Neurotrophic Keratopathy

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

Complications
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):

Secondary bacterial keratitis

Blurred vision secondary to epithelial irregularity, neovascularization, or corneal scarring
Corneal perforation following stromal melting [4]

Mackie classification
Stage 1 of neurotrophic keratopathy 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 inflammatory
action
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 keratopathy 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.

Causes
The causes of neurotrophic keratopathy 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:

Herpes simplex
Herpes zoster [7]
Leprosy
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 keratopathy.
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
Mbius syndrome
Familial corneal hypesthesia
Topical medications that can cause neurotrophic keratopathy are as follows:

Anesthetics
Timolol
Betaxolol
Sulfacetamide
Diclofenac sodium
Ketorolac
Corneal dystrophies include the following:

Lattice
Granular
Systemic diseases that can cause neurotrophic keratopathy 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