Ultrasound measurement of Optic Nerve Sheath Diameter in a Colombian healthy adult population

doi:10.21203/rs.3.rs-1567239/v1

PDF

Research Article

Ultrasound measurement of Optic Nerve Sheath Diameter in a Colombian healthy adult population

https://doi.org/10.21203/rs.3.rs-1567239/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Measurement of optic nerve sheath diameter (ONSD) provides a rapid, safe, and easy method for detecting increased intracranial pressure (ICP). However, normal mean and upper limit values may vary according to age, sex, ethnicity, and ultrasound laboratory.

Aim

We aim to obtain the mean of ONSD in a healthy Colombian adult population and correlate it with demographic and anthropometric measures.

Methods

In a prospective study using a 10-13MHz linear ultrasound probe, transverse bulb diameter (TBD) and ONSD in transverse (ONSD-TP) and sagittal plane (ONSD-SP) were measured in healthy adults volunteers in Bogota, Colombia.

Results

A 100 healthy subjects were included, mean age 26,7 ± 8,3 years with 62 women. For 95% of the subjects the mean TBD, ONSD-TP and ONSD-SP was 23.11mm (CI: 22.90mm-23.32mm), 3.96mm (CI: 3.85mm-4.07mm) and 4.0mm (CI: 3.90mm-4.11mm) respectively. ONSD in both planes ranged from 2.35mm to 5.20mm. There was a correlation between ONSD-SP and ONSD-TP (p < 0.0001) but no correlation between ocular measures and demographic or anthropometric variables (p > 0.05). Intraclass correlation between eyes was statistically significant.

Conclusion

Our study shows that ultrasound measured ONSD in healthy adults in Colombia is similar to those found worldwide. An ONSD of 5.5mm may be considered the upper limit for healthy adults in Colombia. ONSD could be measured in either plane, there is a good correlation between the two eyes and ONSD is not modified by demographic or anthropometric characteristics.

Optic Nerve Sheath Diameter

ONSD

Ultrasonography

Healthy Adults

Latin American

Increased intracranial pressure (ICP) is a common complication of many neurological and systemic disorders. Its presence carries an unfavorable visual and neurological outcome, with an increased risk of mortality(1). Early detection, monitoring and treatment of ICP are associated with better outcomes and decreased mortality (2). Nowadays, a variety of invasive and noninvasive techniques to diagnose and monitor ICP are been implemented; however, invasive methods require highly qualified personnel, expensive equipment, and carry a risk of serious complications of infection, brain hemorrhage and catheter malfunction between 6% and 32.8%(3).

Among the noninvasive methods, ultrasound (US) measurement of the optic nerve sheath diameter (ONSD) provide a faster, safer, easier to perform and real-time assessment; with a good correlation with papilledema and measured intracranial pressure (4, 5). As ICP increases, the subarachnoid space around the optic nerve expands, and on US, protrusion of the optic nerve head and increased ONSD are become evident.

Nevertheless, diagnosis of increased ICP by US measured ONSD requires knowledge of normal parameters and cut-off values. Normal mean and upper limit of the ONSD on US have been previously established in different healthy populations. US ONSD measurements are taken at 3 mm behind the posterior globe margin, from inner-edge to inner-edge of the optic nerve sheath. In healthy adults ONSD measurements of up to 5 mm have been considered normal. Measurements > 5 mm (bilaterally) are correlated with ICP above 20 mmHg, with a linear association up to 7.5 mm, at which the diameter appears to plateau. However, these values vary according to age, sex, ethnicity and US laboratory (6, 7).

To the best of our knowledge, there is scarce information on normal values of ONSD in healthy adults from Colombia and Latin American (8).The aim of this study was to obtain the mean of US measured ONSD, in transverse and sagittal plane, in healthy adults volunteers; and correlate the values with the demographic and anthropometric characteristics of the studied subjects.

A prospective descriptive study was carried out between January 2021 and July 2021 at Fundacion Cardioinfantil in Bogotá, Colombia. Due to the current pandemic, biosafety measures as required by the hospital, local and national authorities were applied in all protocol tasks.

The study was approved by the institutional research ethics committee (Approval number: CEIC-4472-2021) and prior written informed consent was provided by all included subjects.

Participants

Healthy adult volunteers aged 18 years and older, with no past or current neurological or neuro-ophthalmological disease and normal neurological exam were included. Subjects with a disease, condition or treatment that could interfere or alter, as deemed by the investigators, with US measurements or intracranial pressure were excluded. The study subjects consisted mainly of medical students and institutional workers.

For all included subjects the following data were obtained: age, sex, height, weight, Body Mass Index [BMI] head circumference [HC]), blood pressure, heart rate, body temperature, current symptoms, COVID-19 symptoms, and past medical history before the US procedure. A detailed direct bilateral fundoscopy was performed in each of the studied subjects. The height was measured in meters with a standard wall-meter, the weight was measured in kilograms with a calibrated office electronic weight and the HC was measured with a standard non elastic meter at the widest possible occipitofrontal circumference.

Optic nerve sheath Ultrasound

ONSD Ultrasound measurement was performed using a portable Edge Sonosite Fujifilm ecographic system. A standard orbital bidemensional (2D) imaging mode with a 10–13 MHz linear US probe at maximal gain, 6 cm of depth and 0 in the grey scale was used. The system’s error in the B mode within the interval of 0–26 cm in axial, lateral and diagonal distance is of <+/-2%. All ocular measurements were performed with the subjects in supine position with the head at 30 degrees elevation. The probe was applied to the upper closed eyelids with coupling gel, in the superolateral margin of the orbit and eyes in primary gaze. The right eye was assessed first, maximal transverse bulb diameter (TBD) is measured (Fig. 1) followed by ONSD in transverse plane (ONSD-TP) at 3 mm behind the posterior globe margin. The probe is then rotated 90 degrees and the ONSD in the sagittal plane (ONSD-SP) measured at the same distance. The ONSD were measured from inner-edge to inner-edge of the optic nerve sheath Fig. 2. The procedure is repeated for the left eye. Two measures were taken at each position in both eyes; the mean of each measurement was calculated in order to minimize intra-observer variability.

Statistical Analysis

Quantitative variables were reported as mean and standard deviations, whereas qualitative variables were reported as absolute and relative frequencies. In order to estimate mean of TBD, ONSD-TP and ONSD-SP across both eyes, we used random effect model to account for correlation of measures for both eyes for a given patient. From this we were able to obtain an adjusted mean estimate for the parameter of interest as well as the intraclass correlation coefficient. In a further analysis, we aimed to evaluate marginal associations between physiologic characteristics and ocular parameters, this was done with mixed linear models. Al statistical analysis were done in software R version 4.1.1.

From 100 healthy included volunteers, mean age was 26.7 ± 8.3 years, 62 were women. Weight, height, BMI, and HC mean for all included subjects were 65.5 ± 12.5 kg, 167.4 ± 9.9 cm, 23.3 ± 3.4 kg/m² and 56.0 ± 2.6 cm, respectively.

The transverse bulb diameter (TBD) measures ranged from 20.50 mm to 29.20 mm. The ONSD-TP measures ranged from 2.35 mm to 5.15 mm and for ONSD-SP from 2.60 mm to 5.20 mm. For TBD, ONSD-TP and ONSD-SP 95% subjects exhibited a mean of 23.11 mm (CI: 22.90 mm-23.32 mm), 3.96 mm (CI: 3.85 mm-4.07 mm) and 4.0 mm (CI: 3.90 mm-4.11 mm) with intraclass correlation between eyes of 0.73, 0.84 and 0.88, respectively Table 1.

There was a strong correlation between ONSD-SP and ONSD-TP (p < 0.0001) but there was no difference between mean BDT, ONSD-SP and ONSD-TP in terms of age, gender, weight, height, BMI, and HC (p > 0.05).

Table 1

Ultrasound measurements in 100 subjects.
	mean ± SD (95%IC)	mínimum	máximum
BTD (mm)	23.11 ± 0.42(22.90-23.32)	20.5	29.2
ONSD-TP (mm)	3.96 ± .0.21(3.85–4.07)	2.35	5.15
ONSD-SP (mm)	4.0 ± 0.20(3.90–4.11)	2.6	5.2

In an adult healthy volunteer population in Bogota, Colombia, using orbital US we obtained a mean ONSD-TP of 3.96 mm (95% CI: 3.85 mm-4.07 mm) and a mean ONSD-TP of 4.0 mm (95% CI: 3.90 mm-4.11 mm). The range ONSD-TP and ONSD-SP were 2.35 mm to 5.15 mm and from 2.60 mm to 5.20 mm, respectively. We found a strong correlation between ONSD-TP and ONSD-SP (p < 0.0001), intraclass correlation between eyes was statistically significant and comparable with previous reports(9). We did not find any statistical association between age, sex, BMI, HC and US measures of ONSD (p > 0.05), as have been showed in a recent systematic review and metanalysis (8). None of ONSD in either plane in this healthy adult population was greater than 5.2 mm.

Previous studies of US ONSD measures in healthy population (children and adults) are in the range of 2.2 to 5.4 mm. In 67 subjects in United Kingdom the range was 2.4–4.7 mm (mean 3.2–3.6 mm) in 26 subjects in Greece was 2.2–4.9 mm (mean 3.6 mm) and in 136 subjects in Bangladesh was 4.24–4.83 mm (mean 4.41 mm) (10). Higher values of US ONSD have been found in studies in Iran, (range 3.8–5.4 mm, mean 4.6 mm) China (range 4.7–5.4 mm, mean 5.1 mm) and Korea (range 4.6–5.2 mm, mean 4.9 mm) (5). US cut-off values of ONSD for diagnosis of increased ICP have ranged from 4.1 to 5.7 mm with a good correlation with invasive measures. Cut-off measures of US ONSD of 4.7 to 5.7 mm for increased ICP show a sensitivity of 70–100% and specificity of 31.9–100% (11).

US ONSD measures have shown minimal inter-observer and eye to eye variations. Inter-observer variation is +/-0.2-0.3 mm and differences in measures between the axial and sagittal plane of US ONSD are in the range of 0-0.3 mm (mean 0.15 mm)(12). The learning curve for performing an optimal orbital US ONSD measure is between 10 to 25 scans(13). According to the studies mentioned above ONSD in US does not vary in relation to age, weight, and height. A study including HC, did not find a relation between ONSD and HC (14). But ONSD may vary in relation to sex and ethnicity (7).

Although, studies have reported on many parameters of US ONSD in healthy populations, no world consensus exists on normal US ONSD measures and cut-off values for diagnosis of ICP (15). Knowledge of the normal range of US ONSD in healthy local population is essential to interpret the results. Based on the results of our study, previous research and expected deviations when measuring US ONSD, we proposed normal values in Colombian healthy adults of 2.35–5.20 mm and cut-off value for diagnosing increased ICP of 5.5 mm.

The study has strengths and limitations. To the best of our knowledge, this is the first study with exclusively a Latin-American subjects (8). Relationships between demographic (age, gender) and anthropometric (weight, height, BMI, and HC) variables with US ONSD were analyzed. The sample size is robust and there was careful exclusion of subjects with potential pathologic ONSD. Subjects were examined in a systematic and standardised fashion by trained physicians.

This study has some limitations. The mean age of our patient was 26.7 ± 8.3 years; and some authors have suggested the possible influence of ageing and brain atrophy on ONSD. However, previous studies have shown that ONSD remains similar during adult life and do not vary even in healthy adults aged 65 years or older(16). Second, the inter-observer variability was not analyzed as investigators measured ONSD in different volunteers. A direct measurement of ICP was not performed, and how the upper values of US ONSD correlate with ICP could not be determined. Also, for comparisons measurement of ONSD through other non-invasive method were not carried out. Finally, the lack of studies in healthy adult Latin-American populations limit out possibility for comparison. Despite the limitations mentioned and the knowledge that further research is needed for on the US ONSD and its correlation to increased ICP; our study should be perceived in the building of normative data for Latin-American US laboratories.

US measurement of ONSD is a quick, non-invasive, and easy to perform bedside method to diagnose and monitor increased ICP. As there is no world consensus on normal parameters of ONSD, US laboratories should strive to build normative data that allow clinicians to interpret the results of the scans. We consider that 5.5 mm should be use as the upper limit of normal US ONSD in Colombia. More research and training are needed in the measurement of ONSD by US in Latin-America.

ONSD: Optic nerve sheath diameter; ICP: Increased intracranial pressure; TBD: Transverse bulb diameter; ONSD-TP: Optic nerve sheath diameter-Transverse plane; ONSD-SP: Optic nerve sheath diameter-Sagittal plane; US: ultrasound; BMI: Boddy mass index; HC: Head circumference.

Ethics approval and consent to participate: The authors assert that all procedures and data contributing to this work comply with the ethical standards of the relevant national ethic committee (Resolution 8430 of 1993) and with the Helsinki Declaration of 1975. The present study was approved by the institutional research ethic committee of Fundacion Cardioinfantil (Bogota, Colombia: Approval number: CEIC-4472-2021). Prior written informed consent was obtained from all included subjects.

Consent for publication: Subjects signed informed consent regarding publishing their data and photographs.

Availability of data and material: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests: The authors declare that they have not competing interests.

Funding: This research did not receive any external funding.

Author´s contributions: GT, AB and CR participated in the design of the study and drafted the manuscript. GT, AB, CR and JP participated in the data collection and carried out the sonographic examinations. NM-G contributed to the statistical analysis of the data. All authors edited the manuscript and read and approved the final manuscript.

Acknowledgments: Not applicable

Wall M, Kupersmith MJ, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, et al. The idiopathic intracranial hypertension treatment trial clinical profile at baseline. JAMA Neurol. 2014;71(6):693–701.
Koenig MA. Cerebral Edema and Elevated Intracranial Pressure. Contin Lifelong Learn Neurol. 2018;24(6):1588–602.
Fantini S, Sassaroli A, Tgavalekos KT, Kornbluth J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics. 2016;3(3):031411.
Robba C, Santori G, Czosnyka M, Corradi F, Bragazzi N, Padayachy L, et al. Optic nerve sheath diameter measured sonographically as non-invasive estimator of intracranial pressure: a systematic review and meta-analysis. Intensive Care Med [Internet]. 2018;44(8):1284–94. Available from: https://doi.org/10.1007/s00134-018-5305-7
Jeon JP, Lee SU, Kim SE, Kang SH, Yang JS, Choi HJ, et al. Correlation of optic nerve sheath diameter with directly measured intracranial pressure in Korean adults using bedside ultrasonography. PLoS One. 2017;12(9):1–11.
Bäuerle J, Lochner P, Kaps M, Nedelmann M. Intra- and Interobsever Reliability of Sonographic Assessment of the Optic Nerve Sheath Diameter in Healthy Adults. J Neuroimaging. 2012;22(1):42–5.
Goeres P, Zeiler FA, Unger B, Karakitsos D, Gillman LM. Ultrasound assessment of optic nerve sheath diameter in healthy volunteers. J Crit Care [Internet]. 2016;31(1):168–71. Available from: http://dx.doi.org/10.1016/j.jcrc.2015.10.009
Schroeder C, Katsanos AH, Richter D, Tsivgoulis G, Gold R, Krogias C. Quantification of Optic Nerve and Sheath Diameter by Transorbital Sonography: A Systematic Review and Metanalysis. J Neuroimaging. 2020;30(2):165–74.
Yanamandra U, Gupta A, Bhattachar SA, Yanamandra S, Das SK, Patyal S, et al. Comparison of Optic Nerve Sheath Diameter between both eyes: A bedside ultrasonography approach. Indian J Crit Care Med. 2018;22(3):150–3.
Lee SU, Jeon JP, Lee H, Han JH, Seo M, Byoun HS, et al. Optic nerve sheath diameter threshold by ocular ultrasonography for detection of increased intracranial pressure in Korean adult patients with brain lesions. Med (United States). 2016;95(41):1–5.
Messenger N, Carpenter CR. Optic nerve ultrasonography has 94% sensitivity and 87% specificity for diagnosing increased intracranial pressure. Ann Intern Med. 2020;172(8):JC46.
Ballantyne SA, O’Neill G, Hamilton R, Hollman AS. Observer variation in the sonographic measurement of optic nerve sheath diameter in normal adults. Eur J Ultrasound. 2002;15(3):145–9.
Zeiler FA, Ziesmann MT, Goeres P, Unger B, Park J, Karakitsos D, et al. A unique method for estimating the reliability learning curve of optic nerve sheath diameter ultrasound measurement. Crit Ultrasound J. 2016;8(1).
Maude RR, Hossain MA, Hassan MU, Osbourne S, Abu Sayeed KL, Karim MR, et al. Transorbital sonographic evaluation of normal optic nerve sheath diameter in healthy volunteers in Bangladesh. PLoS One. 2013;8(12):10–3.
Aspide R, Bertolini G, Albini Riccioli L, Mazzatenta D, Palandri G, Biasucci DG. A Proposal for a New Protocol for Sonographic Assessment of the Optic Nerve Sheath Diameter: The CLOSED Protocol. Neurocrit Care [Internet]. 2020;32(1):327–32. Available from: https://doi.org/10.1007/s12028-019-00853-x
Avci M, Kozaci N, Komut E, Komut S, Caliskan G, Tulubas G. The measurement of elderly volunteers’ optic nerve sheath diameters by ocular ultrasonography. Med. 2019;55(8):2–9.

No competing interests reported.

PDF

Reviews received at journal
22 May, 2022
Reviewers agreed at journal
08 May, 2022
Reviewers invited by journal
08 May, 2022
Editor assigned by journal
06 May, 2022
Editor invited by journal
06 May, 2022
Submission checks completed at journal
24 Apr, 2022
First submitted to journal
17 Apr, 2022

You are reading this latest preprint version

Ultrasound measurement of Optic Nerve Sheath Diameter in a Colombian healthy adult population

Status:

Version 1

Abstract

Background

Aim

Methods

Results

Conclusion

Figures

Background

Material And Methods

Participants

Optic nerve sheath Ultrasound

Statistical Analysis

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Competing Interests

Status:

Version 1