Neurotrophic Keratitis

Updated: Mar 27, 2023
  • Author: Robert H Graham, MD; Chief Editor: Hampton Roy, Sr, MD  more...
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Neurotrophic keratitis, also known as neurotrophic keratopathy, is a degenerative disease characterized by decreased corneal sensitivity and poor corneal healing. This disorder leaves the cornea susceptible to injury and decreases reflex tearing. Epithelial breakdown can lead to ulceration, infection, melting, and perforation secondary to poor healing. (See Etiology and Pathophysiology.) [1, 2, 3]

Prognostic indicators in neurotrophic keratitis include the degree of sensory loss, the duration of the condition, and the presence of other ocular surface disease. The incidence of neurotrophic keratitis increases with age. (See Presentation and Workup.)


Fifteen percent of anesthetic corneas in the United States develop serious complications; these can include the following (see Etiology and Pathophysiology, Presentation, Workup, Treatment, and Medication):

  • Blurred vision secondary to epithelial irregularity, neovascularization, or corneal scarring

  • Corneal perforation following stromal melting [4]

Mackie classification

Stage 1 of neurotrophic keratitis demonstrates the following:

  • Rose bengal staining of the inferior palpebral conjunctiva

  • Decreased tear breakup time

  • Increased mucous viscosity

  • Punctate epithelial fluorescein staining

Stage 2 is characterized as follows:

  • Epithelial defect - Usually oval and in the superior cornea

  • Defect surrounded by a rim of loose epithelium

  • Edges may become smooth and rolled

  • Stromal swelling with folds in the Descemet membrane

  • Sometimes associated with anterior chamber inflammation

Stage 3 is characterized as follows:

  • Stromal lysis/melting

  • May result in perforation

Patient education

Educate all patients with corneal hypesthesia about their condition. Instruct patients to seek evaluation immediately if the eye becomes red or if their vision changes. Patients need to understand that serious conditions may not cause them any pain.


Etiology and Pathophysiology

The common factor in all cases of neurotrophic keratitis is corneal hypesthesia. Sensory nerves exert a trophic influence on the corneal epithelium. The sensory neuromediators acetylcholine, substance P, and calcitonin gene-related peptide have been shown to increase epithelial cell proliferation in vitro. [5]

Denervation, on the other hand, results in decreased cell metabolism, increased permeability, decreased levels of acetylcholine, and decreased cell mitosis. Because a continuous turnover of corneal epithelial cells occurs, this can lead to an epithelial defect even in the absence of injury. Sympathetic neuromediators and prostaglandins decrease epithelial cell mitosis. In fact, ipsilateral sympathetic denervation appears to mitigate the effects of corneal sensory denervation.


The causes of neurotrophic keratitis are conditions that decrease corneal sensitivity. The most common of these are herpetic infections of the cornea, surgery for trigeminal neuralgia, and surgery for acoustic neuroma. [6]

Infectious causes are as follows:

Of the 40,000-60,000 cases of herpes zoster ophthalmicus occurring each year in the United States, 50% have ocular involvement. Of these, 16% demonstrate some form of neurotrophic keratitis.

Causes associated with fifth-nerve palsy are as follows:

  • Surgery for trigeminal neuralgia
  • Neoplasia (acoustic neuroma)
  • Aneurysms
  • Facial trauma
  • Congenital
  • Familial dysautonomia (Riley-Day syndrome)
  • Goldenhar-Gorlin syndrome
  • Möbius syndrome
  • Familial corneal hypesthesia

Topical medications that can cause neurotrophic keratitis are as follows:

  • Anesthetics
  • Timolol
  • Betaxolol
  • Sulfacetamide
  • Diclofenac sodium
  • Ketorolac

Corneal dystrophies include the following:

  • Lattice
  • Granular

Systemic diseases that can cause neurotrophic keratitis are as follows:

  • Diabetes mellitus [8]
  • Vitamin A deficiency
  • Multiple sclerosis

Iatrogenic causes are as follows:

  • Contact lens wear
  • Trauma to ciliary nerves by laser treatment and surgery
  • Corneal incisions
  • Laser in situ keratomileusis (LASIK) [9]

Toxic causes are as follows:

  • Chemical burns
  • Carbon disulfide exposure
  • Hydrogen sulfide exposure

Miscellaneous causes are as follows:

  • Increasing age
  • Dark eye color
  • Adie syndrome