Neuroprotection: predicting optic nerve damage using MRI

N
Optic neuritis is where the money is when it comes to neuroprotection screening. #MSBlog #MSResearch


“This study provides more evidence and support for using the optic nerve as a read out for focal neurodegeneration. It shows that MRI technique for assessing axonal or nerve fibre function correlates well with other metrics of optic nerve dysfunction.”


“Did you know  that the average person with optic neuritis loses about 20% of the nerve fibres in the optic nerve after a single attack of optic neuritis? This is despite the majority of MSers with optic neuritis recovering vision to near normal. Almost all people who have had an attack of optic neuritis have abnormal visual function when you test their vision using very sensitive tests, for example colour vision or contrast sensitivity. The latter is the detection of boundaries between shades of gray. The visual recovery back to near normal despite losing 20% of your nerve fibres is due to the reserve capacity in the nerve. This is exactly what happens in other pathways and regions of the brain; despite nerve loss or brain shrinkage the average MSer compensates by adapting and using their reserve capacity.  The downside of adaptation is fatigue; it takes a lot more mental energy for an MSer to complete a task than it does for someone who is not using reserve capacity.”

Low Contrast Visual Acuity Chart
“This study supports using the optic nerve as a test bed for neuroprotective drugs. This is why Mouse Doctor and his team have developed and animal model of optic neuritis for this purpose and why we are using acute optic neuritis in our phenytoin trial. I would like to acknowledge the National MS Society and the MS Society of Great Britain and Northern Ireland for funding this work under the PROMISE 2010 umbrella; THANK YOU!” 

van der Walt et al. Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes. PLoS One. 2013 Dec 26;8(12):e83825.

BACKGROUND: Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).

OBJECTIVES: To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.

METHODS: Thirty-seven people presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.

RESULTS: Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each MSer was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.

CONCLUSIONS: These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

9 comments

  • Sorry – but I have to just check. The chart you have printed isn't a real one right i.e. we can't use it to self-test?! No matter how closely I look or turn up the brightness on my screen, I can't see any letters past level 12, yet I don't think my vision is deficient and I can see other contrast vision charts when I Google them… Can you or anyone else read the letters past level 12?!

    • I wouldn't assess yourself on any standard computer screen – the brightness and contrast varies significantly between screens and different types of devices. You would have to be using an exactly calibrated display for the test in question. It's probably why paper based tests are still used in a lot of circumstances as they can be produced to a consistent standard and distributed, and used fairly cheaply. Don't rely on your own computer/mobile/laptop screen as they aren't calibrated for things like colour and contrast.

  • Prof G,

    Many thanks for this article and all your work on the blog.

    I have a conundrum which I'm not sure can be solved. The above article, like the article on Laquinimod, is at the MS wider population level i.e about the possibility of highly beneficial treatments for MSers in the future. So in 10 years time, for example, many MSers are likely to benefit from Laquinimod (or another neuro-protective agent) being used in conjunction with a highly effective anti-inflammatory. This is excellent news for MSers diagnosed in 2024. However, I also visit the blog for purely selfish reasons i.e. what will benefit me – a decade after diagnosis and carrying some deficits from past relapses. I suppose I'm after some hope – but a 10 year wait is too long. It's frustrating that I was diagnosed so near to what appear to be much better times for MSers (sometime in the near future).

  • Anon 7:39:00
    I feel the same way. But I also wonder if people 10 years ago, 20 years ago, 30 years ago, feel like a cure was just around the corner like I do? I think they did.

    • What about those what about those MSers diagnosed 10 years before you? Innovation is a production line that keeps on moving. We should try to be be grateful that we have a production line and keep it well oiled and financed. There are so many naysayers who would like it turned off because the products that come off the end are so expensive. In 2014 innovation is very expensive and we must find ways to keep paying for it. Can you imagine how much combination therapy trials will cost?

  • Why do you think it will be 10 years before combining something like Laquinimod with an anti-inflammatory? Laquinimod is likely to be approved this month in the EU for RRMS. I also suspect it's price will be such that NICE will agree to fund it. Unless they expressly rule out it being prescribed alongside other MS treatments then a neuro with the right approach in the right case will be able to prescribe Laquinimod as well as look at anti-inflammatory treatments. Personally, I'd combine Tysabri (or Alemtuzumab if it was available on the NHS) and Laquinimod.

    As an aside, I wholeheartedly agree with Prof G's comments about needing to keep the production line well oiled and financed. Like it or not, 'Pharma' are the only ones – working with academics potentially – who will produce the treatments that will help us and they need to be able to make enough profit from it to warrant investing in it; bearing in mind that a number of trials may prove unsuccessful etc. The speed with which we'll see a cure or something close to it for MS is simply a factor of the amount of money pharma choose to invest in the space. That may not be palatable but its simply the way of the world. Throw many billions at it and we'd have a cure (or extremely effective treatment) in a few years in my view. That won't happen as there are many, many competing areas for Pharma's investment, but before we all complain about them we should keep that in mind.

  • Re: "Why do you think it will be 10 years before combining something like Laquinimod with an anti-inflammatory?"

    This is how long it will take to do the necessary phase 3 combination trials analyse the data and get the regulatory authorities to approve the combination and to then get the payers to agree to pay for the combination. Science is a slow and arduous process. There are no short-cuts.

    • Do the regulators need to approve the combination? If there are two approved drugs for a condition – who is to say I can't take both? I can take paracetamol and ibuprofen for back pain but are the specifically approved as a "combination"? I doubt it. If laquinimod is approved from RRMS and I also happen to have taken Alemtuzumab in the past, there's nothing to stop a neuro prescribing me laquinimod once approved is there?

By Prof G

Translate

Categories

Recent Posts

Recent Comments

Archives