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Symptoms ⬇

Foggy or blurry vision, red eye, and swollen eyelid. Foreign body sensation or pain is less than expected for the degree of ocular signs.

Signs ⬆ ⬇

Critical

Loss of corneal sensation, interpalpebral SPK, or epithelial defects with fluorescein staining.

Other

  • Early: Perilimbal injection and interpalpebral corneal punctate epithelial defects or a frank nonhealing epithelial defect with rolled edges, stromal edema, and Descemet folds. Typically located inferior to the visual axis.
  • Late: Corneal ulcer usually without infectious infiltrate, although concomitant infectious keratitis may occur. The ulcer often has a gray, heaped-up epithelial border, tends to be in the lower one-half of the cornea, and is horizontally oval. Progressive thinning may occur rapidly and lead to a descemetocele (corneal stromal loss down to Descemet membrane) or corneal perforation.

Differential Diagnosis ⬆ ⬇

See 4.1, SUPERFICIAL PUNCTATE KERATOPATHY.

Etiology ⬆ ⬇

Occurs in eyes with diminished or absent corneal sensation. Denervation causes the corneal epithelium and tear film to become abnormal and unstable. May occur with any of the following conditions:

  • Postinfection with varicella zoster virus (VZV) or herpes simplex virus (HSV).
  • Following ocular surgery, particularly after corneal incisional or laser surgery (e.g., keratoplasty, LASIK, SMILE, PRK).
  • Tumor (especially an acoustic neuroma, where both the fifth and seventh cranial nerves may be affected) or any neurologic insult/disease of the fifth cranial nerve (e.g., brainstem stroke, trauma, multiple sclerosis, Riley–Day syndrome).
  • Chronic contact lens wear.
  • Diabetic neuropathy.
  • Extensive panretinal photocoagulation: May damage the long ciliary nerves (these patients often have concurrent diabetic neuropathy).
  • Complication of trigeminal nerve or dental surgery.
  • Complication of radiation therapy to the eye or an adnexal structure.
  • Chronic topical medications (e.g., nonsteroidal anti-inflammatory agents, timolol).
  • Topical anesthetic abuse.
  • Crack keratopathy: Often bilateral. Take careful history for crack cocaine smoking or potential exposure. Often helpful to admit patient and remove them from their environment.
  • Chemical injury or exposure to hydrogen sulfide or carbon disulfide (used in manufacturing).

Work Up ⬆ ⬇

Workup
  1. History: Previous episodes of a red and painful eye? Prior herpes infection, cold sores, or shingles rash around the eye and/or forehead? Diabetes? History of irradiation, stroke, or hearing problem? Previous refractive procedure or other eye surgery? Chemical exposure? Smoking history? Topical medications?
  2. Prior to anesthetic instillation, test corneal sensation bilaterally with a sterile cotton wisp.
  3. Slit lamp examination with fluorescein staining of cornea and conjunctiva.
  4. Check the skin for herpetic lesions or scars from a previous herpes zoster infection.
  5. Look for signs of a corneal exposure problem (e.g., inability to close an eyelid, seventh cranial nerve palsy, absent Bell phenomenon).
  6. If suspicious of a central nervous system lesion, obtain a computed tomography (CT) or magnetic resonance imaging (MRI) of the brain.

Treatment ⬆ ⬇

Eyes with neurotrophic keratopathy have impaired healing ability. If not treated in a timely manner, an epithelial defect in an eye with this condition may progress to stromal lysis and possibly perforation.

  1. Mild-to-moderate punctate epithelial staining: Preservative-free artificial tears q2–4h and artificial tear ointment q.h.s. Consider punctal plugs and q.h.s. patching.
  2. Small corneal epithelial defect: Antibiotic ointment (e.g., erythromycin or bacitracin q.i.d. to q1–2h) until resolved. Usually requires prolonged artificial tear treatment, as described above. Consider placement of a bandage soft contact lens with prophylactic antibiotic drops (e.g., ofloxacin or moxifloxacin t.i.d. to q.i.d.) along with frequent preservative-free artificial tears (q1–2h) as an alternative to antibiotic ointment.
  3. Corneal ulcer: See 4.11, BACTERIAL KERATITIS, for the workup and treatment of a secondarily infected ulceration. Treatment options for a neurotrophic ulceration include antibiotic ointment q2h, tarsorrhaphy, self-retained amniotic membrane tissue, sutured/glued amniotic membrane graft, or conjunctival flap (See TREATMENT in 4.5, EXPOSURE KERATOPATHY). Oral doxycycline (50 to 100 mg b.i.d.), a collagenase inhibitor, may slow stromal lysis. Systemic ascorbic acid (e.g., vitamin C 1 to 2 g daily) may promote collagen synthesis and reduce the level of ulceration. Autologous serum, albumin, or umbilical cord serum eye drops may also be beneficial.
  4. Cenegermin-bkbj 0.002%, recombinant human nerve growth factor, is the first Food and Drug Administration–approved drug for neurotrophic keratopathy and is very effective in many eyes. It is an ophthalmic solution that is applied six times daily for an 8-week treatment course.
  5. A scleral lens (e.g., prosthetic replacement of the ocular surface ecosystem [PROSE]) may be helpful long term.
  6. Cornea neurotization is a complex surgical procedure whereby nerves are redirected, or more commonly grafted, to reestablish corneal sensation.
NOTE:

Patients with neurotrophic keratopathy and corneal exposure often do not respond to treatment unless a tarsorrhaphy is performed. A temporary adhesive tape tarsorrhaphy (the lateral one-third of the eyelid is taped closed) may be beneficial, pending more definitive treatment.

Follow Up ⬆

  1. Mild-to-moderate epithelial staining: In 3 to 14 days.
  2. Corneal epithelial defect: Every 1 to 3 days until improvement demonstrated and then every 5 to 7 days until resolved.
  3. Corneal ulcer: Daily until significant improvement is demonstrated. Hospitalization may be required for severe ulcers, especially if there is concern that patient may not be properly administering medication in the setting of decreased corneal sensation or the patient may be abusing anesthetic drops (see 4.11, BACTERIAL KERATITIS).