Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma
Identifieur interne : 000093 ( Pmc/Corpus ); précédent : 000092; suivant : 000094Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma
Auteurs : L. Siaudvytyte ; I. Januleviciene ; A. Daveckaite ; A. Ragauskas ; L. Bartusis ; J. Kucinoviene ; B. Siesky ; A. HarrisSource :
- Eye [ 0950-222X ] ; 2015.
Abstract
There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.
Url:
DOI: 10.1038/eye.2015.127
PubMed: 26183286
PubMed Central: 4815687
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma</title><author><name sortKey="Siaudvytyte, L" sort="Siaudvytyte, L" uniqKey="Siaudvytyte L" first="L" last="Siaudvytyte">L. Siaudvytyte</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Januleviciene, I" sort="Januleviciene, I" uniqKey="Januleviciene I" first="I" last="Januleviciene">I. Januleviciene</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Daveckaite, A" sort="Daveckaite, A" uniqKey="Daveckaite A" first="A" last="Daveckaite">A. Daveckaite</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Ragauskas, A" sort="Ragauskas, A" uniqKey="Ragauskas A" first="A" last="Ragauskas">A. Ragauskas</name><affiliation><nlm:aff id="aff2"><institution>Health Telematics Science Centre of Kaunas University of Technology</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Bartusis, L" sort="Bartusis, L" uniqKey="Bartusis L" first="L" last="Bartusis">L. Bartusis</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Health Telematics Science Centre of Kaunas University of Technology</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Kucinoviene, J" sort="Kucinoviene, J" uniqKey="Kucinoviene J" first="J" last="Kucinoviene">J. Kucinoviene</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Siesky, B" sort="Siesky, B" uniqKey="Siesky B" first="B" last="Siesky">B. Siesky</name><affiliation><nlm:aff id="aff3"><institution>Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine</institution>, Indianapolis, IN,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Harris, A" sort="Harris, A" uniqKey="Harris A" first="A" last="Harris">A. Harris</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine</institution>, Indianapolis, IN,<country>USA</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26183286</idno><idno type="pmc">4815687</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815687</idno><idno type="RBID">PMC:4815687</idno><idno type="doi">10.1038/eye.2015.127</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000093</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000093</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma</title><author><name sortKey="Siaudvytyte, L" sort="Siaudvytyte, L" uniqKey="Siaudvytyte L" first="L" last="Siaudvytyte">L. Siaudvytyte</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Januleviciene, I" sort="Januleviciene, I" uniqKey="Januleviciene I" first="I" last="Januleviciene">I. Januleviciene</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Daveckaite, A" sort="Daveckaite, A" uniqKey="Daveckaite A" first="A" last="Daveckaite">A. Daveckaite</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Ragauskas, A" sort="Ragauskas, A" uniqKey="Ragauskas A" first="A" last="Ragauskas">A. Ragauskas</name><affiliation><nlm:aff id="aff2"><institution>Health Telematics Science Centre of Kaunas University of Technology</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Bartusis, L" sort="Bartusis, L" uniqKey="Bartusis L" first="L" last="Bartusis">L. Bartusis</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff2"><institution>Health Telematics Science Centre of Kaunas University of Technology</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Kucinoviene, J" sort="Kucinoviene, J" uniqKey="Kucinoviene J" first="J" last="Kucinoviene">J. Kucinoviene</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation></author><author><name sortKey="Siesky, B" sort="Siesky, B" uniqKey="Siesky B" first="B" last="Siesky">B. Siesky</name><affiliation><nlm:aff id="aff3"><institution>Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine</institution>, Indianapolis, IN,<country>USA</country></nlm:aff></affiliation></author><author><name sortKey="Harris, A" sort="Harris, A" uniqKey="Harris A" first="A" last="Harris">A. Harris</name><affiliation><nlm:aff id="aff1"><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></nlm:aff></affiliation><affiliation><nlm:aff id="aff3"><institution>Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine</institution>, Indianapolis, IN,<country>USA</country></nlm:aff></affiliation></author></analytic><series><title level="j">Eye</title><idno type="ISSN">0950-222X</idno><idno type="eISSN">1476-5454</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Eye (Lond)</journal-id><journal-id journal-id-type="iso-abbrev">Eye (Lond)</journal-id><journal-title-group><journal-title>Eye</journal-title></journal-title-group><issn pub-type="ppub">0950-222X</issn><issn pub-type="epub">1476-5454</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26183286</article-id><article-id pub-id-type="pmc">4815687</article-id><article-id pub-id-type="pii">eye2015127</article-id><article-id pub-id-type="doi">10.1038/eye.2015.127</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma</article-title><alt-title alt-title-type="running">Translaminar pressure difference in open-angle glaucoma: a review</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Siaudvytyte</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Januleviciene</surname><given-names>I</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="caf1">*</xref></contrib><contrib contrib-type="author"><name><surname>Daveckaite</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ragauskas</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bartusis</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kucinoviene</surname><given-names>J</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Siesky</surname><given-names>B</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Harris</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><aff id="aff1"><label>1</label><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Kaunas,<country>Lithuania</country></aff><aff id="aff2"><label>2</label><institution>Health Telematics Science Centre of Kaunas University of Technology</institution>, Kaunas,<country>Lithuania</country></aff><aff id="aff3"><label>3</label><institution>Glaucoma Research and Diagnostic Center, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine</institution>, Indianapolis, IN,<country>USA</country></aff></contrib-group><author-notes><corresp id="caf1"><label>*</label><institution>Eye Clinic, Lithuanian University of Health Sciences</institution>, Eiveniu Street 2, Kaunas 50009, <country>Lithuania</country> Tel: +370 37326760; Fax: +370 37327064. E-mail: <email>ingrida.januleviciene@kaunoklinikos.lt</email></corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>17</day><month>07</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>10</month><year>2015</year></pub-date><volume>29</volume><issue>10</issue><fpage>1242</fpage><lpage>1250</lpage><history><date date-type="received"><day>02</day><month>02</month><year>2015</year></date><date date-type="accepted"><day>10</day><month>06</month><year>2015</year></date></history><permissions><copyright-statement>Copyright © 2015 Royal College of Ophthalmologists</copyright-statement><copyright-year>2015</copyright-year><copyright-holder>Royal College of Ophthalmologists</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link></license-p></license></permissions><abstract><p>There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.</p></abstract></article-meta></front><body><sec><title>Introduction</title><p>Glaucoma is the second leading cause of blindness worldwide.<sup><xref ref-type="bibr" rid="bib1">1</xref></sup> Quigley <italic>et al</italic> reported that there are 60.5 million people suffering from glaucoma in the world and it is predicted that in 2020 this number will increase to 79.6 million, with 74% having open-angle glaucoma (OAG).<sup><xref ref-type="bibr" rid="bib2">2</xref></sup> The prevalence of glaucoma, which increases with age, is increasing primarily as the population ages. According to the World Health Organization (WHO) there is about 2.65% of the global population over 40 years of age who has glaucoma.<sup><xref ref-type="bibr" rid="bib3">3</xref></sup> The global disability adjusted life years of glaucoma has risen for the past 20 years: from 443 000 years in 1990 to 943 000 years in 2010.<sup><xref ref-type="bibr" rid="bib4">4</xref>, <xref ref-type="bibr" rid="bib5">5</xref></sup> Glaucoma is characterized by structural optic nerve head (ONH) and visual field changes that may occur at any intraocular pressure (IOP) level, depending on each person's individual susceptibility. Although lowering IOP helps to decelerate or stabilize the disease, vast numbers of patients still develop and progress in glaucoma, despite an IOP within normal range.<sup><xref ref-type="bibr" rid="bib6">6</xref></sup> It has been shown that in addition to high IOP there are many additional risk factors including: lower ocular perfusion pressure; reduced ocular blood flow; low blood pressure (BP); myopia; and several others.<sup><xref ref-type="bibr" rid="bib7">7</xref>, <xref ref-type="bibr" rid="bib8">8</xref>, <xref ref-type="bibr" rid="bib9">9</xref>, <xref ref-type="bibr" rid="bib10">10</xref></sup> Evidence confirms that these non-IOP factors lead to apoptotic processes associated with glaucoma.<sup><xref ref-type="bibr" rid="bib11">11</xref></sup> Recently, researchers have began to focus on intracranial pressure (ICP) and translaminar pressure difference (TPD) as having a potential role in glaucomatous optic neuropathy.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib13">13</xref></sup> The optic nerve is exposed not only to IOP in the eye, but also to ICP, as it is surrounded by cerebrospinal fluid (CSF) in the subarachnoid space (SAS). The lamina cribrosa demarcates these two pressurized zones and the pressure difference between them is called TPD (TPD=IOP – ICP).<sup><xref ref-type="bibr" rid="bib14">14</xref></sup> Physiologically, the difference between IOP (14.3(2.6) mm Hg) and ICP (12.9(1.9) mm Hg, in the supine position) is small.<sup><xref ref-type="bibr" rid="bib15">15</xref></sup> A higher TPD may lead to abnormal function and damage of the optic nerve due to changes in axonal transportation, deformation of the lamina cribrosa, altered blood flow or a combination thereof leading to glaucomatous damage.<sup><xref ref-type="bibr" rid="bib16">16</xref></sup> Furthermore, it is considered that the TPD may be a primary pressure related factor for glaucoma, as the ONH is located at the junction between the intraocular and retrobulbar spaces.<sup><xref ref-type="bibr" rid="bib17">17</xref></sup> However, the role of TPD in glaucoma pathogenesis and its progression remains unclear as the gold standard for ICP evaluation is an invasive measurement of the pressure in the CSF via lumbar puncture or via implantation of a pressure sensor into a cerebral ventricle.<sup><xref ref-type="bibr" rid="bib18">18</xref>, <xref ref-type="bibr" rid="bib19">19</xref>, <xref ref-type="bibr" rid="bib20">20</xref></sup> Importantly, this invasiveness includes the potential risk for intracranial hemorrhages and infection.<sup><xref ref-type="bibr" rid="bib21">21</xref></sup> To overcome these invasive limitations, several approaches have been proposed to estimate ICP noninvasively including: transcranial Doppler ultrasonography; tympanic membrane displacement; ophthalmodynamometry; and measurement of optic nerve sheath diameter.<sup><xref ref-type="bibr" rid="bib22">22</xref></sup> For instance, Xie <italic>et al</italic> estimated mathematical ICP formula based on three parameters: diastolic BP; age and body mass index (ICP=0.44 × body mass index (kg/m<sup>2</sup>)+0.16 × diastolic BP (mm Hg)−0.18 × age (years)−1.9); and Bland–Altman analysis revealed that 40 of 42 measurements were within the 95% limits of agreement.<sup><xref ref-type="bibr" rid="bib23">23</xref></sup> All of these approaches are based on correlation of anatomical or physiological parameters of the human head and brain with ICP. Unfortunately, correlation-based approaches are not accurate for real-quantitative ICP value measurement. To the best of our knowledge, this is the first review and meta-analysis to present all available qualified data from a systematic review of the literature of the role of TPD in OAG.</p></sec><sec><title>Materials and methods</title><p>A comprehensive literature search was performed via electronic databases of PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases with reference cross-matching to identify all observational studies evaluating TPD in patients with OAG. In our literature search we included a combination of keywords, such as ‘translaminar pressure difference', ‘translaminar pressure gradient', or ‘trans-lamina cribrosa pressure difference' and ‘glaucoma'. Search strategy was carried out on articles published over the past 10 years (from November 2004 to November 2014). The search was performed by two independent researchers (AD and LB) until all relevant articles were identified. The completeness of searches was validated by the primary author (LS) using all available library databases. We included all observational studies despite differences in ICP measurement methods (invasive or noninvasive) as there is no consensus regarding best-practice measurements of ICP in glaucoma.</p><p>Study quality assessment was based on the following criteria:
<list list-type="bullet"><list-item><p>The study type and number of subjects.</p></list-item><list-item><p>Information on the characteristics of the studied population.</p></list-item><list-item><p>Information on the inclusion criteria.</p></list-item><list-item><p>Data processing quality.</p></list-item><list-item><p>Approval of the Ethics Committee.</p></list-item></list></p><p>Data including age, IOP, ICP, and TPD were collected and statistical analysis was performed using the statistical analysis program (SPSS version 22, ‘Insight Solutions', Vilnius, Lithuania). The analysis of the quantitative variables included calculation of the weighted averages mean and SD (× (SD)). Two articles subdivided data into categories based on the form of primary open-angle glaucoma (POAG), thus weighted averages of all data points and SD were calculated.<sup><xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref></sup> One article presented data of IOP and ICP, while TPD was used just in correlations; the data were converted to numerical values using formula TPD=IOP−ICP.<sup><xref ref-type="bibr" rid="bib25">25</xref></sup> The hypothesis of equality among groups was analyzed using <italic>t-</italic>test. The level of significance <italic>P</italic><0.05 was considered significant.</p></sec><sec><title>Results</title><p>A total of 135 articles were identified from the search strategy and five studies that reported quantitative TPD parameters directly were deemed appropriate for inclusion.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup><xref ref-type="fig" rid="fig1">Figure 1</xref> shows the article selection process for studies included in the final meta-analysis. Ninety-two papers including case reports, comments, letters, editorials, abstracts, and review papers/chapters were excluded, as this systematic review was sought observational studies. For clinical applicability, only data from human subjects were included, thus eliminating articles<sup><xref ref-type="bibr" rid="bib27">27</xref>, <xref ref-type="bibr" rid="bib28">28</xref>, <xref ref-type="bibr" rid="bib29">29</xref>, <xref ref-type="bibr" rid="bib30">30</xref>, <xref ref-type="bibr" rid="bib31">31</xref>, <xref ref-type="bibr" rid="bib32">32</xref>, <xref ref-type="bibr" rid="bib33">33</xref></sup> that used experimental models. Twenty-five papers were excluded because there was no evaluation of TPD.<sup><xref ref-type="bibr" rid="bib34">34</xref>, <xref ref-type="bibr" rid="bib35">35</xref>, <xref ref-type="bibr" rid="bib36">36</xref>, <xref ref-type="bibr" rid="bib37">37</xref>, <xref ref-type="bibr" rid="bib38">38</xref>, <xref ref-type="bibr" rid="bib39">39</xref>, <xref ref-type="bibr" rid="bib40">40</xref>, <xref ref-type="bibr" rid="bib41">41</xref>, <xref ref-type="bibr" rid="bib42">42</xref>, <xref ref-type="bibr" rid="bib43">43</xref>, <xref ref-type="bibr" rid="bib44">44</xref>, <xref ref-type="bibr" rid="bib45">45</xref>, <xref ref-type="bibr" rid="bib46">46</xref>, <xref ref-type="bibr" rid="bib47">47</xref>, <xref ref-type="bibr" rid="bib48">48</xref>, <xref ref-type="bibr" rid="bib49">49</xref>, <xref ref-type="bibr" rid="bib50">50</xref>, <xref ref-type="bibr" rid="bib51">51</xref>, <xref ref-type="bibr" rid="bib52">52</xref>, <xref ref-type="bibr" rid="bib53">53</xref>, <xref ref-type="bibr" rid="bib54">54</xref>, <xref ref-type="bibr" rid="bib55">55</xref>, <xref ref-type="bibr" rid="bib56">56</xref>, <xref ref-type="bibr" rid="bib57">57</xref>, <xref ref-type="bibr" rid="bib58">58</xref></sup> Three papers were eliminated because glaucoma patients were not analyzed in these studies.<sup><xref ref-type="bibr" rid="bib59">59</xref>, <xref ref-type="bibr" rid="bib60">60</xref>, <xref ref-type="bibr" rid="bib61">61</xref>, <xref ref-type="bibr" rid="bib62">62</xref></sup> Three articles which did not present quantitative TPD values in OAG group were also excluded<sup><xref ref-type="bibr" rid="bib62">62</xref>, <xref ref-type="bibr" rid="bib63">63</xref>, <xref ref-type="bibr" rid="bib64">64</xref></sup><xref rid="tbl1" ref-type="table">Table 1</xref> shows the characteristics of papers (including 181 POAG patients and 215 healthy subjects) included to systematic review.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup></p><p>Two retrospective studies<sup><xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> and three prospective studies<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref></sup> matched all search criteria. One study evaluated ICP noninvasively using a two-depth transcranial Doppler (TCD) device (Vittamed UAB, Kaunas, Lithuania),<sup><xref ref-type="bibr" rid="bib24">24</xref></sup> based on simultaneous measurements of blood-flow parameters in intracranial and extracranial segments of the ophthalmic artery (OA). The value of external pressure, when OA blood flow in both segments was equal, was fixed and expressed automatically in absolute units mm Hg. The sensitivity, specificity, and diagnostic value of this device was proven in the previous studies with neurological patients.<sup><xref ref-type="bibr" rid="bib65">65</xref>, <xref ref-type="bibr" rid="bib66">66</xref></sup></p><p><xref rid="tbl2" ref-type="table">Table 2</xref> shows the results of the included studies. A meta-analysis of 396 patients was followed out and it was found that IOP, ICP, and TPD statistically significantly differed between POAG and healthy subjects (<italic>P</italic><0.001).<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> Three articles<sup><xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> subdivided patients into normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) categories; thus, meta-analysis of these data was also performed (<xref rid="tbl3" ref-type="table">Table 3</xref>). It was observed that IOP was significantly higher in HTG group than in healthy subjects or NTG groups (<italic>P</italic><0.001). ICP was significantly lower in NTG group compared with HTG or healthy subjects (<italic>P</italic><0.001). Evaluation of TPD revealed statistically significant differences between all groups: between HTG and NTG or healthy subjects, and NTG with healthy subjects (<italic>P</italic><0.001). Importantly, HTG group was significantly younger than NTG group or healthy subjects (<italic>P</italic><0.05). Some of these studies analyzed relationship between TPD and structural/functional glaucomatous changes<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref></sup> and found that higher TPD was associated with glaucomatous visual field loss or bigger structural glaucomatous changes. Summary of these studies is shown in <xref rid="tbl4" ref-type="table">Table 4</xref>.</p></sec><sec><title>Discussion</title><p>Although the importance of ICP and TPD in glaucomatous pathophysiology is beginning to emerge, scarce available data have greatly limited our understanding of this possible contributory mechanism. Therefore, we performed a first of its kind comprehensive meta-analysis to investigate the current state of knowledge of TPD in OAG.</p><p>Our meta-analysis found that ICP was significantly lower in patients with POAG, particularly in NTG, than in healthy subjects.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> TPD was almost two times higher in patients with NTG, and nearly five times higher in patients with HTG, compared with healthy controls.<sup><xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> As the ONH is exposed both to IOP and ICP, the TPD is an important parameter, and its reduction might assist in halting the progression of glaucoma. Jonas <italic>et al</italic> analyzed TPD and found statistically significant difference between glaucomatous and nonglaucomatous eyes (<italic>P</italic><0.001); however, glaucomatous group included not only OAG but also angle-closure glaucoma patients,<sup><xref ref-type="bibr" rid="bib62">62</xref>, <xref ref-type="bibr" rid="bib64">64</xref></sup> therefore, these studies were excluded from meta-analysis.</p><p>Siaudvytyte <italic>et al</italic> found that higher TPD was associated with lower neuroretinal rim area (NRA) in NTG,<sup><xref ref-type="bibr" rid="bib24">24</xref></sup> whereas no association was found in HTG or healthy subjects. This data suggests that NTG patients are more susceptible to TPD differences. Berdahl <italic>et al</italic><sup><xref ref-type="bibr" rid="bib25">25</xref></sup> found similar results in POAG and healthy subjects. It is important to note that this study has a limitation as measurements were obtained inconsistently within 1-year period of lumbar puncture performance. Whereas Siaudvytyte <italic>et al</italic> did not include neurological examination to exclude neurological disorders.<sup><xref ref-type="bibr" rid="bib24">24</xref></sup> Finally, Ren <italic>et al</italic><sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref></sup> found the relation between NRA, mean visual field defects and TPD, analyzing all study group.</p><p>There are several limitations of this meta-analysis to acknowledge. First, the limited uniformity of the available data from differing methodological approaches in the various studies makes direct comparisons difficult and the number of patients in experimental and control groups were often limited. Also, a majority of the selected studies<sup><xref ref-type="bibr" rid="bib24">24</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> did not include a washout period, which may account for differing study results. Specifically, Ren <italic>et al</italic><sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref></sup> included a washout period just for NTG patients, limiting accountability for possible effects of hypotensive agents on ICP. This is especially important in subjects who may have been using carbonic anhydrase inhibitors, as they are known to have systemic effects, which may influence of CSF production and result in ICP reduction.<sup><xref ref-type="bibr" rid="bib67">67</xref></sup></p><p>In addition, it should be mentioned that ICP-measuring methodologies were different between studies. Four studies used golden standard invasive ICP measuring method via lumbar puncture,<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> whereas Siaudvytyte <italic>et al</italic> in their study used noninvasive two-depth TCD device, which is currently the only available method for absolute ICP value numerical and automatic measurement that does not need an individual patient-specific calibration.<sup><xref ref-type="bibr" rid="bib24">24</xref></sup> A prospective study with 108 neurological patients showed that diagnostic sensitivity, specificity and the area under the ROC curve of this noninvasive absolute ICP method were 68.0%, 84.3%, and 0.87, respectively.<sup><xref ref-type="bibr" rid="bib66">66</xref></sup> However, the measuring error still remains, as we can see from the results—ICP values were higher in studies that used invasive ICP measuring methods.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup></p><p>Furthermore, it remains unclear whether the CSF pressure, measured by lumbar puncture, corresponds to the CSF pressure in the orbit around the optic nerve. The CSF dynamics at this area is different, as there are numerous septae present that could limit free flow of CSF. <sup><xref ref-type="bibr" rid="bib68">68</xref></sup> In addition, unlike in other areas, the dura of optic nerve sheath contains atypical meningeal tissue with lymphoid characteristics.<sup><xref ref-type="bibr" rid="bib69">69</xref></sup> Killer and colleagues found that patients with NTG have decreased CSF flow between the basal cisterns and the SAS surrounding the optic nerve. Such a difference has not been established in healthy subjects. This could explain why patients with NTG have lower ICP.<sup><xref ref-type="bibr" rid="bib53">53</xref></sup> However, experimental studies on dogs showed that CSF pressure in optic nerve SAS is equal to CSF pressure in the lateral ventricle of the brain at the level of eye.<sup><xref ref-type="bibr" rid="bib70">70</xref></sup> Moreover, it was established that the CSF pressure measured by lumbar puncture corresponds to ICP in the lateral decubitus position.<sup><xref ref-type="bibr" rid="bib18">18</xref></sup> However, the method depends on the optic nerve path at SAS between the orbital and intracranial parts. It is not known what happens when the optic nerve canal is blocked (for example, in cases of suprasellar meningioma, tuberculous meningitis, or intracanalicular OA aneurysm).</p><p>One important consideration is that IOP, ICP, and TPD are dynamic parameters and changes in posture or individual activities might affect these measurements, respectively. In studies included in meta-analysis, the IOP was measured in the sitting position, whereas ICP was assessed in the supine or lateral decubitus positions.<sup><xref ref-type="bibr" rid="bib12">12</xref>, <xref ref-type="bibr" rid="bib15">15</xref>, <xref ref-type="bibr" rid="bib25">25</xref>, <xref ref-type="bibr" rid="bib26">26</xref></sup> Humans evolved with gravity, and gravity affects human physiology—CSF pools in the caudal spinal canal and CSF pressure at eye level is much lower than CSF pressure in the caudal spinal column in the upright position.<sup><xref ref-type="bibr" rid="bib18">18</xref>, <xref ref-type="bibr" rid="bib71">71</xref></sup> However in microgravity environment, CSF is distributed throughout the SAS tending to equalize pressure in all compartments and negate any posture-induced flow, resulting in higher than normal CSF pressure at eye level.<sup><xref ref-type="bibr" rid="bib72">72</xref></sup> Several studies have shown that changes in posture cause pressure changes in all body fluid spaces, cardiac output, peripheral resistance, and blood flow to various vascular beds.<sup><xref ref-type="bibr" rid="bib73">73</xref>, <xref ref-type="bibr" rid="bib74">74</xref></sup> IOP changes by 2.9 mm Hg in healthy subjects and by 3.9 mm Hg in patients with glaucoma while changing body position from sitting to supine.<sup><xref ref-type="bibr" rid="bib75">75</xref></sup> Furthermore, head elevation decreases ICP by displacing CSF into the spinal canal and by improving cerebral venous drainage by opening alternative venous channels in the posterior circulation that remain closed while patients remain recumbent. Experimental studies showed that CSF pressure in the sitting position at the level of the occipital prominence, equivalent to eye level, ranged between 0 and −10 mm Hg.<sup><xref ref-type="bibr" rid="bib71">71</xref></sup> One of the ways to interpret ICP values in the sitting position is mathematical modeling, whereas standard body position for ICP measuring is lateral decubitus/supine.<sup><xref ref-type="bibr" rid="bib76">76</xref></sup></p><p>Another important aspect to consider is that authors analyzed simplified TPD, calculated by the following formula (TPD=IOP−ICP), and did not clarify the fact that TPD is actually the difference between IOP and the retrolaminar tissue pressure, which is largely determined by the optic nerve SAS pressure and pia mater characteristics. Furthermore, the optic nerve SAS pressure is influenced by orbital pressure from the sides.<sup><xref ref-type="bibr" rid="bib77">77</xref></sup> Morgan <italic>et al</italic>, analyzed correlation between CSF pressure and retrolaminar tissue pressure in dogs and found that retrolaminar tissue pressure was basically identical to the CSF pressure in the ventricles, when CSF pressure was above 2 mm Hg. Below 2 mm Hg, the tissue pressure was approximately constant, perhaps reflecting the orbital tissue pressing against the nerve when CSF pressure is very low.<sup><xref ref-type="bibr" rid="bib14">14</xref></sup> It would be interesting to analyze translaminar pressure gradient (defined as pressure distribution across the lamina cribrosa, altered by lamina cribrosa thickness) as the most obvious changes in glaucoma occur in the lamina cribrosa. It is estimated that lamina cribrosa is thinner and more bowed in glaucomatous eyes (201 microns) compared with normal eyes (457 microns).<sup><xref ref-type="bibr" rid="bib78">78</xref></sup></p><p>To answer the question whether TPD is important in glaucoma, we need longitudinal studies in addition to the retrospective and prospective studies performed thus far. Therefore, noninvasive techniques for ICP measurements would be helpful in the studies with human patients. Moreover, along with clinical studies, suitable animal models will also be helpful in understanding the role of ICP in glaucoma. Chowdhury <italic>et al</italic> published the study on comprehensive animal model where ICP can be manually reduced or increased over an extended period of time, that is valuable to study the balance between IOP and ICP and its role in glaucomatous optic neuropathy.<sup><xref ref-type="bibr" rid="bib79">79</xref></sup> Moreover, there are a lot of points that need explication to further elucidate ICP role in glaucoma. As CSF dynamics are poorly ascertained, there is no clear answer whether normal cardiac variations in ICP exist or how body position or activity of the person affect it. Although it is accepted that IOP diurnal fluctuations are greater in eyes with glaucoma,<sup><xref ref-type="bibr" rid="bib80">80</xref></sup> question is whether there are similar variations in ICP and single measurement of ICP can represent short or long-term pressure variations that could have a role in glaucoma. Furthermore, IOP fluctuations have been proposed as an independent risk factor for glaucomatous damage.<sup><xref ref-type="bibr" rid="bib81">81</xref></sup> Wostyn <italic>et al</italic> arose hypothesis that ICP fluctuations may result in significant fluctuations of the TPD and could exert repetitive shear stress on the lamina cribrosa and ganglion cell axons, leading to glaucomatous damage.<sup><xref ref-type="bibr" rid="bib82">82</xref></sup> Interestingly, other researchers found that Valsalva maneuver led to reduce or reverse of the TPD, which was associated with decreased optic cup-related parameters and enlarged neuroretinal rim-related parameters.<sup><xref ref-type="bibr" rid="bib61">61</xref></sup> Therefore, it would be interesting to estimate if alternative treatment strategies aiming to increase ICP could be beneficial for glaucoma patients.</p></sec><sec><title>Conclusion</title><p>Our meta-analysis of all qualified data shows that patients with NTG and HTG have higher TPD than healthy subjects. Importantly, higher TPD is associated with larger optic disc structural changes in patients with OAG. However, our conclusions are based on the current literature data, which are limited in scope and execution and have significant differences and weaknesses in the methodologies they utilized. With acknowledgement of these weaknesses, the available data suggest that there is a need for further longitudinal prospective clinical and experimental studies investigating the influence of TPD in glaucoma.</p></sec></body><back><ack><p>This research is funded by the European Social Fund under the Global Grant measure.</p></ack><notes><p>AR is an inventor of noninvasive ICP measurement technology, which is patented in the US and EU. 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TPD, translaminar pressure difference; OAG, open-angle glaucoma.</p></caption><graphic xlink:href="eye2015127f1"></graphic></fig><table-wrap id="tbl1"><label>Table 1</label><caption><title>Characteristics of the studies</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Authors</italic></th><th align="left" valign="top" charoff="50"><italic>Ren</italic> et al<sup><xref ref-type="bibr" rid="bib12">12</xref></sup></th><th align="left" valign="top" charoff="50"><italic>Ren</italic> et al<sup><xref ref-type="bibr" rid="bib15">15</xref></sup></th><th align="left" valign="top" charoff="50"><italic>Siaudvytyte</italic> et al<sup><xref ref-type="bibr" rid="bib24">24</xref></sup></th><th align="left" valign="top" charoff="50"><italic>Berdahl</italic> et al<sup><xref ref-type="bibr" rid="bib25">25</xref></sup></th><th align="left" valign="top" charoff="50"><italic>Berdahl</italic> et al<sup><xref ref-type="bibr" rid="bib26">26</xref></sup></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Study type</td><td align="left" valign="top" charoff="50">Observational, prospective</td><td align="left" valign="top" charoff="50">Observational, prospective</td><td align="left" valign="top" charoff="50">Observational, prospective</td><td align="left" valign="top" charoff="50">Observational, retrospective</td><td align="left" valign="top" charoff="50">Observational, retrospective</td></tr><tr><td align="left" valign="top" charoff="50">Included groups</td><td align="left" valign="top" charoff="50">POAG (NTG+HTG), OH</td><td align="left" valign="top" charoff="50">NTG, HTG, healthy</td><td align="left" valign="top" charoff="50">NTG, HTG, healthy</td><td align="left" valign="top" charoff="50">POAG and healthy</td><td align="left" valign="top" charoff="50">POAG (NTG+HTG), NTG, OH, healthy</td></tr><tr><td align="left" valign="top" charoff="50">ICP measurement method</td><td align="left" valign="top" charoff="50">Invasive</td><td align="left" valign="top" charoff="50">Invasive</td><td align="left" valign="top" charoff="50">Noninvasive</td><td align="left" valign="top" charoff="50">Invasive</td><td align="left" valign="top" charoff="50">Invasive</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50"> </td></tr><tr><td colspan="6" align="left" valign="top" charoff="50"><italic>Other data</italic></td></tr><tr><td align="left" valign="top" charoff="50"> Day of IOP and ICP measurements</td><td align="left" valign="top" charoff="50">Same day</td><td align="left" valign="top" charoff="50">Same day</td><td align="left" valign="top" charoff="50">Same day</td><td align="left" valign="top" charoff="50">Maximum IOP before lumbar puncture</td><td align="left" valign="top" charoff="50">Maximum IOP before lumbar puncture</td></tr><tr><td align="left" valign="top" charoff="50"> Wash-out period</td><td align="left" valign="top" charoff="50">1 month for NTG, HTG – did not include</td><td align="left" valign="top" charoff="50">1 month for NTG, HTG – did not include</td><td align="left" valign="top" charoff="50">Did not include</td><td align="left" valign="top" charoff="50">Did not include</td><td align="left" valign="top" charoff="50">Did not include</td></tr><tr><td align="left" valign="top" charoff="50"> Neurologist consultation</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">—</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td></tr><tr><td align="left" valign="top" charoff="50"> Approval of the Ethics Committee</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td><td align="left" valign="top" charoff="50">+</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p>Abbreviations: HTG, high-tension glaucoma; ICP, intracranial pressure; IOP, intraocular pressure; NTG, normal tension glaucoma; OH, ocular hypertension; POAG, primary open-angle glaucoma.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2"><label>Table 2</label><caption><title>Results of meta-analysis between primary open-angle glaucoma and healthy subjects</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Group</italic></th><th align="left" valign="top" charoff="50"><italic>Parameters</italic></th><th align="center" valign="top" char="(" charoff="50"><italic>Ren</italic> et al<sup><xref ref-type="bibr" rid="bib12">12</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Ren</italic> et al<sup><xref ref-type="bibr" rid="bib15">15</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Siaudvytyte</italic> et al<sup><xref ref-type="bibr" rid="bib24">24</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Berdahl</italic> et al<sup><xref ref-type="bibr" rid="bib25">25</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Berdahl</italic> et al<sup><xref ref-type="bibr" rid="bib26">26</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Total</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">POAG group</td><td align="left" valign="top" charoff="50">Number of patients (<italic>N</italic> (%))</td><td align="center" valign="top" char="(" charoff="50">35 (19.3%)</td><td align="char" valign="top" char="(" charoff="50">43 (23.8%)</td><td align="char" valign="top" char="(" charoff="50">18 (9.9%)</td><td align="center" valign="top" char="(" charoff="50">28 (15.5%)</td><td align="center" valign="top" char="(" charoff="50">57 (31.5%)</td><td align="char" valign="top" char="(" charoff="50">181 (100%)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Age (years)</td><td align="center" valign="top" char="(" charoff="50">45.0 (16.0)</td><td align="char" valign="top" char="(" charoff="50">43.4 (4.4)</td><td align="char" valign="top" char="(" charoff="50">55.7 (1.0)</td><td align="center" valign="top" char="(" charoff="50">71.5</td><td align="center" valign="top" char="(" charoff="50">70.5 (12.9)</td><td align="char" valign="top" char="(" charoff="50">57.8 (12.7)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IOP (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">21.0 (5.0)</td><td align="char" valign="top" char="(" charoff="50">21.6 (3.9)</td><td align="char" valign="top" char="(" charoff="50">19.2 (5.7)</td><td align="center" valign="top" char="(" charoff="50">24.3 (6.1)</td><td align="center" valign="top" char="(" charoff="50">22.2 (6.4)</td><td align="char" valign="top" char="(" charoff="50">21.9 (1.4)*</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">ICP (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">11.0 (3.0)</td><td align="char" valign="top" char="(" charoff="50">11.0 (1.0)</td><td align="char" valign="top" char="(" charoff="50">8.2 (0.8)</td><td align="center" valign="top" char="(" charoff="50">9.2 (2.9)</td><td align="center" valign="top" char="(" charoff="50">9.3 (3.2)</td><td align="char" valign="top" char="(" charoff="50">9.9 (1.0)**</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">TPD (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">11.0 (5.0)</td><td align="char" valign="top" char="(" charoff="50">10.6 (2.8)</td><td align="char" valign="top" char="(" charoff="50">11.0 (4.8)</td><td align="center" valign="top" char="(" charoff="50">15,1</td><td align="center" valign="top" char="(" charoff="50">11.6 (11.0)</td><td align="char" valign="top" char="(" charoff="50">11.7 (1.5)***</td></tr><tr><td align="left" valign="top" charoff="50">Control group</td><td align="left" valign="top" charoff="50">Number of patients (<italic>N</italic> (%))</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">71 (33.0%)</td><td align="char" valign="top" char="(" charoff="50">9 (4.2%)</td><td align="center" valign="top" char="(" charoff="50">49 (22.8%)</td><td align="center" valign="top" char="(" charoff="50">86 (40.0%)</td><td align="char" valign="top" char="(" charoff="50">215 (100%)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Age (years)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">45.7 (11.3)</td><td align="char" valign="top" char="(" charoff="50">51.9 (6.6)</td><td align="center" valign="top" char="(" charoff="50">68.9</td><td align="center" valign="top" char="(" charoff="50">68.2 (8.6)</td><td align="char" valign="top" char="(" charoff="50">60.2 (10.8)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IOP (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">14.3 (2.6)</td><td align="char" valign="top" char="(" charoff="50">15.9 (2.1)</td><td align="center" valign="top" char="(" charoff="50">16.4 (2.8)</td><td align="center" valign="top" char="(" charoff="50">16.1 (2.7)</td><td align="char" valign="top" char="(" charoff="50">15.6 (0.9)*</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">ICP (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">12.9 (1.9)</td><td align="char" valign="top" char="(" charoff="50">10.5 (3.0)</td><td align="center" valign="top" char="(" charoff="50">13.0 (4.2)</td><td align="center" valign="top" char="(" charoff="50">11.8 (0.71)</td><td align="char" valign="top" char="(" charoff="50">12.7 (0.5)**</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">TPD (mm Hg)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">1.4 (1.7)</td><td align="char" valign="top" char="(" charoff="50">5.4 (3.3)</td><td align="center" valign="top" char="(" charoff="50">3.4</td><td align="center" valign="top" char="(" charoff="50">3.3 (4.0)</td><td align="char" valign="top" char="(" charoff="50">2.8 (1.1)***</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>Abbreviations: ICP, intracranial pressure; IOP, intraocular pressure; POAG, primary open-angle glaucoma; TPD, translaminar pressure difference.</p></fn><fn id="t2-fn2"><p>*<italic>P</italic>, **<italic>P</italic>, and ***<italic>P</italic> are <0.05, significant difference between two groups (<italic>t</italic>-test).</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl3"><label>Table 3</label><caption><title>Results of meta-analysis between normal tension glaucoma, high tension glaucoma and healthy subjects</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col><col align="char" char="("></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Group</italic></th><th align="left" valign="top" charoff="50"><italic>Parameters</italic></th><th align="center" valign="top" char="(" charoff="50"><italic>Ren</italic> et al<sup><xref ref-type="bibr" rid="bib15">15</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Siaudvytyte</italic> et al<sup><xref ref-type="bibr" rid="bib24">24</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Berdahl</italic> et al<sup><xref ref-type="bibr" rid="bib26">26</xref></sup></th><th align="center" valign="top" char="(" charoff="50"><italic>Total</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">NTG group</td><td align="left" valign="top" charoff="50">Number of patients (<italic>N</italic> (%))</td><td align="char" valign="top" char="(" charoff="50">14 (41.2%)</td><td align="char" valign="top" char="(" charoff="50">9 (26.5%)</td><td align="char" valign="top" char="(" charoff="50">11 (32.3%)</td><td align="char" valign="top" char="(" charoff="50">34 (100%)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Age (years)</td><td align="char" valign="top" char="(" charoff="50">49.6 (12.1)</td><td align="char" valign="top" char="(" charoff="50">56.6 (10.4)</td><td align="char" valign="top" char="(" charoff="50">68.0 (17.1)</td><td align="char" valign="top" char="(" charoff="50">57.4 (8.0)*</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IOP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">16.1 (1.9)</td><td align="char" valign="top" char="(" charoff="50">13.7 (1.6)</td><td align="char" valign="top" char="(" charoff="50">17.3 (2.7)</td><td align="char" valign="top" char="(" charoff="50">15.9 (1.4)**</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">ICP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">9.5 (2.2)</td><td align="char" valign="top" char="(" charoff="50">7.4 (2.7)</td><td align="char" valign="top" char="(" charoff="50">9.3 (3.2)</td><td align="char" valign="top" char="(" charoff="50">8.7 (0.9)***</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">TPD (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">6.6 (3.6)</td><td align="char" valign="top" char="(" charoff="50">6.3 (3.1)</td><td align="char" valign="top" char="(" charoff="50">7.4 (4.8)</td><td align="char" valign="top" char="(" charoff="50">6.8 (0.5)****</td></tr><tr><td align="left" valign="top" charoff="50">HTG group</td><td align="left" valign="top" charoff="50">Number of patients (<italic>N</italic> (%))</td><td align="char" valign="top" char="(" charoff="50">29 (76.3%)</td><td align="char" valign="top" char="(" charoff="50">9 (23.7%)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">38 (100%)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Age (years)</td><td align="char" valign="top" char="(" charoff="50">40.4 (16.1)</td><td align="char" valign="top" char="(" charoff="50">54.7 (15.6)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">43.8 (6.2)*</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IOP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">24.3 (3.2)</td><td align="char" valign="top" char="(" charoff="50">24.7 (6.8)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">24.4 (0.2)**</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">ICP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">11.7 (2.7)</td><td align="char" valign="top" char="(" charoff="50">8.9 (1.9)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">11.0 (1.2)***</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">TPD (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">12.5 (4.1)</td><td align="char" valign="top" char="(" charoff="50">15.7 (7.7)</td><td align="center" valign="top" char="(" charoff="50">—</td><td align="char" valign="top" char="(" charoff="50">13.3 (1.4)****</td></tr><tr><td align="left" valign="top" charoff="50">Control group</td><td align="left" valign="top" charoff="50">Number of patients (<italic>N</italic> (%))</td><td align="char" valign="top" char="(" charoff="50">71 (42.8%)</td><td align="char" valign="top" char="(" charoff="50">9 (5.4%)</td><td align="char" valign="top" char="(" charoff="50">86 (51.8%)</td><td align="char" valign="top" char="(" charoff="50">166 (100%)</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Age (years)</td><td align="char" valign="top" char="(" charoff="50">45.7 (11.3)</td><td align="char" valign="top" char="(" charoff="50">51.9 (6.6)</td><td align="char" valign="top" char="(" charoff="50">68.2 (8.6)</td><td align="char" valign="top" char="(" charoff="50">57.7 (11.0)*</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">IOP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">14.3 (2.6)</td><td align="char" valign="top" char="(" charoff="50">15.9 (2.1)</td><td align="char" valign="top" char="(" charoff="50">16.1 (2.7)</td><td align="char" valign="top" char="(" charoff="50">15.3 (0.9)**</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">ICP (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">12.9 (1.9)</td><td align="char" valign="top" char="(" charoff="50">10.5 (3.0)</td><td align="char" valign="top" char="(" charoff="50">12.7 (3.9)</td><td align="char" valign="top" char="(" charoff="50">12.2 (0.7)***</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">TPD (mm Hg)</td><td align="char" valign="top" char="(" charoff="50">1.4 (1.7)</td><td align="char" valign="top" char="(" charoff="50">5.4 (3.3)</td><td align="char" valign="top" char="(" charoff="50">3.3 (4.0)</td><td align="char" valign="top" char="(" charoff="50">2.6 (1.1)****</td></tr></tbody></table><table-wrap-foot><fn id="t3-fn1"><p>Abbreviations: HTG, high-tension glaucoma; ICP, intracranial pressure; IOP, intraocular pressure; NTG, normal tension glaucoma; TPD, translaminar pressure difference.</p></fn><fn id="t3-fn2"><p>*<italic>P</italic>, **<italic>P</italic>, ***<italic>P</italic> and ****<italic>P</italic> are <0.05, significant difference between three groups (<italic>t</italic>-test).</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl4"><label>Table 4</label><caption><title>Summary of the correlations between translaminar pressure difference and structural/functional glaucomatous changes</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="char" char="."></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="char" char="."></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50"><italic>Authors</italic></th><th align="center" valign="top" char="." charoff="50"><italic>Number of patients</italic></th><th align="left" valign="top" charoff="50"><italic>Subjects</italic></th><th align="left" valign="top" charoff="50"><italic>Analyzed parameter</italic></th><th align="left" valign="top" charoff="50"><italic>Technology</italic></th><th align="center" valign="top" charoff="50"><italic>Correlation</italic></th><th align="center" valign="top" char="." charoff="50">P<italic>-value</italic></th></tr></thead><tbody valign="top"><tr><td align="left" valign="top" charoff="50">Ren <italic>et al</italic><sup><xref ref-type="bibr" rid="bib12">12</xref></sup></td><td align="center" valign="top" char="." charoff="50">52</td><td align="left" valign="top" charoff="50">POAG and OH</td><td align="left" valign="top" charoff="50">NRA</td><td align="left" valign="top" charoff="50">HRT</td><td align="center" valign="top" charoff="50"><italic>r</italic>=−0.38</td><td align="char" valign="top" char="." charoff="50">0.006</td></tr><tr><td align="left" valign="top" charoff="50"> </td><td align="center" valign="top" char="." charoff="50"> </td><td align="left" valign="top" charoff="50"> </td><td align="left" valign="top" charoff="50">Mean defect</td><td align="left" valign="top" charoff="50">HFA</td><td align="center" valign="top" charoff="50"><italic>r</italic>=0.38</td><td align="char" valign="top" char="." charoff="50">0.007</td></tr><tr><td align="left" valign="top" charoff="50">Ren <italic>et al</italic><sup><xref ref-type="bibr" rid="bib15">15</xref></sup></td><td align="center" valign="top" char="." charoff="50">114</td><td align="left" valign="top" charoff="50">NTG, HTG, healthy</td><td align="left" valign="top" charoff="50">Mean defect</td><td align="left" valign="top" charoff="50">HFA</td><td align="center" valign="top" charoff="50"><italic>r</italic>=0.69</td><td align="char" valign="top" char="." charoff="50">0.005</td></tr><tr><td align="left" valign="top" charoff="50">Siaudvytyte <italic>et al</italic><sup><xref ref-type="bibr" rid="bib24">24</xref></sup></td><td align="center" valign="top" char="." charoff="50">9</td><td align="left" valign="top" charoff="50">NTG</td><td align="left" valign="top" charoff="50">NRA</td><td align="left" valign="top" charoff="50">HRT</td><td align="center" valign="top" charoff="50"><italic>r</italic>=−0.83</td><td align="char" valign="top" char="." charoff="50">0.01</td></tr><tr><td align="left" valign="top" charoff="50">Berdahl <italic>et al</italic><sup><xref ref-type="bibr" rid="bib25">25</xref></sup></td><td align="center" valign="top" char="." charoff="50">77</td><td align="left" valign="top" charoff="50">POAG and healthy</td><td align="left" valign="top" charoff="50">Cup-to-disc ratio</td><td align="left" valign="top" charoff="50">Medical records</td><td align="center" valign="top" charoff="50"><italic>r</italic><sup>2</sup>=0.399</td><td align="char" valign="top" char="." charoff="50"><0.0001</td></tr></tbody></table><table-wrap-foot><fn id="t4-fn1"><p>Abbreviations: HFA, Humphrey Field Analyzer; HRT, Heidelberg Retina Tomograph; HTG, high-tension glaucoma; Mean defect, Mean glaucomatous visual field defect (dB); NRA, neuroretinal rim area; NTG, normal tension glaucoma; OH, ocular hypertension; POAG, primary open-angle glaucoma.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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