MS is a demyelinating inflammatory disorder of the CNS associated with a progressive neurodegeneration [8].

ON represents the initial manifestation in about 25% of MS patients and occurring in around 50% of patients at some point of the disease course [9].

The goal of our study was to compare retinal VD between MS patients and healthy volunteers, and to explore whether vasculopathy could be part of MS pathogenesis. Our study also aimed at correlating between the nerve thickness detected by OCT and the VD detected by OCT-A to provide a possibility that the retinal vasculature may be a biomarker of neurodegeneration and disease progression. This study included 30 RRMS patients (60 eyes) and 10 healthy volunteers (20 eyes). The MS group was further subdivided into two subgroups, MS with ON (25 eyes) and MS without history of ON (35 eyes). Our results showed that SD-OCT parameters were significantly different between the 2 groups of MS and control. We found that all RNFL and GCC parameters were significantly lower in MS group than in control group (p =  < 0.001).

Many previous studies reported a similar significant finding in patients when compared to control.

Lanzillo and colleagues in 2018 carried a study, using SD-OCT, on a total of 50 MS patients with and without history of ON and 46 healthy control. The study revealed that all GCC and RNFL parameters were lower in patients than in controls [8].

Khalil and colleagues in 2017 carried a similar study on 68 MS patients and 23 healthy controls, they found that the thickness of RNFL and GCC were significantly lower in MS eyes when compared to controls. Progressive axonal loss could explain the RNFL thinning found in eyes of MS patients with and without a history of ON [10].

In a study by Soufi and colleagues in 2015, MS patients’ eyes showed statistically significantly lower values of the total RNFL than the Healthy Control eyes [11].

Pillay and colleagues showed in their study in 2018 that the mean values of average RNFL thickness and values in superior, temporal, and inferior quadrant were significantly reduced when compared to control groups. As well as overall mean values of average GCL-inner plexiform layer thickness and values in superior, superonasal, superotemporal, inferonasal, and inferotemporal quadrant were significantly reduced in all groups except Fellow eye of ON group when compared to control group. In addition, in the inferior and superonasal quadrant, thickness was reduced even in Fellow eye of ON group [12].

In our study, when comparing between SD-OCT parameters of MS patients with ON and those without ON, there was no significant difference in all RNFL and GCC parameters between the two subgroups; there was a statistically significant negative correlation between SD-OCT parameters and both EDSS (R = -0.377, P = 0.003) and disease duration (R = -0.314, P = 0.014).

Most prior studies found a similar significant correlation. Khalil and colleagues in 2017 found a statistically significant negative correlation between the average RNFL thickness of MS eyes and disease duration; the longer the disease duration, the thinner the RNFL, this could be explained by with longer disease duration there is more axonal degeneration. They also found a statistical negative correlation between the average RNFL thickness and neurological disability quantified by EDSS; when the EDSS score increased the RNFL thickness decreased [10].

Another study by Garcia-Martin and colleagues in 2014 showed that the retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS [13].

Also, Soufi and colleagues in 2015, studied 62 MS eyes with and without ON, they found a negative correlation between the total RNFL thickness and both EDSS and disease duration [11].

Our study also showed a significant correlation between VA and all SD-OCT parameters.

This was similar to the studies done by Soufi and colleagues in 2015 [11] and Siepman and colleagues in 2010 [14] who proved that reduction in RNFL thickness was associated with a decrease in VA.

In our study we used OCT-A to measure retinal SVP and DVP densities. We found that there was a lower SVP density percentage in eyes of RRMS when compared to control group; this difference was statistically significant in the whole scan and in all grid sectors (fovea and parafovea). There was also a strong statistical significance when comparing eyes with ON to controls and eyes without ON to controls.

A study by Farci and colleagues in 2020 showed a reduction of retinal perfusion in a significant portion of MS patients independently if they had a previous history of optic nerve inflammation or not on performing an OCT-A at the optic nerve head level and at the macular region [15].

Our study was similar to the study by Murphy and colleagues in 2019 [16] conducted on 42 MS eyes and 26 healthy control eyes; the results showed that SVP density was lower in MSON and MSNON, when compared to healthy controls.

Those findings were also similar to results by Lanzillo and colleagues in 2018 [8] who found a lower SVP density in MS eyes with and without history of ON when compared to control group.

In 2019, Murphy and colleagues had a potential explanation as vascular abnormalities in the retina were not just a transient effect, but represented a process possibly contributing in the pathophysiology of MS [16].

In our study, there was no significant difference between SVP density between eyes with ON and eyes without ON.

This was concordant with the results of Lanzillo and colleagues in 2018 [8], where there were no statistically significant differences found regarding OCT-A measurements, except for VD in inferior sector.

On the contrary, Murphy and colleagues in 2019 revealed significant reductions in SVP density in MSON eyes when compared to MSNON eyes. It was explained as ON could cause more inflammation, neurodegeneration and accordingly more decreased VD [16].

In our study, regarding DVP density, when comparing eyes with RRMS to the control group, there was lower DVP density percentage in eyes of RRMS which was statistically significant in whole scan, superior hemisphere, superior and inferior sectors. On the other hand, the fovea and the rest of grid sectors showed no statistically significant difference between the 2 groups. Again, when comparing eyes with ON to the control group, there was a statistically significant difference in the whole scan, superior hemisphere, superior and inferior sectors. However, when comparing eyes without ON to control, there was only statistical significance in the whole scan. When we compared the density of DVP in eyes with ON and eyes without ON, we found no statistical significance in any of the grid sectors.

In the study of Murphy and colleagues in 2019, the results showed no difference in the mean DVP density between MS eyes and those of control group, or between the MSON eyes when compared to MSNON eyes [16]. The study proposed two theories to explain the variation between SVP and DVP; the first was that the DVP is only supplied by anastomoses from the SVP which makes the vessels less prominent in the DVP. The second hypothesis stated that SVP supplies RNFL, GCC, and inner plexiform layer, while DVP supplies inner nuclear layer (INL) and outer plexiform layer (OPL). MS causes atrophy of the inner retinal layers (RNFL and GCC) but not to INL and outer retinal layers [17].

Consequently, this variable degree of neurodegeneration among the retinal layers in MS patients explains why SVP density is affected unlike DVP. The study emphasized that those two theories need further research.

A review by Mihai and colleagues in 2023 showed that the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly lower in MS patients compared to controls, and correlated with clinical and paraclinical variables, such as visual function, disability, and magnetic resonance imaging (MRI). The superficial capillary plexus (SCP) was the best OCT-A microvasculature parameter for the detection of MS. The reduced retinal vessel density (VD) was correlated with the disability in MS [18].

Our study found a significant correlation between VA and VD of both SVP and DVP. This was similar to the results of the study of Murphy and colleagues in 2019 [16] who stated that lower SVP densities in MS patients are associated with worse visual function. The study stated that those findings were similar to collective studies done with SD-OCT. This proves that the affection of the retinal structure in patients with MS also affects the retinal function and results in decreased visual function. One important finding of our study, is the presence of strong significant correlation between all SD-OCT parameters and the densities of retinal vessels of both the SVP and DVP in all OCT-A grid sectors.