Optical coherence tomography angiography detects retinal vascular alterations in different phases of multiple sclerosis

Dear Editor,

We read with interest the elegant paper by Feucht et al., ¹ who explored the vascular layers of the retina in early multiple sclerosis (MS) and healthy controls (HCs) through optical coherence tomography angiography (OCT-A). This study was conducted on early MS and clinically isolated syndrome (CIS) patients, with 2-year disease duration on average and relatively low disability (median Expanded Disability Status Scale (EDSS) 1.0). Their results suggest that retinal vascular density (VD) might be reduced as a consequence of optic neuritis (ON). Authors concluded that patients with longer disease duration and more severe disability should have been assessed to complete their findings and, ultimately, to understand the role of retinal vasculature through the course of MS.

In our previous paper recently published on your journal, ² we applied OCT-A to assess retinal VD in MS patients with different forms of disease (relapsing–remitting (RR), secondary-progressive (SP), and primary-progressive (PP)), and HCs. Of note, our population was older (mean age 41 years), with longer disease duration (mean 11 years), and more severely disabled (median EDSS 3.5), when compared with the study of Feucht et al. Hereby, we found VD being lower in MS when compared with HC, independently from previous ON, and being associated with higher disability on EDSS. In keeping with this, another very recent report by Spain et al. ³ showed that reduction in VD at OCT-A was not only more obvious in eyes with ON but also evident in clinically unaffected eyes.

Overall, these findings could be considered as complementary, since different MS populations were included, depicting different stages of the same disease. Our hypothesis is that Feucht et al. caught a phenomena taking place at the beginning of the disease, in particular, in CIS patients, with a recent history of ON, and, thus, VD reduction was evident only in affected eyes. We believe that VD might progressively reduce, much earlier in the case of ON but also in later stages of MS without ON.

Of note, OCT-A technique from Feucht et al. was different from ours, since they measured retinal layers independently and found an association between high choriocapillary layer vessel density and recent disease activity, as measured by clinical relapses or magnetic resonance imaging (MRI) activity. Intriguingly, the higher VD in choriocapillary layer could be the consequence of endothelial pro-angiogenetic factors upregulation, occurring in the course of relapses and MRI activity, ⁴ opening an intriguing scenario into the pathogenesis of MS.

In conclusion, we think that our efforts should be gathered to shed light on OCT-A as a pathologically and clinically meaningful marker in MS. We are currently following up our population, besides studying another cohort of CIS patients, in order to clarify our findings.