J Neurosurg 121:680–687, 2014

©AANS, 2014

Diagnostic accuracy of intraocular pressure measurement for

the detection of raised intracranial pressure: meta-analysis

A systematic review
Daniel Yavin, M.D.,1,2 Judy Luu, M.D., 3,4 Matthew T. James, M.D., Ph.D.,1,4
Derek J. Roberts, M.D., 2,5 Garnette R. Sutherland, M.D.,1,6
Nathalie Jette, M.D., M.Sc.,1,2,6,7 and Samuel Wiebe, M.D., M.Sc.1,2,6,7
Departments of 1Clinical Neurosciences, 2Community Health Sciences, 3Cardiac Sciences, 4Medicine, and
5
Surgery, 6Hotchkiss Brain Institute, and 7Institute for Public Health, University of Calgary, Alberta, Canada

Object. Because clinical examination and imaging may be unreliable indicators of intracranial hypertension,
intraocular pressure (IOP) measurement has been proposed as a noninvasive method of diagnosis. The authors con-
ducted a systematic review and meta-analysis to determine the correlation between IOP and intracranial pressure
(ICP) and the diagnostic accuracy of IOP measurement for detection of intracranial hypertension.
Methods. The authors searched bibliographic databases (Ovid MEDLINE, Ovid EMBASE, and the Cochrane
Central Register of Controlled Trials) from 1950 to March 2013, references of included studies, and conference
abstracts for studies comparing IOP and invasive ICP measurement. Two independent reviewers screened abstracts,
reviewed full-text articles, and extracted data. Correlation coefficients, sensitivity, specificity, and positive and nega-
tive likelihood ratios were calculated using DerSimonian and Laird methods and bivariate random effects models.
The I2 statistic was used as a measure of heterogeneity.
Results. Among 355 identified citations, 12 studies that enrolled 546 patients were included in the meta-analysis.
The pooled correlation coefficient between IOP and ICP was 0.44 (95% CI 0.26–0.63, I2 = 97.7%, p < 0.001). The
summary sensitivity and specificity for IOP for diagnosing intracranial hypertension were 81% (95% CI 26%–98%,
I2 = 95.2%, p < 0.01) and 95% (95% CI 43%–100%, I2 = 97.7%, p < 0.01), respectively. The summary positive and
negative likelihood ratios were 14.8 (95% CI 0.5–417.7) and 0.2 (95% CI 0.02–1.7), respectively. When ICP and IOP
measurements were taken within 1 hour of another, correlation between the measures improved.
Conclusions. Although a modest aggregate correlation was found between IOP and ICP, the pooled diagnostic
accuracy suggests that IOP measurement may be of clinical utility in the detection of intracranial hypertension. Given
the significant heterogeneity between included studies, further investigation is required prior to the adoption of IOP
in the evaluation of intracranial hypertension into routine practice.
(http://thejns.org/doi/abs/10.3171/2014.4.JNS13932)

Key Words      •      intracranial pressure      •      intracranial hypertension      •     

intraocular pressure      •      meta-analysis      •      systematic review      •      diagnostic accuracy

I
ntracranial hypertension represents a life-threaten-
ing emergency. Left untreated, intracranial hyperten-
sion may lead to progressive cerebral ischemia, her-
niation, and death.28 Alternatively, the early diagnosis and
treatment of intracranial hypertension improves patient
survival.34 Recognizing intracranial hypertension is often
difficult, however, as clinical examination and imaging
are unreliable measures of intracranial pressure (ICP).27
Abbreviations used in this paper: ED = emergency department;
ICP = intracranial pressure; ICU = intensive care unit; IOP = intra-
ocular pressure; LP = lumbar puncture; QUADAS = Quality Assess-
ment of Diagnostic Accuracy Studies.
While the delayed diagnosis of intracranial hypertension
results in ongoing brain injury, the liberal placement of
invasive ICP monitors is associated with significant iatro-
genic morbidity due to intraparenchymal hemorrhage and
bacterial colonization.20,21
The accurate noninvasive measurement of ICP would
allow early recognition of intracranial hypertension while
sparing patients with normal ICP from the risks associ-
ated with invasive monitoring. The long-recognized
indirect transmission of ICP to the orbit via the inter-
vening venous anatomy has resulted in the proposal of
various methods of noninvasive ICP measurement.1,9,12,33
Intraocular pressure (IOP) measurement, as opposed to

680 J Neurosurg / Volume 121 / September 2014

Intraocular and intracranial pressure: a meta-analysis
alternative surrogate ICP measures such as optic nerve
sheath diameter or central retinal venous pressure, may
be obtained rapidly at the bedside with the use of widely
available handheld tonometers by clinicians without spe-
cialized training.
The accuracy of IOP measurement in the noninva-
sive diagnosis of intracranial hypertension has been the
subject of multiple previous studies.2,4,5,11,15,16,19,24,25,31,32,35,36
As these often small, disparate reports have produced
conflicting results, IOP measurement in the evaluation of
patients suspected of intracranial hypertension has yet to
be adopted into clinical practice. We therefore conduct-
ed a systematic review and meta-analysis to determine
the correlation between IOP and ICP and the diagnostic
accuracy of IOP measurement for detecting raised ICP
among patients with suspected intracranial hyperten-
sion. We also sought to determine whether heterogene-
ity among these pooled estimates could be explained by
various patient- or study-level covariates to guide future
research.
Methods
This meta-analysis was conducted in accordance
with guidelines for the performance of diagnostic accu-
racy systematic reviews and reported in adherence to the
PRISMA (Preferred Reporting Items for Systematic Re-
views and Meta-analysis) statement.17,23
Search Strategy
We searched electronic bibliographic databases
(Ovid MEDLINE, Ovid EMBASE, and the Cochrane
Central Register of Controlled Trials [CENTRAL]) be-
tween 1950 and March 2013, and reference lists of in-
cluded articles. Keywords used in the search strategy
were “brain injury,” “intraocular pressure,” “intracranial
hypertension,” “intracranial pressure,” “tonometry,” “in-
traventricular catheter,” and “cerebrospinal fluid pres-
sure.” To identify additional citations, we also searched
conference proceedings from the American Association
of Neurological Surgeons (AANS), Congress of Neuro-
logical Surgeons (CNS), and Canadian Neurologic Fed-
eration of Neurological Surgeons (CFNS) from 2009 to
2013. One reviewer performed the search (D.Y.), while
another assessed the results (J.L.).
Study Selection
Two reviewers (D.Y. and J.L.) independently screened
identified abstracts and articles in duplicate. Studies de-
scribing IOP and ICP in their title or abstract were retrieved
for full text review. We used the following inclusion crite-
ria: 1) study participants underwent measurement of both
IOP and ICP; and 2) a Pearson, Spearman, Lin, or linear
regression analysis-derived correlation coefficient or a 2
by 2 contingency table could be formulated from the avail-
able data for the calculation of sensitivity and specificity.
Studies meeting inclusion criteria were incorporated into
the analysis irrespective of the setting of the study, age
of participants, patients’ intracranial pathology, publica-
tion status of the trial, or written language of the report.
J Neurosurg / Volume 121 / September 2014
Reports involving only patients with known intraocular
pathology were excluded.
Data Extraction
Two reviewers (D.Y. and J.L.) independently ex-
tracted data from included studies in duplicate. Disagree-
ment was resolved by consensus. We extracted the fol-
lowing data: 1) patient demographics, including pathol-
ogy responsible for suspected intracranial hypertension,
mean age, sex, mean IOP, mean ICP, and prevalence of
intracranial hypertension; 2) study design and setting; 3)
thresholds used to define intracranial hypertension and
elevated IOP; 4) number of IOP and ICP measurements
performed; 5) number of centers involved; 6) method of
invasive ICP measurement; 7) device used to measure
IOP; 8) relative timing of IOP and ICP measurement; and
9) publication year. Outcomes extracted included the cor-
relation coefficient between IOP and ICP and its variance,
and the number of true and false positive and negative
observations between IOP and invasive ICP measurement
as the reference standard for the presence of intracranial
hypertension.
Quality Assessment
The methodological quality of the studies included
in the meta-analysis was graded independently by two re-
viewers (D.Y. and J.L.) with the Quality Assessment Of
Diagnostic Accuracy Studies (QUADAS) tool.37 Question
12 of the QUADAS tool (interpretation of test results) was
excluded as both IOP and ICP measurement are automat-
ed and therefore do not require subjective interpretation.
Thus, a component analysis according to the QUADAS
tool was performed and illustrated as a proportional bar
graph for each of the 13 individual applicable criteria.
Disagreement between the two reviewers was resolved by
consensus.
Statistical Analysis
In recognition of interstudy variability, correlation
coefficients were pooled using a DerSimonian and Laird
random effects model.6 When not reported, measures
of dispersion were calculated based upon the studies’
sample size.10 Fisher transformation was not performed
on correlation coefficients prior to aggregation due to the
associated risk of an overestimation of correlation in the
summary estimate.14 Heterogeneity among trials was as-
sessed using the I2 test with values of 25%, 50%, and 75%
classified as low, moderate, and high degrees of heteroge-
neity, respectively.13 Meta-regression was conducted ac-
cording to study characteristics (quality, timing of IOP
and ICP measurement, and method of invasive ICP as-
sessment). Publication bias was assessed via Egger preci-
sion-weighted linear regression.7
Summary estimates of sensitivity and specificity were
obtained through a bivariate random effects model.30 Indi-
vidual and summary estimates of sensitivity and specificity
were illustrated through a hierarchical summary receiver
operating characteristic plot with the x- and y-axes repre-
senting the index test’s sensitivity, and 1 - specificity, re-
spectively. Pretest and posttest probabilities were obtained
681

through Fagan’s nomogram.8 Statistical analysis was per-
formed through metan,3 midas (http://fmwww.bc.edu/
repec/bocode/m/midas.html), and metandi (http://ideas.
repec.org/c/boc/bocode/s456932.html) modules of Stata
version 12.0 software (STATA Corp.).
Results
The database search yielded 355 studies, of which 326
were excluded following screening of titles and abstracts
(Fig. 1). The remaining 29 studies were retrieved. Seven-
teen studies where excluded after full text review due to a
lack of either IOP or invasive ICP measurement (12 stud-
ies), duplicate publications of results reported in greater
detail elsewhere (3 studies), or the indirect measurement
of IOP (2 studies). The remaining 12 studies enrolling 546
participants identified in our literature search were includ-
ed in our meta-analysis (Table 1).2,4,5,11,15,16,19,24,25,31,32,35,36 Al-
though all of these 12 studies contributed to the calculation
of a pooled estimated correlation coefficient, only 4 pre-
sented outcomes required for the calculation of summary
diagnostic accuracy estimates (Table 2).16,19,25,36
Study Characteristics
The characteristics of the studies included in our anal-
ysis are presented in Table 1. Patients were recruited from
outpatient neurology clinics,11,15,19,31,32 the emergency de-
partment (ED),25 and intensive care units (ICUs).2,4,5,16,24,35,36
Participants were adult patients with the exception of 1
study performed in a pediatric ICU setting.36 In half of the
included studies, invasive ICP measurement was obtained
Fig. 1.  Flow chart of study identification, exclusion, and inclusion in the meta-analysis.
682
D. Yavin et al.
through lumbar puncture (LP)11,15,19,25,31,32 while the remain-
der measured ICP through intracranial monitors.2,4,5,16,24,35,36
The interval between IOP and ICP measurement ranged
from simultaneous measurements4,5,16,24,35,36 to up to 5
hours.11 Among studies reporting diagnostic accuracy
estimates, the thresholds for assigning elevated IOP and
intracranial hypertension were defined as a measurement
greater than 20 cm H20.16,25,32,36
Assessment of the Risk of Bias
The average QUADAS score was 8 out of a poten-
tial 13 points (range 6–11), reflecting the overall modest
quality of included studies (Fig. 2). Spectrum bias was
the most pertinent source of systematic error in the in-
cluded studies. This source of systematic error arises
from study populations whose spectrum of diseased and
nondiseased states is not reflective of the test’s intended
patient population, resulting in falsely elevated measures
of “rule-in” or “rule-out” performance.29 While studies
performed in an outpatient setting enrolled participants
with an extremely low index of suspicion of intracranial
hypertension that would not have otherwise warranted
invasive ICP measurement (as reflected by the absence
of patients with intracranial hypertension in 1 study),31
others recruited study participants who were comatose,
meeting criteria for brain death on clinical examination.2
Review bias was present in the majority of studies, as
only 1 design involved the blinding of investigators to the
results of both index and reference test results.32 Given the
limited subjective interpretation involved in either IOP or
invasive ICP measurement, the presence of diagnostic
J Neurosurg / Volume 121 / September 2014
Intraocular and intracranial pressure: a meta-analysis
TABLE 1: Characteristics of studies included in the meta-analysis*

Mean Intracranial
No. of Age Mean IOP Mean ICP Hypertension Timing of ICP &
Authors & Year Country Patients (yrs) Setting (mm Hg) (mm Hg) Assessment of ICP Prevalence (%) IOP Measurement
Blank & Spring, 1988 Germany 20 68 ICU 15.1 9.9 ICP monitor 39 >1 hr delay
Czarnik et al., 2009 Poland 40 54 ICU 14.2 28.3 ICP monitor NR simultaneously
Han et al., 2008 US 55 48 clinic 14.4 14.1 LP NR >1 hr delay
Kirk et al., 2011 US 45 45 clinic 13.9 18.3 LP NR >1 hr delay
Lashutka et al., 2004 US 27 60 ICU NR NR EVD/ICP monitor 68 simultaneously
Li et al., 2012 China 130 37 clinic 14.4 12.8 LP 29 <1 hr delay
Morgan et al., 2012 Australia 9 39 ICU 15.1 4.4 EVD/ICP monitor 0 simultaneously
Muchnok et al., 2012 US 32 41 ED NR NR LP NR <1 hr delay
Ren et al., 2011 China 71 46 clinic 14.3 12.9 LP 0 <1 hr delay
Sajjadi et al., 2006 Iran 50 34 clinic 20.4 19.1 LP 54 <1 hr delay
Sheeran et al., 2000 UK 31 NR ICU NR NR EVD/ICP monitor NR simultaneously
Spentzas et al., 2010 US 36 5 ICU NR NR ICP monitor 34 simultaneously

*  EVD = external ventricular drain; NR = not reported.

review bias among included studies is unlikely to be a
significant contributor of bias in the measured correlation
coefficients. Lastly, given the known temporal variation
present in ICP, particularly among those patients with in-
tracranial hypertension, the asynchronous measurement
of IOP and ICP in the majority of included studies repre-
sents a significant potential source of disease progression
bias.2,11,15,19,25,28,31,32
Pooled Estimates of Correlation Between IOP and ICP
The summary correlation coefficient obtained
through a DerSimonian and Laird random effects model
aggregating outcomes from 12 studies was 0.44 (95% CI
0.26–0.63; Fig. 3).2,4,5,11,15,16,19,24,25,31,32,35,36 A high degree of
heterogeneity was present between studies (I2 = 97.7%, p
< 0.0001).
Meta-regression revealed a significant association
between the timing of IOP and ICP measurement and ag-
gregate correlation coefficients (p < 0.03; Table 3). Mea-
surements taken greater than 1 hour apart showed no cor-
relation (0.02, 95% CI -0.12 to 0.16) while those taken
within an hour significantly correlated with one another
(0.56, 95% CI 0.38–0.75). Conversely, study quality and
the method of invasive ICP measurement were not signifi-
cantly associated with summary correlation coefficients.
Egger’s test for small study effects was statistically signif-
icant (p < 0.02), reflecting possible publication bias due
TABLE 2: The sensitivity and specificity of IOP for intracranial hypertension*
to an absence of published studies reporting a negative
correlation between IOP and ICP.
Pooled Estimates of Diagnostic Accuracy of IOP Versus
ICP for Identification of Intracranial Hypertension
When the outcomes of the 4 studies reporting mea-
sures of diagnostic accuracy were pooled, summary es-
timates of sensitivity and specificity were 81% (95% CI
26%–98%) and 95% (95% CI 43%–100%), respectively
(Fig. 4).16,19,24,25,36 A high degree of variability between
studies was noted in individual estimates of both sensitiv-
ity and specificity, as reflected by I2 values of 95% and
98%, respectively. The aggregate diagnostic odds ratio
was 74.5 (95% CI 0.4–15,166.8) while the positive and
negative likelihood ratios of IOP measurement in the di-
agnosis of intracranial hypertension were 14.8 (95% CI
0.5–417.7) and 0.2 (95% CI 0.02–1.7), respectively. With
a pretest probability of 35% based on the accuracy of cur-
rent guidelines for invasive ICP monitoring, the positive
posttest probability of intracranial hypertension with the
use of IOP measurement was 89%, while the correspond-
ing negative posttest probability was 10% (Fig. 5).
Discussion
The indirect transmission of ICP to the orbit via the
intervening cavernous sinus, superior ophthalmic vein,

Authors & Year TP FP TN FN Sensitivity (%) Specificity (%) + LR − LR

Lashutka et al., 2004† 53 1 25 1 98 96 24.5 48.0
Li et al., 2012 26 33 59 12 68 64 1.9 2.0
Muchnok et al., 2012 5 4 7 16 24 64 0.7 0.8
Spentzas et al., 2010† 68 5 177 24 74 97 26.9 3.7

*  FN = false negative, FP = false positive, LR = likelihood ratio, TN = true negative, TP = true positive.
†  These studies collected repeated measurements of the same patients at different time points during the study periods.

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 D. Yavin et al.

and episcleral veins was first recognized in 1925 when

Fig. 2.  Quality assessment of studies included in the meta-analysis.
Values on the x axis represent percentages of studies.
Baurmann observed that central retinal vein distension
varied with ICP.1 Subsequent animal studies performed in
Rhesus monkeys and canines confirmed a linear associa-
tion between IOP and ICP.18,26 The difficulty involved in
the measurement of IOP at the bedside restricted its clini-
cal application in the diagnosis of intracranial hyperten-
sion. The recent advent of handheld tonometers that allow
rapid measurement of IOP by health care providers with-
out subspecialty training in ophthalmology has renewed
interest in IOP as a noninvasive means of intracranial
hypertension diagnosis.22,33 Despite the initial promise of
preclinical reports, studies of the utility of IOP in the de-
termination of ICP in humans have reported conflicting
results. To clarify the clinical role of IOP in the diagnosis
of intracranial hypertension, we have performed the only
meta-analysis to date on this subject.
The pooled correlation coefficient demonstrated an as-
sociation between IOP and ICP (0.44, 95% CI 0.26–0.63).
However, the broad confidence interval and high degree
of heterogeneity associated with the summary estimate
prevent a definitive conclusion on the clinical application
of IOP for assessment of ICP. Our meta-analysis suggests
that the variability in the summary estimates of correla-
tion likely reflects the disparate methods used in individual
studies. The asynchronous measurement of IOP and ICP
contributed to the loss of association between the two
measures and represented a significant potential source
of disease progression bias. The improved correlation ob-

Fig. 3.  Forest plot of the correlation between IOP and ICP. The dashed line indicates the pooled correlation coefficient be-
tween IOP and ICP.

684 J Neurosurg / Volume 121 / September 2014

Intraocular and intracranial pressure: a meta-analysis
TABLE 3: Meta-regression: estimated influence of study characteristics on correlation coefficient

Study Characteristic Correlation Coefficient (95% CI) I2 (%) p Value†

quality*
 <9 0.47 (0.24–0.70) 92 0.95
  ≥9 0.42 (0.12–0.73) 98
method of ICP measurement
 LP 0.44 (0.26–0.63) 98 0.77
  ICP monitor 0.49 (0.23–0.75) 96
timing of IOP & ICP measurement
  <1 hr 0.56 (0.38–0.75) 98 <0.03
  >1 hr 0.02 (−0.12 to 0.16) 0

*  Quality as measured by the QUADAS tool on a 13-point scale.

†  The p value was obtained by joint test on the basis of Knapp-Hartung modification.

served when studies using measurements taken beyond 1
hour were excluded (0.56, 95% CI 0.38–0.75) imply that
the pooled estimate of all studies is an underestimate of the
true association between ICP and IOP.
Given the potentially ominous clinical consequences
of failing to recognize intracranial hypertension, a high
sensitivity is required of a noninvasive test of intracranial
hypertension. The pooled estimate of sensitivity (81%,
95% CI 26%–98%) limits the clinical application of IOP
in screening for intracranial hypertension. Conversely,
while the pooled specificity of 95% (95% CI 43%–100%)
indicates that IOP may provide a useful means of ruling
in the diagnosis of intracranial hypertension, the relative-
ly high specificity suggests that a lower threshold value
for a positive result may improve the clinical utility of
IOP measurement in detecting intracranial hypertension.
As with the aggregate estimate of correlation, the impli-
cations of the pooled sensitivity and specificity estimates
are limited by their imprecision due to the relatively small
number of studies with disparate designs contributing to
the estimate. In addition, the pooled estimates of diag-
nostic accuracy were subject to spectrum bias as a result
of the wide-ranging prevalence of intracranial hyper-
tension (29% to 68%) among participants of individual
studies.16,19,24,25,36 Despite the promising pooled estimates
of diagnostic accuracy of IOP in the detection of intra-
cranial hypertension, given the large associated CIs, the
results of this meta-analysis do not, at this time, support
the routine clinical adoption of IOP in the screening for
intracranial hypertension.
Even in light of the above-mentioned limitations,
among those patients in whom clinical equipoise ex-
ists regarding the placement of an invasive ICP monitor,
IOP measurement may still improve upon current clini-

Fig. 4. Hierarchical summary receiver operating curve (HSROC) Fig. 5.  Pre- and posttest probabilities of intracranial hypertension as
plot of IOP for the diagnosis of intracranial hypertension. a function of IOP measurement.

J Neurosurg / Volume 121 / September 2014 685


cal decision-making. As existing practice guidelines for
ICP monitoring following severe traumatic brain injury
correctly predict intracranial hypertension in only 53%
to 63% of patients, the measurement of IOP may signifi-
cantly improve upon the ability to correctly identify in-
tracranial hypertension among head-injured patients.27
In this setting, positive and negative likelihood ratios of
14.8 and 0.2 would improve patient outcomes through the
avoidance of complications resulting from unnecessary
invasive ICP monitoring and the earlier diagnosis of those
patients suffering from intracranial hypertension.
Given the correlation observed between IOP and ICP,
the lack of morbidity associated with IOP measurement,
and the dramatic improvements in patient outcomes that
may be achieved through the more accurate detection of
intracranial hypertension, further investigation of IOP in
the diagnosis of intracranial hypertension is warranted.
Future studies should take place in settings in which
clinical equipoise exists regarding the use of invasive ICP
monitoring. Furthermore, the accuracy of IOP in predict-
ing intracranial hypertension should be evaluated in con-
junction with existing clinical and radiological features
associated with elevated ICP. Lastly, further evaluation of
the correlation between IOP and ICP should involve their
simultaneous measurement.
Disclosure
Vanier Canada graduate scholarships from the Canadian Insti-
tutes of Health Research and the Alberta Innovates Health Solutions
Clinician Fellowship were awarded to Dr. Yavin. Dr. James received
an honorarium from Amgen for a presentation at an industry-spon-
sored conference.
Author contributions to the study and manuscript prepara-
tion include the following. Conception and design: all authors.
Acquisition of data: Yavin, Luu. Analysis and interpretation of data:
Yavin, Luu, Jette. Drafting the article: Yavin, Luu, Jette. Critically
revising the article: all authors. Reviewed submitted version of
manuscript: all authors. Approved the final version of the manuscript
on behalf of all authors: Wiebe. Statistical analysis: Yavin, James,
Roberts, Sutherland. Administrative/technical/material support: Luu,
Roberts. Study supervision: Wiebe, James, Sutherland, Jette.
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Manuscript submitted August 8, 2013.
Accepted April 7, 2014.
Please include this information when citing this paper: pub-
lished online May 23, 2014; DOI: 10.3171/2014.4.JNS13932.
Address correspondence to: Samuel Wiebe, M.D., M.Sc., Divi-
sion of Neurology, Departments of Clinical Neurosciences and Com-
munity Health Sciences, University of Calgary, 12th Floor, Foothills
Medical Centre, 1403 - 29 St. NW, Calgary, AB T2N 2T9, Canada.
email: swiebe@ucalgary.ca.
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