Multiple sclerosis seen through new eyes

The visual system provides an excellent basis for studying many diseases of the brain for a number of reasons. First, the retina is the only place where central nervous system tissue (including both neural and vascular elements) is directly visible under normal circumstances; second, the anatomy of the visual pathway is very well established, and there is a high degree of topographical preservation of the visual fields along its course; third, the visual pathways occupy a significant proportion of the total brain volume, meaning that they are often affected by diffuse brain pathology; and fourth, the optic nerve represents pure ‘white matter’ as there are no neuronal cell bodies along its length. In recent years, technology has evolved to develop tools that allow increasingly precise assessment of various aspects of the anatomy and function of the visual pathway. It is hardly surprising, therefore, that these new tools, for example, optical coherence tomography (OCT), multifocal visual evoked potentials (mfVEPs) and sophisticated magnetic resonance imaging (MRI) techniques have been applied to the study of vision in patients with multiple sclerosis (MS). In this issue, Graham and Klistorner provide an excellent review of the role of these tools in the assessment of the anterior and posterior visual pathways in MS and examine possible ways in which they might assist in improving clinical management, with particular reference to visual evoked responses (VERs ) of various types. The link between delayed VEPs and optic neuritis (ON) has been known for many years. Unfortunately, conventional VEPs can only detect abnormalities reliably in eyes that have been affected by ON. Recent evidence in MS patients suggests that eyes that have not experienced ON (NoON) also show abnormalities. These take the form of functional changes (e.g. amplitude reduction or latency increase) when assessed by mfVEPs, as well as anatomical changes, for example, retinal nerve fibre layer (RNFL) and retinal ganglion cell (RGC) loss, when assessed by OCT. The precise mechanism underlying this axonal atrophy and retinal ganglion cell loss in the absence of ON is currently unknown. Subclinical inflammation is obviously a possibility, but some authors have suggested that some of the functional changes may be, at least in part, due to compensatory strategies. Whatever the aetiology, there is considerable interest in the possibility of using information from this non-invasive, low-cost technique to enhance the diagnosis and management of MS. In recent years, our understanding of the underlying pathology of MS has evolved from thinking of it as an auto-immune disease characterized principally by recurrent episodes of inflammation to believing it to be something much more complex involving correlated apoptotic death of oligodendrocytes and microglial activation in addition to inflammation, as well as involving abnormalities in blood flow in the normal appearing white matter (NAWM). Graham and Klistorner review the recent literature showing that abnormalities of NAWM can be seen in the optic radiations and that this, in turn, is associated with visual dysfunction. Another pathological process that has recently been investigated in the visual pathways is trans-neuronal degeneration, in both anterograde and retrograde directions. OCT demonstrates abnormalities of the RNFL and macular RGC layer, which correspond to lesions in the optic radiations, and focal atrophy of the visual cortex on MRI correlates with focal lesions of the optic radiations. The number of treatments available for MS has increased greatly over the last two decades. This has, in turn, led to an increase in the rate of MRI scanning as clinicians modify their patientsˈ treatment with the principal objective of reducing relapses and, hopefully, slowing disease progression. MRI scans are principally used as a surrogate marker of disease activity, but a more useful measure would be to look at disease progression itself. Unfortunately, most easily available MRI markers, for example, the total volume of lesions on T1-weighted or T2-weighted scans, while reasonably well-correlated with a history of relapses, are poorly correlated with current clinical state as measured using the Extended Disability Status