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Corneal neuropathic pain

For open discussion, these are my current thoughts in trying to find a solution to what I think should first of all be treated as a matter of utmost health urgency.

Corneal neuralgia is a condition of poorly understood complexity and high challenge. It is a severe unrelenting discomfort pain felt in and around the eyes which knocks quality of life sideways. Patients experiencing this will usually already have been on a long journey to diagnosis and no doubt realised treatment difficulty.

This relatively newly recognised condition demands to be respected. Maximum clinical attention and patient support are required. Carlos Belmonte and Perry Rosenthal first described and carefully considered the existence of this entity between 2007-9. Patients are often inaccurately diagnosed with ‘dry eye’. The scenario goes where there is a disconnect, a disproportionately high level of dry eye symptoms and/or pain which out-weigh minimal if any observed ocular signs. So called ‘pain without stain’ is a pointer to the correct diagnosis, a lack of fluorescein dye ocular surface uptake confusing ophthalmologists usually expecting to observe this as a major feature of most cases of dry eye.

The purpose of pain in evolutionary terms is of course to act as an acute warning system. A call to stop, rest and heal. Subjective and unpleasant, it is a sensory experience dependent upon complex physiology and with individual thresholds. Chronic pain is that which persists, signifying some form of permanent damage which cannot by natural means be repaired or undone. Continuing pain is a depressing thought, not easy to escape, relieve or adapt to. Neurologists, rheumatologists and oncologists have much more practice experience in this field compared to eye specialists. The question arises, within ophthalmic practice, has there been an under-appreciated long-suffering cohort to which we have been impervious?

The regularity of seeing patients complaining of dry eyes in busy clinics has had a blinkering effect. Symptoms of dry gritty irritation soreness alone are highly suggestive for the diagnosis of dry eye disease, but lack specificity. A thorough history and ocular examination is required in support of classical systemic associations, drug side effects, vital dye ocular surface staining pattern and other somewhat subjective signs such as marginal tear meniscus height and tear break-up time. The important exclusions include common mimics such as allergy; underlying causes such as blepharitis, trichiasis, floppy lids, conjunctivochalasis and lagophthalmos; and rarities such as ocular cicatricial pemphigoid and vitamin A deficiency.

Corneal neuropathic pain is expressed in various terms of high severity, constant disabling nature, and often with associated features of hyper-sensitivity eg to light, breeze and air conditioning (photophobia and allodynia). A patient’s general functioning deteriorates as behaviour becomes adversely and broadly affected. Stress increases and mood decreases. Anxiety and depression can be precipitated or exacerbated, even to the point of contemplating ending it all.

At present, corneal neuralgia is a diagnosis of exclusion, supported by clinical features, associated chronic dry eyes or other temporal precipitant such as prior ocular surgery, and without other identifiable cause. Numerous consultations and a poor symptomatic response to traditional artificial tears should start to raise the possibility. Clouding effects of psychological overlay and the complex matter of somatization may have been questioned. Pain which does not resolve completely after topical anaesthesia is a significant pointer, suggesting a more centralised neuropathic component cause. The confocal microscope may provide evidence of corneal nerve irregularities, but it is not clear whether by what extent or character which cases can be causally associated.


I here describe an objective test (undertaken once) which may be useful in cases where any doubt exists:



























For severe dry eye and corneal neuralgia patients, even the most experienced eye doctors tend to bow out as being unable to further assist once eg artificial tears, punctal plugs and Ikervis have been deployed. Particular attention and care are needed at this juncture for those patients showing increasing levels of debilitation and desperation, for the mind set of suicidal ideation is a sure sign characteristic of having corneal neuralgia. This is precisely where medical reinforcement needs to be called upon.

There is an interesting clinical comparison to be drawn. The close neighbouring condition of trigeminal neuralgia more usual in V2 and V3 shares many clinical similarities with corneal neuralgia, but seems completely overlooked by inter-specialty correlation. Consideration might well be given that corneal neuralgia may well represent a form of V1 trigeminal neuralgia.


So what causes corneal neuralgia? It has been linked to occur after variously induced severe chronic dry eyes, and acute injuries such as various ocular surgeries, including keratorefractive procedures. Corneal laser surgery cuts in part the superficial sub-basal nerve plexus; ongoing inflammation and abnormal axonal healing may be responsible. The pain process in all probability originates in the peripheral nerve endings; it can only be hypothesized chronicity may lead to centralisation. Is this because of a physically hyper-stimulated neural receptor pathway that in a pathophysiological sense can no longer turn off? Or a form of physical damage, such as aberrant regeneration or ganglionic insult, where there is constant firing of upregulated nociceptors which become hyper-responsive? There may well be predisposing factors, genetic, dietary (vitamin B12 & D deficiency), other neurological, psychological or pain disorders (migraine, fibromyalgia, irritable bowel syndrome). Is the central nervous system susceptible to certain psychopathological priming events? Distorted neuronal excitability would seem to hold the key to improving our understanding.

Corneal neuralgia is distressing for patients and family; inevitably some of that rubs off on involved clinicians. Consults are demanding and treatment strategies a patience testing hard slog. A multidisciplinary team needs to pull expertise from ophthalmology, neurology, psychology, psychiatry, and pain management specialists to assist in the step-wise therapeutic escalation.

More clinical evidence to support effective targeted treatment options are certainly required. Here are my current views:



a) Artificial tears - ineffective

b) Steroids, Ikervis - ineffective

c) Blepharitis - aim elimination

d) Cautery occlusion of lower +/- upper lid puncti following temporary plug trials (consider upper flow control       plugs if epiphora with occlusive plug) - definitely useful but rarely sufficient

e) Moisture goggles - wear as needed - a must for home / screen use relief

f)  Scleral contact lenses - rarely tolerated

g) Amitriptyline, duloxetine, pregabalin, gabapentin, topiramate, naltrexone - as tablets - not impressive

h) Salagen - rarely tolerated

i) Autologous serum eyedrops / PRP - recommended EARLY for superior lubricant & potential healing

    properties (as near to a natural tear substitute containing nutrients & growth factors). USE MIN 2 YEARS




j) Forced yawns - stimulates tear production

kPeri-ocular capsaicin cream - thin smears around eyelids (do not get in eyes)

l) Peri-ocular lignocaine gel 5%

m) Peri-ocular botox - easy & helpful in about 2/3 cases

n) Peri-ocular steroid + local anaethetic agent injections

o) Greater occipital nerve blocks

p) Peri-ocular TENS device - eg Cephaly device

q) Acupuncture / hypnotherapy - limited knowledge, may help if pain radiates to face

r) LACRISERTs – manufacturing issue by B+L; if become re-available, via international pharmacy

s) Vismitin - anti-oxidant drops

t) iTear100 electronic device external nose stimulator

u) TYRVAYA (varenicline) new nasal spray to stimulate tear flow - expensive order from USA

v) Amniotic membrane (Omnilenz in UK, contact lens £240 ) - easy to fit, pain reported to dampen ~2/3 in 60%



1) NGF - Oxervate (extremely expensive) or self-mix a self-bought recombinant version (cheaper agent,

     purchased for ‘research’ purposes)

2) LASIK flap lift / Flap create - cleave abnormal nerve sprouts in a healing re-programme - only one

     ophthalmologist known to be willing, use with reported success in 3 patients

3) If it comes down to considering the final nerve block options below, I suggest a brief closely monitored trial

     on regular anaesthetic drops first. A partial respite from pain whilst assessing corneal resilience. The risk of

     neurotrophic ulcers should be controllable eg with serum eye drops / bandage contact lens / cessation

4) Epi-off CXL - induce reduction in corneal sensitivity; risk epithelial defects - few ophthalmologists would be

     willing to undertake

5) Pulsed radiofrequency therapy to trigeminal ganglion - never performed for this indication, but theoretically

     might work well & be more delicate than gamma knife

6) Gamma knife stereotactic radiotherapy to trigeminal ganglion - success in trigeminal neuralgia reported

     75-85%; risks numbness / paraesthesia in face

7) Lacrimal gland parotid nerve or microvascular autologous submandibular gland transplantation - needs specialist oculoplastic / ENT team

8) C1-C2 intrathecal drug delivery / electrostimulation - neurosurgery in USA, 3 case reports

     - noteworthy is a suggested 1:1000 risk of paralysis


i) Libvatrep (SAF312) - Novartis. Extract of capsaicin as eye drops. Undergoing trials still in recruitment

ii) Lacosamide 1% - eye drops compounded from an anti-epileptic medicine

iii) Naltrexone - eye drops compounded from the opioid antagonist medicine

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Comparison corneal vs trigeminal neuralgia.png
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