Worldwide, the prevalence of MS varies widely within different populations. According to a hospital-based study, the prevalence of MS in Oman from 2006 to 2019 was 15.9 cases per 100,000 individuals . This rate is extremely low compared to much higher rates reported in North America and Europe (over 100 cases per 100,000 individuals), as well as elsewhere in the Arabian Gulf region (31–55 cases per 100,000 individuals), thus suggesting that the country is a low or medium-risk zone for MS [11,12,13]. Nevertheless, previous data indicates that the prevalence of MS in Oman from 1990 to 2000 was only four cases per 100,000 individuals . Thus, the rate of MS in Oman seems to mirror global trends in showing an increase in prevalence over time. In addition, the clinical profile of Omani MS patients appears to be very similar to that of other populations reported in Asia, in that a high proportion present with visual and motor symptoms and approximately one-third are diagnosed with opticospinal disease .
The main goal of the current study was to determine whether RNFL loss occurs in the presence or absence of ON in MS patients. This was achieved by detecting changes in RNFL thickness among Omani MS patients both with and without ON over a period of 4 years in comparison to healthy controls. Our findings indicated that there was a significant reduction in RNFL thickness in the affected eyes of MS patients with ON when comparing baseline and final OCT imaging measurements over a prolonged period of time.
These results are consistent with those from previous reports. Costello et al.  observed that 74% of MS patients demonstrated RNFL thinning within 3–6 months of an ON diagnosis, with a significant reduction in RNFL thickness in ON-affected compared to non-affected eyes. A prior study by Garcia-Martin et al  concluded that MS patients with ON experienced a significant reduction in RNFL thickness over a period of 5 years. Balk et al  similarly reported that the loss of RNFL thickness in eyes with MS-associated ON occurs over time (mean thickness at baseline: 78 μm, absolute change over time: − 1.1 μm, 95% confidence interval: 1.4–0.7 μm; P < .001). According to Feng et al , disease duration was inversely related to average RNFL thickness among MS patients. In contrast, Henderson et al  reported that there was no relationship between disease duration and RNFL thinning in ON-affected eyes. Likewise, both Eyre et al  and Balk et al  found no significant relationship between number of ON episodes or relapses and mean RNFL thickness.
In the present study, a comparison of baseline and follow-up OCT measurements indicated that changes in RNFL thickness over time among MS patients without ON were not statistically significant. Similarly, a study performed by Henderson et al  found a non-significant association between mean RNFL thickness and disease duration in selected eyes with no known history of ON. Khanifar et al  stated that RNFL thinning was correlated with an increased risk of ON, and that such thinning may represent a predictive cutoff point for the presence or absence of ON. However, other studies have reported conflicting findings. A study conducted by Gelfand et al  in the United States demonstrated that RNFL reduction begins in the early stages of MS, independently of ON. Similarly, Balk et al  found that the eyes of MS patients without a history of ON also demonstrated a significant reduction in RNFL thickness. In a two-year follow-up study, Garcia-Martin et al  found that RNFL changes occurred at a similar rate in non-affected eyes with no evidence of ON. Eslami et al  found a significant inverse correlation between MS duration and RNFL thickness, regardless of the presence or absence of ON.
No significant difference in RNFL thickness were observed between ON-affected and non-affected eyes at a four-year follow-up in the current study. However, there was a significantly greater loss of RNFL thickness in ON-affected eyes compared to non-affected eyes. In line with these findings, Gelfand et al  reported that even though eyes affected by ON demonstrated greater RNFL thinning compared to those without ON, the difference between the two groups was not statistically significant. Another study also revealed non-significant differences in RNFL thinning between affected and unaffected eyes of unilateral ON patients (80.72 ± 18.18 μm versus 99.53 ± 13.26 μm; P = .149) . These assumptions are also supported by findings from other research [24, 25]. Nevertheless, a study by Feng et al  conducted in China concluded that there was a significant difference in mean RNFL thickness between the eyes of MS patients with and those without a history of ON (71.8 ± 19.2 μm versus 92.0 ± 8.5 μm; P = .001). Khanifar et al  also reported similar results (83.0 versus 90.5 μm; P = .02). Other studies have also found reduction in RNFL thickness to be significantly greater in eyes with a history of ON compared to unaffected eyes and the eyes of healthy controls [26, 27].
In our study, we demonstrated a significant reduction in mean RNFL thickness among MS patients compared to healthy controls. In line with these results, a study performed in Germany by Bock et al  indicated that average RNFL loss was significantly greater among MS patients compared to healthy controls. Studies from China (81.9 ± 17.8 μm versus 102.1 ± 8.1 μm; P = .00) and the USA (88.5 versus 97 μm; P < .001) confirmed significant RNFL thinning in the MS group compared to the control group [6, 18]. Saxena et al  also reported a significant difference in RNFL thickness in the nasal (66.23 ± 12.4 μm versus 88.93 ± 22.18 μm; P < .001) and superior (106.77 ± 17.92 μm versus 132.33 ± 15.42 μm; P < .001) quadrants of the eyes of MS patients when compared to the healthy group. These findings can be explained by the fact that the optic nerve has a high density of axons, which makes it vulnerable to atrophy. However, Garcia-Martin et al  reported non-significant differences in RNFL changes over a prolonged follow-up period of 5 years when comparing the eyes of MS patients with those of a healthy control group.
Finally, there was significant RNFL thinning in the eyes of MS patients both with and without ON in the present study when compared separately with the control group. These significant correlations can be understood in light of previous studies. A study from Spain noted progressive thinning over 5 years in the eyes of MS patients both with and without a history of ON when compared to healthy controls (change over time: − 3.5 μm, − 4.7 μm, and − 2.2 μm, respectively) . Garcia-Martin et al  also found that MS patients exhibited a greater reduction in RNFL thickness than healthy controls, regardless of ON history. However, a prior study conducted in the United Kingdom found that there was no significant difference in RNFL thickness between MS eyes with no history of ON compared to a healthy control group .
The current study provides valuable information on OCT changes in Omani MS patients. However, the main limitation was the small sample size, a factor which the authors attribute to the rarity of the disease in the Omani population. This limitation of low sample size due to the rarity of MS in Oman might be the reason that no significant reduction of RNFL over time was identified in MS patients without ON, even though there was a reduction from 85.35 to 81.81 μm. Moreover, due to the retrospective design of the study and the reliance on chart review as the primary method of data collection, it is possible that some data might be missing which may have resulted in selective bias. Finally, the majority of patients in the study had bilateral ON, a relatively rare finding in MS patients; unfortunately, testing of myelin oligodendrocyte glycoprotein antibodies could not be performed as this facility has only been implemented at SQUH within the last 3 years. Further studies are therefore recommended to address these limitations. In addition, the authors recommend the assessment of ganglion cell-inner plexiform layer thickness as another line of research into potential biomarkers of MS severity and disease progression.