Neurotrophic Keratitis

Neurotrophic keratitis is a degenerative corneal disease caused by reduced or absent corneal sensation (trigeminal nerve V1 dysfunction), with loss of trophic neuropeptides, impaired epithelial healing, and reduced blink and tear reflexes.

• Causes: herpes simplex and herpes zoster keratitis (commonest), trigeminal nerve surgery or ablation for neuralgia, cerebellopontine angle tumours, stroke, diabetic neuropathy, chemical burns, topical drug toxicity (preservatives, topical anaesthetic abuse, beta blockers), refractive and corneal surgery, contact lens wear, leprosy, and congenital insensitivity (familial dysautonomia, congenital corneal anaesthesia).
• Hallmark: persistent epithelial defect with smooth rolled edges that is painless or mildly painful.

• Staging:
  • Stage 1: punctate epitheliopathy, epithelial irregularity, decreased tear break up time, conjunctival staining.
  • Stage 2: persistent epithelial defect, oval, with smooth edges and heaped up grey rims, stromal oedema.
  • Stage 3: corneal ulcer with stromal melt, risk of perforation, secondary infection.
• Reduced or absent blink, patients complain of little pain despite red, damaged eyes; often reduced vision.
• Look for associated facial anaesthesia, V1 distribution scars, and facial nerve palsy.

• Corneal sensation testing: cotton wisp (cotton tip) of a twisted strand touching the cornea centre and four quadrants, comparing with the other eye; Cochet-Bonnet esthesiometer (normal 5 to 6 cm; neurotrophic below 2 cm); or non-contact air esthesiometer.
• Slit lamp with fluorescein, tear film assessment, and in vivo confocal microscopy to image the subbasal nerve plexus.
• Search for the cause: history of herpes or zoster, neurological examination of the cranial nerves, MRI brain and orbits with contrast (cerebellopontine angle, pons), HbA1c, drug history.
• Exclude infection with scraping and culture for any infiltrate.

• Treatment is staged by severity.
• Stage 1: preservative free lubricants hourly to every 2 hours, lubricating ointment at night, stop toxic drops, punctal plugs; consider autologous serum 20 percent four to six times daily.
• Stage 2:
  • Cenegermin (recombinant human nerve growth factor) 20 micrograms/mL one drop six times daily in the affected eye for 8 weeks, with healing in about 70 percent; common adverse effects are eye pain and inflammation.
  • Autologous serum 20 to 50 percent, or platelet rich plasma drops 4 to 6 times daily; umbilical cord serum.
  • Bandage soft contact lens or scleral lens, with antibiotic prophylaxis (moxifloxacin 0.5 percent four times daily).
  • Amniotic membrane (inlay or overlay), or self-retained cryopreserved amniotic membrane.
  • Temporary lateral or medial tarsorrhaphy, or botulinum toxin A injection into the levator (2.5 to 5 units) to induce protective ptosis for 8 to 12 weeks.
• Stage 3: manage melts with tarsorrhaphy, glue and bandage lens (small perforation), conjunctival flap (Gundersen), lamellar or penetrating keratoplasty (high failure rate in anaesthetic corneas), and treat infection with fortified antibiotics.
• Corneal neurotisation (direct, using supraorbital or supratrochlear nerves, or indirect with sural nerve graft) for refractory disease.
• Prevention of recurrence: lifelong lubrication, avoid topical steroids and NSAIDs when possible (they delay healing and risk melt), regular review, patient education to protect the eye and check it daily.
• In herpetic disease: maintenance oral aciclovir 400 mg twice daily.