Tuesday, 13 September 2016

Is the eye the window to the brain? Using OCT to assess response to treatment

Patients and doctors are always on the lookout for ways of monitoring disease activity in MS that are both accurate and non-invasive. Being able to monitor disease activity well makes it easier to determine whether a patient is on the right treatment, or whether they would be better off switching to another disease-modifying therapy (DMT). Whilst lumbar puncture is helpful, it’s unpleasant for patients and, like any invasive procedure, not without risk. MRI is useful but not perfect, as there is a complex and difficult-to-interpret relationship between MRI abnormalities and clinical disease activity.

Optical coherence tomography (OCT) is a non-invasive method for measuring the thickness of the layer of nerve cells at the back of the eye (the retina). There has been lots of interest in using retinal thickness as a measure of disease activity in MS, as it correlates well with loss of brain volume and cord atrophy, both of which are thought to be important determinants of disability.

This new study published by Korn and co. looked at whether OCT could be used to monitor disease activity and response to treatment in a cohort of people with relapsing-remitting MS (RRMS). Their cohort started with 121 people with RRMS and 40 healthy controls. They excluded people who had significant optic neuritis or other eye disease, leaving 108 people with MS and the 40 controls.

People with MS were found to have reduced retinal thickness compared to controls. Two metrics – the total macular volume (TMV) and inner nuclear layer (INL) – were associated with disease activity. A reduction in TMV was associated with an increase in disease activity, i.e. more lesions on MRI and more relapses. Conversely, a reduction in INL was associated with a better chance of remission (i.e. no further relapses during the study period). While untreated patients did not show any change in INL over the study period, patients receiving their 1st or 2nd DMT showed a reduction in INL. These effects of treatment were seen within 6-9 months of starting the therapy.

These results provide good evidence that OCT should be part of the arsenal of clinical and imaging measures that we use to monitor disease activity in MS. An important caveat is that this technique may not work well for people who have had (or still have) optic neuritis, which rules out a lot of people with MS. The authors also excluded people with CIS and with progressive MS – it would be good to know whether OCT is also useful in monitoring response to treatment at these extremes of the disease.  

This study only took place over a year - follow-up over more than a year will be necessary to determine the relationship between clinical, MRI, and OCT measures of disease activity over a clinically-relevant timescale. Once this is known, OCT could become a non-invasive, accurate aid in the long-term medical care of people with MS.

The paper
Assessment of inflammatory disease activity during multiple sclerosis is crucial for selecting appropriate disease-modifying therapies. Previous studies suggested that the retinal inner nuclear layer reflects inflammatory disease severity within the central nervous system. In our study, correlations of longitudinal retinal layer changes as measured by retinal optical coherence tomography with ongoing disease activity were evaluated in 108 multiple sclerosis patients without therapy, on first-line therapy, or on second-line therapy. Healthy subjects served as controls. Inner nuclear layer volume at baseline correlated positively with paraclinical disease activity during the subsequent 12 months. Longitudinal thinning of the inner nuclear layer and thickening of total macular volume were associated with reduced inflammatory disease activity. Reduction in inner nuclear layer volume after 1 year indicated efficient control of inflammatory disease activity including ‘no evidence of disease activity’. In conclusion, the retinal inner nuclear layer could serve as biomarker to monitor sustained control of autoimmune central nervous system inflammation by therapeutic interventions.


2 comments:

  1. Excellent post. Those on Fingolimod like myself who had an OCT prior to start of treatment could be primed for monitoring. This is now added to my bag of questions next neuro visit. Thank you.

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  2. DrBenJ excavations in the optic nerve "of aging" and identified in OCT have some relationship to disease progression for those who have MS?

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