Introduction

Multiple sclerosis (MS) is an inflammatory auto-immune disease causing demyelination and axonal loss in the central nervous system (CNS) with varying geographical prevalence and incidence rates [1, 2]. The presence of myelin-reactive T cells in MS plaques and the effective response of MS patients to immunomodulatory drugs targeting these cells supports the theory that MS primarily results from dysregulation in the cellular immune system [3]. Aside from immune-based etiologies, there is now growing attention to discovering possible metabolic and vascular elements contributing to the pathogenesis of this disorder [4]. Because of a higher incidence among young adults, this condition can result in considerable disability for affected individuals [5, 6]. Therefore, the importance of finding clinically useful, non-invasive, and objective biomarkers to detect MS in the early stages is important.

The eye offers one gateway to studying the CNS tissue. The retina and brain share the same diencephalic origin and have analogous neuronal layers, including a ganglion cell layer (GCL), a retinal nerve fiber layer (RNFL) in addition to a vascular supply [7, 8]. Thus, the retina can be highly influenced by pathologies, such as Alzheimer’s disease, migraine, MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-associated disease (MOGAD), which are primarily known to also involve other parts of the CNS [9,10,11,12]. Optic neuritis (ON), characterized by acute visual loss and eye pain, is a common manifestation of MS [13, 14]. Approximately half of MS patients experience ON during the course of their disease [15].

The location of the eye makes the retina a highly accessible structure for non-invasive imaging, and it may serve as a surrogate for brain pathology [8]. Optical coherence tomography (OCT), which uses low-coherence light to capture cross-sectional and high-resolution images from the retinal and choroidal layers, has been broadly employed [16].

Application of OCT to examine the retinal layers in MS-associated optic neuritis (MSON) and MS without optic neuritis (MSNON) has revealed thinning and neurodegeneration in the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer and inner plexiform layer (GCIPL) of the patients compared to the healthy controls [10]. Furthermore, investigating the role of vascular abnormalities in the establishment and progression of MS lesions is gaining popularity. These abnormalities can stem from cerebral endothelial cell dysfunction and may lead to hypoperfusion and hypoxia of CNS tissue [17]. Likewise, the anterior visual pathway requires a high blood flow rate to meet the supply and demand characteristics of this highly active metabolic system [18]. A recent study showed an abnormal retinal microcirculation in patients with relapsing–remitting multiple sclerosis (RRMS) [19]. In addition, blood flow in the ocular vascular system may be diminished in association with ON, potentially resulting in impaired visual acuity [20].

As a promising novel imaging technique, OCT–angiography (OCT-A) provides in-vivo depth-resolved images of the retinal and choroidal microvasculature [21]. The results of a meta-analysis on the application of OCT-A in dementia revealed a significant increase in the foveal avascular zone (FAZ) area in patients with Alzheimer’s disease [9].

To date, a considerable number of studies have examined retinal vasculature in MS patients using different OCT-A devices and methods, unveiling significant changes compared to healthy controls (HC) and correlations with several variables including disability scores, highlighting the promising capability of this technology to improve our current understanding of this disorder [8, 22]. MS, NMOSD, and MOGAD, which have different prognoses and treatments, may have overlap** presentations, such as ON, making it difficult to distinguish them in the acute clinical setting [23,24,25,26]. Qualitative differences in retinal microvasculature captured by OCT-A together with regular OCT may help to mitigate the challenge in the differentiation of these disorders [27,28,70, 71] or field of view, may act as sources of bias and explain the dissimilarity of findings.

Conclusion

OCT-A provides a quantitative tool to explore alterations in the retinal and optic nerve vascular networks that might be disrupted by optic neuritis and MS. This systematic review and meta-analysis of the studies reporting OCT-A measurements of patients with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas. As the current OCT-A techniques produce two-dimensional pictures, they are unable to truly differentiate between constriction, shrinkage, or loss of vasculature. Future technological advancements should address this problem. Further studies with larger populations, longitudinal designs, and standardized segmentation and imaging analysis protocols are required to better understand the temporality and chronology of vascular alterations occurring in MS eyes. Such advances will make the application of OCT-A more practical while potentially offering a better understanding of the pathogenesis of MS.