Neurotrophic Keratitis Treatment & Management

Updated: Sep 13, 2018
  • Author: Robert H Graham, MD; Chief Editor: Hampton Roy, Sr, MD  more...
  • Print

Approach Considerations

Pharmacologic care for neurotrophic keratitis varies by stage with regard to the number and types of drugs used for treatment.

Surgical care may be necessary in stage 2 or 3 neurotrophic keratitis. Such treatment has 3 goals, as follows:

  • Protect the epithelium by lid closure
  • Close a persistent epithelial defect
  • Repair a deep ulceration

Inpatient care

Patients with stage 3 neurotrophic keratitis should be hospitalized for daily follow-up care until significant improvement is seen.


Consult a neurologist if the cause of corneal hypesthesia is not apparent or if any associated neurologic deficits are present. [12]


Patients with stage 1 neurotrophic keratitis can be monitored on an outpatient basis every 3-7 days.

Patients with stage 2 disease should be monitored on an outpatient basis every 1-2 days until improvement is seen, then every 3-5 days until resolution.


Medications to avoid in patients with neurotrophic keratitis are as follows:

  • Topical corticosteroids - These may increase collagenase activity and stromal melting
  • Topical NSAIDs - These have not shown any benefit in wound healing, and diclofenac and ketorolac use can decrease corneal sensitivity

Pharmacologic Therapy

Treatment for stage 1 neurotrophic keratitis is as follows:

  • Topical lubrication with preservative-free artificial tears, gels, and ointments
  • Discontinuation of any topical ocular therapies, especially those that can decrease corneal sensitivity (eg, timolol, betaxolol, sulfacetamide, diclofenac, ketorolac) or that contain preservatives [13]
  • Reevaluation of the need for systemic drugs, such as neuroleptics, antipsychotics, and antihistamines.
  • Punctal occlusion may need to be considered.
  • Oral tetracycline (250 mg PO bid) or doxycycline (100 mg PO qod) can reduce the amount of mucus produced
  • Weyns et al proposed scleral contact lenses as a valid long-term alternative to standard treatment options in patients with neurotrophic keratitis. [14]
  • Gaudilla et al note 20% autologous topical serum is an effective treatment for stages 1 and 2 neurotrophic keratitis. [15]
  • Lee and Kim reported that oral nicergoline helped heal corneal epithelial defects among patients who did not respond to conventional therapy. Additionally, in patients treated with nicergoline, levels of tear nerve growth factors were higher than levels before treatment. [16]

Stage 2 treatment is as follows:

  • All of stage 1 treatments
  • Topical tetracycline reportedly increases the healing of epithelial defects (not available in an ophthalmic drop preparation)
  • Topical cycloplegia with atropine 1% or scopolamine 0.25% once daily in the presence of anterior chamber inflammation
  • Patients with stage 2 disease are more likely to require surgical intervention than are those with stage 1 disorder

Treatment for stage 3 neurotrophic keratitis is as follows:

  • All of stage 1 and stage 2 treatments
  • Surgical intervention

Surgical Repair of Eyelids, Epithelial Defects, and Ulcerations

Closure of the eyelids

In the presence of severe or total loss of corneal sensation, keratitis sicca, or exposure keratopathy, a lateral tarsorrhaphy, palpebral spring, or botulinum A toxin injection in the levator muscle may prevent progression to stage 2.

Closure of a persistent epithelial defect

Repair options for such lesions include the following [17] :

  • Conjunctival flap - Effective, but poor cosmetic and visual result [18]

  • Amniotic membrane transplantation [19]

Repair of a deep ulceration

The following can be used in ulceration repair:

  • Lamellar keratoplasty

  • Penetrating keratoplasty - For large defects

  • Multilayer amniotic membrane transplantation - Has been used in defects as deep as 90% of the depth of the stroma [20, 21]

  • Cyanoacrylate glue with a soft bandage contact lens - For defects smaller than 2 mm


Medical Care

In August 2018, the FDA approved the first drug for neurotrophic keratitis, cenegermin (Oxervate). Cenegermin is a recombinant nerve growth factor.

Approval was based on the REPARO study (n=156). Patients were randomized 1:1:1 to cenegermin 10 mcg/mL, 20 mcg/mL, or vehicle. At week 4, 19.6% of vehicle-treated patients achieved corneal healing (< 0.5-mm lesion staining) compared with 54.9% receiving cenegermin 10 mcg/mL (+35.3%; 97.06% confidence interval [CI], 15.88–54.71; P< 0.001) and 58% receiving cenegermin 20 mcg/mL (P< 0.001).

At week 8, 43.1% of vehicle-treated patients achieved corneal healing compared with 74.5% receiving cenegermin 10 mcg/mL (P = 0.001) and 74% receiving 20 mcg/mL (P = 0.002). Post hoc analysis of corneal healing by the more conservative measure (0-mm lesion staining and no other persistent staining) maintained statistically significant differences between cenegermin and vehicle at weeks 4 and 8. More than 96% of patients who healed after controlled cenegermin treatment remained recurrence free during 48-week follow-up. [22]

Currently not FDA approved, but available in Europe, is a heparin sulfate biomimetic (Cacicol), which acts as a matrix regenerating agent; this agent has been shown to be effective in treating neurotrophic keratitis and to have antiviral effects against HSV-1 and VZV. [23, 24]


Surgical Care

Corneal Re-innervation Surgery

Recent studies have shown that corneal neurotization using contralateral supraorbital or supratrochlear nerves, or via sural nerve transplantation from the calf, can successfully restore corneal sensation and improve ocular surface health in patients with neurotrophic keratitis. [25, 26, 27]