Retinal thinning and MS. Why?

January 5, 2013 at 3:02pm

The OCT (optical coherence tomography) test for retinal thinning in MS is in the news again.  You may have seen the press releases on "the eyes have it" and MS.   OCT has been around for many years.  It is a test which uses light instead of sound waves to visualize an area of the body.  Because the eyeball can let light in, OCT scans are a great way to monitor what's going on inside and behind the eyeball.  The retina is made up of light sensitive neurons that form layers at the back of the eye.

The retina is a very important part of monitoring the MS process.  But something which is NEVER mentioned in this discussion is that, unlike the optic nerve,  the retina does not have myelin.  Myelination is rarely extended into the retina.  

If MS is an inflammatory disease which targets myelin, why is the retina being affected during an MS relapse?

Something else that is never mentioned in these MS OCT stories is that retinal thinning is seen in other diseases of neurodegeneration, including Parkinson's and Alzheimer's Disease.  Retinal thinning is not unique to MS.  The Michael J. Fox Foundation is looking at retinal thinning in Parkinson's, and there have been other "eyes may be a window" stories on OCT and Parkinson's

http://www.familypracticenews.com/news/print-friendly/retinal-thinning-may-be-a-window-on-parkinson-s/71227dfc82.html

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Here's the new study from Johns Hopkins MS Center:

Peter Calabresi, MD. and team recruited 164 participants from Johns Hopkins MS Center. They all underwent eye scans every six months to check for thinning of a part of their retinas. Repeat scans were carried out for an average of 21 months. Fifty-nine of the volunteers had no MS disease activity.

Here are some of the findings.

• MS patients with gadolinium-enhancing lesions (inflammatory lesions) had 54% faster thinning
• MS patients with new T2 lesions had 36% faster thinning that those with MS who did not have these features of MRI activity
• Participants whose level of disability got worse during the study had 37% more thinning, compared to patients whose level of disability did not change
• Participants who had the disease less than five years showed 43 percent faster thinning than those who had the disease more than five years

The editorial authors also noted that the study results provide indirect evidence that active inflammation — even if subclinical or occurring in a different functional system — is connected with greater rates of retinal neurodegeneration.

The more inflammation and swelling the researchers found in the retinas of the MS patients, the more inflammation showed up in their brain MRIs.

http://www.medicalnewstoday.com/articles/254469.php

So, optical coherence tomography appears to be a good test to monitor MS relapses, maybe better/easier/less expensive than MRI.

But some questions need to be asked-----

The retina does not have myelin.  Why is the retina thinning during an MS relapse?  What is happening?  Why is there retinal atrophy during an MS relapse?

Dr. Dake has written about this conundrum.  Why should the retina, which does not have myelin, be thinning during active MS relapses?  

Dr. Dake on "retinal vein sheathing": MS-like lesions, but no myelin

September 16, 2011 at 7:57pm

Dr. Dake made a very important point for the CIRSE conference with his in depth essay on the importance of CCSVI research. 

Retinal Vein Sheathing in MS--  The veins of the retina in pwMS become enlarged and thickened and there is damage to the retinal nerves.  Without myelin.  99% of the time, there is no myelin on retinal nerves, but there is MS damage.  

Here's Dr. Dake---

Underappreciated in the midst of these clashing positions is one other example of a similar venous lesion with potential relevance to MS – sheathing of retinal veins. This cuffing or sheathing of veins can be appreciated on fundoscopic examination of the eyes and may be associated with retinal vein thrombosis, optic neuritis and vision loss. 

In the majority of cases when it is diagnosed during an evaluation of disturbed vision, it occurs in patients with MS. Studied extensively at the Mayo Clinic, it is not however singularly associated with cases of established MS. Its frequency among MS patients is estimated to range from 11% to 42%. After fluoroscein dye administration, it is possible to observe leakage of dye around the retinal veins and histologically, the veins display a thickened wall similar to appearances observed in other chronically obstructed venous territories.

When contemplating the possible association between venous obstruction, blood-brain barrier leakage, myelin destruction and immune mechanisms responsible for the initiation of MS, it is interesting to note that the retinal nerve fibres are not myelinated in 99% of the population.

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Lesions due to MS, occuring on nerves that do not have myelin.  Leaking veins--in people who develop MS.  "Cuffs" that contain immune cells around these leaking veins.

The optic nerve, which exits the back of the eyeball, DOES have myelin.  The retinal nerve sheath, inside the eyeball, does not.

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These vascular abnormalities of the eyes in pwMS have been noted by opthamologists for decades.

Here's a paper from 1986

EAE in mice vs. the new Stanford animal model of CCSVI by Dr. Michael Dake

May 17, 2011 at 7:39pm

Here is part of Dr. Dake's lecture from the Hubbard Foundation conference:

http://www.youtube.com/watch?v=Xp2aWE7W8_w&feature=related

First, Dr. Dake explains how the current model of EAE is created in mice.  It is a rather convoluted procedure--

"There's an animal model, but it's not really, unfortunately, like most animal models, it's not really a human model.  Basically, you take like a mish of ground up spinal cord and brain from some other species, you mix it with some oily substance, some TB bacilli, and some bordadella pertussis, some whooping cough toxin, and inject into peridium,  and what you get is this whopping inflammatory response, and that's good because you get the accelerated disease process, but obviously in humans, it's a much more chronic and progressive thing.  

So, what we've done is taken mice and ligated (the jugular veins)  and we're going to move now up to marmosets, because that's the next level of the species, and marmosets you can actually partially occlude the veins and keep them open without totally ligating them.

 And these mice and their veins, we've got a recipe that we think is right where we want it.  We're starting to see not only clinical performance differences between mice that are ligated and mice that aren't  ligated, but now there's a way to tomographically, in a little mouse brain, to make these wafer thin micron sections thru the whole brain and we're learning a whole lot.  I think it's going to be very interesting as we move up to a larger model to really see....but we think that we're seeing an accentuation of the venous ligation on the disease process."

No words to describe how much I respect this man.  He listened to us and was interested, treated my husband's venous malformations,  and continues to speak out on CCSVI.  Thanks, Dr. Dake.