IOVS Papers in Press. Published on March 31, 2015 as Manuscript iovs.14-15869
Influence of Translaminar Pressure Dynamics on the Position of the Anterior Lamina Cribrosa Surface Running title: Translaminar pressure dynamics and LC position Dae Seung Lee,1 Eun Ji Lee,1 Tae-Woo Kim,1 Young Ho Park,2 Jungeun Kim,2 Joon Woo Lee,3 SangYun Kim2
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Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul
National University College of Medicine 2
Department of Neurology, Seoul National University Bundang Hospital, Seoul
National University College of Medicine 3
Department of Radiology, Seoul National University Bundang Hospital, Seoul
National University College of Medicine Supported by a grant from the National Research Foundation of Korea funded by the Korean Government (no. 2013R1A1A1A05004781). The funding organizations had no role in the design or conduct of this research. The authors have no proprietary or commercial interest in any of the materials discussed in this article. Word count: 4,003 Corresponding author: Eun Ji Lee, M.D. Assistant Professor Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine 82, Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do 463-707, Korea Tel.: +82-31-7877378 Fax: +82-31-7874057 E-mail :
[email protected] 1
Copyright 2015 by The Association for Research in Vision and Ophthalmology, Inc.
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Abstract
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Purpose: To determine how the translaminar pressure difference (TLPD) and
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gradient (TLPG) influence the position of anterior lamina cribrosa (LC) surface.
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Methods: Twenty-six eyes of 26 healthy subjects were subjected to enhanced-
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depth-imaging volume scanning of the optic nerve using spectral-domain optical
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coherence tomography (SD-OCT). The anterior LC surface depth (LCD) relative to
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the Bruch’s membrane (BM) opening was measured at 11 equidistant planes, and
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the LC thickness (LCT) was measured at three locations (superior midperipheral,
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midhorizontal, and inferior midperipheral). Intraocular pressure (IOP) and lumbar
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cerebrospinal fluid pressure (CSFP) were measured on the same day as the SD-
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OCT examination. The TLPD was defined as the difference between IOP and CSFP
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(i.e., IOP – CSFP), and the TLPG as the TLPD divided by LCT (i.e., TLPD/LCT).
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Results: Subjects were aged 63.4±8.0 years and comprised 12 males and 14
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females. Regression analyses revealed a significant association between a larger
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mean LCD and male gender (P=0.002), and between a larger central LCD and male
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gender (P≤0.012), larger TLPD (P=0.048) and higher TLPG (P=0.029). There was no
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significant association between IOP, CSFP, and LCT, and either the mean LCD
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(P=0.438, 0.368, and 0.416, respectively) or central LCD (P=0.284, 0.085, and 0.144,
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respectively).
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Conclusions: A larger central LCD was associated with larger TLPD and higher
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TLPG in healthy eyes, which indicates that the translaminar pressure dynamics may
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play a role in the position of the anterior LC surface relative to BM opening in healthy
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human eyes. 2
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The lamina cribrosa (LC) is a key structure in the pathogenesis of glaucoma. It has
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been postulated that intraocular pressure (IOP)-related stress may cause
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compression or posterior deformation of the LC, which may induce kinking or
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pinching of the axons that pass through the laminar pores, leading to a blockade of
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axoplasmic transport of the retinal ganglion cell axons.1–6 In addition, the
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compressive effect on the laminar capillaries in the course of LC deformation may
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confer ischemic insult to the axons.6,7 On the other hand, even in the absence of LC
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deformation, IOP can still increase the strain within the LC and induce laminar
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connective-tissue remodeling, which may compromise axon physiology.8–11 Moreover,
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the increased LC strain may have a substantial influence on the axonal flow where
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the LC is thin, because those axons may experience a steep transition between IOP
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and retrolaminar tissue pressure, termed the translaminar pressure gradient
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(TLPG).8,12–16
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Because the LC forms a barrier between two differentially pressurized
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compartments: the intraocular space with a higher pressure (IOP) and the
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retrobulbar space with a lower pressure [retrobulbar cerebrospinal fluid (CSF)
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pressure (CSFP), a pressure gradient is formed across the LC. The pressure
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difference between the two compartments is termed the translaminar pressure
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difference (TLPD), and is defined as IOP – CSFP. At a given IOP, subjects with a
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lower CSFP have a larger TLPD, which can result in posterior deformation of the
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LC.17,18 Conversely, in subjects with a higher CSFP, the TLPD is smaller, and thus
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the LC is less likely to be deformed.
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The ability of the LC to tolerate a given TLPD without being deformed may be 3
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associated with the material properties (e.g., compliance, stiffness, or structural
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rigidity) and geometry (e.g., thickness, shape, or curvature) of the LC and the
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peripapillary connective tissues.6,19 For example, eyes with a stiffer LC may be more
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resistant to deformation when the LC thickness is the same. Likewise, for a fixed LC
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stiffness, it is possible that eyes with a thinner LC are more susceptible to LC
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deformation. Regardless of its susceptibility to deformation, a thinner LC also
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contributes to a steeper TLPG as a result of the reduced distance between the
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intraocular space and the retrolaminar space, and may interrupt both orthograde and
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retrograde axoplasmic transport.1–5
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Studies have found a link between a larger TLPD or TLPG and glaucoma. It has
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been shown that patients with primary open-angle glaucoma had a lower lumbar
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CSFP than nonglaucomatous control subjects.20,21 Other studies have shown that
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patients with normal-tension glaucoma have a lower lumbar CSFP and a larger
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TLPD than those with high-tension glaucoma.22,23 Moreover, a larger TLPD was
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correlated with glaucomatous neural-rim loss or visual-field defects.22,23 Based on
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the notion that the translaminar pressure dynamics may influence LC deformation
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and optic-nerve axoplasmic transport, it can be speculated that eyes with a larger
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TLPD or TLPG may have an increased susceptibility for glaucomatous damage.
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In this context, it would be of interest to know how translaminar pressure dynamics
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(i.e., TLPD or TLPG) influence the LC position. Several experimental studies have
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demonstrated that a larger TLPD is associated with posterior LC displacement.17,18
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However, there have been no reports on how either TLPD or TLPG could influence
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the LC in living human eyes. 4
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The purpose of the present study was to determine the influence of TLPD or TLPG
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on the anterior LC surface depth (LCD), as evaluated by enhanced-depth-imaging
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(EDI) spectral-domain optical coherence tomography (SD-OCT).
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Methods
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This study was based on the data of healthy subjects included in the Study for
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Usefulness and Standardization of Cerebrospinal Fluid and Plasma Amyloid
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Biomarkers in Alzheimer’s Disease, which is an ongoing prospective study of
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patients with Alzheimer’s disease and healthy participants at the Neurocognitive
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Behavior Center in collaboration with Glaucoma Clinic of Seoul National University
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Bundang Hospital. The present study was approved by the Seoul National University
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Bundang Hospital Institutional Review Board. Informed written consent to participate
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was obtained from all subjects, according to the Declaration of Helsinki.
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Study subjects
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Subjects were enrolled by the advertisement between May 2012 and April 2014. All
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subjects submitted to a complete ophthalmic examination, including visual acuity
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assessment, Goldmann applanation tonometry, refraction test, slit-lamp
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biomicroscopy, gonioscopy, dilated stereoscopic examination of the optic disc,
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fundus photography (VX-10 fundus camera, Kowa, Tokyo, Japan), measurement of
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central corneal thickness (Orbscan II, Bausch & Lomb Surgical, Rochester, NY, USA), 5
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corneal curvature (KR-1800, Topcon, Tokyo, Japan), and axial length (IOL Master,
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Carl Zeiss Meditec, Dublin, CA, USA), and EDI SD-OCT (Spectralis OCT,
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Heidelberg Engineering, Heidelberg, Germany) scanning of the optic disc and
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circumpapillary retinal nerve fiber layer (RNFL). IOP was measured three times at
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15-minute intervals, and the mean of the three values was considered as the
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baseline IOP. Subjects underwent CSF sampling with CSFP measurement on the
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same day as the ophthalmic examination (see Evaluation of CSFP).
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The inclusion criteria for eyes in this study were a best-corrected visual acuity of
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≥20/40, a spherical refraction of –8.0 to +5.0 diopters (D), cylinder correction of –
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3.0 to +3.0 D, and a normal-appearing optic disc without glaucomatous optic
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neuropathy, pallor, or swelling of the optic disc. The exclusion criteria were any
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ocular diseases other than cataract, a history of intraocular surgery including laser
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treatment other than cataract extraction, and subjects with a neurologic disease, a
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history of intracranial surgery or lumbar puncture prior to enrollment to this study, a
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condition that could affect the intracranial pressure [idiopathic intracranial
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hypo/hypertension, intracranial tumors, or medications (e.g., tetracycline, rofecoxib,
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mannitol, and carbonic anhydrase inhibitor)], or any contraindication for lumbar
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puncture [i.e., infectious diseases or infection around a lumbar puncture site,
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elongated prothrombin time (international normalized ratio >1.7), thrombocytopenia
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