Neurotrophic Keratitis (NK) is a rare, degenerative corneal disease that poses a significant threat to vision. It develops when damage to the corneal nerves causes a profound reduction or complete loss of sensation on the eye’s surface. This loss of sensation impairs the cornea’s ability to protect itself and initiate proper healing, resulting in progressive tissue breakdown. Because severe damage occurs without pain, NK is often referred to as a “silent” corneal disease.
The Underlying Mechanism of Neurotrophic Keratitis
The health of the cornea is maintained by sensory nerves originating from the ophthalmic branch (V1) of the trigeminal nerve. These nerves serve a dual function, acting as both sensory detectors and suppliers of essential growth factors. Damage to the trigeminal nerve pathway affects the cornea in two principal ways that lead to disease progression.
First, the loss of sensory input eliminates protective reflexes, such as the involuntary blink response and reflex tearing, which normally clear debris and keep the surface moist. Without this feedback loop, the cornea is prone to drying out and suffering mechanical trauma that goes unnoticed by the patient.
Second, the damaged nerves can no longer supply the necessary neuropeptides and neurotrophic factors that regulate the growth and metabolism of the corneal epithelial cells.
These trophic factors, including Nerve Growth Factor (NGF), are normally released by nerve endings to nourish and support the constant regeneration of the cornea’s outermost layer. When this support is withdrawn, epithelial cells become unstable and unable to heal properly, resulting in spontaneous breakdown of the surface tissue. This combination of trauma, dryness, and impaired healing creates the cycle of degeneration that defines neurotrophic keratitis.
Primary Causes and Risk Factors
The causes of neurotrophic keratitis are diverse, but all involve damage to the trigeminal nerve pathway between the brainstem and the corneal surface. Infectious diseases are a frequent source of injury, particularly viral infections like Herpes Simplex Keratitis and Herpes Zoster Ophthalmicus. These viruses cause lasting damage to the nerve fibers, leading to a permanent reduction in corneal sensation.
Systemic conditions that cause generalized nerve damage (neuropathy) also increase the risk of developing NK, with diabetes mellitus being a common example. Other neurological disorders, such as multiple sclerosis or leprosy, or intracranial lesions like tumors, can compress or impair the trigeminal nerve.
Iatrogenic causes, resulting from medical intervention, include neurosurgical procedures for trigeminal neuralgia or acoustic neuroma, which can inadvertently injure the nerve.
Ocular procedures, such as complex corneal surgeries or LASIK, can sever peripheral nerve bundles, disrupting corneal innervation. Chronic exposure to certain topical eye medications containing preservatives, or the misuse of topical anesthetic drops, can also be toxic to the corneal nerves, contributing to NK onset.
Recognizing the Stages and Symptoms
The clinical progression of neurotrophic keratitis is categorized into three stages, following the modified Mackie classification, which guides treatment decisions.
Stage 1 represents the mildest form and is characterized by subtle epithelial changes. Symptoms are minimal due to reduced sensation, but examination reveals a dry, cloudy corneal surface with superficial punctate keratopathy (tiny erosions).
Stage 2 is marked by the development of a persistent epithelial defect (PED). This non-healing wound on the corneal surface is typically oval or circular and lacks the inflammation or pain expected with an open wound. The edges of this defect appear smooth and rolled, indicating a significant failure of the cornea’s repair mechanisms.
The most severe form is Stage 3, where the persistent epithelial defect advances into a corneal ulcer. This involves the underlying stroma, leading to stromal melting or lysis, where the tissue begins to thin. Without intervention, this thinning can rapidly lead to corneal perforation, an ophthalmic emergency that carries a high risk of permanent vision loss.
Diagnosis across all stages relies on testing for reduced corneal sensation, a finding that distinguishes NK from other surface diseases.
Current Approaches to Treatment and Management
The management of neurotrophic keratitis follows a stepped approach, beginning with conservative therapies aimed at protecting the vulnerable ocular surface and promoting healing. The initial strategy focuses on lubrication, using preservative-free artificial tears and gels to combat dryness and reduce friction. Autologous serum eye drops (ASDs), made from the patient’s own blood serum, are employed because they contain natural growth factors and vitamins that provide nutritional support to epithelial cells.
Specialized devices like therapeutic soft bandage contact lenses or scleral lenses are used to create a protective, moist environment over the persistent defect. Scleral lenses vault over the cornea and rest on the white of the eye, offering continuous hydration and protection without touching the damaged surface.
If the defect fails to heal, mechanical closure of the eyelids, called tarsorrhaphy, may be performed temporarily or permanently. This procedure physically shields the cornea from the environment and promotes epithelial resurfacing.
Advanced therapies focus on addressing the underlying nerve deficiency, primarily using Cenegermin (Oxervate). Cenegermin is a recombinant human nerve growth factor (rhNGF) administered as an eye drop, replacing the missing trophic support from damaged nerves. This biologic agent influences the differentiation and maintenance of neurons, stimulating epithelial cell proliferation and promoting nerve re-innervation.
The standard treatment course for Cenegermin involves one drop six times a day for eight weeks, and clinical trials show that a significant percentage of patients achieve complete corneal healing. For the most severe cases of Stage 2 or Stage 3 disease, surgical nerve transplantation, known as corneal neurotization, is an option. This procedure reroutes a healthy sensory nerve from elsewhere in the body to the affected eye, aiming to restore both sensation and the delivery of trophic factors.