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

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

 

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?

 

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

 

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.

 

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.