Noninvasive Ultrasound Assessment of the Normal Optic Nerve Sheath Diameter in Healthy Adults: an Islamabad-based Pakistani Population Study

Aim: The noninvasive B-mode transocular ultrasound (TOU) measurement of the optic nerve sheath diameter (ONSD) is becoming popular to monitor intracranial pressure (ICP). Different studies report varied values for normal ONSD. Our primary aim was to find the TOUmeasured normal ONSD in healthy adult Pakistanis living in Islamabad Capital Territory (ICT). Methodology: One hundred healthy adult volunteers participated in this cross-sectional study, conducted at the Pakistan Atomic Energy Commission (P.A.E.C.) General Hospital, Islamabad. Each eye was scanned for the optic nerve (ON) via TOU using a B-mode 7-15 MHz linear probe. The investigators measured ONSD in a transverse plane three millimeters behind the retina. They recorded an average of three readings as a mean ONSD value for both eyes. Results: The overall normal mean ONSD was 4.80±0.26 mm with a minimum of 4.25 mm and a maximum of 5.20 mm. The mean ONSD for the age group of 20-35 years was 4.79±0.27 mm and for 36-50 years, it was 4.81±0.24 mm (p = 0.7952), for the male eye it was 4.83±0.26 mm and for the female eye was 4.75±0.25 mm (p = 0.1238), and for the right eye was 4.79±0.27 mm and for the left eye was 4.80±0.26 mm with (p = 0.2434) and (r = 0.9455). There was no statistically significant J Ophthalmol Res 2020; 3 (3): 86-95 DOI: 10.26502/fjor.2644-00240027 Journal of Ophthalmology and Research Vol. 3 No. 3-December 2020 87 difference in the mean ONSD of the four ethnic groups (p = 0.7141). Conclusion: The normal mean optic nerve sheath diameter in the studied healthy adult Pakistanis, as measured through noninvasive B-mode transorbital ultrasound is 4.80±0.26 mm.

Literature supplies a detailed account of techniques, clinical applications, and limitations of the B-mode TOU of ONSD [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Overall, there is satisfactory reliability of the B-mode TOU to measure the ONSD [16]. Several human studies from different parts of the world report a significant correlation between the ONSD and ICP [7,8,17]. However, there is no established consensus among these studies for a normal mean ONSD, and also for an optimal upper limit of the normal [7,8,17,18]. The reasons for the varied values of TOU-measured reportedly normal ONSD and cut-off values might be attributed to equipment, technique, patients' gender, age, ethnicity, and right or left eye [7,8,17,22]. Therefore, a knowledge of the range and mean normal human ONSD would help in finding the reliable standard reference values and delimiting an optimal cut-off value for indicating a rise in ICP and saving the patients from complications ICH.
Asghar et al. and Rehman et al. have reported measurements of ONSD in healthy subjects, but without consideration of local major ethnic groups [12,23]. The current single-center hospital-based cross-sectional study reckons the patients' age, gender, ethnicity, and right or left eye while recording the observations. The primary objective of this study was to find the TOU-measured range and the mean normal ONSD in healthy adults in a diverse section of the local Pakistani population living in the ICT. The secondary outcome gained was an expected upper limit which could probably predict a rise in ICP to save the patient from the grave consequences of ICH.

Participants and Methodology
This was a single-center cross-sectional study, conducted in the Radiology Department of the tertiary-care P.A.E.C. General Hospital, Islamabad from 1st April 2017 to 30th August 2017. The Hospital Ethical Committee approved the study proposal and investigators adhered to the World Medical Association Declaration of Helsinki. An earlier Pakistani study found normal ultrasound measured ONSD in 100 healthy volunteers, but without forming age or ethnic groups [13]. Therefore, the current study also targeted one hundred healthy adult Pakistani volunteers to make a closer comparison.

Sampling and sample
Investigators used consecutive non-probability sampling with the 95% confidence interval and a standard The participants were divided into separate groups to correlate and compare the possible differences among them. There were two groups by age, two by gender, four groups by ethnicity, and two by the right and the left eye, as presented in the table1.

Statistical analysis
The

Results
One The table1 shows the comparison of ONSD according to demographics and side of measurement. Table 2 illustrates the descriptive statistics and analysis of age and right and left eye ONSD.     ONSD in the current study is closer to that, however, with a slightly wider range.
A study from Turkey [9] reported an ONSD of 4.1±0.5 mm for the group of 50 adults with a normal head CT, and the cut-off value was 4.5 mm in the presence of intracranial pathology. A study of healthy adult Nepalese [13] had a range of 3.1 to 4.6 mm and a median value of 4.1 mm for normal ONSD. The Bangladeshi study [29] reported a median ONSD of 4.41 mm, 95% of values falling between 4.25 to 4.75 mm, in 136 healthy children (12.5% <16 years), and adults. A study of 500 healthy subjects of South India [30] showed a mean ONSD for males 4.5-5.1 mm (4.8±0.3 mm) and females 4.7-5.1 mm (4.9±0.2 mm). A Chinese study [12] reported a mean ONSD of 5.1 ± 0.5 mm and the 95th percentile of 5.9 mm in 519 healthy volunteers. In comparison to these regional studies, the values for the normal ONSD in the current study were similar to those reported from India [30]. Asghar et al. [12] studied 100 healthy volunteers in Karachi without forming age groups. They described that 95% of the study sample had an ONSD <4.82 mm.
Rehman et al. [23] studied 52 subjects in Rawalpindi and compared the mean ONSD in patients with idiopathic intracranial hypertension (IIH) to ONSD in a normal control group. They reported a mean ONSD of 4.33±0.38 mm in the normal group. A study of 26 tumor patients in Karachi [24] to decide the pre-anesthetic status of ICP by ONSD, reported 5.0 mm as an upper limit of ONSD. In another study of 100 mass-effectstroke intensive care unit (ICU) patients in Islamabad, [25] the authors expressed an ONSD >5.8 mm as the cut-off limit. In a study of 60 traumatic brain injury (TBI) patients conducted in Rawalpindi, [26] described an ONSD >5.0 mm as a cut-off value. In another Karachi study, [27]

Limitations
The same investigator took and recorded all readings; therefore, we could not assess the interobserver variability. We have not compared our results with studies using MRI or CT scans, which because of higher spatial resolution may provide a better image and measurement of ONSD. A comparison of directly measured ICP can better validate the correlation between TOU-measured ONSD and ICP. A-scan was not considered. The available sample age range of 20-50 years was narrow. We tried to include the four major ethnic groups of the Pakistani population, however, a comparable number of subjects from all ethnic groups were not available for this small study.

Recommendations
We would recommend the use of TOU-measured ONSD as a POCUS screening tool for all patients suspected of a raised ICP. We would also recommend using the ONSD values of the current study as the baseline for future reference in large multi-center human studies, especially in our country, to validate the use of TOU of ONSD in ICH patients.

Conclusion
The Measurements beyond the upper limit warrant additional investigations to find raised ICP in patients suspected of ICH, and to avoid potential brain injury.