Optic nerve sheath diameters in nontraumatic brain injury: A scoping review and role in the intensive care unit

Table 1 Basic characteristics of the studies on optic nerve sheath diameter in patients with non-traumatic increased intracranial pressure, n (%)

Study characteristic	Number of studies, n = 37
Year of publication
2013	1 (2.7)
2014	3 (8.1)
2015	5 (13.5)
2016	3 (8.1)
2017	4 (10.8)
2018	2 (5.4)
2019	4 (10.8)
2020	1 (2.7)
2021	3 (8.1)
2022	2 (5.4)
2023	7 (18.9)
2024	2 (5.4)
Country of origin
China	8 (21.6)
India	7 (18.9)
Turkey	5 (13.5)
South Korea	3 (8.1)
Iran	2 (5.4)
Brazil	2 (5.4)
Italy	2 (5.4)
United States	2 (5.4)
Uganda	1 (2.7)
Spain	1 (2.7)
Saudi Arabia	1 (2.7)
Greece	1 (2.7)
South Africa	1 (2.7)
Germany	1 (2.7)
Comparator parameter
Intraventricular ICP monitoring	3 (8.1)
CSF opening pressure for lumbar puncture	20 (54)
MRI/CT scans	14 (37.8)
Type of study
Prospective observational study	17 (45.9)
Prospective case control study	12 (32.4)
Prospective cohort study	4 (10.8)
Retrospective case study	2 (5.4)
Case reports	2 (5.4)

ICP: Intracranial pressure; CSF: Cerebro-spinal fluid; MRI: Magnetic resonance imaging; CT: Computed tomography.

Table 2 Summary of studies on optic nerve sheath diameter in patients with non-traumatic raised intracranial pressure

Ref.	Country	Type of study	Number of participants	Patient characteristics	Comparator parameter and P value, r value	ONSD cut off, AUROC	Results	Limitations
Amini et al[7], 2013	Iran	Descriptive prospective	50	Non-traumatic patients requiring lumbar puncture	CSF pressure on LP, (P = 0.05; r = 0.88)	5.5, NA	The ONSD of greater than 5.5 mm predicted an ICP of ≥ 20 cmH2O with sensitivity and specificity of 100% (95%CI: 100-100) (P = 0.001)	Small sample size
Caffery et al[8], 2014	United States	Prospective observational trial	51	Non-traumatic causes of raised ICP	Opening pressure on LP, r = 0.53	> 5.0 mm, 0.69	Sensitivity 0.75, specificity of 0.44	Use of a convenience sample could introduce bias. Sample size was small with large confidence intervals. One physician with specialized training, patients were not matched for demographic variables such as age or sex
Nabeta et al[9], 2014	Uganda	Prospective descriptive study	57	HIV positive, ART naïve adults suspected with meningitis	CSF opening pressure, P < 0.001	5	Sensitivity 86% and specificity 63% for predicting a CSF ICP > 200 mm PPV was 77% and NPV was 75%. Also, in ONSD > 5mm had a RR of 2.39 for IICP > 200 cmH2O	Inter-operator variability, with training being essential
Shirodkar et al[10], 2014	India	Prospective, observational case control study	101, 60 study, 41 control	Non traumatic cause of increased ICP	Increased ICP on CT/MRI, P < 0.001	4.71, 0.986	Sensitivity of 77.8% and specificity of 100%	Small size
Wang l et al[11], 2015	China	Prospective observational cohort study	279	Non-traumatic cause of increased ICP	CSF opening pressure, P < 0.001	4.1, 0.965	Sensitivity of 95% and a specificity of 92%	Average of 8 measurements of ONSD to decrease variability. May not be feasible practically
Du Toit et al[12], 2015	South Africa	Prospective observational study	76	Meningitis	CSF opening pressure, Cohen’s kappa was 0.41	4.8, 0.73	Sensitivity of 50% and specificity of 89.8% PPV of 54.8% and NPV of 88.3% PLR of 4.92 and NLR of 0.56	The study was unable to establish inter-observer variability owing to the large number of operators and the small number of patients with increased ICP
Sangani et al[13], 2015	India	Prospective observational study	25	Tubercular meningitis	CSF opening pressure, P < 0.001	NA	Those patients with TBME had a mean ONSD of 5.81 mm	Small sample size
Singleton et al[14], 2015	United States	Case report	1	Idiopathic ICH	CSF opening and closing pressure which was 36 cm H2O and 19.5 cm H2O after removal of 19 cc of CSF	NA	Pre-LP ONSD of left and right eye were 72 and 6.8 mm, respectively. Second study after 30 minutes left and right ONSD were 58 and 6.2 mm, respectively
Karzamni et al[15], 2015	Iran	Prospective case control study	60, 30 cases and 30 controls	Intracranial SOL and ICH	Increased ICP on CT, P < 0.001	4.53	Sensitivity and specificity of 100%. ONSD was the most sensitive and specific parameter, followed by RI, PI and EDV. ONSD correlated significantly with GCS (r = −0.40, P = 0.003) and ventricular shift on CT images (r = 0.37, P = 0.02)	Small size, lack of direct ICP measurement
Komut et al[16], 2016	Turkey	Prospective case control study	100	Nontraumatic intracranial event in ED	Increased ICP on CT, P < 0.05	5.3, 0.728	Sensitivity 70%, specificity 74%	Lack of direct ICP measurement
del Saz-Saucedo et al[17], 2016	Spain	Prospective case control study	30	IIH	CSF opening pressure, P = 0.005	6.3 to predict CSF pressure of 25, 0.93	Sensitivity 94.7%, specificity 90.9% and PLR of 10.4. After a therapeutic lumbar puncture an 87% of cases had a partial reduction of ONSD values	Small size
Salahudd et al[1], 2016	Saudi Arabia	Prospective cohort study	102	Non traumatic raised ICP	Increased ICP on CT, P < 0.001	5.7, 0.785	Sensitivity 84 % and specificity 71%. PLR = 2.89, NLR = 0.22	Study did not include a detailed neurological exam or record any specific localizing neurologic signs, individual GCS
Jeon et al[18], 2017	Korea	Prospective case control study	62	Nontraumatic cases requiring EVD placement	Opening pressure on EVD insertion, P < 0.01	> 5.6, 0.936	Sensitivity of 93.75% and a specificity of 86.67% for identifying increased ICP	To reduce selection bias, patients with severely increased ICP which required emergency surgical decompression before ICP monitor insertion. Study reflects increased ICP due to moderate hematoma in a Korean population
Gökcen et al[19], 2017	Turkey	Retrospective comparative study	191	Acute ischemic stroke	Raised ICP on CT, P < 0.001	Right ONSD 5.4, 0.941, Left ONSD 5.3, 0.922	CVD subgroups were compared with the control group the highest ONSD was in TACI group and the lowest was in LACI group (P < 0.001)	Unequal number of cases in the subgroups and adjustment of baseline charecteristics not mentioned
Wang et al[20], 2017	China	Prospective case control study	316	Nontraumatic increased ICP requiring LP	CSF opening pressure, r = 0.758, P < 0.001	NA	Xing and Wang mathematical equation for predicted ICP = −111.92 + 77.36 × ONSD (Durbin-Watson value = 1.94)	Equation may underestimate the true ICP value in patients with extremely high ICP. The Bland-Altman analysis in this study suggested that any estimate might be deviate by as much as ± 80mmH2O
Liu et al[21], 2017	China	Prospective observational study	110	Non-traumatic increased ICP requiring LP	CSF opening pressure, P < 0.001	5.6, 0.861	Sensitivity of 86.2% and specificity of 73.1%	5%–15% of the cases were classified
Wang et al[22], 2018	China	Prospective case and control study	60	Nontraumatic causes of IICP requiring LP	CSF opening pressure, P < 0.001. The ultrasonographic ONSD and ICP were measured on admission and follow-up	NA	ONSD was strongly correlated with ICP (r = 0.702, P < 0.001)	Small size, ONSD cut off not obtained
Canakci et al[24], 2018	Turkey	Prospective case control study	100	Non-traumatic headache presenting to ER	Raised ICP on CT, P < 0.001	5.5, NA	ONSD value in the ipsilateral side with the lesion was significantly higher than the contralateral side (P < 0.001). Discharge, clinical hospitalization, referral, ICU stay, emergency surgery	ER based study including patients with nontraumatic headache not exclusively patients with clinical features of raised ICP. No AUROC calculated
Naldi et al[24], 2019	Italy	Prospective case control study	46 cases, 40 controls	Primary ICH	Increased ICP on CT, P < 0.01	5.6, 1.0	Sensitivity 100%, Specificity 100%	ICP was presumed to be normal in control, limited predictive value of abnormal CT findings. Second CT scan was performed not on a given day, but depending on clinical conditions
Gupta et al[25], 2019	India	Prospective observational study	100	Raised ICP requiring LP	CSF opening pressure, P < 0.001	6.3 to predict CSF pressure of > 20 cm of water	Sensitivity 77.3%, specificity 92.3%, PLR = 10.05, NLR = 0.25	Did not include any condition causing a mass effect, malignant infarcts, ICH or obstructive hydrocephalus
Gupta et al[26], 2019	India	Retrospective case series study	100	Raised ICP requiring LP	CSF opening pressure, P < 0.001	4.8	Sensitivity of 85% and specificity of 88%	Single center, retrospective, small size
Wang et al[27], 2019	China	Case reports	2	Venous sinus stenosis and venous sinus thrombosis	CSF opening pressure	NA	Case 1 A predicted ICP by ONSD was 346 mmH2O. and CSF opening pressure was 355 mmH2O. Case 2 ONSD was 5.95 mm with CSF opening pressure higher than 400 mmH2O
Zoerle et al[28], 2020	Italy	Prospective observational study	20	Aneurysmal SAH with EVD	Intraventricular ICP, P > 0.05	NA	ONSD measurements were accurate, very similar to the diameters measured by MRI (the mean difference in the Bland–Altman plot was 0.08 mm, 95% limits of agreement: −1.13; + 1.23 mm). No clear relationship was detectable between the ICP and ONSD, and a linear regression model showed an angular coefficient very close to 0 (P > 0.05). US-ONSD and ICP values were in agreement after CSF drainage and shifts in ICP in a limited number of patients	Measured ICP in the ICU after the patients were stabilized, the aneurysm repaired, and large intracerebral hematomas surgically removed, with EVD and CSF drainage. As a consequence, the ICP values in our cohort were relatively low for the majority of cases
Sahu et al[29], 2021	India	Prospective, double blinded observational study	30	Nontraumatic increased ICP	Direct intraventricular ICP, P = 0.01	5.5 to predict ICP > 20 mmHg, 0.904	Sensitivity 100% and specificity 75%. The ONSD values predicting ICP at 25-, 30-, and 35-mm Hg were was 6.3 mm, 6.5 mm, and 6.7 mm, respectively	Small number of patients having ICP > 30 mm of Hg, appropriate ONSD values could not be predicted
Yildiz et al[30], 2021	Turkey	Prospective, observational study	82	Acute ischaemic stroke	Increased ICP on CT, P < 0.05	NA	ONSD on the 3rd day and 5th day was larger (> 5 mm) than on first day (P < 0.05). In the patients who received tPA right eye ONSD on the 5th day were significantly raised P < 0.05)	ONSD only after the symptoms started, and were also not measured during the decline periods and response to treatment
Kim et al[31], 2021	South Korea	Prospective, observational study	199	Suspected raised ICP	Increased ICP on CT, P < 0.001	5.3, 0.903	Sensitivity of 75.4%, specificity of 90.8%, PPV of 76.8%, and NPV of 90.2%	Single centre, 2 observers hence there can be variability
Qamar Akhtar et al[32], 2022	India	Prospective case control study	100	Non traumatic emergencies with suspected raised ICP	Raised ICP on CT/MRI (P = 0.05; r = 0.88)	≥ 6.3, 0.956	Sensitivity of 100%, specificity of 89.2%, PPV of 83.3%, NPV of 100%, and diagnostic accuracy of 93% for detection of raised ICP by bedside USG ONSD measurement compared to CT/MRI brain	CT or MRI brain scan which is an indirect indicator of raised ICP, and use of a high ONSD mean value (mm) cut-off
Oliveira et al[33], 2022	Brazil	Prospective observational study	40	Malignant MCA infarct requiring decompressive craniotomy	Increased ICP on CT, P: NA	5.4 mm, ROC for, Right eye: 0.82, Left eye: 0.77	Post craniectomy, there was a decrease in the mean value of 1.04mm in the right eye 086 mm in left. (P = 0.003)	Small size, CT unreliable for increased ICP. DC individualized is routinely adopted at this center, the neurosurgical team was allowed to perform surgery using individual interpretations of criteria, with controversial decisions on some patients
Roemer et al[34], 2022	Germany	Prospective observational study	23	Increased ICH	CSF opening pressure, P = 0.9	NA	No correlation between CSF opening pressure and ONSD was found	Small size, results could be biased by the ongoing treatment of the patients
Bhide et al[35], 2023	India	Prospective observational study	114	Non-traumatic causes of raised ICP	Increased ICP on CT/MRI, P < 0.001	5.75, 0.844	Sensitivity and specificity of 77.55% and 89.06%. PLR and NLR of 7.09 and 0.25	Comparator used was CT or MRI brain scan which is an indirect indicator of raised ICP, and use of a high ONSD mean value (mm) cut-off
Yu et al[36], 2023	China	Prospective observational study	107	Non traumatic increased ICP requiring LP	CSF opening pressure, P < 0.001	6.3 mm	73% sensitivity and 83% specificity, ODH with ONSD showed the highest value under the receiver operating characteristic curve of 0.965 with a sensitivity of 93% and a specificity of 92%	Single lumbar puncture
Batur et al[37], 2023	Turkey	Prospective case control study	105	Acute ischemic stroke	Features of raised ICP on MRI (P < 0.001)	5.05, 0.978	Sensitivity 96.8%, specificity 95.6%. The cut-off for need for treatment 4.95 mm with AUC of 0.807 (sensitivity = 71.4%, specificity = 79.6%)	Single-centered study. Although 30-day mortality rates were recorded, a detailed information about the outcome could be given by monitoring the neurological healing rate and time of the patients
Li et al[38], 2023	China	Prospective observational study	56	Suspected encephalitis	CSF pressure, r = 0.769, P < 0.01	NA	Both ODH and ONSD had the ability to predict ICP (P < 0.05), but with time factors, ONSD displayed a stronger ability to predict ICP than ODH	Single-center design and small sample size. Cut-off value with AUROC not calculated
de Moraes et al[39], 2023	Brazil	Prospective observation study	18	Acute stroke (ischemic and hemorrhagic)	A 5-point visual scale for n raised ICP on CT and two parameters (time-to-peak and P2/P1 ratio) of a noninvasive ICP wave morphology monitor (r = 0.29)	5.2, 0.69	Sensitivity was 71.4%, the specificity was 70.4%, the PPV was 43.5%, and the NPV was 88.6%	Small size, assessment intervals varied, Non blinded, correlation modest to moderate strengths
Cheng et al[40], 2023	China	Prospective cohort study	223	Non-traumatic causes of raised ICP requiring LP	CSF opening pressure, P < 0.001	5.47, 0.933	ICP values were strongly correlated with ONSD, ONSD, and ONSD/ETD. ONSD and OND combined model predicted ICP = 139.394 × ONSD-112.428 × OND267.461 prediction accuracy was the highest. (ICC = 0.88)	Underestimated the ICP in very high cases, the maximum limit of our ICP values was 330 mmH2O, and values greater than 330 mmH2O were counted as 330 mmH2O
Bakola et al[41], 2024	Greece	Prospective center case-control study	31 case and 34 controls	Idiopathic ICH	CSF opening pressure on LP, (r = 0.716, P < 0.001)	5.15, 0.914	Sensitivity and specificity of TOS for diagnosis of IIH were 85% (95%CI: 66%-95%) and 90% (95%CI: 76%-98%), respectively. PPV 83% (95%CI: 74%-96%), NPV 94% (95%CI: 83-98%)	Subsequent measurements to estimate the potential treatment response using TOS were not part of our study protocol.
Kim et al[42], 2024	Korea	Retrospective analysis of prospectively gathered data ONSD measurements were conducted using a handheld ultrasonography device during the course of endovascular treatment	126	Aneurysmal SAH	CSF opening pressure on LP, (P < 0.001), the association between ONSD and ICP was validated through the application of a linear regression machine learning model. The correlation between ICP and various factors was explored through the modeling	5.45, 0.90, SHAP 5.58	Sensitivity 92.50, specificity 78.00, PPV 82.70 NPV 90.20	Small size, single center

ONSD: Optic nerve sheath diameter; ICP: Intracranial pressure; AUROC: Area under receiver operating curve; CSF: Cerebro spinal fluid; LP: Lumber puncture; NA: Not available; HIV: Human immunodeficiency virus; ART: Anti-retroviral therapy; PPV: Positive predictive value; NPV: Negative predictive value; RR: Relative risk; CT: Computed tomography; MRI: Magnetic resonance imaging; PLR: Positive likelihood ratio; NLR: Negative likelihood ratio; TBME: Tuberculous meningo-encephalitis; IIH: Idiopathic intracranial hypertension; LP: Lumber puncture; SOL: Space occupying lesion; ICH: Intracranial hypertension; RI: Resistive index; PI: Pulsatility index; EDV: End diastolic velocity; GCS: Glasgow coma score; EVD: Extra-ventricular drain; TACI: Total anterior circulation infarct; LACI: Lacunar infarct; SAH: Subarachnoid haemorrhage; MCA: Middle cerebral artery; DC: Decompressive craniotomy; ODH: Optic disc height; TOS: Transorbital sonography.

Table 3 Pertinent concerns regarding optic nerve sheath diameter measurement in medical intensive care unit

	Related issues
How to measure ONSD?
(1)	A scan or B scan? What is blooming effect?
(2)	CLOSED protocol?
(3)	Transverse or horizontal?
(4)	How many values before obtaining a mean?
(5)	ONSD or OND or ratio?
What is the body of evidence in various subset of patients?
(1)	Acute ischemic stroke and CVST
(2)	Acute hemorrhagic stroke
(3)	Hydrocephalus
(4)	Idiopathic intracranial hemorrhage
(5)	Meningitis
(6)	Septic metabolic encephalopathy
Can ONSD be used as a management tool?
Can ONSD be a reliable outcome measure?
(1)	Post cardiac arrest
(2)	Dysnatremia

ONSD: Optic nerve sheath diameter; OND: Optic nerve diameter; CVST: Central venous sinus thrombosis

Table 4 Differences between A scan and B scan on ultrasonography

A scan	B scan
Amplitude modulation scan	Brightness modulation scan
8 mHertz frequency with small non focused probe	10 mHertz with a larger focused probe
One-dimensional image of spikes of varying amplitudes along a baseline	Two-dimensional image
Provides quantitative information: Ex length of eyeball before surgery.	Provides topographical information
Basis of ocular biometry	Evaluation of ocular pathology
No blooming effect	Blooming effect while measuring ONSD
Not available as bedside equipment	Part of point-of-care ultrasonography, easily available

ONSD: Optic nerve sheath diameter.