Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head Biomechanics

Hua, Yi; Voorhees, Andrew; Sigal, Ian A.

doi:10.1167/iovs.17-22488

Cited by 66 publications

(71 citation statements)

References 77 publications

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“…The logical next step would be to include the CRV geometry in our model, which has been attempted in a computational study. 66 Because the CZH structure was more elusive, we would need more information about its morphology before we could include it in a computational model.…”

Section: Discussionmentioning

confidence: 99%

Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa

Chuangsuwanich

Hung

Wang

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We developed a combined biomechanical and hemodynamic model of the human eye to estimate blood flow and oxygen concentration within the lamina cribrosa (LC) and rank the factors that influence LC oxygen concentration. METHODS. We generated 5000 finite-element eye models with detailed microcapillary networks of the LC and computed the oxygen concentration of the lamina retinal ganglion cell axons. For each model, we varied the intraocular pressure (IOP) from 10 mm Hg to 55 mm Hg in 5-mm Hg increments, the cerebrospinal fluid pressure (13 ± 2 mm Hg), cup depth (0.2 ± 0.1 mm), scleral stiffness (±20% of the mean values), LC stiffness (0.41 ± 0.2 MPa), LC radius (1.2 ± 0.12 mm), average LC pore size (5400 ± 2400 μm 2), the microcapillary arrangement (radial, isotropic, or circumferential), and perfusion pressure (50 ± 9 mm Hg). Blood flow was assumed to originate from the LC periphery and drain via the central retinal vein. Finally, we performed linear regressions to rank the influence of each factor on the LC tissue oxygen concentration. RESULTS. LC radius and perfusion pressure were the most important factors in influencing the oxygen concentration of the LC. IOP was another important parameter, and eyes with higher IOP had higher compressive strain and slightly lower oxygen concentration. In general, superior-inferior regions of the LC had significantly lower oxygen concentration than the nasal-temporal regions, resulting in an hourglass pattern of oxygen deficiency. CONCLUSIONS. To the best of our knowledge, this study is the first to implement a comprehensive hemodynamical model of the eye that accounts for the biomechanical forces and morphological parameters of the LC. The results provide further insight into the possible relationship of biomechanical and vascular pathways leading to ischemia-induced optic neuropathy.

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Section: Discussionmentioning

confidence: 99%

Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa

Chuangsuwanich

Hung

Wang

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…CSFP effects are therefore limited to the ONH and contained lamina cribrosa. 2,[21][22][23] Given this interplay of pressures acting on the ONH, it is plausible that the translaminar pressure (TLP = IOP-CSFP) is more relevant to glaucoma than either IOP or CSFP alone, 24 although IOP and CSFP may affect the ONH differently according to some numerical simulations 22 and experimental studies. 23 It is also important to note that TLP is different from the TLP gradient (TLPG = (IOP-CSFP)/laminar thickness), which is the pressure gradient acting across the thickness of the lamina cribrosa.…”

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confidence: 99%

Diurnal Cycle of Translaminar Pressure in Nonhuman Primates Quantified With Continuous Wireless Telemetry

Jasien

Samuels

Johnston

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Recent retrospective clinical studies and animal experiments have suggested that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of the translaminar pressure (TLP), which directly effects the optic nerve head. This study measured the diurnal cycle of TLP using continuous wireless telemetry in nonhuman primates (NHPs), a common animal model of glaucoma. METHODS. We have developed an implantable wireless telemetry system based on a small piezoelectric pressure transducer with low drift. Unilateral IOP was measured in the anterior chamber of the eye, and intracranial pressure (ICP, a surrogate measure of CSFP) was measured in the brain parenchyma in four awake, behaving NHPs for periods of 22 to 281 days. IOP and ICP telemetry transducers were calibrated with direct pressure measurements in the eye (every 2 weeks) and brain (monthly). TLP was quantified in real time as IOP-ICP, and hourly means of IOP, ICP, and TLP were analyzed. RESULTS. Results show that mean ICP is significantly higher by an average of 4.8 ± 0.8 mmHg during sleeping hours in NHPs (P < 0.01). IOP showed a small but significant nocturnal elevation in two of four animals despite NHPs sleeping upright (P < 0.05). TLP was significantly lower during sleep (7.1 ± 0.6 mmHg; P < 0.01) than when the animals were awake and active (11.0 ± 0.9 mmHg), driven primarily by the large increase in ICP during sleep. CONCLUSIONS. The 56% increase in TLP during waking hours in NHPs matches the increase in TLP due to postural change from supine to upright reported previously in humans.

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“…Computational models indicate that IOP has a much greater influence on optic nerve head biomechanics than ICP and that TLP alone is insufficient to capture their complex interaction with material properties (Hua et al . ; Tong et al . ).…”

Section: Discussionmentioning

confidence: 99%

“…One might expect a complete restoration of baseline TLP based on the CSFP hypothesis (Berdahl & Allingham, 2010), but this was not observed and might not be necessary for a protective effect. Computational models indicate that IOP has a much greater influence on optic nerve head biomechanics than ICP and that TLP alone is insufficient to capture their complex interaction with material properties (Hua et al 2018;Tong et al 2019). The feedback mechanism does not operate in reverse given that ICP was unaffected by IOP elevation, and it appears inactive under normal operating conditions because TTX application had no effect on outflow facility at resting ICP.…”

Section: Figure 6 Efferent Feedback Model Of Iop Modulationmentioning

confidence: 99%

Intracranial pressure modulates aqueous humour dynamics of the eye

Ficarrotta

Passaglia

2020

The Journal of Physiology

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Key points An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP‐driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy. Abstract While intraocular pressure (IOP) is a well‐known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown‐Norway rats were cannulated with fine‐gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n = 18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.

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Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head Biomechanics

Cited by 66 publications

References 77 publications

Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa

Morphometric, Hemodynamic, and Biomechanical Factors Influencing Blood Flow and Oxygen Concentration in the Human Lamina Cribrosa

Diurnal Cycle of Translaminar Pressure in Nonhuman Primates Quantified With Continuous Wireless Telemetry

Intracranial pressure modulates aqueous humour dynamics of the eye

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