Optical coherence tomography in multiple sclerosis: contributions to understanding its use in clinical practice

Danko Coric

    Research output: PhD ThesisPhD-Thesis - Research and graduation internal

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    Abstract

    Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) affecting more than two million people worldwide. The disease is characterised by inflammation in the CNS (leading to episodes of focal neurological dysfunction, i.e. relapses) and neurodegeneration (leading to progressive and permanent disability). Depending on the localisation of the CNS damage, patients exhibit a wide range of symptoms including muscle weakness, sensory disturbances, problems with coordination, fatigue and cognitive impairment. Visual symptoms are common as well, with more dan 50% of MS patients experiencing one or more episodes of optic neuritis (ON) during the course of the disease. The disease course in MS is highly variable and difficult to predict. However, predicting the disease course is crucial for determining the proper treatment. This thesis focuses on how optical coherence tomography (OCT) can aid in monitoring and predicting the disease course in patients with MS. OCT is an imaging technique that generates high resolution images of the retina and all its layers. The inner two retinal layers consist of the retinal ganglion cells and their axons that will eventually form the optic nerve. Thereby, these two layers are directly connected to the brain. Previous research has demonstrated that previous episodes of ON result in atrophy (thinning) of these two layers. Sometimes, it can be challenging to establish whether a patient has ever experienced an episode of optic neuritis clinically. The absolute thickness of the retinal layers is not a good indicator for this. Our research shows that the difference in retinal layer thickness between the eyes of a single patient can, with high accuracy, discriminate ON patients from non-ON patients. Being able to establish the presence of a previous episode of ON in this way, might lead to an earlier diagnosis of MS and earlier treatment. In another study described in this thesis, we found that atrophy of the inner retinal layers was not only related to poorer visual functioning but also to a decreased vision-related quality of life (i.e., quality of life based on vision related problems). Patients who have not experienced an episode of ON also show atrophy of the inner retinal layers. The degree of retinal atrophy depends on the amount of brain atrophy measured on MRI and the degree of physical disability. Our study shows that inner retinal layer atrophy is also associated with cognitive impairment. In addition, in a longitudinal follow-up study we also found that progressive atrophy of the retina was also associated with cognitive decline (i.e., worsening of cognitive functioning over time). The results of our research and research performed by others confirm that damage to the brain in MS is reflected in atrophy of the inner retinal layers. Lastly, we have investigated the relationship between OCT measures and inflammation in MS. As stated previously, inflammation is considered responsible for the typical relapses experienced by MS patients. In one study we found that thickening of a third layer of the retina, called the ‘inner nuclear layer’, was associated with the development of new episodes of ON as well as relapses elsewhere in the body. In addition, expanding on the tradition OCT technique, we have also investigated whether (subclinical) clouding of the vitreous body, which is usually a sign of uveitis, is associated with inflammatory disease activity in MS. We could not find a relationship between the two. In conclusion, there is growing evidence that damage to the CNS is reflected in changes in the retina in MS. This makes OCT a valuable instrument in the clinical assessment of MS patients with regard to visual, cognitive and physical problems.
    Original languageEnglish
    QualificationDr.
    Awarding Institution
    • Vrije Universiteit Amsterdam
    Supervisors/Advisors
    • Uitdehaag, B.M.J., Supervisor, External person
    • Petzold, A.F.S., Co-supervisor, External person
    • Balk, Lisanne Johanna, Co-supervisor, External person
    Award date2 Dec 2021
    Place of Publications.l.
    Publisher
    Print ISBNs9789464168723
    Publication statusPublished - 2 Dec 2021

    Keywords

    • multiple sclerosis
    • optical coherence tomography
    • neurodegeneration
    • neuroinflammation
    • cognition
    • visual system
    • optic nerve
    • optic neuritis
    • retina
    • neuro-ophthalmology

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