Neurotrophic keratitis: a numb cornea that struggles to heal

The cornea is the clear window at the front of the eye. It is one of the most sensitive tissues in the body, and that sensitivity is part of how it protects itself: a speck of dust causes pain, tears and blinking. In neurotrophic keratitis, also called neurotrophic keratopathy, the nerves that supply the cornea are damaged. EyeWiki describes a corneal degenerative disease characterised by a reduction or absence of corneal sensitivity, in which corneal innervation by the trigeminal nerve is impaired.

EyeWiki explains that partial or complete loss of corneal sensation can result in epithelial keratopathy, an epithelial defect, stromal ulceration and eventually corneal perforation. EyeWiki also notes that the defects in this condition have smooth, rolled margins because of impaired epithelial healing, so the surface is both more easily injured and slower to repair.

EyeWiki says any ocular or systemic condition that alters corneal sensory nerves can result in the disease. The most common eye conditions associated with it are herpes simplex and herpes zoster keratitis, abuse of topical anaesthetic, chemical and thermal burns, contact lens abuse, topical drug toxicity, radiation to the eye and corneal surgery. It notes that chronic use of eye drops containing the preservative benzalkonium chloride may reduce corneal sensation, and that laser refractive procedures and corneal transplantation have been linked to it, with reduced sensitivity after some transplant types for up to 12 months.

Non-ocular causes listed include neurosurgical procedures or trauma damaging the fifth cranial nerve, stroke, aneurysm, multiple sclerosis, intracranial masses, diabetes, leprosy, vitamin A deficiency, some drugs and congenital hypoplasia of the trigeminal nerve. The NHS lists herpes simplex, herpes zoster (the virus that causes shingles) and an injury to the eye among causes of uveitis, and the same viruses are important in the cornea.

The surprising feature is how little may be felt. EyeWiki says that because corneal nerves are impaired, patients do not commonly complain of ocular surface symptoms, which makes it particularly challenging as people may seek advice months or years after the disease starts. Blurred vision can be reported because of surface irregularity, defects, scarring or swelling. Babies and young children with reduced corneal sensation may blink only to menacing gestures and may injure their corneas.

The NHS red eye advice applies: an eye that is very painful and red, a red eye in a contact lens wearer, changes to your sight, light sensitivity or an eye injury need an urgent appointment with a GP or optician, NHS 111 or A&E as the page directs. Because pain may be absent, redness, a cloudy cornea, new blurring or a feeling of something in the eye should be taken seriously in anyone known to have reduced corneal sensation.

EyeWiki describes the Mackie classification. Stage I has epithelial irregularity, most commonly punctate keratopathy without a defect. Stage II is recurrent or persistent epithelial defects without stromal involvement, with an oval defect whose margins are smooth and rolled because of impaired healing. Stage III is stromal involvement leading to corneal ulcer, melting and perforation.

Staging matters because treatment is escalated to match it. EyeWiki also notes that severe corneal staining or an epithelial defect in the absence of discomfort is highly suspicious of the condition, and that corneal sensation is tested with an esthesiometer before any eye drops are put in.

Diagnosis is made by an ophthalmologist. EyeWiki describes a review of medical and surgical history, assessment of the eyelids and blink rate, testing corneal sensitivity (qualitatively with a cotton wisp or quantitatively with an esthesiometer), staining with fluorescein to show surface changes, tear production testing and slit-lamp examination. Confocal microscopy can show the nerves directly. Other conditions that can look similar include dry eye, exposure keratopathy, contact lens disorders, chemical injury and herpetic corneal disease, and infection must be considered in any corneal ulcer.

EyeWiki says management aims to promote corneal healing and avoid complications. General measures include preservative-free medications, treating associated dry eye and lid problems, taping the lids closed at night if they do not close properly, and avoiding topical NSAIDs, which do not help healing and can further reduce sensitivity. Stage-based treatment starts with preservative-free artificial tears and lubricating ointment, then autologous serum drops, therapeutic soft contact lenses or patching, amniotic membrane, and tarsorrhaphy (partially stitching the eyelids) or botulinum toxin induced ptosis. Topical antibiotics may be prescribed to prevent infection, and steroids used cautiously.

Recombinant human nerve growth factor drops, known as cenegermin, are described by EyeWiki as the first approved topical medicine for the condition. A published review of the National Institute for Health and Care Excellence appraisal found that two phase II trials showed improved corneal healing at 8 weeks compared with vehicle, but that because of uncertainties in the clinical and cost-effectiveness evidence the appraisal committee concluded it could not be recommended within its marketing authorisation at that time. Access can therefore vary, and current NICE guidance and local commissioning should be checked with your specialist.

Outcomes depend on the stage at diagnosis and the underlying cause. The aim is to heal the surface and prevent ulceration and perforation, and many people need long-term lubrication and regular review. Protecting the eye from injury, using drops exactly as prescribed, avoiding contact lens overuse (listed by EyeWiki among the causes) and attending follow-up are the most useful things a person can do.

Because the warning pain is missing, people with the condition may be advised by their specialist to watch for redness or changes in vision and to seek help promptly rather than wait for pain.

In the UK, suspected neurotrophic keratitis is assessed by hospital eye services, often a cornea clinic. Treatments such as autologous serum drops, amniotic membrane and surgery are provided by specialist units. Private ophthalmology is also available, though access to specialist drops depends on funding arrangements. No UK patient leaflet specific to this condition was found while preparing this page, so the main sources are clinician-facing and the American Academy of Ophthalmology material is not UK-specific.