addition, pathology associated with the optic nerve vasculature, such as disc hemorrhages (DHs), can be an important indicator in the development and progression of glaucoma.…”

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confidence: 99%

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Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma

Silva

Chiou

Wang

et al. 2019

Journal of Glaucoma

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Purpose: To assess optic nerve head (ONH) and peripapillary microvasculature in primary open-angle glaucoma (POAG) of mild to moderate severity using swept-source optical coherence tomography angiography (OCTA). Materials and Methods: In a cross-sectional study, swept-source OCTA images were analyzed for 1 eye from each of 30 POAG patients with glaucomatous Humphrey visual field loss and 16 controls. The anatomic boundary of ONH was manually delineated based on Bruch’s membrane opening and large vessels were removed from en face angiography images to measure vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS), suggestive of flow, in the ONH and peripapillary region. POAG subgroup analysis was performed based on a history of disc hemorrhage (DH) matched by visual field mean deviation (MD). Results: POAG (mean MD ± SD, −3.3 ± 3.0 dB) and control groups had similar demographic characteristics and intraocular pressure on the day of imaging. Groups did not differ in superficial ONH VD or flow indicated by IOS (P ≥ 0.28). POAG eyes showed significantly lower VD (39.4% ± 4.0%) and flow (38.8% ± 5.6%) in deep ONH, peripapillary VD (37.9% ± 2.9%) and flow (43.6% ± 4.0%) compared with control eyes (44.1% ± 5.1%, 44.7% ± 6.9%, 40.7% ± 1.7%, 47.8% ± 2.5%, respectively; P ≤ 0.007 for all). In the subgroup analysis, POAG eyes with (n = 14) and without DH (n = 16) had similar measured OCTA parameters (P > 0.99 for all). Conclusions: The image processing methodology based on the anatomic boundary of ONH demonstrated compromised microvasculature in the deep ONH and peripapillary region in eyes with mild to moderate POAG, regardless of the history of DH.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma

Silva

Chiou

Wang

et al. 2019

Journal of Glaucoma

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“…In fact, the posterior lamina is implicated as the primary site of disruption in glaucoma, and emerging studies show a significant decrease in vessel density and blood flow in POAG in the deeper layers of the ONH compared with controls (Nascimento et al, 2019). Microvascular density correlates with RGC axon volume across all areas at the ONH, but the correlation is greater at the posterior lamina cribrosa, further emphasizing the importance of changes in vascular parameters at this site (Kang et al, 2018). Narrowing of retinal blood vessels is also characteristic of advanced glaucomatous optic nerve damage, indicating that vascular changes occur in the retina in addition to the site of injury at the ONH Rankin and Drance, 1996).…”

Section: Vascular Dysfunction In Glaucomamentioning

confidence: 98%

The Neurovascular Unit in Glaucomatous Neurodegeneration

Wareham

Calkins

2020

Front. Cell Dev. Biol.

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Glaucoma is a neurodegenerative disease of the visual system and leading cause of blindness worldwide. The disease is associated with sensitivity to intraocular pressure (IOP), which over a large range of magnitudes stresses retinal ganglion cell (RGC) axons as they pass through the optic nerve head in forming the optic projection to the brain. Despite clinical efforts to lower IOP, which is the only modifiable risk factor for glaucoma, RGC degeneration and ensuing loss of vision often persist. A major contributor to failure of hypotensive regimens is the multifactorial nature of how IOP-dependent stress influences RGC physiology and structure. This stress is conveyed to the RGC axon through interactions with structural, glial, and vascular components in the nerve head and retina. These interactions promote pro-degenerative pathways involving biomechanical, metabolic, oxidative, inflammatory, immunological and vascular challenges to the microenvironment of the ganglion cell and its axon. Here, we focus on the contribution of vascular dysfunction and breakdown of neurovascular coupling in glaucoma. The vascular networks of the retina and optic nerve head have evolved complex mechanisms that help to maintain a continuous blood flow and supply of metabolites despite fluctuations in ocular perfusion pressure. In healthy tissue, autoregulation and neurovascular coupling enable blood flow to stay tightly controlled. In glaucoma patients evidence suggests these pathways are dysfunctional, thus highlighting a potential role for pathways involved in vascular dysfunction in progression and as targets for novel therapeutic intervention.

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“… 69 Recently, confocal imaging of thick sections has been used to look at capillary and RGC axon density. 70 This method also lacks the ability to image the vasculature at multiple levels of IOP, but it has the benefit of being able to label capillaries and other tissues that the plastic cast method removes. Others have been able to investigate the effects of IOP on ONH vessel function in live rats through OCT-A.…”

Section: Discussionmentioning

confidence: 99%

Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases

Brazile

Yang

Waxman

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases. Methods Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging. Capillaries and collagen beams were visualized with structured light illumination enhanced imaging at IOPs from 5 to 50 mm Hg at each 5 mm Hg increment. Capillary tortuosity was measured from the images and paired two-sample t -tests were used to assess for significant changes in relation to changes in IOP. Results Capillaries were highly tortuous at 15 mm Hg (up to 1.45). In all but one eye, tortuosity decreased significantly as IOP increased from 15 to 25 mm Hg ( P < 0.01), and tortuosity decreased significantly in every eye as IOP increased from 15 to 40 mm Hg ( P < 0.01). In only 16% of capillaries, tortuosity increased with elevated IOP. Capillaries had a surprisingly different topology from the collagen beams. Conclusions Although high capillary tortuosity is sometimes regarded as potentially problematic because it can reduce blood flow, LC capillary tortuosity may provide slack that mitigates against reduced flow and structural damage caused by excessive stretch under elevated IOP. We speculate that low capillary tortuosity could be a risk factor for damage under high IOP.

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Microvascular Density Is Associated With Retinal Ganglion Cell Axonal Volume in the Laminar Compartments of the Human Optic Nerve Head

Cited by 7 publications

References 44 publications

Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma

Microvasculature of the Optic Nerve Head and Peripapillary Region in Patients With Primary Open-Angle Glaucoma

The Neurovascular Unit in Glaucomatous Neurodegeneration

Lamina Cribrosa Capillaries Straighten as Intraocular Pressure Increases

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