REVIEW
Bedside Optic Nerve Ultrasonography for Diagnosing Increased
Intracranial Pressure
A Systematic Review and Meta-analysis
Alex Koziarz, MSc; Niv Sne, MD; Fraser Kegel, BSc; Siddharth Nath, BSc; Jetan H. Badhiwala, MD; Farshad Nassiri, MD;
Alireza Mansouri, MD; Kaiyun Yang, MD; Qi Zhou, PhD; Timothy Rice, MD; Samir Faidi, MD; Edward Passos, MD;
Andrew Healey, MD; Laura Banfield, MLIS; Mark Mensour, MD; Andrew W. Kirkpatrick, MD; Aussama Nassar, MD;
Michael G. Fehlings, MD; Gregory W.J. Hawryluk, MD; and Saleh A. Almenawer, MD
Background: Optic nerve ultrasonography (optic nerve sheath
diameter sonography) has been proposed as a noninvasive,
quick method for diagnosing increased intracranial pressure.
Purpose: To examine the accuracy of optic nerve ultrasonogra-
phy for diagnosing increased intracranial pressure in children
and adults.
Data Sources: 13 databases from inception through May 2019,
reference lists, and meeting proceedings.
Study Selection: Prospective optic nerve ultrasonography di-
agnostic accuracy studies, published in any language, involving
any age group or reference standard.
Data Extraction: 3 reviewers independently abstracted data
and performed quality assessment.
Data Synthesis: Of 71 eligible studies involving 4551 patients,
61 included adults, and 35 were rated as having low risk of bias.
The pooled sensitivity, specificity, positive likelihood ratio, and
negative likelihood ratio of optic nerve ultrasonography in pa-
tients with traumatic brain injury were 97% (95% CI, 92% to 99%),
86% (CI, 74% to 93%), 6.93 (CI, 3.55 to 13.54), and 0.04 (CI, 0.02
to 0.10), respectively. Respective estimates in patients with non-
I ncreased intracranial pressure can result from a head
injury, intracranial lesion, disturbance of cerebrospi-
nal fluid circulation, or obstruction to major venous si-
nuses; it may also be idiopathic (1). A patient's progno-
sis depends on early diagnosis and prompt intracranial
pressure reduction to prevent permanent neurologic
sequelae and brain herniation (2). Several measures are
used for intracranial pressure diagnosis, such as
computed tomography, magnetic resonance imaging,
intracranial pressure monitor, and lumbar puncture.
However, these tests are limited by invasiveness,
contraindications, radiation exposure, availability, and
need for patient transportation. Recently, optic nerve
ultrasonography, also known as optic nerve sheath di-
ameter sonography, has emerged as an alternative
See also:
Editorial comment . . . . . . . . . . . . . . . . . . . . . . . . . 935
Web-Only
Supplement
CME/MOC activity
896 © 2019 American College of Physicians
Annals of Internal Medicine
traumatic brain injury were 92% (CI, 86% to 96%), 86% (CI, 77%
to 92%), 6.39 (CI, 3.77 to 10.84), and 0.09 (CI, 0.05 to 0.17).
Accuracy estimates were similar among studies stratified by pa-
tient age, operator specialty and training level, reference stan-
dard, sonographer blinding status, and cutoff value. The optimal
cutoff for optic nerve sheath dilatation on ultrasonography was
5.0 mm.
Limitation: Small studies, imprecise summary estimates,
possible publication bias, and no evaluation of effect on
clinical outcomes.
Conclusion: Optic nerve ultrasonography can help diagnose in-
creased intracranial pressure. A normal sheath diameter mea-
surement has high sensitivity and a low negative likelihood ratio
that may rule out increased intracranial pressure, whereas an el-
evated measurement, characterized by a high specificity and
positive likelihood ratio, may indicate increased intracranial pres-
sure and the need for additional confirmatory tests.
Primary Funding Source: None. (PROSPERO: CRD42017055485)
Ann Intern Med. 2019;171:896-905. doi:10.7326/M19-0812 Annals.org
For author affiliations, see end of text.
This article was published at Annals.org on 19 November 2019.
noninvasive, quick, and easy-to-perform method for di-
agnosing increased intracranial pressure.
Both optic nerves are encapsulated by a dural
sheath derived from the meninges that protrudes to-
ward the orbit. This communication allows for similar
cerebrospinal fluid pressure changes between the in-
tracranial and intraorbital subarachnoid spaces, sug-
gesting that sheath dilatation reflects increased intra-
cranial pressure. Optic nerve ultrasonography involves
applying a layer of gel to the closed eyelid with the
patient in supine position. Diameter of the optic nerve
sheath is measured using a linear array transducer 3
mm posterior to the orbit, typically in the coronal plane
with the patient in supine position (Figure 1). Most pro-
tocols involve binocular measurements, although some
physicians use monocular measurements because bi-
lateral diameters of the optic nerve sheath correlate
strongly.
Despite the applicability of optic nerve ultrasono-
graphy in various clinical settings, its use outside clini-
cal research remains sparse (3). Previous studies pre-
dominantly involved small sample sizes and were done
in specific patient populations and settings (4, 5). In
addition, little is known about the accuracy and opti-
mal cutoff of optic nerve ultrasonography according
Bedside Optic Nerve Ultrasonography for Increased Intracranial Pressure
to patient population and operator training level and
medical specialty. Therefore, we conducted a system-
atic review and meta-analysis of prospective diagnostic
test studies to evaluate the accuracy of optic nerve
ultrasonography among various patient populations
and health care settings.
METHODS
We followed the PRISMA (Preferred Reporting
Items for Systematic reviews and Meta-Analyses) for Di-
agnostic Test Accuracy studies (6) and the Cochrane
Handbook for Systematic Reviews of Diagnostic Test
Accuracy (7). Our protocol is registered with the Inter-
national Prospective Register of Systematic Reviews
(PROSPERO: CRD42017055485) and is published (8).
Search Strategy
We electronically searched 13 databases, including
MEDLINE, EMBASE, and Web of Science, without lan-
guage restrictions from inception through May 2019.
Search strategies were developed in collaboration with
a multidisciplinary team, including librarians experi-
enced in conducting systematic reviews (Supplement
Table 1, available at Annals.org). We also screened ref-
erences of eligible articles, reviews, and proceedings of
pertinent meetings and contacted clinical experts in the
field.
Study Selection
Using a 2-step process, reviewers (A.K., F.K., and
S.A.A.) independently screened titles and abstracts and
then the full text of selected records to identify pro-
spective diagnostic test accuracy studies of optic nerve
ultrasonography for increased intracranial pressure.
Studies could involve patients of any age and sonogra-
phers of any training level or medical specialty. They
could use any cutoff value or reference standard. Stud-
ies that did not present data about the accuracy of op-
tic nerve ultrasonography were excluded. Correspond-
ing authors of studies were contacted to resolve
questions about eligibility. Disagreements about inclu-
sion were resolved collegially through discussion and
consensus by the research team.
Data Extraction and Quality Assessment
Three reviewers (A.K., F.K., and S.A.A.) indepen-
dently extracted study data. Two attempts were made
to contact corresponding authors about additional data
that would allow for the construction of a 2 × 2 table.
Three reviewers (A.K., F.K., and S.A.A.) independently
performed quality assessment using the QUADAS-2
(Quality Assessment of Diagnostic Accuracy Studies-2)
tool to evaluate the risk of bias across 4 domains (pa-
tient selection, index test, reference standard, and flow
and timing) and applicability across 3 domains (patient
selection, index test, and reference standard) (9). If a
study had 1 or more high-risk domains, it was rated as
having an overall high risk of bias. Disagreements
about extraction or quality assessment were resolved
by consensus and an additional reviewer (N.S.).
Annals.org
REVIEW
Figure 1. Optic nerve ultrasonography.
Left. A sagittal schematic view of gel applied on top of the closed,
right eyelid with the orientation of the operator hand and ultrasono-
graphy probe to the orbit. Right. An ultrasonography machine screen
showing a coronal section of the orbit and optic nerve sheath. The
distance between the stars represents the diameter of the optic nerve
sheath.
Data Synthesis and Analysis
We performed a meta-analysis using the hierarchi-
cal summary receiver-operating characteristic (SROC)
model with random-effects weighting to obtain the
SROC curve and to determine the summary point for
diagnosis of increased intracranial pressure (10, 11).
We calculated diagnostic measures using 2 × 2 contin-
gency tables reconstructed from each study's data for
true- and false-positive and true- and false-negative
results.
Heterogeneity was explored visually using the hier-
archical SROC model. The magnitude of heterogeneity
was depicted by evaluating the degree of proximity of
observed study results to the SROC curve (11). Hetero-
geneity was also depicted when the 95% prediction re-
gions were substantially larger graphically relative to
the 95% confidence regions.
We evaluated the accuracy of optic nerve ultra-
sonography in various medical and methodological
settings. The bivariate model (12) was used with
random-effects weighting to pool diagnostic test accu-
racy variables for the following comparisons: cause of
increased intracranial pressure (traumatic vs. nontrau-
matic brain injury), patient age (adults ≥18 years vs.
children <18 years), training of operator (trained vs. un-
trained), timing of ultrasonography relative to reference
standard (<1 hour vs. ≥1 hour), cutoff value (4.5 to 4.8
mm vs. 5.0 to 5.3 mm vs. 5.5 to 5.8 mm), reference
standard (computed tomography scan vs. intracranial
pressure monitor vs. lumbar puncture), and medical
specialty of the operator (radiologist vs. critical care
specialist vs. emergency medicine clinician vs. neurolo-
gist vs. neurosurgeon). We performed subgroup analy-
ses related to the cutoff calculation method (post hoc
vs. a priori), risk of bias assessment (low vs. high), and
Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019 897
REVIEW
blinding of sonographer to intracranial pressure status
(blinded vs. unblinded). Optimal cutoff point evaluation
for increased intracranial pressure on ultrasonography
was done using the method by Steinhauser and
colleagues (13).
We explored potential publication bias by examin-
ing asymmetry of funnel plots constructed using the
Deeks model (14). Meta-analyses were done using
STATA, version 15.1 (StataCorp), and the NLMIXED
procedure in the SAS software package, version 9.3
(SAS Institute) (Supplement Table 2, available at Annals
.org).
Role of the Funding Source
This study received no funding.
RESULTS
Searches identified 2354 unique records, of which
245 full-text articles were reviewed and 71 met eligibil-
ity criteria (Figure 2). In total, the 71 prospective studies
involved 4551 patients (4, 5, 15– 83). The characteris-
tics, quality assessment, and outcomes of these studies
are presented in Supplement Tables 3 and 4 (available
at Annals.org).
Of 71 studies, 18 included patients with traumatic
brain injury (5, 17, 19, 26, 28, 29, 32, 33, 39, 43, 51, 59,
61, 66, 67, 78, 81, 83), 26 included patients with non-
traumatic brain injury (22, 24, 27, 34 –38, 42, 46, 47, 49,
50, 52–54, 57, 58, 64, 68, 71, 72, 74, 75, 77, 78), and 27
included mixed populations (4, 15, 16, 18, 20, 21, 23,
25, 30, 31, 40, 41, 44, 45, 48, 55, 56, 60, 62, 63, 65, 69,
70, 73, 76, 79, 80). Meta-analysis of proportions found
respective pooled proportions of 54.6%, 44.3%, and
53.3% for these patient populations. Ten studies (n =
356) were conducted in pediatric patients: 1 included
patients with traumatic brain injury, 3 included patients
with nontraumatic brain injury, and 6 included mixed
populations. Sixty-one studies (n = 4195) were done in
adult patients, of which 17 included traumatic brain in-
jury patients, 23 included nontraumatic brain injury pa-
tients, and 21 included mixed populations. Nineteen
Figure 2. Evidence search and selection.
Records identified through systematic search of 13
electronic databases after removal of duplicates (n = 2354)
Records excluded (n = 2109)
Records selected for full-text review (n = 245)
Records excluded (n = 174)
Did not evaluate diagnostic test accuracy: 89
Did not examine increased intracranial pressure: 42
Case reports, reviews, letters, correspondences: 34
Duplicates: 6
Animal model studies: 3
Prospective studies included in analysis (n = 71)
898 Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019
Bedside Optic Nerve Ultrasonography for Increased Intracranial Pressure
studies determined the cutoff for optic nerve ultra-
sonography a priori. Thirty-five studies were rated as
having low risk of bias (3 pediatric and 32 adult; 7
traumatic brain injury, 16 nontraumatic brain injury,
and 12 mixed population) and 36 were rated as hav-
ing high risk of bias (7 pediatric and 29 adult; 11
traumatic brain injury, 10 nontraumatic brain injury,
and 15 mixed population).
Patients presenting with suspected increased intra-
cranial pressure were younger than those presenting
with nontraumatic brain injury. The most common spe-
cialty of the provider performing optic nerve ultra-
sonography was emergency medicine, followed by crit-
ical care, neurology, neurosurgery, and radiology.
Among the included studies, 1842 (40.5%) patients had
optic nerve ultrasonography done by a trained opera-
tor and 2342 (51.5%) patients had optic nerve sonog-
raphy done by a blinded operator. Sixty studies re-
ported no funding, whereas 11 (18, 30, 37, 40, 53, 54,
63, 73, 76, 78, 82) reported funding for conducting or
publishing their study (Supplement Table 2).
Figure 3 depicts the sensitivity and specificity of
studies, categorized by patient population and risk of
bias; studies done in pediatric populations and those
published as conference abstracts are labeled. Table 1
presents the pooled estimates of performance charac-
teristics stratified according to medical and method-
ological settings (Supplement Figures 1 to 22, available
at Annals.org).
Sensitivity and specificity of optic nerve ultrasono-
graphy for identifying increased intracranial pressure in
patients presenting with traumatic brain injury were
97% (95% CI, 92% to 99%) and 86% (CI, 74% to 93%),
respectively. In patients with nontraumatic injury, sensi-
tivity and specificity were 92% (CI, 86% to 96%) and
86% (CI, 77% to 92%), respectively. A patient present-
ing with suspected traumatic brain injury demonstrated
6.93 (CI, 3.55 to 13.54) times the odds of having in-
creased intracranial pressure after a positive result on
optic nerve ultrasonography.
Summary estimates of performance characteristics
were similar for adult and pediatric patients and trained
and untrained operators (Table 1). They also seemed
roughly similar regardless of timing between the ultra-
sonography and reference standard (<1 vs. ≥1 hour),
cutoff value used, type of reference standard, and med-
ical specialty of the operator (Table 1). Analyses by cut-
off calculation method, risk of bias assessment, and
blinding of sonographer showed similar summary per-
formance characteristics for all subgroups (Table 2).
The SROC curve showed a pooled sensitivity and
specificity of 94% (CI, 91% to 96%) and 87% (CI, 82% to
91%), respectively (Figure 4). The SROC curves for each
comparison showed similar estimates of accuracy of
optic nerve ultrasonography when stratified by brain
injury cause, patient age, sonographer training, and
reference standard. Funnel plots constructed using the
Deeks model showed no evidence of asymmetry on
visual inspection (Supplement Figure 23, available at
Annals.org). Steinhauser and colleagues' method was
randomly applied across all groups but was statistically
Annals.org
 Figure 3. Forest plot of sensitivity and specificity for studies categorized by patient population and risk of bias.

Annals.org
Study, Year TPs, n FPs, n FNs, n TNs, n Patient Population Risk of Bias Sensitivity (95% CI) Specificity (95% CI) Sensitivity (95% CI) Specificity (95% CI)
Al Tayar et al, 2017* (67) 17 0 0 5 Traumatic brain injury Low 1.00 (0.80–1.00) 1.00 (0.48–1.00)
Amini et al, 2013 (33) 27 9 1 185 Traumatic brain injury Low 0.96 (0.82–1.00) 0.95 (0.91–0.98)
Geeraerts et al, 2007 (17) 15 0 0 16 Traumatic brain injury Low 1.00 (0.78–1.00) 1.00 (0.79–1.00)
Goel et al, 2008 (19) 72 2 1 25 Traumatic brain injury Low 0.99 (0.93–1.00) 0.93 (0.76–0.99)
Maissan et al, 2015 (43) 17 0 1 0 Traumatic brain injury Low 0.94 (0.73–1.00) Not estimable
Tayal et al, 2007 (5) 8 19 0 32 Traumatic brain injury Low 1.00 (0.63–1.00) 0.63 (0.48–0.76)
Agrawal and Brierley, 2012† (28) 7 0 0 4 Traumatic brain injury High 1.00 (0.59–1.00) 1.00 (0.40–1.00)
Le and Ben 2017 (59) 43 8 7 58 Traumatic brain injury High 0.86 (0.73–0.94) 0.88 (0.78–0.95)
Li et al, 2014 (39) 25 4 0 37 Traumatic brain injury High 1.00 (0.86–1.00) 0.90 (0.77–0.97)
Zhang et al, 2012 (32) 19 2 3 11 Traumatic brain injury High 0.86 (0.65–0.97) 0.85 (0.55–0.98)
Širanović et al, 2011 (26) 11 7 0 2 Traumatic brain injury High 1.00 (0.72–1.00) 0.22 (0.03–0.60)
Tong et al, 2017 (61) 60 3 3 12 Traumatic brain injury High 0.95 (0.87–0.99) 0.80 (0.52–0.96)
Amini et al, 2013 (34) 14 0 0 36 Nontraumatic brain injury Low 1.00 (0.77–1.00) 1.00 (0.90–1.00)
Caffery et al, 2014 (35) 18 15 6 12 Nontraumatic brain injury Low 0.75 (0.53–0.90) 0.44 (0.25–0.65)
del Saz-Saucedo et al, 2016 (49) 18 1 1 10 Nontraumatic brain injury Low 0.95 (0.74–1.00) 0.91 (0.59–1.00)
Frumin et al, 2014 (36) 5 0 1 21 Nontraumatic brain injury Low 0.83 (0.36–1.00) 1.00 (0.84–1.00)
lrazuzta et al, 2016† (50) 10 0 0 3 Nontraumatic brain injury Low 1.00 (0.69–1.00) 1.00 (0.29–1.00)
Lee et al, 2016 (53) 80 4 1 23 Nontraumatic brain injury Low 0.99 (0.93–1.00) 0.85 (0.66–0.96)
Lochner et al, 2016 (54) 20 7 1 14 Nontraumatic brain injury Low 0.95 (0.76–1.00) 0.67 (0.43–0.85)
Nabeta et al, 2014 (37) 33 11 6 16 Nontraumatic brain injury Low 0.85 (0.69–0.94) 0.59 (0.39–0.78)
Patterson et al, 2018 (77) 17 4 5 18 Nontraumatic brain injury Low 0.77 (0.55–0.92) 0.82 (0.60–0.95)
Bäuerle and Nedelmann, 2011 (24) 9 4 1 21 Nontraumatic brain injury Low 0.90 (0.55–1.00) 0.84 (0.64–0.95)
Salahuddin et al, 2016 (57) 26 21 5 50 Nontraumatic brain injury Low 0.84 (0.66–0.95) 0.70 (0.58–0.81)
Dixit et al, 2018* (74) 126 8 3 51 Nontraumatic brain injury Low 0.98 (0.93–1.00) 0.86 (0.75–0.94)
Tarzamni et al, 2016 (58) 30 0 0 30 Nontraumatic brain injury Low 1.00 (0.88–1.00) 1.00 (0.88–1.00)
du Tait et al, 2015 (46) 7 6 7 53 Nontraumatic brain injury Low 0.50 (0.23–0.77) 0.90 (0.79–0.96)
Golshani et al, 2015 (42) 38 63 0 30 Nontraumatic brain injury Low 1.00 (0.91–1.00) 0.32 (0.23–0.43)
Wang et al, 2015 (47) 96 14 5 164 Nontraumatic brain injury Low 0.95 (0.89–0.98) 0.92 (0.87–0.96)
Lin et al, 2019† (71) 3 9 2 18 Nontraumatic brain injury High 0.60 (0.15–0.95) 0.67 (0.46–0.83)
Liu et al, 2017 (68) 50 14 8 38 Nontraumatic brain injury High 0.86 (0.75–0.94) 0.73 (0.59–0.84)
Moretti et al, 2009 (22) 18 21 1 66 Nontraumatic brain injury High 0.95 (0.74–1.00) 0.76 (0.65–0.84)
Kerscher et al, 2017*† (64) 72 2 1 25 Nontraumatic brain injury High 0.99 (0.93–1.00) 0.93 (0.76–0.99)
Komut et al, 2016 (52) 19 6 8 17 Nontraumatic brain injury High 0.70 (0.50–0.86) 0.74 (0.52–0.90)
Bedside Optic Nerve Ultrasonography for Increased Intracranial Pressure

Naldi et al, 2018* (75) 22 1 0 59 Nontraumatic brain injury High 1.00 (0.85–1.00) 0.98 (0.91–1.00)
Shirodkar et al, 2014 (38) 28 3 7 22 Nontraumatic brain injury High 0.80 (0.63–0.92) 0.88 (0.69–0.97)
Agrawal et al, 2019 (73) 9 3 0 8 Mixed population Low 1.00 (0.66–1.00) 0.73 (0.39–0.94)
Blaivas et al, 2003 (16) 14 1 0 20 Mixed population Low 1.00 (0.77–1.00) 0.95 (0.76–1.00)
Chen et al, 2017 (69) 19 6 1 44 Mixed population Low 0.95 (0.75–1.00) 0.88 (0.76–0.95)
Major et al, 2011 (4) 6 0 1 19 Mixed population Low 0.86 (0.42–1.00) 1.00 (0.82–1.00)
Padayachy et al, 2016 (55) 69 26 5 74 Mixed population Low 0.93 (0.85–0.98) 0.74 (0.64–0.82)
Aduayi et al, 2015 (40) 56 0 13 11 Mixed population Low 0.81 (0.70–0.90) 1.00 (0.72–1.00)
Rajajee et al, 2011 (25) 25 2 1 37 Mixed population Low 0.96 (0.80–1.00) 0.95 (0.83–0.99)
Driessen et al, 2012† (30) 3 0 0 2 Mixed population Low 1.00 (0.29–1.00) 1.00 (0.16–1.00)
Jeon et al, 2017 (63) 30 4 2 26 Mixed population Low 0.94 (0.79–0.99) 0.87 (0.69–0.96)
Le et al, 2009† (21) 19 13 5 27 Mixed population Low 0.79 (0.58–0.93) 0.68 (0.51–0.81)
Qayyum and Ramlakhan, 2013 (31) 20 1 0 3 Mixed population Low 1.00 (0.83–1.00) 0.75 (0.19–0.99)
Raj et al, 2017 (70) 23 1 3 9 Mixed population Low 0.88 (0.70–0.98) 0.90 (0.55–1.00)
Mehrpour et al, 2015 (44) 22 2 0 8 Mixed population High 1.00 (0.85–1.00) 0.80 (0.44–0.97)
Padayachy et al, 2019† (76) 18 2 1 7 Mixed population High 0.95 (0.74–1.00) 0.78 (0.40–0.97)
Beare et al, 2008† (18) 13 0 1 7 Mixed population High 0.93 (0.66–1.00) 1.00 (0.59–1.00)
Bolesch et al, 2015 (41) 8 0 7 20 Mixed population High 0.53 (0.27–0.79) 1.00 (0.83–1.00)
Rehman Siddiqui et al, 2018† (80) 26 8 0 14 Mixed population High 1.00 (0.87–1.00) 0.64 (0.41–0.83)
Hansen et al, 1994 (15) 14 0 2 20 Mixed population High 0.88 (0.62–0.98) 1.00 (0.83–1.00)
Lahkar et al, 2016* (65) 5 2 0 1 Mixed population High 1.00 (0.48–1.00) 0.33 (0.01–0.91)
Li et al, 2017 (60) 26 6 4 34 Mixed population High 0.87 (0.69–0.96) 0.85 (0.70–0.94)
Weidner et al, 2015* (48) 8 1 1 5 Mixed population High 0.89 (0.52–1.00) 0.83 (0.36–1.00)
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1

FN = false-negative; FP = false-positive; TN = true-negative; TP = true-positive.

* Published as a conference abstract.
† Pediatric population. The overall pooled meta-analysis demonstrates a pooled sensitivity of 94% (95% Cl, 91% to 96%), specificity of 87% (CI, 82% to 91%), positive predictive value of 88% (CI,
83% to 92%), negative predictive value of 94% (CI, 90% to 96%), positive likelihood ratio of 7.19 (CI, 5.15 to 10.04), and negative likelihood ratio of 0.07 (CI, 0.05 to 0.11).

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Table 1. Summary of Main Comparisons

Comparison Value (95% CI)

Sensitivity, % Specificity, % Positive Negative Positive Negative

Predictive Predictive Likelihood Likelihood
Value, % Value, % Ratio Ratio
Cause
Traumatic brain injury 97 (92–99) 86 (74–93) 89 (77–95) 97 (88–99.5) 6.93 (3.55–13.54) 0.04 (0.02–0.10)
Nontraumatic brain injury 92 (86–96) 86 (77–92) 85 (74–92) 93 (87–96) 6.39 (3.77–10.84) 0.09 (0.05–0.17)

Age
Adult (≥18 y) 94 (90–96) 88 (81–92) 88 (81–93) 95 (91–97) 7.80 (4.97–12.22) 0.07 (0.04–0.11)
Pediatric (<18 y) 92 (79–97) 80 (61–92) 92 (68–99) 87 (67–95) 4.73 (2.15–10.41) 0.10 (0.03–0.28)

Training of operator
Trained 95 (92–97) 88 (81–92) 86 (79–92) 96 (93–98) 7.75 (4.92–12.20) 0.06 (0.03–0.10)
Untrained 93 (87–96) 86 (78–92) 90 (82–95) 90 (83–94) 6.68 (4.09–10.90) 0.09 (0.05–0.15)

Timing of optic nerve ultrasonography

relative to reference standard
<1 h 91 (85–95) 82 (73–89) 85 (70–93) 89 (82–94) 5.07 (3.22–7.98) 0.11 (0.07–0.19)
≥1 h 92 (87–95) 83 (74–90) 88 (81–93) 90 (82–95) 5.57 (3.41–9.09) 0.10 (0.06–0.16)

Cutoff value
4.5–4.8 mm 94 (81–98) 94 (89–96) 92 (79–97) 95 (86–99) 14.96 (8.17–27.42) 0.07 (0.02–0.22)
5.0–5.3 mm 91 (86–94) 82 (71–90) 85 (76–91) 89 (82–93) 5.20 (3.02–8.94) 0.06 (0.03–0.12)
5.5–5.8 mm 97 (91–99) 89 (81–93) 89 (81–94) 96 (91–98) 8.58 (5.04–14.60) 0.04 (0.01–0.11)

Reference standard
Computed tomography scan 95 (90–98) 90 (82–95) 91 (81–96) 96 (90–98) 9.74 (5.25–18.08) 0.05 (0.03–0.11)
Intracranial pressure monitor 93 (88–96) 85 (72–93) 88 (77–94) 93 (84–97) 6.35 (3.24–12.43) 0.09 (0.05–0.14)
Lumbar puncture 91 (83–96) 86 (75–92) 86 (75–92) 91 (83–96) 6.32 (3.57–11.19) 0.12 (0.04–0.37)

Medical specialty of operator

Radiologist 89 (73–96) 87 (78–92) 90 (82–94) 85 (68–94) 6.67 (3.93–11.32) 2.50 (0.00–28799)
Critical care specialist 94 (76–99) 87 (43–98) 86 (54–98) 94 (67–99) 7.32 (1.10–48.53) 0.07 (0.02–0.30)
Emergency medicine clinician 96 (88–99) 85 (69–94) 77 (56–89) 98 (93–99.6) 6.59 (2.82–15.39) 0.04 (0.01–1.16)
Neurologist 95 (82–99) 91 (74–98) 92 (77–98) 95 (80–99) 11.00 (3.24–37.31) 0.21 (0.00–446.8)
Neurosurgeon 92 (81–97) 89 (71–96) 91 (78–97) 90 (75–96) 8.29 (2.89–23.82) 0.22 (0.00–65.14)

unstable, with the exception of 1 group, resulting in 5.0
mm being the optimal cutoff value for optic nerve
sheath dilation on ultrasonography for diagnosing in-
creased intracranial pressure.
DISCUSSION
Our review suggests that optic nerve ultrasonogra-
phy, a noninvasive, quick, and easy-to-use test, is an accu-
rate tool to diagnose increased intracranial pressure. We
found a pooled sensitivity and specificity of 97% and 86%
for patients presenting with traumatic brain injury, with
corresponding positive and negative likelihood ratios of
6.93 and 0.04. Patients presenting with increased intracra-
nial pressure secondary to nontraumatic brain injury had
respective pooled sensitivity and specificity of 92% and
86%, with corresponding positive and negative likelihood

Table 2. Subgroup Analyses

Comparison Value (95% CI)

Sensitivity, % Specificity, % Positive Negative Positive Negative

Predictive Predictive Likelihood Likelihood
Value, % Value, % Ratio Ratio
Cutoff point method
Post hoc 94 (91–96) 88 (82–92) 89 (83–92) 94 (91–97) 7.45 (5.24–10.60) 0.07 (0.05–0.10)
A priori 93 (82–97) 86 (74–93) 88 (74–95) 91 (83–96) 6.76 (3.36–13.58) 0.09 (0.03–0.21)

Risk of bias
Low 95 (91–97) 89 (82–93) 89 (81–94) 95 (91–97) 8.25 (5.06–13.47) 0.06 (0.04–0.10)
High 92 (87–96) 85 (77–90) 88 (81–93) 91 (84–95) 6.09 (4.02–9.22) 0.09 (0.05–0.16)

Blinding of sonographer
Blinded 93 (89–96) 89 (83–93) 90 (83–94) 93 (89–96) 8.34 (5.30–13.11) 0.08 (0.05–0.12)
Unblinded 94 (90–97) 83 (74–89) 86 (77–92) 94 (88–97) 5.57 (3.54–8.78) 0.07 (0.04–0.13)

900 Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019 Annals.org
Bedside Optic Nerve Ultrasonography for Increased Intracranial Pressure
ratios of 6.39 and 0.09. Accuracy estimates were similar
for studies stratified by reference standards, use of sonog-
raphers who were blinded or unblinded to reference
standard results, and use of different cutoff values to de-
fine increased intracranial pressure.
Traumatic brain injury is increasingly viewed as a
global health priority because of its preventability, high
mortality rate, and costly medical care. In 2016, there
were an estimated 27 million new cases of traumatic
brain injury, and increased age-standardized incidence
rates have been noted since 1990 (84). Guidelines rec-
ommend and detail criteria for intracranial pressure
monitor insertion among patients with severe traumatic
brain injury (85). However, placement of the monitor in
intracranial pressure monitoring is invasive and has
risks, including infection or hemorrhage, and may com-
plicate patient care.
Traditional diagnostic tests for increased intracra-
nial pressure have many limitations. Computed tomo-
graphy, the most commonly used test for suspected
increased intracranial pressure, may expose patients to
unnecessary radiation and increase risk for complica-
tions associated with patient transportation (86). In ad-
dition, a computed tomography scan is a static image
that does not allow for continuous monitoring. Mag-
netic resonance imaging can be done, but it may not
be as readily available, takes longer to perform, and is
more expensive. Lumbar puncture can be contraindi-
cated when increased intracranial pressure secondary
to a space-occupying lesion is suspected (87).
Our meta-analysis differs from several systematic
reviews and meta-analyses identified in our searches of
13 databases from inception through May 2019 (88 –
94). Previous analyses examined a single cutoff value
for diagnosing increased intracranial pressure, in-
cluded few studies, included and mixed data from ret-
rospective and prospective studies, or did not analyze
accuracy for traumatic versus nontraumatic brain inju-
ries. Our review includes stratified analyses by patient
age, reference standards, and specialty, training level,
and blinding of sonographers, which were not pre-
sented in other reviews. Finally, our review is the first to
compare variable cutoff values and calculation meth-
ods of optic nerve sheath dilatation on sonography and
to identify 5.0 mm as being an optimal cutoff to diag-
nose increased intracranial pressure.
Our meta-analysis has several limitations. Most in-
cluded studies had small sample sizes, and summary
estimates were imprecise. Studies used different refer-
ence standards, and comparisons were limited by strat-
ification based on 1 factor at a time. Because of a lim-
ited number of studies in particular populations, we
could not reliably compare performance characteristics
of elderly versus younger or general populations. Data
were not sufficiently granular to examine accuracy
among patients with specific causes of nontraumatic
brain injuries, such as craniosynostosis, spontaneous
hemorrhage, or space-occupying lesions. We were un-
able to evaluate the specific time interval from onset of
increased intracranial pressure to patient presentation
whereby optic nerve ultrasonography would be most
Annals.org
REVIEW
Figure 4. Summary receiver-operating characteristic
curve.
1
0.9
0.8
0.7
0.6
Sensitivity
0.5
0.4
0.3
0.2
0.1
0
1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0
Specificity
Summary curve of meta-analysis. The size of each point is scaled ac-
cording to the sensitivity and specificity for the corresponding study.
The black circle represents the summary point of sensitivity and spec-
ificity. The summary point is surrounded by a dotted line representing
the 95% confidence region and the dashed line representing the 95%
prediction region.
accurate. Study findings were not all consistent. One
study showed a particularly low specificity (42), perhaps
due to its a priori selected cutoff value that did not
result in a favorable balance between sensitivity and
specificity in its patient population. Although we con-
sidered 35 studies to have low risk of bias, we could not
conduct multiple sensitivity analyses within this subset
of studies. Publication bias was not detected across all
funnel plots; however, it cannot be completely ruled
out. Finally, the effect of optic nerve ultrasonography
on clinical outcomes was not evaluated.
Although we found similar performance character-
istics for trained and untrained sonographers, we be-
lieve these results should be interpreted with caution.
Sensitivity (95%) among trained operators seemed
slightly superior to that of untrained operators (93%),
and some training and experience is obviously impor-
tant. For instance, B-scan ultrasonography has the
blooming effect, whereby a low-sensitivity setting will
result in a larger optic nerve measurement relative to
an image obtained at a high-sensitivity setting (95). In
contrast, A-scan ultrasonography does not have this
measurement error but is known to be more difficult,
and accordingly may require more experienced opera-
tors (96). Other factors that may bias measurement
include level of magnification, frequency of linear
probes, position of the patient, and whether monocular
or binocular measurements were done.
Optic nerve ultrasonography cannot be done for
patients presenting with globe trauma or ophthalmo-
Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019 901
REVIEW Bedside Optic Nerve Ultrasonography for Increased Intracranial Pressure
logic diseases (such patients were excluded from stud-
ies). Included reports examined optic nerve ultrasono-
graphy as an additional tool to standard measures of
examining patients with suspected increased intracra-
nial pressure. It is not meant to replace well-known meth-
ods of measuring intracranial pressure—rather, it may help
diagnose patients with increased intracranial pressure.
Whether particular measurements of optic nerve
sheath dilatation correlate closely with the magnitude
of increased intracranial pressure is still unclear. A
slightly higher sensitivity and negative predictive value
was noted among the patients with traumatic brain in-
jury than with those without traumatic injury. This could
be explained by the unique pathophysiology, preva-
lence, research focus, and other characteristics of the
traumatic brain injury populations that were studied.
In conclusion, a normal reading on optic nerve
sheath ultrasonography (<5.0 mm) with high sensitivity
and low negative likelihood ratio may rule out in-
creased intracranial pressure, whereas an elevated
reading (≥5.0 mm) with high specificity and positive
likelihood ratio may indicate increased intracranial
pressure and require confirmatory diagnostic tests.
Thus, optic nerve ultrasonography is an accurate diag-
nostic tool that may be useful for various patient popu-
lations and situations. It is noninvasive, quick, and easy-
to-use and can enable health care professionals to
triage patients with suspected increased intracranial
pressure.
From University of Toronto, Toronto, Ontario, Canada (A.K.,
J.H.B., F.N., A.M., M.G.F.); McMaster University, Hamilton, On-
tario, Canada (N.S., K.Y., Q.Z., T.R., S.F., E.P., A.H., L.B., S.A.A.);
McGill University, Montreal, Quebec, Canada (F.K.); School of
Medicine, McMaster University, Hamilton, Ontario, Canada
(S.N.); Northern Ontario School of Medicine, Sudbury, On-
tario, Canada (M.M.); University of Calgary, Calgary, Alberta,
Canada (A.W.K.); Stanford University, Stanford, California
(A.N.); and University of Utah School of Medicine, Salt Lake
City, Utah (G.W.H.).
Disclosures: Dr. Kirkpatrick reports a grant from Acelity Cor-
poration and personal fees from Innovative Trauma Care Cor-
poration outside the submitted work. Authors not named here
have disclosed no conflicts of interest. Disclosures can also be
viewedatwww.acponline.org/authors/icmje/ConflictOfInterest
Forms.do?msNum=M19-0812.
Reproducible Research Statement: Study protocol:
PROSPERO, CRD42017055485. Statistical code and data set:
See the Supplement (available at Annals.org).
Corresponding Author: Saleh A. Almenawer, MD, McMaster
University, 1280 Main Street West, Hamilton, Ontario L8S 4L8,
Canada; e-mail, almenawers@gmail.com.
Current author addresses and author contributions are avail-
able at Annals.org.
902 Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019
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doi:10.1155/2018/6154357

IN THE CLINIC

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agement of patients with common clinical conditions. It offers evidence-
based answers to frequently asked questions about screening, prevention,
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Annals.org Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019 905
Current Author Addresses: Mr. Koziarz: University of Toronto,
1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Drs. Sne, Yang, Zhou, Rice, Faidi, Passos, Healey, and Al-
menawer: McMaster University, 1280 Main Street West, Ham-
ilton, Ontario L8S 4L8, Canada.
Mr. Kegel: McGill University, 3655 Promenade Sir William Os-
ler, Montreal, Quebec H3G 1Y6, Canada.
Mr. Nath: School of Medicine, McMaster University, 1280
Main Street West, Hamilton, Ontario L8S 4L8, Canada.
Drs. Badhiwala, Nassiri, Mansouri, and Fehlings: University of
Toronto, 149 College Street, Toronto, Ontario M5T 1P5,
Canada.
Ms. Banfield: Health Sciences Library, McMaster University,
1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Dr. Mensour: Northern School of Medicine, 935 Ramsey Lake
Road, Sudbury, Ontario P3E 2C6, Canada.
Dr. Kirkpatrick: University of Calgary, 2500 University Drive
Northwest, Calgary, Alberta T2N 1N4, Canada.
Dr. Nassar: Stanford University, 300 Pasteur Drive, Stanford,
CA 94305.
Dr. Hawryluk: University of Utah School of Medicine, 30 North
1900 East, Salt Lake City, UT 84132.
Annals.org
Author Contributions: Conception and design: A. Koziarz, N.
Sne, F. Kegel, S. Faidi, S.A. Almenawer.
Analysis and interpretation of the data: A. Koziarz, N. Sne, F.
Kegel, S. Faidi, L. Banfield, S.A. Almenawer.
Drafting of the article: A. Koziarz, S.A. Almenawer.
Critical revision of the article for important intellectual con-
tent: A. Koziarz, N. Sne, F. Kegel, S. Nath, J.H. Badhiwala, F.
Nassiri, A. Mansouri, K. Yang, Q. Zhou, T. Rice, S. Faidi, E.
Passos, A. Healey, L. Banfield, M. Mensour, A.W. Kirkpatrick,
A. Nassar, M.G. Fehlings, G.W.J. Hawryluk, S.A. Almenawer.
Final approval of the article: A. Koziarz, N. Sne, F. Kegel, S.
Nath, J.H. Badhiwala, F. Nassiri, A. Mansouri, K. Yang, Q.
Zhou, T. Rice, S. Faidi, E. Passos, A. Healey, L. Banfield, M.
Mensour, A.W. Kirkpatrick, A. Nassar, M.G. Fehlings, G.W.J.
Hawryluk, S.A. Almenawer.
Provision of study materials or patients: S.A. Almenawer.
Statistical expertise: A. Koziarz, Q. Zhou, and S.A. Almenawer.
Administrative, technical, or logistic support: S.A. Almenawer.
Collection and assembly of data: A. Koziarz, N. Sne, F. Kegel,
S.A. Almenawer.
Annals of Internal Medicine • Vol. 171 No. 12 • 17 December 2019