Medicine, Faculty of
Non UBC
Emergency Medicine, Department of
DSpace
St. Paul's Hospital (Vancouver, B.C.)
Vancouver General Hospital
Lau, Torey
Ahn, Justin S.
Manji, Rahim
Kim, Daniel J.
Point of care ultrasound (POCUS) of the optic nerve is easy to learn and has great diagnostic potential. Within emergency medicine, research has primarily focused on its use for the assessment of increased intracranial pressure, but many other applications exist, though the literature is heterogeneous and largely observational. This narrative review describes the principles of POCUS of the optic nerve including anatomy and scanning technique, as well as a summary of its best studied clinical applications of relevance in emergency medicine: increased intracranial pressure, idiopathic intracranial hypertension, optic neuritis, acute mountain sickness, and pediatric intracranial pressure assessment. In many of these applications, sonographic optic nerve sheath diameter (ONSD) has moderately high sensitivity and specificity, but the supporting studies are heterogeneous. Further studies should focus on standardization of the measurement of ONSD, establishment of consistent diagnostic thresholds for elevated intracranial pressure, and automation of ONSD measurement.
Citation: Lau, T.; Ahn, J.S.; Manji, R.;Kim, D.J. A Narrative Review ofPoint of Care Ultrasound Assessmentof the Optic Nerve in EmergencyMedicine. Life 2023, 13, 531. https://doi.org/10.3390/life13020531Academic Editors: Alfredo Conti andLivio VitielloReceived: 29 December 2022Revised: 5 February 2023Accepted: 14 February 2023Published: 15 February 2023Copyright: © 2023 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).lifeReviewA Narrative Review of Point of Care Ultrasound Assessment ofthe Optic Nerve in Emergency MedicineTorey Lau 1,2 , Justin S. Ahn 1,3, Rahim Manji 1,2 and Daniel J. Kim 1,4,*1 Department of Emergency Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada2 Department of Emergency Medicine, St. Paul’s Hospital, Vancouver, BC V6Z 1Y6, Canada3 Department of Emergency Medicine, Royal Columbian Hospital, New Westminster, BC V3L 3W7, Canada4 Department of Emergency Medicine, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada* Correspondence: dkim000@gmail.com; Tel.: +1-604-875-4855Abstract: Point of care ultrasound (POCUS) of the optic nerve is easy to learn and has great diagnosticpotential. Within emergency medicine, research has primarily focused on its use for the assessmentof increased intracranial pressure, but many other applications exist, though the literature is hetero-geneous and largely observational. This narrative review describes the principles of POCUS of theoptic nerve including anatomy and scanning technique, as well as a summary of its best studiedclinical applications of relevance in emergency medicine: increased intracranial pressure, idiopathicintracranial hypertension, optic neuritis, acute mountain sickness, and pediatric intracranial pressureassessment. In many of these applications, sonographic optic nerve sheath diameter (ONSD) hasmoderately high sensitivity and specificity, but the supporting studies are heterogeneous. Furtherstudies should focus on standardization of the measurement of ONSD, establishment of consistentdiagnostic thresholds for elevated intracranial pressure, and automation of ONSD measurement.Keywords: ultrasound; point of care ultrasound (POCUS); optic nerve; optic nerve sheathdiameter (ONSD); intracranial pressure; idiopathic intracranial hypertension; optic neuritis; acutemountain sickness1. IntroductionPoint of care ultrasound (POCUS) is an essential diagnostic and evaluative tool inemergency medicine (EM). While applications such as focused assessment with sonographyfor trauma (FAST) and focused echocardiography are well established, other applications suchas ultrasound assessment of the optic nerve may be less familiar to the average emergencyphysician (EP). Like other POCUS applications, the advantage of ultrasonography is theability to perform rapid bedside assessment using a relatively inexpensive, portable, and non-invasive device. It does not require transportation of critically ill patients out of a monitoredsetting for conventional neuroimaging such as computed tomography (CT) and magneticresonance imaging (MRI) [1,2]. Further, its use can evaluate the eye in challenging patientpopulations, such as in pediatrics or in the setting of trauma where swelling of the eyelid caninterfere with conventional examination and direct ophthalmoscopy of the eye [3].Ultrasonography of the optic nerve is best described in the literature for the evaluationof elevated intracranial pressure (ICP), but other applications exist. These include itsuse in idiopathic intracranial hypertension (IIH), optic neuritis, acute mountain sickness(AMS), and ventriculoperitoneal (VP) shunt assessment [2]. POCUS of the optic nerve mayassist EPs in identifying critically ill patients, facilitating advanced imaging, or expeditingtransportation to appropriate referral centers if advanced neuroimaging capabilities are notavailable locally [2].Through this review, we aim to describe the principles of POCUS of the optic nerveincluding anatomy and scanning technique and provide a narrative summation of itsvarious clinical applications of relevance in EM.Life 2023, 13, 531. https://doi.org/10.3390/life13020531 https://www.mdpi.com/journal/lifeLife 2023, 13, 531 2 of 212. Materials and MethodsA literature review was performed to identify publications relating to ocular POCUSassessment of the optic nerve in patients presenting to the emergency department (ED).The authors performed the search in October 2022 and searched PubMed, Embase, andGoogle Scholar from inception up to September 2022 using the keywords “emergency opticnerve ultrasound” and the MeSH terms “optic nerve/diagnostic imaging” combined with“ultrasonography”. The authors included retrospective and prospective studies, systematicreviews, meta-analyses, narrative reviews, clinical guidelines, and case series. Case reports,editorials, letters, and non-English language studies were excluded. Article inclusion wasdetermined by author review and consensus based on clinical relevance to EM evaluationand management.3. ResultsA total of 43 articles were determined to be of relevance to EM clinicians and wereincluded in this narrative review. Of these, 26 papers were quantitative clinical studiespertaining to clinical applications and are summarized in Tables 1–5.Life 2023, 13, 531 3 of 21Table 1. Summary of quantitative clinical studies to diagnose increased intracranial pressure.Author and Year Study Design Study Population Intervention Comparator ResultsKim et al., 2021 [4]Prospectiveobservational study199 adults with suspectedraised ICPSonographic ONSD CT scanMedian sonographic ONSD wider in raisedICP patients (5.7 mm vs. 4.3 mm)Ideal cut point of 5.3 mmSensitivity 75%Specificity 91%Hanafi et al., 2019 [5]Prospectiveobservational study112 adults with traumaticheadache vs. controlsSonographic ONSD CT scanMean sonographic ONSD wider in patients(6.06 mm vs. 3.04 mm)Ideal cut point of 5.3 mm yielding:Sensitivity 96%Specificity 71%Ohle et al., 2015 [6] Meta-analysis 478 adults across 12 studieswith suspected raised ICP Sonographic ONSD CT scanSensitivity 96%Specificity 92%+LR 12.5−LR 0.05Robba et al., 2018 [7] Meta-analysis 320 adults across 7 studieswith suspected raised ICP Sonographic ONSDInvasive ICPmeasurementDOR 68+LR 5.4−LR 0.09Aletreby et al., 2022 [8] Meta-analysis 619 adults across 16 studieswith suspected raised ICP Sonographic ONSDInvasive ICPmeasurementSensitivity 90%Specificity 85%+LR 6.1−LR 0.11DOR 46.7Koziarz et al., 2019 [9] Meta-analysis4551 patients of any ageacross 71 studies withsuspected raised ICPSonographic ONSDAny reference standard(CT or invasive ICPmeasurement)Traumatic brain injury:Sensitivity 97%Specificity 86%+LR 6.9−LR 0.04Non-traumatic injurySensitivity 92%Specificity 86%+LR 6.9−LR 0.09Life 2023, 13, 531 4 of 21Table 1. Cont.Author and Year Study Design Study Population Intervention Comparator ResultsOptimal cut point of 5.0 mmKim et al., 2019 [10] Meta-analysis 352 adults across 6 studieswith suspected raised ICPSonographic ONSD witha cut point of 5.0 mm inall included studiesCT scanSensitivity 99%Specificity 73%+LR 4.6−LR 0.05DOR 178Fernando et al., 2019 [11] Meta-analysis5123 adults across 40 studieswith suspected raised ICPPhysical exam,sonographic ONSD, or CTimagingInvasive ICPmeasurement orcraniotomy withoperative diagnosis ofraised ICPPupillary dilation:Sensitivity 28%Specificity 86%Motor posturing:Sensitivity 54%Specificity 64%Decreased level of consciousness:Sensitivity 76%Specificity 40%Sonographic ONSD:AUROC 0.94CT absence or compression of basal cisterns:Sensitivity 86%Specificity 61%CT any midline shift:Sensitivity 81%Specificity 43%CT severe midline shift:Sensitivity 21%Specificity 89%Life 2023, 13, 531 5 of 21Table 2. Summary of quantitative clinical studies to diagnose idiopathic intracranial hypertension.Author and Year Study Design Study Population Intervention Comparator ResultsDag˘delen et al., 2022 [12] Case-control study 47 adults with IIH Sonographic ONSD 50 healthy controlsMean sonographic ONSD wider in cases(6.4 mm vs. 4.9 mm)Ideal cut point of 5.7 mm yielding:Sensitivity 100%Specificity 98%Kishk et al., 2018 [13] Case-control study99 females with IIH (90 definiteIIH, 9 probable IIH)Sonographic ONSD 35 age-matched healthycontrolsMean sonographic ONSD wider in cases(6.57 mm vs. 5.50 mm)Ideal cut point of 6.05 mm yielding:Sensitivity 73%Specificity 91%del Saz-Saucedo et al.,2016 [14]Prospectiveobservational30 patients with suspected IIH Sonographic ONSDLumbar puncture withCSF opening pressure of≥25 cmH2OMean sonographic ONSD wider in IIH patients(6.8 mm vs. 5.7 mm)Idea cut point of 6.3 mm yielding:Sensitivity 95%Specificity 91%+LR 10.4−LR 0.06Ebraheim et al., 2018 [15] Case-control study24 adults with IIH (20 definiteIIH, 4 probable IIH). All casesreceived acetazolamidetreatment.Sonographic ONSD 30 controlsMean sonographic ONSD higher in IIH patients(6.7 mm vs. 5.5 mm)ONSD was not correlated with CSF openingpressure1 week post-LP (10–15 mL withdrawn), meanONSD not significantly different from baseline(6.6 mm vs. 6.7 mm)4 weeks post-LP and after treatment withacetazolamide, mean ONSD decreased frombaseline (6.4 mm vs. 6.8 mm)Ideal cut point of 6.2 mm yielding:Sensitivity 88%Specificity 100%Life 2023, 13, 531 6 of 21Table 2. Cont.Author and Year Study Design Study Population Intervention Comparator ResultsJeub et al., 2020 [16] Case-control study19 adults with IIH (15 definiteIIH, 4 probable IIH)Sonographic ONSD 20 healthy controlsMean sonographic ONSD higher in IIH patients(values not provided)24 h after LP (30 mL withdrawn), mean ONSDdecreased (mean reduction right eye 0.4 mm,left eye 0.5 mm)Ideal cut point of 5.8 mm yielding:Sensitivity 81%Specificity 80%Table 3. Summary of quantitative clinical studies to diagnose optic neuritis.Author and Year Study Design Study Population Intervention Comparator ResultsLochner et al., 2014 [17] Case-control study 21 adults with unilateralfirst episode optic neuritis Sonographic ONSDUnaffected eye and 21 healthyage- and sex-matched controlsMedian ONSD higher in affected eye thanthe unaffected eye (6.3 mm vs. 5.5 mm) andcontrols (6.3 mm vs. 5.2 mm)Kwon et al., 2019 [18] Prospectiveobservational study17 adults with unilateralfirst episode optic neuritis Sonographic ONSD Unaffected eyeMedian ONSD higher in affected eye than inunaffected eye (5.5 mm vs. 5.0 mm)Table 4. Summary of quantitative clinical studies to diagnose acute mountain sickness.Author and Year Study Design Study Population Intervention Comparator ResultsFagenholz et al.,2009 [19]Prospectiveobservational study69 adults with AMS travelingthrough Pheriche, Nepal (4240 m)SonographicONSD217 adultswithout AMSMean ONSD higher in patients with AMS (5.3 mm vs. 4.5 mm)ONSD positively correlated with total LLSONSD associated with AMS (OR 6.3)Sutherland et al.,2008 [20]Prospective cohortstudy13 adult mountaineers ascendingMount EverestSonographicONSDN/AAn increase in 1000 m is associated with ONSD increase of 0.1 mmONSD positively correlated with LLSLawley et al.,2012 [21]Prospective cohortstudy23 adults at sea level passivelytransported to 3777 m via cable carSonographicONSDN/AMean ONSD higher in patients at high-altitude than at sea level(5.6 mm vs. 5.2 mm)ONSD did not change when headache resolved withacclimatizationLife 2023, 13, 531 7 of 21Table 4. Cont.Author and Year Study Design Study Population Intervention Comparator ResultsKeyes et al.,2013 [22]Prospective cohortstudy57 adults at 1400 m passivelytransported to 4300 m via carSonographicONSDN/AMean ONSD higher in AMS patients at altitude when comparedwith their baseline altitude (4.3 mm vs. 4.0 mm).Mean ONSD decreased in AMS patients at altitude after oxygentherapy (4.3 mm vs. 4.1 mm)Mean ONSD higher in AMS patients at altitude compared withnon-AMS patients (4.3 mm vs. 4.0 mm)Strapazzon et al.,2014 [23]Prospective cohortstudy19 adults ascending from 262 m to3830 m passively via helicopterSonographicONSDN/AMean ONSD higher at altitude than at baseline (6.4 mm vs.5.5 mm). ONSD increased in a parabola, peaking at 24 h andremained elevated at 8 days.ONSD associated with diagnosis of AMSKanaan et al.,2015 [24]Prospective cohortstudy86 adults ascending from 1240 m to3545 m passively via car, thenhiked and slept at 3810 mSonographicONSDN/AMean ONSD higher at altitude than at baseline (6.1 mm vs.5.6 mm). This increase was larger in subjects with AMS than thosewithout (mean 0.57 mm vs. 0.21 mm increase)Change in ONSD associated with diagnosis of AMS (OR 1.99)Table 5. Summary of quantitative clinical studies to diagnose increased ICP or VP shunt failure in pediatric populations.Author and Year Study Design Study Population Intervention Comparator ResultsBhargava et al., 2020 [25] Meta-analysis543 children aged <18 yearsacross 11 studies withsuspected raised ICPSonographic ONSDCT, MRI, invasive ICPmeasurement, or operativediagnosisWith any reference standard:Sensitivity 93%Specificity 74%+LR 3.6−LR 0.10DOR 39With an invasive reference standard:Sensitivity 89%Specificity 74%+LR 3.4−LR 0.15DOR 22Life 2023, 13, 531 8 of 21Table 5. Cont.Author and Year Study Design Study Population Intervention Comparator ResultsS¸ik et al., 2022 [26]Prospectiveobservational study147 children aged 1 month to18 years with suspectedraised ICP after head traumaSonographic ONSD CT scanSubjects with abnormal CT scans:ONSD associated with reduced level ofconsciousness and elevated ICP on CTreportIdeal cut point of 5.1 mm yielding:Sensitivity 93%Specificity 94%Subjects without elevated ICP and with aspace occupying lesion on CTIdeal cut point of 4 mm yielding:Sensitivity 75%Specificity 63%Padayachy et al., 2016 [27]Prospectiveobservational study56 children aged <1 year and118 children between 1 and14 years undergoing invasiveICP measurement undergeneral anesthesiaSonographic ONSD Invasive ICP measurementSubjects <1 year old, ideal cut point of5.16 mm yielding:Sensitivity 80%Specificity 76%PPV 42%NPV 95%DOR 12.7Subjects 1–14 years old, ideal cut point of5.75 mm yielding:Sensitivity 86%Specificity 70%PPV 78%NPV 81%DOR 14.5Subjects with an open anterior fontanelle,ideal cut point of 5.16 mm yielding:Sensitivity 86%Specificity 75%PPV 50%NPV 95%DOR 18Life 2023, 13, 531 9 of 21Table 5. Cont.Author and Year Study Design Study Population Intervention Comparator ResultsLin et al., 2019 [28]Prospectiveobservational study32 patients aged <21 yearswith suspected VP shuntfailureSonographic ONSD withpre-determined cut pointof >4 mm in infants ≤1year and 4.5 mm inchildren >1 yearCT, MRI, or neurosurgicalimpression of VP shuntfailureCompared to neuroimaging (CT/MRI):Sensitivity 60%Specificity 67%+LR 1.8−LR 0.6PPV 25%NPV 90%Compared to neurosurgical impression:Sensitivity 75%Specificity 68%+LR 2.3−LR 0.37PPV 25%NPV 95%Hall et al., 2013 [29]Prospectiveobservational study39 encounters with childrenaged 6 months to 18 yearswith suspected VP shuntfailureSonographic ONSD withpre-determined cut pointsof >4 mm in infants≤1 year and 4.5 mm inchildren >1 yearNeurosurgical decision tooperate on VP shunt failureMean ONSD lower in those with VP shuntfailure (4.5 mm vs. 5.0 mm)Sensitivity 61%Specificity 22%PPV 44%NPV 36%Life 2023, 13, 531 10 of 214. Discussion4.1. Anatomy and PhysiologyThe optic nerve carries approximately 1.2 million nerve fibers from retinal ganglioncells that join together at the optic disc before traveling through the optic chiasm towardsthe brain [30]. The nerve is surrounded by the pia mater, subarachnoid space, arachnoidmater, and dura mater, together forming the optic nerve sheath [31,32].There are four segments to the optic nerve (Figure 1): the intraocular, intraorbital,intracanalicular, and intracranial segments. The intraocular segment is approximately 1 mmdeep, 1.5 mm in diameter, and is clinically visible by direct ophthalmoscopy as the opticdisc. Next, the intraorbital segment is 25–30 mm long and is the subject of POCUS of theoptic nerve. It extends from the globe towards the optic foramen, measuring approximately3–4 mm in diameter. The intracanalicular segment measures approximately 6 mm inlength and travels through the optic canal. Ultimately the intracranial segment joins theoptic chiasm [30].Life 2023, 12, x FOR PEER REVIEW 13 of 24 4. Discussion 4.1. Anatomy and Physiology The optic nerve carries approximately 1.2 million nerve fibers from retinal ganglion cells that join together at the optic disc before traveling through the optic chiasm towards the brain [30]. The nerve is surrounded by the pia mater, subarachnoid space, arachnoid mater, and dura mater, together forming the optic nerve sheath [31,32]. There are four segments to the optic nerve (Figure 1): the intraocular, intraorbital, intracanalicular, and intracranial segments. The intraocular segment is approximately 1 mm deep, 1.5 mm in diameter, and is clinically visible by direct ophthalmoscopy as the optic disc. Next, the intraorbital segment is 25–30 mm long and is the subject of POCUS of the optic nerve. It extends from the globe towards the optic foramen, measuring ap-proxi ately 3–4 mm in diameter. The intracanalicular segment measures approximately 6 mm in length and travels through the optic canal. Ultimately the intracranial segment joins t e optic chiasm [30]. Figure 1. Schematic of the optic nerve and its different segments. Figure 1. Schematic of the optic nerve and its different segments.Life 2023, 13, 531 11 of 21The cranium is a fixed space containing the brain, blood, and cerebrospinal fluid(CSF) within the subarachnoid space, with little tolerance for increased volume. Significantincreases in volume of any of the cranial components will lead to increased ICP [33].Etiologies that increase the volume of cranial contents include cerebral edema, tumors,intracranial hemorrhage, increased CSF production, and CSF outflow obstruction [33,34].The subarachnoid space of the optic nerve is continuous with the brain, and CSFslowly percolates throughout the entire subarachnoid space [8,30]. Experimental studiesdemonstrate a linear relationship between ICP and the subarachnoid pressure of theoptic nerve [35]. Since the optic nerve sheath is distensible, it fluctuates in size basedon changes in ICP [35,36]. This has been confirmed with in vivo studies demonstratingincreases in sonographic optic nerve sheath diameter (ONSD) after intrathecal infusions,and normalization of ONSD after CSF decompression [37].4.2. Indications and ContraindicationsEPs working in a busy department will most effectively use POCUS to answer specificclinical questions to guide further management of patients. The primary question is whetherthere is sonographic evidence of elevated ICP. As such, clinical indications generally revolvearound the suspicion of raised ICP, including presentations of head trauma, headache,stroke, or altered level of consciousness [2]. In trauma patients with periorbital swelling,POCUS allows ocular assessment for elevated ICP without requiring eyelid retractors orsedation to examine for papilledema. Furthermore, POCUS of the optic nerve may beuseful for assessing and monitoring ICP in patients who are sedated and paralyzed, suchas the intubated patient, where neurological examination is unreliable. Other indicationsrelate to the inability to access advanced neuroimaging or lack of specialist support, such asin rural or remote settings, or in patients that are too unstable to leave a monitored settingfor advanced imaging [38].The main contraindication to POCUS of the eye and optic nerve is suspected orconfirmed globe rupture, but this may not be apparent to the clinician due to periorbitalswelling or hematoma. Therefore, it is imperative to use plenty of ultrasound gel and toavoid direct ocular pressure while scanning in the setting of trauma [39]. Another relativecontraindication is uncontrolled open angle or acute angle glaucoma [2].4.3. Scanning Technique and Sonographic AnatomyPOCUS of the optic nerve is performed using a high-frequency linear transducer(5–14 MHz) on an ultrasound machine, with a smaller probe footprint providing bettersonographic contact with the eye [33,40]. An ocular preset should be used, limiting thermalindex to ≤1 and mechanical index to ≤0.23 in accordance with the as low as reasonablyachievable (ALARA) principle [39,41]. Patients are placed in a comfortable position, gener-ally supine, and asked to close their eyes with their head in a neutral position (Figure 2) [42].Copious sterile ultrasound gel should be placed on the closed eyelids of the patient, andthe probe should be placed gently on top of the gel to avoid direct pressure on the eye.The sonographer’s hand can be steadied over the patient’s zygomatic process or nasalbone to regulate the amount of downward pressure applied by the probe. If preferred, atransparent protective film may be placed over the eye to protect it, but care must be takento avoid air entrapment between the film and external eyelids, as this will degrade imagequality [41]. Scanning should be performed using B-mode in the transverse orientation.The patient should be asked to look forward at a fixed point in neutral gaze to minimizeeye movement [2].Life 2023, 13, 531 12 of 21ife , 2, x FOR PEER REVIEW 15 of 4 Figure 2. Demonstration of point of care ultrasound of the eye. Plenty of ultrasound gel should be used and the hand can be steadied over the patient’s zygomatic process to minimize downward pressure on the eye applied by the probe. A clear, protectant film may be used to protect the eye if desired. This image was obtained with consent from the model for publication. The optic nerve can be identified as a homogeneous hypoechoic linear structure ex-tending far-field from the anechoic ocular globe [41]. It is surrounded by a more hyperech-oic band representing the optic nerve sheath, analogous to the arachnoid membrane sur-rounding the subarachnoid space, which is further enclosed by a hypoechoic outer band representing the dura mater [2,43]. Finally, hyperechoic retrobulbar fat surrounds the op-tic nerve. The central retinal artery and vein run through the middle of the optic nerve, while the ophthalmic artery runs parallel adjacent to the optic nerve [44]. Traditionally, ONSD is measured 3 mm behind the globe where the sheath is the most distensible and its measurements are reproducible [36,40]. Though there is recent evidence suggesting no difference in ONSD when measured between 3 and 5 mm poste-rior to the globe [45], most studies base their measurements at 3 mm [43]. The ONSD is measured between the outer hyperechoic borders of the subarachnoid space (Figure 3) [2,46]. If no hyperechoic stripe is visualized, the diameter is measured at the border of the hypoechoic optic nerve and the hyperechoic retrobulbar fat [32]. The measured diameter should be perpendicular to the longitudinal axis of the optic nerve [43]. Color doppler may aid visualization of a tortuous optic nerve by visualizing the midline central retinal artery and vein, allowing for accurate measurement of the ONSD perpendicular to the true course of the optic nerve [44,47]. However, the use of doppler must be minimized to avoid ocular injury [39]. Averaging 2–3 measurements in transverse or sagittal planes may Figure 2. Demonstration of point of care ultrasound of the eye. Plenty of ultrasound gel should beused and the hand can be steadied over the patient’s zygomatic process to minimize downwardpressure on the eye applied by the probe. A clear, protectant film may be used to protect the eye ifdesired. This image was obtained with consent from the model for publication.The optic nerve can be identified as a homogeneous hypoechoic linear structureextending far-field from the anechoic ocular globe [41]. It is surrounded by a more hyper-echoic band representing the optic nerve sheath, analogous to the arachnoid membranesurrounding the subarachnoid space, which is further enclosed by a hypoechoic outer bandrepresenting the dura mater [2,43]. Finally, hyperechoic retrobulbar fat surrounds the opticnerve. The central retinal artery and vein run through the middle of the optic nerve, whilethe ophthalmic artery runs parallel adjacent to the optic nerve [44].Traditionally, ONSD is measured 3 mm behind the globe where the sheath is the mostdistensible and its measurements are reproducible [36,40]. Though there is recent evidencesuggesting no difference in ONSD when measured between 3 and 5 mm posterior to theglobe [45], most studies base their measurements at 3 mm [43]. The ONSD is measuredbetween the outer hyperechoic borders of the subarachnoid space (Figure 3) [2,46]. If nohyperechoic stripe is visualized, the diameter is measured at the border of the hypoechoicoptic nerve and the hyperechoic retrobulbar fat [32]. The measured diameter should beperpendicular to the longitudinal axis of the optic nerve [43]. Color doppler may aidvisualization of a tortuous optic nerve by visualizing the midline central retinal artery andvein, allowing for accurate measurement of the ONSD perpendicular to the true course ofthe optic nerve [44,47]. However, the use of doppler must be mini ized to avoid ocularLife 2023, 13, 531 13 of 21injury [39]. Averaging 2–3 measurements in transverse or sagittal planes may minimizemeasurement errors [40,41]. Like other ultrasound applications, repeated measurements asclinically indicated may provide additional dynamic information [2].Life 2023, 12, x FOR PEER REVIEW 16 of 24 minimize measurement errors [40,41]. Like other ultrasound applications, repeated meas-urements as clinically indicated may provide additional dynamic information [2]. Figure 3. Ultrasound image of the eye and optic nerve. A: eyelid, B: cornea, C: anterior chamber, D: iris, E: vitreous chamber, F: retina, G: optic nerve with optic nerve sheath diameter of 3.8 mm, meas-ured at 3 mm from the retina. This figure was obtained with consent from the model for publication. POCUS of the optic nerve can easily be learned by novice users with minimal ultra-sound experience after a brief training session [48]. EPs can accurately measure ONSD with ultrasound when compared to ONSD measurements on CT by a radiologist [49], and generally have good inter-rater reliability regardless of level of ultrasound training, though some variations exist amongst residency-level physicians [38,50]. 4.4. Clinical Applications: Increased Intracranial Pressure The most prominent clinical application of optic nerve POCUS is its diagnostic ability to detect elevated ICP. Kim et al. conducted a prospective observational study in 2021, comparing ultrasound assessment of ONSD with CT of the brain performed within 30 min in patients suspected of raised ICP in the ED [4]. From a total of 199 enrolled patients, 57 were found to have signs of raised ICP on CT scan. The median ONSD on ultrasound in the raised ICP group was significantly higher compared with the normal ICP group (5.7 mm vs. 4.3 mm, p < 0.001). These results confirm the findings of another prospective ob-servational study from 2019 by Hanafi et al. where 62 trauma patients were compared with 50 healthy controls [5]. Of the 55 trauma patients with increased ICP on CT scan, Figure 3. Ultrasound image of the eye and optic nerve. A: eyelid, B: cornea, C: anterior chamber, D: iris,E: vitreous chamber, F: retina, G: optic nerve with optic nerve sheath diameter of 3.8 mm, measured at3 mm from the retina. This figure was obtained with consent from the model for publication.POCUS of the optic nerve can easily be learned by novice users with minimal ultra-sound experience after a brief training session [48]. EPs can accurately measure ONSDwith ultrasound when compared to ONSD measurements on CT by a radiologist [49], andgenerally have good inter-rater reliability regardless of level of ultrasound training, thoughsome variations exist amongst residency-level physicians [38,50].. . li i l li i : I r i li i i. t i ti al st y i ,ti ts suspected of raised ICP in the ED [4]. From a total of 199 enrolled patients,57 were found to have signs of raised ICP on CT scan. The median ONSD on ultrasoundin the raised ICP group was s gnificantly igher compared with the normal ICP group(5.7 mm vs. 4.3 mm, p < 0.001). Th e results confirm the findings of another prospectiveobservational study from 2019 by Hanafi et al. where 62 trauma patients rLife 2023, 13, 531 14 of 21with 50 healthy controls [5]. Of the 55 trauma patients with increased ICP on CT scan,sonographic ONSD was 6.06 mm in these patients compared to 4.02 mm in healthy controls.Ohle et al. published a systematic review and meta-analysis in 2015 comparingtrials assessing sonographic ONSD to diagnose elevated ICP compared to CT as the ref-erence standard [6]. They included 12 studies with 478 study subjects in ED and ICUsettings and found that ONSD had a sensitivity of 96% (95% CI, 88–99%), specificity 92%(95% CI, 78–98%), diagnostic odds ratio (DOR) 319 (95% CI 79–1290), positive likelihood ra-tio (+LR) 12.5 (95% CI 4.2–37.5), and negative likelihood ratio (–LR) 0.05 (95% CI 0.02–0.14).The major limitation of this meta-analysis was the moderate-to-high heterogeneity of theincluded studies.Recognizing that invasive monitoring is more accurate than CT to detect raised ICP,Robba et al. performed a meta-analysis in 2018 that only included studies using invasiveICP measurement (intraparenchymal, intraventricular, or lumbar puncture [LP]) as thereference standard [7]. Raised ICP was defined as >20 mmHg or >25 cmH2O. They includedseven studies with a total of 320 patients and found a pooled DOR of 68 (95% CI 29–135),+LR 5.4 (95% CI 3.8–7.5) and −LR 0.09 (95% CI 0.05–0.15). Their results are more modestcompared to Ohle’s systematic review, but this likely relates to a more robust referencestandard, fewer included studies, and lower heterogeneity. An updated meta-analysisby Aletreby et al. in 2022 assessed ONSD compared to invasive ICP measurement asthe reference standard [8]. They included nine additional studies compared to Robba’ssystematic review for a total of 619 patients. Their results were similar: pooled sensitivityof 90% (95% CI 85–94%), specificity 85% (95% CI 80–89%), DOR 47 (95% CI 26–83), +LR 6.1(95% CI 4.4–8.5), and −LR 0.11 (95% CI 0.07–0.18).The largest meta-analysis of optic nerve POCUS was published by Koziarz et al. in2019 and included trials with participants in all age groups, sonographers of any traininglevel, and used any reference standard as the comparator [9]. Their analysis included71 studies with a total of 4551 patients and found a sensitivity and specificity in thetraumatic brain injury subgroup of 97% (95% CI 92–99%) and 86% (95% CI 74–93%),respectively. In non-traumatic brain injury, sensitivity was mildly reduced at 92% (95% CI86–96%) while specificity was similar at 86% (95% CI 77–92%).Most studies used differing ONSD thresholds to diagnose increased ICP [4,8]. In 2019,Kim et al. attempted to establish a single sonographic ONSD cut point to detect elevatedICP [10]. They included six studies with 352 participants in their final analysis, all utilizing5 mm as a cut point. They found this cut point provided a pooled sensitivity of 99%(95% CI 96–100%), specificity 73% (95% CI 65–80%), DOR 178 (95% CI 53–599), +LR 4.6(95% CI 2.0–10.9), and −LR 0.05 (95% CI 0.02–0.14).In comparison, the physical exam is generally poorly sensitive and specific for elevatedICP. Fernando et al. compared multiple modalities to diagnose elevated ICP, includingphysical exam and sonographic ONSD. Their meta-analysis found pupillary dilation wasinsensitive at 28% but moderately specific at 86%. Motor posturing had poor sensitivity andspecificity at 54% and 64%, respectively. Decreased level of consciousness was more sensi-tive at 76% but less specific at 40% [11]. In comparison, sonographic ONSD measurementhad a pooled area under the receiver operating characteristic (ROC) curve of 0.94. Theseauthors did not calculate pooled sensitivity and specificity as the included studies usedmany different optimal cut points for elevated ICP. Finally, while direct ophthalmoscopycan detect elevated ICP based on the presence of papilledema, it is infrequently and poorlyperformed by EPs [51].Based on the literature, optic nerve POCUS using an ONSD threshold of 5 mm appearsto be a clinically useful and accurate tool to detect elevated ICP in the emergency setting. Ingeneral, it seems to be more sensitive than specific, which is clinically appropriate given thatit would be undesirable to miss a case of high ICP. However, the lack of large randomizedcontrolled studies limits the widespread use of this tool. POCUS assessment of ONSDcannot replace CT or invasive monitoring to diagnose elevated ICP, but it can be usedin an appropriate clinical context to monitor at-risk patients, in patients too unstable toLife 2023, 13, 531 15 of 21leave a monitored setting, or as a supplementary test in settings where access to advancedneuroimaging is limited.4.5. Clinical Applications: Idiopathic Intracranial HypertensionIIH is a neurologic disorder characterized by diffuse headache, visual abnormalities,and papilledema, most commonly affecting young females with increased body massindex (BMI) [16]. Physicians who are not ophthalmologists may have difficulty performingophthalmoscopy for a variety of reasons, including limited equipment, lack of experience,or patient factors [52]. Therefore, POCUS of the optic nerve can be an effective alternativemeans to assess for elevated ICP and assist with the diagnosis of IIH.Case-control studies have assessed the diagnostic accuracy of sonographic ONSD todetect elevated ICP to diagnose IIH, generally finding good sensitivity and specificity withvarying diagnostic thresholds. Dag˘delen et al. measured ONSD in 47 subjects with IIHand 50 healthy controls. They found the mean ONSD in IIH patients was increased at6.4 mm compared with 4.9 mm in controls (p < 0.001). They identified an optimal cut pointof 5.7 mm, yielding a sensitivity of 100% and specificity of 98% [12]. However, Kishk et al.found more modest results when they compared 99 females with both clinically definiteand probable IIH to 35 healthy controls. All cases had both neurologic and ophthalmologicassessment including neuroimaging to rule out other diagnoses. ONSD measurement wasperformed prior to diagnostic LP. Mean sonographic ONSD was higher in cases than controls(6.57 mm vs. 5.50 mm, p < 0.001). Using a cut point of 6.05 mm, sonographic ONSD hadonly modest sensitivity but good specificity at 73% and 91%, respectively [13]. Their moremodest results may be due to the inclusion of nine cases with probable IIH. Smaller studieshave demonstrated good diagnostic utility for ONSD measurement. Del Saz-Saucedo et al.studied 30 subjects with suspected IIH, of which 19 were diagnosed with a positive LP.Using a higher cut point of 6.3 mm, sonographic ONSD had a sensitivity of 95% (95% CI82–100%) and specificity of 91% (95% CI 69–100%) [14]. Finally, Ebraheim et al. studied24 patients with suspected IIH, of which 20 were diagnosed with a positive LP. SonographicONSD had a sensitivity of 88% and specificity of 100% using a cut point of 6.2 mm [15].Multiple studies have demonstrated dynamic changes in sonographic ONSD afterLP. Jeub et al. found that removal of 30 mL of CSF by LP led to a reduction in ONSD by0.4 mm and 0.5 mm in the right and left eyes, respectively [16]. In another study, Del Sez-Saucedo found that ONSD decreased by a mean of 0.9 mm after therapeutic LP achieved aCSF pressure of <15 cmH2O [14]. Even without therapeutic LP, Ebraheim found that after4 weeks of treatment with acetazolamide alone, ONSD decreased by a mean of 0.4 mm [15].ONSD appears to have good sensitivity and specificity to diagnose IIH. Further, itcan be used to monitor the response to treatment. However, no standardized cut pointscurrently exist, limiting its use as a diagnostic tool. Ultimately, more studies are required toestablish a standard cut point to serve as a diagnostic threshold for IIH.4.6. Clinical Applications: Optic NeuritisOptic neuritis is an acute inflammatory disorder of the eye that causes vision distur-bance or loss and ocular pain. It is most commonly idiopathic but may be secondary toother disease states, most notably multiple sclerosis [30]. Diagnosis is largely clinical and isaided by MRI [30,53]. Numerous case reports describe increased ONSD when measuredby POCUS in patients with optic neuritis, leading to observational studies to research itspotential as a diagnostic tool [54–56].Lochner et al. studied 21 patients with first-episode demyelinating unilateral opticneuritis and 21 matched controls. All patients underwent MRI imaging to rule out othercauses for their symptoms. They determined that sonographic ONSD was significantlyincreased compared to the unaffected eye, median 6.3 mm vs. 5.5 mm, respectively, andONSD was larger in affected eyes than in controls. ONSD of the unaffected eye was similarto controls [17]. Kwon et al. studied 17 patients with new-onset unilateral optic neuritisand found median ONSD to be modestly higher in affected eyes than in unaffected eyes,Life 2023, 13, 531 16 of 21measuring 5.51 mm and 5.05 mm, respectively [18]. While their findings are modest, they aresupportive of the findings from Lochner’s study. As only two studies exist, more research isrequired to establish sonographic ONSD as a useful tool to diagnose optic neuritis.4.7. Clinical Applications: Acute Mountain SicknessOptic nerve sheath sonography has also been explored as a portable and non-invasivesurrogate measure for increased ICP in acute altitude illnesses. Although causality isnot clearly established, increased ICP has been reported in patients with AMS and high-altitude cerebral edema (HACE). Both entities often overlap with high altitude pulmonaryedema (HAPE) [57,58].Analysis of trekkers at high altitude has demonstrated positive correlation betweenONSD and AMS. Fagenholz et al. studied travelers at 4240 m and found the mean ONSDin 69 patients with AMS was significantly larger than 218 patients without AMS. They alsoidentified a positive correlation between ONSD and the Lake Louise Score (LLS) used todiagnose AMS [19]. Similarly, Sutherland et al. followed 13 mountaineers and took serialmeasurements from sea level to 6400 m, finding a positive correlation between increasingaltitude, ONSD, and LLS [20].However, analysis of healthy volunteers with non-exertional ascent to high altitudehas shown conflicting results. Lawley et al. measured ONSD in 23 subjects at sea level andthen at 3777 m via cable car ascent. They found ONSD increased significantly with altitudecompared to baseline, but the increase was similar in those with and without symptoms ofaltitude illness [21]. Keyes et al. measured ONSD in a cohort of healthy patients at 1400 m,after rapid ascent to 4300 m via vehicle, and again after oxygen therapy. They found a smallincrease in mean ONSD in patients with AMS compared to patients without AMS [22].However, the association was weak, and the majority of ONSD measurements were<5 mm, which is below the typical cut point for elevated ICP.In contrast, Strapazzon et al. followed a cohort of 19 healthy volunteers and measuredONSD at baseline (262 m) and after helicopter ascent to 3830 m. They found that ONSDincreased with altitude in all participants with a peak at 24 h and remained increased at8 days [23]. In particular, the increase was more pronounced in patients who developedAMS, although this only comprised three participants. Kanaan et al. followed a cohortof 86 healthy adults who drove from 1240 m to 3545 m and then hiked up to 3810 m. Alltheir subjects had an increase in ONSD with ascent that was not statistically significant,regardless of AMS diagnosis [24]. However, the degree of increase was higher in patientswith AMS than patients without AMS. This suggests individual variability, so changes inan individual’s ONSD from baseline may be more important for the diagnosis of AMScompared to a standardized cut point.The discrepant results are best summarized by Lochner’s systematic review. Theyincluded six studies with 436 patients but found considerable clinical and methodologicalheterogeneity across the studies that prevented them from performing a meta-analysis. Thestudies varied with respect to variables such as ascent time, confounding factors relatedto method of transport to altitude, interval measurements, and scanning protocol. Withregards to ONSD, there was a significant degree of individual variability across the studiesand within each study, limiting ONSD as a diagnostic tool for AMS [59].Further research is necessary to clearly establish whether there is a correlation betweenONSD and AMS. Ideally, there needs to be a large longitudinal cohort study measuringONSD at baseline followed by a range of altitudes at consistent time intervals, using astandardized scanning protocol with assessment of interobserver reliability, and controllingfor confounding factors such as medication use (such as acetazolamide and dexamethasone),ascent time, and acclimatization periods.4.8. Clinical Applications: PediatricsThere is particular interest in POCUS of the optic nerve in pediatric populationswhere radiation exposure for diagnostic imaging and invasive procedures are ideallyLife 2023, 13, 531 17 of 21avoided if reasonably possible. However, the measurement of ONSD in children is morecomplicated than in adults. ONSD increases with age, most rapidly in the first year oflife [60]. Furthermore, ONSD may be affected by the patency of the anterior fontanelle andhead circumference [27,41,61,62]. Because of these factors, no standardized ONSD normalvalue exists, though numerous diagnostic cut points for raised ICP have been suggested.One commonly cited ONSD cut point is 4 mm in children ≤1 year old, 4.5 mm in children1 to 15 years old, and 5 mm in children >15 years old [41,60].Bhargava et al. performed a systematic review and meta-analysis of 11 publicationsto investigate the performance of sonographic ONSD to detect increased ICP in a pedi-atric population. Their study included patients with acute or chronic causes of elevatedICP. When compared to any reference standard, they found a pooled sensitivity of 93%(95% CI 74–99%), specificity 74% (95% CI 52–88%), +LR 3.55 (95% CI 1.67–7.54), −LR 0.10(95% CI 0.02–0.46), and DOR 39 (95% CI 4.16–365) with moderate-to-high heterogeneitywhen compared to any reference standard. When limited to an invasive reference stan-dard, sensitivity was 89% (95% CI 63–97%), specificity 74% (95% CI 47–90%), +LR 3.36(95% CI 1.36–8.31), −LR 0.15 (95% CI 0.04–0.68), and DOR 22 (95% CI 2–192) withminimal heterogeneity [25].S¸ik et al. studied 147 children presenting to the ED with head trauma requiring a CThead. ONSD ultrasound was performed by a pediatric EM fellow who was blinded toclinical and radiologic findings. When compared to CT as the reference standard, they founda high sensitivity of 93% and specificity of 94% when using a cut point of 5.1 mm amongstall age groups [26]. However, others found sonographic ONSD to have lower diagnosticperformance consistent with the results of Bhargava’s systematic review. Padayachy et al.performed a relatively large observational study comparing sonographic ONSD to invasiveICP measurements. They included 56 children ≤1 year old and 118 children >1 year ofage. In children ≤1 year old using a cut point of 5.16 mm to detect ICP above 20 mmHg,sonographic ONSD had a sensitivity of 80% (95% CI 44–98%) and specificity of 76% (95% CI61–87%), while in children >1 year, a cut point of 5.75 mm produced a sensitivity of 86%(95% CI 75–93%) and specificity of 70% (95% CI 56–82%). They found children with an openanterior fontanelle had the poorest correlation between sonographic ONSD measurementsand the reference standard [27]. Ultimately, ONSD appears to have high sensitivity andonly modest specificity to detect raised ICP in pediatric populations, but further research isrequired, especially to determine age-appropriate cut points.There has been increasing interest in utilizing sonographic ONSD to detect VP shuntfailure. While VP shunt malfunction results in raised ICP, children often present withnon-specific symptoms overlapping with benign childhood ailments [63]. While imaging isheavily relied upon to diagnose VP shunt failure, CT and MRI are insensitive and childrenoften require repeat CT imaging, thereby raising the risk of malignancy due to cumulativeradiation exposure [64]. Lin et al. studied 32 patients with suspected VP shunt failureand compared sonographic ONSD measured by pediatric EPs against neuroimaging anda neurosurgical clinical diagnosis as reference standards. When compared to neuroimag-ing, sonographic ONSD had a sensitivity of 60% (95% CI 23–88%) and specificity of 67%(95% CI 48–81%). When compared to neurosurgical opinion, sensitivity rose to 75%(95% CI 30–95%) and specificity to 68% (95% CI 49–82%) [28]. Hall et al. studied39 encounters suspicious for VP shunt failure and compared sonographic ONSD by pedi-atric EPs with neurosurgical diagnosis. They found sensitivity to be 61% (95% CI 36–83%)and specificity to be 22% (95% CI 6–48%) [29]. Unfortunately, sonographic ONSD appearsto have poor diagnostic value in VP shunt failure, though larger studies in the future mayprovide clarity in this emerging area of interest.4.9. Limitations and Future DirectionsIn general, clinical studies of sonographic ONSD are small and almost entirely observa-tional. The literature is limited by heterogeneous patient populations, reference standards,and cut points. One contributing factor is the inconsistent reporting on how ONSD is mea-Life 2023, 13, 531 18 of 21sured which may contribute to varying diagnostic cut points [40]. Until larger and moremethodologically rigorous studies are published, sonographic ONSD is more likely to playa complementary role, rather than replace advanced imaging or invasive monitoring. Theremay be a greater role for sonographic ONSD in rural EDs or austere environments whereadvanced imaging or invasive monitoring is unavailable or impractical. Establishing awidely accepted diagnostic threshold for raised ICP should be a priority before sonographicONSD can be broadly adopted for clinical use. Automation and machine learning may beuseful to standardize ONSD measurements, eliminating the risk of human measurementerror in the future [65].The pediatric literature is limited by the lack of established and broadly accepteddiagnostic cut points for increased ICP. Future studies should clarify the specific factorsaffecting pediatric ONSD measurement and should identify widely accepted, standardizedcut points based on age or other body measurements such as head circumference [25].5. ConclusionsPOCUS of the optic nerve appears to be a useful tool for several clinical applications,including traumatic brain injury, IIH, and optic neuritis. Though evidence for its use islargely observational, sonographic ONSD generally has high sensitivity and moderatespecificity to diagnose conditions that have a pathophysiologic process resulting in elevatedICP. It may also detect evidence of optic nerve inflammation in acute optic neuritis. WhilePOCUS of the optic nerve should generally complement traditional diagnostic algorithmsand modalities until larger randomized trials exist, it may be an important decision-makingtool in specific circumstances such as the unstable patient or in rural or remote settings. Fu-ture studies should prioritize standardizing ONSD measurement techniques and diagnosticcut points in both pediatric and adult populations.Author Contributions: Conceptualization, D.J.K. and T.L. Methodology, T.L., J.S.A., R.M. and D.J.K.Analysis, T.L., J.S.A. and D.J.K. Writing—original draft preparation T.L., J.S.A. and D.J.K. Writing—review and editing, T.L., J.S.A., R.M. and D.J.K. Supervision, D.J.K. All authors have read and agreedto the published version of the manuscript.Funding: This research received no external funding.Conflicts of Interest: T.L., J.S.A., and R.M. declare no conflict of interest. D.J.K. provides consultantservices to Fujifilm Sonosite.References1. Jimenez Restrepo, J.N.; León, O.J.; Quevedo Florez, L.A. Ocular ultrasonography: A useful instrument in patients with traumabrain injury in emergency service. Emerg. Med. Int. 2019, 2019, 9215853. [CrossRef] [PubMed]2. Lochner, P.; Czosnyka, M.; Naldi, A.; Lyros, E.; Pelosi, P.; Mathur, S.; Fassbender, K.; Robba, C. Optic nerve sheath diameter:Present and future perspectives for neurologists and critical care physicians. Neurol. Sci. 2019, 40, 2447–2457. [CrossRef] [PubMed]3. Kilker, B.A.; Holst, J.M.; Hoffmann, B. Bedside ocular ultrasound in the emergency department. Eur. J. Emerg. Med. 2014, 21,246–253. [CrossRef] [PubMed]4. Kim, D.Y.; Kim, S.Y.; Hong, D.Y.; Sung, B.Y.; Lee, S.; Paik, J.H.; Jung, H.M. 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Neuroimaging 2021, 31, 724–732. [CrossRef] [PubMed]Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individualauthor(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury topeople or property resulting from any ideas, methods, instructions or products referred to in the content.
Article
eng
Reviewed
Vancouver : University of British Columbia Library
Multidisciplinary Digital Publishing Institute
CC BY 4.0
Faculty
Researcher
ultrasound
point of care ultrasound (POCUS)
optic nerve
optic nerve sheath diameter (ONSD)
intracranial pressure
idiopathic intracranial hypertension
optic neuritis
acute mountain sickness
A Narrative Review of Point of Care Ultrasound Assessment of the Optic Nerve in Emergency Medicine
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