# Transbulbar B-Mode Sonography for Clinical Phenotyping Multiple Sclerosis
## 3 Results  
No statistical difference was found between the mean age of all MS patients (41.4 y; SD 2.5) and healthy controls (40.2 y; SD 1.78). Mean DD was 11.5 y (95% CI = 9.50-14.10); mean MI were 0.84 (95% CI = 0.83-0.89), and 0.89 (95% CI = 0.86-0.90), respectively. Mean ONSD in patients at 3 and 5 mm from the eyeball was respectively 0.49 cm (95% CI = 0.45-0.52; SD 0.074) and 0.57 cm (95% CI = 0.55-0.60; SD 0.064). Mean ONSD in healthy controls at 3 and 5 mm from the eyeball was respectively 0.65 cm (95% CI = 0.62-0.68; SD 0.077) and 0.73 cm (95% CI = 0.70-0.78; SD 0.065). These differences between diseased patients and healthy subjects were highly significant. Specifically, at both 3 and 5 mm, the ONSD was found to be smaller in patients than in healthy controls (\(p<0.001\) in both cases). The demographic and clinical features of all patients and healthy subjects are summarized in Table 2.  
Statistical differences between RRMS and SPMS groups were found for mean age and DD. Specifically, the mean age was 39.5 y for RRMS patients (SD 7.9; 95% CI 36.4-42.2) and 46.7 y for SPMS patients (SD 8.1; 95% CI 41.2-51.7); mean DD was 10.0 y (SD 6.6; 95% CI 7.8-12.5) for RRMS patients and 15.8 y (SD 8.6; 95% CI 3.9-11.8) for SPMS patients. Mean EDSS was 2.2 (SD 0.8; 95% CI 1.9-2.5) in the RRMS group and 5.3 in the SPMS group (SD 0.7; 95% CI 4.8-5.7). The mean COV of ONSD was 0.065. Mean ONSD in RR patients at 3 and 5 mm from the eyeball was respectively 0.51 cm (95% CI 0.48-0.53, SD 0.072) and 0.59 cm (95% CI 0.56-0.62, SD 0.081). Mean ONSD in SP patients at 3 and 5 mm from the eyeball was respectively 0.46 cm (95% CI 0.42-0.51, SD 0.077) and 0.55 cm (95% CI 0.51-0.58, SD 0.065). Specifically, at 5 mm, the ONSD was found to be smaller in SP patients than in RR patients (\(p<0.001\)), but no significant difference was noted between the two groups at 3 mm (\(p=0.134\)). Considering the overall MS population, P100A and P100L correlated with the pyramidal EDSS sub-score as follows: \(r=-0.37\); \(p=0.03\) and \(r=0.46\); \(p=0.007\), respectively (Figure 1). The mean MI of the RR and SP groups was 0.86 (SD 0.083; 95% CI 0.85-0.88) and 0.83 (SD 0.11; 95% CI 0.76-0.87) respectively, the difference not being statistically significant (\(p=0.211\)). The demographic and clinical/paraclinical features of RR and SP patients are summarized in Tables 3 and 4. \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Parameter** & **All MS Patients** & **Healthy Controls** & \(p\) \\ \hline \(N\) & 60 & 35 & \\ Age (y) & 41.4 \(\pm\) 2.5 \({}^{\ddagger}\) & 40.2 \(\pm\) 1.8 & \\ Female-to-male ratio & 1.14 & 1.06 & \\ Disease duration (y) & 11.5 (9.50–14.10) & - & \\ Optic nerve sheath diameter (cm) & & & \\ At 3 mm & 0.49 \(\pm\) 0.074 (0.45–0.52) & 0.65 \(\pm\) 0.077 (0.62–0.68) & \textless{}0.001 \\ At 5 mm & 0.57 \(\pm\) 0.064 (0.55–0.60) & 0.73 \(\pm\) 0.065 (0.70–0.78) & \textless{}0.001 \\ Myelination index & 0.84 (0.83–0.89) & 0.89 (0.86–0.90) & \textless{}0.001 \\ \hline \hline \end{tabular} \({}^{\dagger}\) Note that the optic nerve sheath diameter at both 3 and 5 mm was found to be lower in patients than in healthy controls patients (\(p<0.001\) in both cases). The Wilcoxon–Mann–Whitney test was applied to the difference between means. \({}^{\ddagger}\) Values are given as the mean or mean \(\pm\) standard deviation and, if necessary, with the 95% confidence interval in parentheses.  
\end{table} 
Table 2: Demographic and clinical characteristics of all MS (multiple sclerosis) patients and healthy controls \({}^{\ddagger}\). Statistical similarity analysis of the global population (RR + SP) blindly identified two clusters, one characterized by low MI (MI\({}^{\rm{L}}\) = 0.84) and another by high MI (MI\({}^{\rm{H}}\) = 0.90). The ANOVA found the distance between the variables' centres for the two groups to be statistically significant (\(p\) = 0.050).