Introduction
Background
Neurotrophic keratopathy is a degenerative disease characterized by decreased corneal sensitivity and poor corneal healing. This disease leaves the cornea susceptible to injury and decreases reflex tearing. Epithelial breakdown can lead to ulceration, infection, melting, and perforation secondary to poor healing.
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.
Denervation 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.
Frequency
United States
Of anesthetic corneas, 15% develop serious complications.
Of the 40,000-60,000 cases of herpes zoster ophthalmicus occurring each year, 50% have ocular involvement. Of these, 16% demonstrate some form of neurotrophic keratopathy.
Mortality/Morbidity
- Blurred vision secondary to epithelial irregularity, neovascularization, or corneal scarring
- Secondary infection of nonhealing epithelial defects
- Corneal perforation following stromal melting
Race
No racial differences exist.
Sex
No gender differences exist.
Age
The incidence of neurotrophic keratopathy increases with age.
Clinical
History
- A careful medical and surgical history should be obtained. Inquire about the following:
- Previous surgical or traumatic injury to the trigeminal nerve, ocular surgery, or laser treatment, which may have damaged the ciliary nerves
- Previous herpetic eye disease or a history of herpes zoster ophthalmicus
- Diabetes mellitus
- Use of topical medications, including potential abuse of topical anesthetics or nonsteroidal anti-inflammatory drugs (NSAIDs)
- Use of contact lenses
- Exposure to chemical fumes
Physical
- Cranial nerve examination
- A cranial nerve examination can help localize the cause of corneal hypesthesia.
- Pupillary abnormality may indicate pathology of the intraconal orbit or cavernous sinus or may reveal an Adie pupil.
- Dysfunction of cranial nerves III, IV, and VI may indicate an aneurysm or cavernous sinus pathology.
- Dysfunction of cranial nerves VII and VIII may indicate acoustic neuroma or injury from its resection.
- External examination
- Cranial nerve VII function should be assessed not only for its value in localizing the cause of hypesthesia but also for its prognostic value. Poor lid closure promotes exposure and can hasten progression.
- The presence of scars from surgery, chemical burns, or thermal burns can provide clues as to the cause of the hypesthesia.
- Ectropion, lagophthalmos, or thyroid ophthalmopathy increase the risk of progression.
- Ocular surface examination
- The function of the tear film should be carefully examined for its impact on the management of neurotrophic keratopathy.
- Corneal sensitivity should be assessed. To do so, a piece of twisted cotton or the corner of a tissue is used. A Cochet-Bonnet esthesiometer is a device that can give a quantitative measurement of corneal sensitivity. It consists of a nylon filament, which can be extended from the device to different lengths and touched to the cornea until it bends or the patient responds. The small diameter of the instrument allows accurate testing of different areas of the cornea. The shorter the length of filament required, the less sensitive the cornea. In one study, only those patients with readings of 2 cm or less developed epithelial sloughing and ulceration.
- Slit lamp examination may show indications of the underlying cause of corneal hypesthesia. These include herpetic epithelial disease, stromal scarring from previous infection, lattice or granular stromal dystrophy, and enlarged or beaded corneal nerves from leprosy.
- Mackie classification for neurotrophic keratopathy
- Stage 1
- Rose bengal staining of the inferior palpebral conjunctiva
- Decreased tear break-up time
- Increased mucous viscosity
- Punctate epithelial fluorescein staining
- Stage 2
- 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
- Stromal lysis/melting
- May result in perforation
- Stage 1
- Anterior segment examination may reveal iris atrophy from a prior herpetic infection or an anterior chamber inflammatory reaction.
- Dilated funduscopy
- Optic nerve swelling or pallor may indicate an orbital lesion or a retroorbital lesion. Diabetic retinopathy could indicate the likelihood of diabetic neuropathy.
- Laser scars from panretinal photocoagulation may indicate ciliary nerve damage.
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.
- Infection
- Herpes simplex
- Herpes zoster
- Leprosy
- Fifth nerve palsy
- 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
- Anesthetics
- Timolol
- Betaxolol
- Sulfacetamide
- Diclofenac sodium
- Ketorolac
- Corneal dystrophies
- Lattice
- Granular
- Systemic disease
- Diabetes mellitus
- Vitamin A deficiency
- Multiple sclerosis
- Iatrogenic
- Contact lens wear
- Trauma to ciliary nerves by laser treatment and surgery
- Corneal incisions
- Laser in situ keratomileusis (LASIK)
- Toxic
- Chemical burns
- Carbon disulfide exposure
- Hydrogen sulfide exposure
- Miscellaneous
- Increasing age
- Dark eye color
- Adie syndrome
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References
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Further Reading
Keywords
neurotrophic keratopathy, neurotrophic keratitis, neuroparalytic keratitis
