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):
Secondary bacterial keratitis
Blurred vision secondary to epithelial irregularity, neovascularization, or corneal scarring
Corneal perforation following stromal melting 
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 inflammatory
Stage 3 is characterized as follows:
May result in perforation
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.
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. 
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. 
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:
Topical medications that can cause neurotrophic keratitis are as follows:
Corneal dystrophies include the following:
Systemic diseases that can cause neurotrophic keratitis are as follows:
Iatrogenic causes are as follows:
Toxic causes are as follows:
Miscellaneous causes are as follows:
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Robert H Graham, MD Consultant, Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona
Disclosure: Partner received salary from Medscape/WebMD for employment.
Mark A Hendrix, MD Consulting Staff, Department of Ophthalmology, Suburban Hospital, Shady Grove Hospital
Disclosure: Nothing to disclose.
Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Disclosure: Nothing to disclose.
Stephen D Plager, MD, FACS Chief, Department of Ophthalmology, Dominican Hospital; Assistant Clinical Professor, Department of Ophthalmology, Stanford University Hospital
Stephen D Plager, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and California Medical Association
Disclosure: Nothing to disclose.
Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; EyeGate Pharma Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
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