It’s in your eyes!

I
Human eye (image from familyhealthtale.com)

I know what you’re thinking. You’re thinking that I’m going to write about optic neuritis since this is what everyone writes about. But, you will be wrong. This post is about the lesser well known portion of the eye – the conjunctiva.

In a small cross-sectional study of MS patients and controls, a group of investigators from Turkey have found that dry eyes are far commoner in MS than you’d expect by chance. The Schirmer test was below 10mm in 66.7% of the participants, whilst the TBUT was below 10s in 81.8% of MS patients. On average the Schirmer test result was 8.45mm in MS vs 17.36mm in controls and the TBUT was 8.12s vs 13.06s in controls.

As a result, on corneal biopsies showed that the degradation of the cornea was greater in MS; with 33% demonstrating grade 2 scores and 9.1% demonstrating grade 3 scores (see figure below).

figure1
Figure: Representative images of the Nelson’s CIC grades 0–3. The nucleocytoplasmic ratio of squamous epithelial cells decreases with the progression in CIC grade. In grade 3, the nuclei in epithelial cells are pyknotic or absent. Goblet cells are observed as vacuolated or cylindrical cells with hematoxylin and eosin stain, and decrease in number with the progression in CIC grade. (Arrows show goblet cells.) A Nelson’s grade 0, B Nelson’s grade 1, C Nelson’s grade 2, D Nelson’s grade 3

It is thought that the dry eyes occur as a result of reduced corneal nerve innervation to the eye. In addition to providing sensation to the cornea, they provide growth support as well. With a reduction in the corneal nerve fibre density there is an obvious reduction in the health of the cornea.

Abstract

Int Ophthalmol. 2021 Oct 1. doi: 10.1007/s10792-021-02031-5. Online ahead of print.

Conjunctival impression cytology and tear film parameters in patients with multiple sclerosis

Selman BelviranliPembe OltuluAli Ulvi UcaAli Osman GundoganEnver MirzaMustafa AltasNazli Turk Refik Oltulu 

Purpose: To evaluate conjunctival impression cytology (CIC) findings and tear film parameters in patients with multiple sclerosis (MS) compared with controls.

Methods: Thirty-three patients with MS (MS group) and 33 age- and sex-matched healthy subjects (control group) were included in this cross-sectional comparative study. CIC grades, tear break-up time (TBUT), Schirmer 1 test results, and Ocular Surface Disease Index (OSDI) scores were compared between the two groups, and correlations between CIC grade, TBUT, Schirmer 1 test result, OSDI score, Expanded Disability Status Scale score, and disease duration were analyzed.

Results: Mean CIC grade was higher in the MS group than in the control group (1.48 ± 0.71 and 0.39 ± 0.56, respectively; p < 0.001). In the MS group, CIC of the 14 participants (42.4%) was grade 2-3. In the control group, CIC of the only one participant (3.3%) was grade 2, and none of them was grade 3. TBUT (8.12 ± 3.16, 13.06 ± 4.23 s in MS and control groups, respectively; p < 0.001) and Schirmer 1 test results (8.45 ± 5.75, 17.36 ± 10.89 mm in MS and control groups, respectively; p < 0.001) were lower, and OSDI score (36.36 ± 19.19, 13.70 ± 15.36 in MS and control groups, respectively; p < 0.001) was higher in the MS group compared to the control group.

Conclusion: In patients with MS, objective findings of dry eye, subjective symptoms related to dry eye, and CIC abnormalities, including high grades of conjunctival squamous metaplasia and goblet cell loss, are more common. Patients with MS should be monitored for ocular surface alterations and dry eye disease.

About the author

Neuro Doc Gnanapavan

22 comments

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  • Also many patients are on anticholinergics for neurogenic bladder spasticity which cause dry eyes by reduced lacrimal gland secretion. I have noticed this as well as reduced body sweat in general.

      • They work well for frequency and urgency of voiding but need to ensure there isn’t a significant residual urine volume in the bladder before starting.

  • Interesting read. Reading more and more, seems there are many silent symptoms of MS due to nerve damages on passive functions of the body. Are passive functions controlled by different parts of the brain? There would be causal links between where the lesions are?

    If there are known damages, would there be a way to stimulate lost passive functions periodically to reduce damage?

  • Hi is this a very new finding?
    About 3 years ago I started getting very sore eyes which would resolve in lots of water which felt very acidic in my eyes. It Could Happen any time of the day.
    I have Graves disease from alemtuzumab but was told by an endocrinologist if was not thyroid related as that was under control. I even had an MRI of my eye to rule out thyroid related problems! Having seen an ophthalmologist he finally diagnosed dry eyes and prescribed viscotears! He mentioned something about not closing my eyes completely at night so no idea why I got this symptom in the day!
    How would I get the checks you recommended? Should my neurologist know about this?

    • Just to correct something in my post above it should read result in my eyes watering a lot which felt very acidic and not ‘resolve’

  • So, this is another symptom that many of us have that remains untreated , or are the eye drops recommended by my optician sufficient?

    • It should be helpful as it protects the eye by preventing other forms of damage. The nerve fibre layer issue is likely part of the MS, preventing activity in MS would be key.

  • Is there any function that MS doesn’t affect? I can’t think of any. That’s what puts MS in a league of its own compared with other so-called autoimmune diseases. No wonder MSers often suffer from depression.

    Given time, it’s a truly grim disease. We really need to be moving on from studies which identify the extent of the damage, to studies which identify how to stop the disease in its tracks and stop any further damage.

  • OMG thank you for posting this!

    The worst months of my life have been due to dry eyes rather than any of my other ‘MS symptoms’. Just before I was diagnosed with MS, I had months of severe eye pain/aching in my face/light sensitivity, Moorfields did so many tests on me and put it all down to dry eye – however, the ophthalmologist would also say my eyes were not that dry considering how severe my symptoms were, it was as though my reaction to the pain was really over the top. It was affecting my life so badly, I had time off work. I felt like the Dr’s thought I was imagining it or being hysterical, which then really impacted my anxiety and I had to go back on anti-depressants. At the time I read about corneal neuralgia but didn’t know I had MS. I still wonder is corneal neuralgia something MS can cause?

    After I was diagnosed with MS (9 months after my eye problems began!) I came across this one article about MS & Ocular surface disease from the Review of Optometry, which made me feel like I wasn’t completely crazy to assume the two were possible connected, to me, I always feel like they have to be connected, as I never had any issues with my eyes before:

    “The relationship between MS and ocular surface disease is very interesting. In MS patients, associated ocular surface disease may be triggered by the underlying condition itself or may occur secondary to neural interruption.

    MS causes the myelin sheath around some of the most important neurologic components to become inflamed. Myelin is a critical component in the conduction of electrical impulses for proper nerve function. When inhibited, sensory impulses are not conducted properly and can result in poor motor control. Also, the motor response itself can be interrupted by poor signaling/conduction to the end target.

    For eye care providers, it is important to know that MS patients can develop severe ocular surface disease from insufficient tear production (which is a motor response to a dry eye stimulus), failure to recognize dryness (corneal sensory issues), lagophthalmos (the lid failing to
    close properly due to muscle limitatioms) and an increased risk for uveitis.”

    https://www.reviewofoptometry.com/CMSDocuments/2012/1/ro0112i.pdf
    (page 68 – paragraph about dry eye and MS)

    Initially at my worst point I had some steroid drops that seemed to help a bit, but didn’t get rid of the pain. Still to this day (years later) I have to follow a really strict routine with my eyes or the aching comes back. Hot compresses/tea tree wipes to keep the lids clean and eye drops all day without fail – I have to continually keep them moist. It’s a massive hassle but it seems to keep it under control for now. I sometimes worry it will come back as bad again and that terrifies me.

    • p.s for anyone else who may have these issues, I have tried possibly every single eye drop brand/version on the block so here are my recommendations:
      The best are: Hycosan Dual (purple container) for daily use – (I find the red version of Hycosan gets sticky if you need to use them a lot, and the blue ones are not good enough), or Theoloz Duo.
      Systane Gel Eye drops (at night before sleeping, they are thicker)

  • Very timely piece. I had an eye test last week and optician said I had dry eyes. When I asked if this was anything to do with MS he said yes, it was. Optician told me to get some eye drops on prescription or from the local pharmacy which I did. As far as I am aware this article is he first time anyone has written about this MS symptom, Well done

    • I also had a routine eye test, by chance a few weeks following a brainstem relapse and guess what I was told – “dry eyes”. I hadn’t noticed anything unusual, I actually put the optician’s comments down to the amount of crying I’d done at the time of the relapse. I was also advised to use eye drops. Interesting article, thank you for sharing it.

  • I have worn hard contact lenses for 25 years without any problems. A few years ago I couldn’t stand water or lenses in my eyes. After a positive Schirmer test I was diagnosed with ‘dry eyes’. I only go outside when I have ‘Duratears’ eye ointment in my eyes and I need eyedrops all the time. My eyes hurt constantly, wind and heat are terrible and make life quite unbearable. Rubbing my eyes regularly results in hard to heal corneal damage. There has been extensive research into Sjogren’s syndrome, but luckily I only have ‘non-Sjogren sicca syndrome’.
    My heart skipped a beat when I read this blog post this morning and the connection with my MS was made for the first time.

  • Yes … and this! Thanks for posting Doc. I’m another grateful reader today.
    I hope more opticians will learn this information instead of telling clients like me that I ‘don’t blink enough’
    I will stop using her comments as one of my comedic accounts of HCP encounters; not knowing isn’t helpful to anyone.
    Am looking forward to a post which explains my earaches 😉
    Thanks again, and thanks to Hannah for her eyedrop recommendations.

  • Thank you, everyone for your comments and Doc Gnanapavan for this very useful post. It has to be said that we are finally linking eye conditions and in particular dry eyes to MS. Having experience 3 bouts of iritis and been given antibiotics for my first experience (which made it worse, or did little so it just got worse) – that I finally took myself off to a local (ish) eye hospital and was finally given steroid drops and had a proper eye consultation – to feel the relief from the drops and to understand which it was, it obviously, made me feel exasperated by the lack of knowledge from my MS team at the time!

    You feel quite alone and extremely vulnerable if you have anything go wrong with your eyes – as you rely on someone to help you with almost everything. We need to educate and inform as much as possible about this part of the disease and help anyone suffering with eye problems – a quick and easy pathway to have their problem helped. The Maxidex eye drops helped relieve the inflammation and Clinitas eye gel drops help soothe them afterwards and are great for ongoing eye dryness.

  • Thank you for all your comments and a great post Doc Gnanapavan. Finally eye problems with MS being recognised. I had 3 bouts of iritis and after much distress with my first time, I was prescribed Maxidex which gave me instant relief to the burning and redness. I felt like I was going blind as my eye started to swell and close up! My GP and MS team were unhelpful and I was prescribed antibiotics first time and they did not relate it to MS or were helpful supporting my distress. I was then prescribed Clinitas which is a gel drop and helps with dry eyes.

    I feel we need to educate and inform so that some sort of protocol is in place for anyone in the future with eye problems who has MS – or linking it to early stages of diagnosis. You are extremely vulnerable when your eyes are compromised and you need to rely on someone.

    I hope this post will help more medical professionals and opticians understand the complexity of the disease and to not rule out the connection. I also, know and as a consequence of DMDs that eye conditions appear too! Again, more info, discussions and informing folk is the way forward.

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