Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults
Chen et al. BMC Neurology
Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults
Han Chen 0 2
Gui-Sheng Ding 1
Yan-Chun Zhao 1
Rong-Guo Yu 2
Jian-Xin Zhou 0
0 Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University , No 6, TiantanXili, Dongcheng District, Beijing 100050 , China
1 Department of Ultrasonography, Fujian Provincial Clinical College, Fujian Medical University , No. 134, Dongjie Street, Gulou District, 350001 Fuzhou, Fujian , China
2 Surgical Intensive Care Unit, Fujian Provincial Clinical College, Fujian Medical University , No. 134, Dongjie Street, Gulou District, Fuzhou, Fujian 350001 , China
Background: Measurement of optic nerve sheath diameter (ONSD) is a fast and non-invasive method in detecting elevated intracranial pressure. However, the reported normal range of ONSD was inconsistent. The objective of the study was to determine the normal range of ONSD in healthy Chinese adults. Methods: Eyeball transverse diameter (ETD), optic nerve diameter (OND), and ONSD were measured by ultrasound examination in healthy adult volunteers. The OND and ONSD were assessed 3 mm behind the globe. The section showing maximal transverse diameter of the eyeball was frozen and the diameter was measured. Each ETD, OND and ONSD was examined twice and the mean value was calculated. Results: A total of 519 healthy volunteers were included in the study. The median (interquartile range) of ETD, OND and ONSD were 22.3 (21.6 to 23.1) mm, 3.2 (2.9 to 3.4) mm, and 5.1 (4.7 to 5.4) mm, respectively. The 95 % percentile of ONSD was 5.9 mm. There was no significant difference in ETD, OND or ONSD between male and female, or between left and right eye. ONSD was significantly correlated with OND (r = 0.62, P < 0.001), and the median OND/ONSD ratio (interquartile range) was 0.63 (0.59 to 0.67). Conclusions: The median and the 95 % percentile of sonographic measurement of ONSD are 5.1 mm and 5.9 mm in healthy Chinese adults. The ONSD is correlated with OND, while independent of gender, age, height, weight and ETD. The median OND/ONSD ratio is 0.63 and this parameter warrants further investigation in patients with brain injury.
Optic nerve diameter; Optic nerve sheath diameter; Ultrasonography; Volunteer
Intracranial hypertension is a life-threatening syndrome,
which is caused by a variety of neurological and
nonneurological diseases. Catastrophic deterioration of brain
function and death may occur if intracranial
hypertension is left undetected and untreated [1–3]. Monitoring
of intracranial pressure (ICP) is recommended in the
management of intracranial hypertension .
Invasive intracranial devices including intra-ventricular
catheters and intra-parenchymal probes are considered
the gold standard for ICP measurement [5, 6]. However,
invasive ICP monitoring may lead to complications
including hemorrhage, infection and catheter blockage or
dislodgement. Moreover, it is contraindicated in the
situation of coagulopathy or thrombocytopenia [7–9].
Therefore, non-invasive ICP monitoring has been of a major
interest in clinical practice .
Although elevated ICP can be detected by computed
tomography or magnetic resonance imaging, these
techniques are expensive, time-consuming and requiring
patient’s transportation. In recent years, measurement of
optic nerve sheath diameter (ONSD) by ultrasonography
has been developed and suggested as a possible indicator
of intracranial hypertension . The optic nerve sheath
is a membrane covering the optic nerve behind the eye,
and is continuous with the dura mater over the brain.
Elevation in ICP can be transmitted through the
subarachnoid space, causing extension of the space. The
rapid and non-invasive nature of ultrasonography results
in its increasingly use for detecting elevated ICP at
bedside in the emergency and critical care settings.
However, there has been no consensus on the optimal
cut-off value of abnormal ONSD to indicate elevated ICP;
and the existing thresholds are only from patients with
brain injury. The normal range of ONSD in healthy
population is indispensable information to interpret the
measurement of ONSD as a marker of intracranial hypertension.
Moreover, it is still unknown whether there is a difference
of ONSD values between Chinese and other races, due
to the lack of related studies. We carried out this
prospective observational study to determine the normal
range of ONSD in healthy Chinese adults.
Healthy volunteers were prospectively included in the
study from October 2014 to January 2015. All subjects
were aged 18 years or older. Subjects were excluded if they
had a history of neurological disorders, hyperthyroidism
or diseases of the optic nerve. Written informed consent
was obtained from all subjects before enrollment. The
study was approved by the local ethics committee of
Fujian Provincial Hospital and performed according to the
ethical standards of the latest Declaration of Helsinki.
At study entry, the gender, age, height and weight of
the subject were collected. The ultrasound examination
was conducted in B-mode by using a Philips Envisor C
(M2540A) ultrasound system and a 12–3 MHz linear
array probe (Philips Medical Systems, Bothell WA,
USA), by one of the two sonographers (GS.D. and
YC.Z.). Volunteers were examined in supine position
with their head elevated to the angle of 20-30°. A thick
layer of gel was applied over the closed upper eyelid.
The probe was placed on the gel in the temporal area of
the eyelid to prevent pressing the eye. The ETD, OND
and ONSD were measured. OND and ONSD were
assessed 3 mm behind the globe using an electronic
caliper along the axis perpendicularly the retina (Fig. 1). In
order to gauge the ETD, horizontal sections of eyeball
were obtained by scanning from the superior to the
inferior side. The section showing the maximal ETD was
frozen and the diameter was measured using the
electronic caliper. Each ETD, OND and ONSD was
examined twice and the mean value was calculated. We also
calculated the OND/ONSD ratio.
Statistical analysis was performed by using SPSS 19.0
(IBM Corporation, New York, USA). Basic descriptive
statistics were calculated (including median and
quartiles, mean ± SD, max, min, and 95 % percentile).
Comparison of continuous variables was performed by using
Mann–Whitney U-test. Kruskal-Wallis test was used to
compare the difference of ONSD between subjects with
different heights. Spearman rank correlation test was
used to determine the correlation between the ONSD
Fig. 1 Transbulbar sonography of the optic nerve and the optic nerve
sheath. OND and ONSD were measured 3 mm behind the globe using
an electronic caliper along the axis. The interval between “+” marks
was OND, and the interval between “x” marks was ONSD
and other parameters including age, gender, height, body
mass, OND and the ETD. Two-tailed P values of < 0.05
were considered to be statistically significant.
A total of 519 healthy volunteers were enrolled during the
study period, consisting of 207 (39.9 %) males and 312
females (60.1 %). Mean (± SD) age, height and weight
of the subjects were 46.1 ± 14.2 years, 163.2 ± 7.7 cm
and 60.9 ± 11 kg, respectively.
Measurements of ETD, OND and ONSD
All parameters of eye measurement were non-normal
distribution (Fig. 2). The median (IQR) of ETD, OND
and ONSD were 22.3 (21.6 to 23.1) mm, 3.2 (2.9 to 3.4)
mm, and 5.1 (4.7 to 5.4) mm, respectively (Table 1). In
addition, the 95 % percentile of ONSD was 5.9 mm.
There was no significant difference in ETD, OND and
ONSD between the male and female, or between the left
and right eye (Table 2). ONSD was significantly
correlated with OND (r = 0.62, P < 0.001). The median OND/
ONSD ratio (IQR) was 0.63 (0.59 to 0.67). Although a
statistically significant correlation was found between
ONSD and height, the correlation coefficient was
suboptimal (r = 0.063, P = 0.041). Therefore we compared
the ONSD between different height and no difference
was observed (P = 0.109, Fig. 3). There was no linear
relationship of ONSD with ETD (r = 0.044, P = 0.155),
with age (r = 0.023, P = 0.467), or with weight (r = −0.005,
P = 0.866).
Fig. 2 Histograms of ETD, OND, ONSD and OND/ONSD ratio. All the measurements were non-normal distributed. The ETD and OND/ONSD ratio
were positive-skewed distribution while the OND and the ONSD were negative-skewed distribution
In this large-sample-size study we identified the normal
range of ETD, OND, ONSD and OND/ONSD ratio in
Chinese adult population. The main findings were: the
ONSD were correlated with OND; the median (IQR)
OND/ONSD ratio 0.63 ± 0.07 0.63 (0.59 - 0.67) 0.37
This table shows the combined results of both eyes (n = 1038). All the
measurements were non-normal distributed
ETD eyeball transverse diameter, OND optic nerve diameter, ONSD optic nerve
sheath diameter, SD standard deviation
ONSD was 5.1 (4.7 to 5.4) mm and the median OND/
ONSD ratio (IQR) was 0.63 (0.59 to 0.67).
The measurement of ONSD by ultrasonography is a
rapid, noninvasive and repeatable technique, and the
result is not affected by change in position .
Moreover, previous studies demonstrated a good intra- and
inter-observer reliability of the measurement of ONSD
by ultrasonography [12, 13]. It has been suggested as
an indicator of intracranial hypertension in recent years
[10, 14–19]. However, there is still no unified standard
threshold of enlarged ONSD to determine intracranial
hypertension, which varies from 5.0 mm to 5.9 mm .
In studies of healthy volunteers, the range of ONSD
measured by ultrasonography also varied obviously.
Ballantyne et al. reported that the mean ONSDs measured
by 3 observers were 3.2, 3.4 and 3.6 mm, respectively .
However, after carefully inspecting the method of
measurement in this study, we found that the authors actually
Table 2 Comparisons of measurements between genders and between left/right eyes
0.63 (0.59 – 0.67)
Data were presented as median and inter-quartile range
ETD eyeball transverse diameter, OND optic nerve diameter, ONSD optic nerve sheath diameter
reported the OND value, rather than the ONSD .
In Romagnuolo et al.’s study conducted in the USA, the
mean ONSD varied from 4.4 to 4.8 mm in different
positions . Maude et al. reported that median ONSD
was 4.41 mm with 95 % of subjects in the range of 4.25
to 4.75 mm in Bangladesh . While Bauerle et al.
reported that the mean ONSD was 5.4 mm with a range
of 4.3-7.6 mm in German .
Compared to previous ultrasonographic studies, we
found that our data of OND was similar to Ballantyne et
al.’s study, while slightly smaller than Bauerle et al.’s study;
the ONSD was greater in our study than Maude et al.’s
and Romagnuolo et al.’s studies. The study with largest
sample size which measured ONSD using
ultrasonography was conducted by Maude et al. in Bangladesh (n
= 136) . The median (5.1 mm versus 4.41 mm) and
range of ONSD (3.5 to 6.4 mm versus 4.2 to 4.8 mm)
in our study was higher than Maude et al.’s report,
which compromising 12.5 % subjects with age under
16 years old . This might be the possible
explanation of the discrepancy in ONSD measurements. In
Romagnuolo et al.’s study, because the authors primarily
intended to detect difference with positions rather than to
establish the normal range of ONSD, they only enrolled 10
subjects . Data obtained from a smaller sample size
may lead to greater sampling error. The difference between
these two studies may be due to sampling error.
There are also studies using CT or MRI scan, which
can provide high spatial resolution, to determine normal
range of ONSD. Vaiman et al. reported the mean distal
(3 mm behind the globe) ONSD (range) was 4.94 ± 1.51
(3.5-7.5) mm in the right eye and 5.17 ± 1.34 (3.8-7.9)
mm in the left eye in CT scans with healthy Israeli
volunteers . Geeraerts et al. reported that the ONSD
was 5.08 ± 0.52 mm in T2-weighted MRI in British
volunteers . The results of these studies were similar to
ours. Previous study had shown a good correlation and
agreement between ultrasound and MRI measurement
of the ONSD 3 mm behind the papilla . However, it
is unknown whether it is comparable between CT and
ultrasound measurement of ONSD. While Bauerle et al.
reported the ONSD was 5.69 ± 0.77 mm in MRI scan in
German . Another study conducted by same authors
using ultrasonography also exhibited greater ONSD
value in German . Therefore we assume that the
difference may be caused by difference of ethnicities.
We also compared our data to the reports of elevated
ICP patients. The 95 % percentile of ONSD in our
healthy volunteer study was 5.9 mm; whereas the lower
bound of 95 % confidence interval of ONSD in those
patients with elevated ICP (with a ICP value ≥ 20 mmHg)
were ≥ 5.9 mm in most of the studies [14, 17–19, 25, 26],
except Kimberly et al.’s study (approximate 5.1 mm)
. Our data suggested that 95 % of normal Chinese
adults have an ONSD value ≤ 5.9 mm and it is reasonable
to speculate that an ONSD value > 5.9 mm could be
considered as abnormal.
We found that OND correlated with ONSD. It is
known that the ONSD is strongly correlated with
increased ICP while the OND is not . Since the optic
nerve is part of the central nervous system, which is
surrounded by a subarachnoid space, elevation in ICP
can be transmitted through the subarachnoid space and
cause extension of the space (e.g. increased ONSD).
The change of correlation of OND with ONSD will
occur, and therefore the OND/ONSD ratio might be
useful in detecting intracranial hypertension. To the
best of our knowledge, there is no study report the
OND/ONSD ratio. Our data indicate that OND/ONSD
ratio had a relatively narrow normal range and maybe a
promising surrogate of ONSD. Our research provides
reference data for further investigations in patients with
Our data suggested that the ONSD and the height were
statistically correlated. However, a P value < 0.05 only
indicates the rejection of the null hypothesis (rho = 0),
a correlation coefficient of 0.063, although statistically
significant, was too low and should be considered
independent in clinical interpretation. Moreover, we
stratified subjects based on different height and the
subgroup analysis demonstrated no difference of ONSD
between different heights.
This study had several limitations. First, a direct
measure of intracranial hypertension was not included thus
intracranial pressure was presumed to be normal by taking
history. Second, two investigators measured the ONSDs in
different patients; therefore it was not possible to
determine inter-observer variability in this study. Furthermore,
this study included only adult volunteers, and thereby
it is unable to determine the normal range of ONSD in
The median (IQR) sonographic measurement of ONSD
is 5.1 (4.7 to 5.4) mm at 3 mm behind globe and the
95 % percentile of ONSD is 5.9 mm in healthy Chinese
adults. The ONSD is correlated with OND, while
independent of gender, age, height, weight and ETD. The
median OND/ONSD ratio (IQR) was 0.63 (0.59 to 0.67),
and this parameter warrants further investigation in
population of patients with brain injury.
HC, RGY and JXZ participated in the design of the study, data analysis and
drafted the manuscript. GSD and YCZ participated in the data collection. All
authors edited the manuscript and read and approved the final manuscript.
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