Neurotrophic keratitis (NK) is a degenerative disease of the cornea caused by damage of the trigeminal nerve, which results in impairment of corneal sensitivity, spontaneous corneal epithelium breakdown, poor corneal healing and development of corneal ulceration, melting and perforation. This is because, in addition to the primary sensory role, the nerve also plays a role maintaining the integrity of the cornea by supplying it with trophic factors and regulating tissue metabolism. Neurotrophic keratitis is classified as a rare disease, with an estimated prevalence of less than 5 in 10,000 people in Europe. It has been recorded that on average, 6% of herpetic keratitis cases may evolve to this disease, with a peak of 12.8% of cases of keratitis due to varicella zoster virus. The diagnosis, and particularly the treatment of neurotrophic keratitis are the most complex and challenging aspects of this disease, as a satisfactory therapeutic approach is not yet available.
Causes The cornea lacks blood vessels and is among the most densely innervated structures of the human body. Corneal nerves are responsible for maintaining the anatomical and functional integrity of the cornea, conveying tactile, temperature and pain sensations, playing a role in the blink reflex, in wound healing and in the production and secretion of tears. Most corneal nerve fibres are sensory in origin and are derived from the ophthalmic branch of the trigeminal nerve. Congenital or acquired ocular and systemic diseases can determine a lesion at different levels of the trigeminal nerve, which can lead to a reduction (hypoesthesia) or loss (anesthesia) of sensitivity of the cornea. The most common causes of loss of corneal sensitivity are viral infections (herpes simplex and herpes zoster ophthalmicus), chemical burns, physical injuries, corneal surgery, neurosurgery, chronic use of topical medications, or chronic use of contact lenses. Possible causes also include systemic diseases such as diabetes mellitus, multiple sclerosis or leprosy. Other, albeit less frequent, potential causes of the disease are: intracranial space-occupying lesions such as neuroma, meningioma and aneurysms, which may compress the trigeminal nerve and reduce corneal sensitivity. Conversely, congenital conditions that may lead to this disorder are very rare.
Diagnosis NK is diagnosed on the basis of the patient's medical history and a careful examination of the eye and surrounding area. With regard to the patient's medical history, special attention should be paid to any herpes virus infections and possible surgeries on the cornea, trauma, abuse of anaesthetics or chronic topical treatments, chemical burns or, use of contact lenses. It is also necessary to investigate the possible presence of diabetes or other systemic diseases such as multiple sclerosis. The clinical examination is usually performed through a series of assessments and tools:
General examination of cranial nerves, to determine the presence of nerve damage. Eye examinations: Complete eye examination: examination of the eyelids, blink rate, presence of inflammatory reactions and secretions, corneal epithelial alterations. Corneal sensitivity test: performed by placing a cotton wad or cotton thread in contact with the corneal surface: this only allows to determine whether corneal sensitivity is normal, reduced or absent; or using an esthesiometer that allows to assess corneal sensitivity. Tear film function test, such as Schirmer's test, and tear film break-up time. Fluorescein eye stain test, which shows any damage to the corneal and conjunctival epithelium
Classification According to Mackie's classification, neurotrophic keratitis can be divided into three stages based on severity:
Stage I: characterized by alterations of the corneal epithelium, which is dry and opaque, with superficial punctate keratopathy and corneal oedema. Long-lasting neurotrophic keratitis may also cause hyperplasia of the epithelium, stromal scarring and neovascularization of the cornea. Stage II: characterized by development of epithelial defects, often in the area near the centre of the cornea. Stage III: characterized by ulcers of the cornea accompanied by stromal oedema and/or melting that may result in corneal perforation.
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