Neurotrophic keratopathy (ORPHA:137596)
Neurotrophic keratopathy is a rare degenerative disease of the cornea characterized by reduction or loss of corneal sensitivity that can be asymptomatic or present with red-eye and, during the early stages of the disease, a minor decrease in visual acuity. It eventually leads to loss of vision.
Epidemiology
No epidemiological data are available. However, prevalence can be estimated at around 1/2,380 in Europe.
Clinical description
Neurotrophic keratopathy (NK) most commonly occurs in adults, and rarely presents in children. It is often asymptomatic, but early signs can include red-eye, blurred vision, and decreased visual acuity. As the disease progresses, epithelial defects and corneal ulcers may develop; corneal scarring and astigmatism can lead to further reduction of visual function. Eventually, progression towards corneal melting and perforation can result in vision loss.
Etiology
NK results from an impairment of trigeminal innervation that provides trophic support to the cornea. The most common causes are viral infection (e.g. herpes simplex) and surgery that damages the trigeminal nerve. Other causes of corneal nerve impairment include: chronic use of topical medications (e.g. timolol, betaxolol), iatrogenic injury (e.g. long-term use of contact lenses), systemic diseases (e.g. diabetes mellitus, multiple sclerosis), chemical burns, and intracranial masses (e.g. schwannoma, aneurysms). Congenital causes (e.g. HSAN4) are extremely rare and most often reported in children.
Diagnostic methods
Diagnosis is based on clinical findings of impaired corneal sensitivity, associated with corneal epithelial changes and medical history. Corneal sensitivity is commonly evaluated using the wisp of a cotton-tipped applicator (although the quantitative method is Cochet-Bonnet aesthesiometry). Slit-lamp and dilated fundus oculi examinations should be carried out and Schirmer and tear ﬁlm break-up time tests prove useful. Corneal and conjunctival vital staining (with fluorescein, rose Bengal or lissamine green) highlight epithelial defects. Corneal nerve morphology is evaluated by in vivo corneal confocal microscopy. Microbiological examination excludes infections. NK staging uses the Mackie classification system: stage 1) punctate keratopathy, epithelial irregularities, stromal scarring, and superficial neovascularization; stage 2) persistent corneal epithelial defect (PED), possible stromal swelling; stage 3) involvement of the corneal stroma, with corneal ulcer progressing to perforation and/or stromal lysis.
Differential diagnosis
Differential diagnoses include all ocular surface and corneal diseases involving the epithelium or causing stromal ulceration: dry-eye, exposure keratitis, corneal limbal stem-cell deficiency, topical drug toxicity, contact-lens abuse, infectious keratitis, corneal dystrophies, and endothelial decompensation.
Management and treatment
Management depends on stage of the disease. In stage 1, artificial tears every 2-4 hours and lubricant ointment at night is prescribed to prevent epithelial breakdown. In addition to artificial tears and lubricant ointment, patients with stage-2 NK, are managed with corneal/scleral contact lenses and topical antibiotic eye drops. Surgery is generally reserved for refractory cases, with partial or total tarsorrhaphy being the most common procedure. For refractory neurotrophic corneal ulcers and severe cases with impending perforation, amniotic membrane transplantation and conjunctival flap surgery is performed, respectively. Small perforations are repaired with cyanoacrylate glue, and a soft-bandage contact lens. Frequent monitoring, ranging from every 1-2 weeks for stage 1 NK to daily for stage 3 disease, is necessary. New treatment methods (e.g. neuropeptides and nerve growth factors), aiming to restore corneal nerves and sensitivity, are currently under investigation.
Prognosis
The prognosis of NK is variable and depends on many factors. A longer duration of the disease, together with severe comorbidities, results in a poorer prognosis.

                            Last update: 
                            March 2017


                            - Expert reviewer(s): 
                            Dr Paolo RAMA  - Dr Marta SACCHETTI