Corneal confocal microscopy identifies corneal nerve fibre loss and increased dendritic cells in patients with long COVID, 2021, Bitirgen et al

[Andy]

Abstract

Background/Aims: Long COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.

Methods: Forty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.

Results: The mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=−0.436; p=0.005, ρ=−0.387; p=0.038, respectively) and CNFL (ρ=−0.404; p=0.010, ρ=−0.412; p=0.026, respectively).

Conclusion: Corneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.

Open access, https://bjo.bmj.com/content/early/2021/07/08/bjophthalmol-2021-319450

 

[Hutan]

This Turkish group have found corneal nerve fibre loss in some other conditions.

Corneal confocal microscopy (CCM) is a real-time, non-invasive, high-resolution imaging technique which allows objective quantification of corneal sub-basal nerve fibres and dendritic cells (DCs). We have previously utilised CCM to show corneal nerve fibre loss in patients with idiopathic small fibre neuropathy,10 painful diabetic neuropathy11 and fibromyalgia,12 and an increase in DCs in patients with diabetic neuropathy13 and inflammatory and immune mediated nerve damage including multiple sclerosis and chronic inflammatory demyelinating polyneuropathy.14 15

40 people who had a Covid-19 infection, 22 of whom had Long Covid symptoms at 4 weeks, and 30 healthy controls.

Cornea nerves - healthy controls; people with Covid-19 plus LC symptoms; people with Covid-19 minus LC symptoms

Grading of the corneal nerve fibre loss was done blinded.

The picture makes it look very cut and dried. The charts and the statistics aren't nearly so clear at the 4 week mark - there is quite a lot of overlap and the best p-value os 0.2.

Where it gets interesting is at 12 weeks. By this time, they just had 29 people post-Covid, with 13 of them with Long Covid symptoms. And the differences were very significant - lots of highly significant p-values for various measures of nerve cell health when comparing the LC people with the healthy controls and the 'post-Covid but no LC' people.

I haven't read the discussion yet, but I thought this was a nice, albeit small study. I'd like to see it replicated.

 

[Peter T]

I haven't read the discussion yet, but I thought this was a nice, albeit small study. I'd like to see it replicated.

I am assuming this investigation of the corneal nerves is because it offers noninvasive access to the nerve fibres/dendritic cells rather than suspecting a specific ocular disease process, which makes it potentially a very useful tool.

It would be interesting to see this replicated with a range of different conditions and repeated with the same individuals over a period of time, to get:

• a clearer idea of how specific to which diseases this phenomenon is,
• an idea of whether it is a result of individual disease processes or the result of more general health/circulation issues,
• whether it reflects damage from a one-off acute episode or is part of an ongoing process
• and some confirmation as to whether it definitely reflects a whole body phenomenon rather than being confined to specific nerves (eg all or some of the cranial nerves or just the ophthalmic division of the trigeminal nerve) or to only the cornea.

Given the suggestion that this is observed in a number of conditions, can the authors reasonably say that it “could be used to objectively identify patients with long COVID”, certainly it is not likely to be a uniquely diagnostic feature of Long Covid, though it might be a useful prognostic indicator for those with the various groupings of post Covid symptoms?

 

[Snow Leopard]

Is this corneal nerve fibre loss associated with neuropathic eye pain?

 

[Mithriel]

I have heard of corneal eye pain being associated with nerve damage to the trigeminal nerve

 

[rvallee]

I have heard of corneal eye pain being associated with nerve damage to the trigeminal nerve

Weird. It's almost like nerves are all connected to one another. You'd almost think they actually are.

 

[jaded]

I’ve had burning eyes as my ME, FM and PoTS has gradually progressed over the years. Nobody has ever explained this to me. Although I’m aware that the corneal nerves can apparently be affected in FM according to the current research.

 

[Hutan]

I have heard of corneal eye pain being associated with nerve damage to the trigeminal nerve

Weird. It's almost like nerves are all connected to one another. You'd almost think they actually are.

from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697388/

Ophthalmic branches of the trigeminal nerve are rich in distribution on the cornea

 

[Mithriel]

I’ve had burning eyes as my ME, FM and PoTS has gradually progressed over the years. Nobody has ever explained this to me. Although I’m aware that the corneal nerves can apparently be affected in FM according to the current research.

In ME there can be a pain like a knife across your eye though it is not much mentioned these days. Eye problems and vision problems are very under researched in ME.

Dry eyes were once dismissed as an old woman's problem and pain in the eyes thought of as imaginary. It all changed when LASIK surgery became popular and many young people became affected (the nerves are cut in that). The companies put money into research and the patient community became active mainly thanks to the internet. A woman called Rebecca Petris, who had been a CEO before her eye problems, worked with sympathetic doctors and they have moved the field, now called ocular surface disease, forward immensely with the patients being closely involved. I dream of what could have happened with ME if we had had the same respect from the medical community.

If we could get some basic knowledge of what our problems are with pain, dry eyes, ocular surface diseases and damage to the parts of the brain interpreting the signals from the eyes it would be a great step forward.