Magnetic resonance imaging and optical coherence tomography correlations in multiple sclerosis beyond anatomical landmarks

https://doi.org/10.1016/j.jns.2020.117180Get rights and content

Highlights

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    SC correlates with nasal-predominant pRNFL sectors in eyes with HON.

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    SC correlates with PMB, GCL and IPL in eyes without HON.

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    INL correlates inversely with BPF and cerebellum in PMS without HON.

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    OCT correlates with CNS volumes, even with no anatomical or functional linkage.

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    OCT stands as a useful neurodegeneration and inflammation surrogate marker.

Abstract

Objective

To investigate multiple sclerosis (MS) optical coherence tomography (OCT) cross-sectional correlations with central nervous system (CNS) magnetic resonance imaging (MRI).

Material and methods

Peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner (INL) and outer nuclear layer (ONL) of 54 relapsing remitting (RRMS) and 38 progressive (PMS, 9 primary and 29 secondary) patients were measured. With less than 3 months brain parenchymal fraction (BPF), spinal cord (SC), total gray matter (GM) and white matter volumes were calculated. Demographical and clinical data was compared according to the history of optic neuritis (HON). Relationships between OCT and MRI data were assessed using multivariable linear regression models, adjusting for age, gender and disease duration, taking into account HON and disease subtype.

Results

Cerebellum (p = 0.008), pRNFL (p = 0.001), GCL (p = 0.001) and IPL (p = 0.001) were thinner, while INL was thicker (p = 0.02) if HON. SC correlated better with nasal pRNFL sectors in eyes with HON (all eyes: average pRNFL p = 0.035 η2 = 0.213; N-pRNFL p = 0.04 η2 = 0.36, NI-pRNFL p = 0.0001 η2 = 0.484. RRMS eyes: N-pRNFL p = 0.034 η2 = 0.348; NI-pRNFL p = 0.013 η2 = 0.441), while it correlates with PMB (p = 0.032 η2 = 0.144), GCL (p = 0.03 η2 = 0.147) and IPL (p = 0.028 η2 = 0.151) in eyes without HON regardless of the disease subtype. INL presented no microcystic macular oedema and was inversely associated with BPF (p = 0.029 η2 = 0.363) and cerebellum (p = 0.015 η2 = 0.428) in PMS eyes without HON.

Conclusions

OCT data correlates with different CNS compartments, even with no anatomical or functional linkage, serving as useful neurodegeneration and inflammation surrogate marker.

Introduction

Visual pathway is a preferred place of acute and chronic damage in multiple sclerosis (MS), in which the retina and the optic nerve fibers devoid of myelin are an easily accessible model for the study, among others, of MS pathogenesis [1].

Inflammation and neurodegeneration are the two main different MS pathological processes that develop in different proportions from the beginning of the disease [2] and, although immune-regulatory and neuroprotective mechanisms may be activated from a relatively early onset of the clinical relapses [3], the course of the disease leads to an irreversible neuro-axonal loss, which is the principal cause of disability [4]. Neurodegeneration is considered a chronic, diffuse, silent, ongoing process that spreads all over the central nervous system (CNS) [2]. Sensitive accessible imaging biomarkers validation that assess objectively neurodegeneration is a priority goal in daily clinical assessment and research trials, with a potential capacity in diagnosis and monitoring MS patients [5].

Optical coherence tomography (OCT) has emerged as a safe, non-invasive, rapid imaging technique that permits obtaining cross-sectional images of the retina and the optic nerve, from which quantitative and qualitative reliable data are analyzed with a reasonable cost. Its excellent reproducibility, well correlation with clinical and paraclinical measures of disease activity and progression [6,7], and therapeutic efficacy [8], makes this ophthalmological tool an ideal complement to magnetic resonance imaging (MRI) in MS practice.

The aim of this study is to evaluate OCT correlations (macular layers and optic nerve sectors) with CNS MRI parameters according to the history of optic neuritis (HON) in different MS disease subtypes, with the hypothesis that the visual pathway is a good marker of neurodegeneration and inflammation beyond anatomical landmarks.

Section snippets

Study design

This is an observational cross-sectional study carried out by the Neurology and Ophthalmology departments of La Fe University and Polytechnic Hospital (Valencia, Spain) from October 2017 to May 2019 after the approval of the research ethics committee of our institution.

Study population and clinical assessment

Out of the 160 MS volunteers who signed written informed consent, 92 met the inclusion criteria (age over 18 years and MS diagnosed following the 2010 revised McDonald criteria [9]) and none of them met the exclusion criteria

Influence of HON in clinical, ophthalmological and neurological characteristics

Flow of participants through the study is represented in Supplementary file 3. The final cohort is characterized clinically and neuroradiologically (Table 1) as well as ophthalmologically (Table 2). Table 3, Table 4 present the aforementioned characteristics dividing the sample according to the HON for its comparison.

According to the HON, no statistically significant demographic or clinical differences are observed. In eyes with HON average pRNFL and its sectors, GCL and IPL are significantly

Discussion

There is a growing interest of studies addressing OCT measures (thicknesses or volumes) with CNS structures, mainly those involved in visual processing. That is why RNFL has been related with thalamus [18,19], visual cortex [18,[20], [21], [22]], WM lesion [20,23], and fractional anisotropy [24] of optic radiation; GCL (alone or combined with IPL) with thalamus [19,25], visual cortex [21,22], and fractional anisotropy of optic radiation [24]; INL with thalamus [19,25]; ONL with thalamus [19];

Funding

Bonaventura Casanova was supported by a fellowship from Health Institute Carlos III, Spain (FIS 17/551). The funding agency had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Declaration of Competing Interest

Francisco Pérez-Miralles has received compensation for serving on scientific advisory boards or for speaking honoraria from Almirall, Biogen Idec, Genzyme, Merk-Serono, Mylan, Novartis, Roche, Sanofi-Aventis and Teva, outside the submitted work. Bonaventura Casanova has received compensation from Novartis, Roche, Biogen, Merk, Teva and Sanofi outside the submitted work. All other authors have no conflicts of interest to declare.

Acknowledgements

We are extremely grateful to the multiple sclerosis participants without whose contribution this study would not be possible.

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