Keratopathy, Neurotrophic ?>

Keratopathy, Neurotrophic

Keratopathy, Neurotrophic

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
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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