Updated on  April 30, 2024
8 min read

What is Neurotrophic Keratitis?

12 sources cited
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Neurotrophic keratitis (NK) is a rare condition affecting visual acuity (sharpness of vision) and even leads to blindness. When you have a healthy cornea, the corneal epithelium undergoes important cell processes.

These processes benefit you in the following ways:

  • Maintain structural integrity
  • Encourage proliferation
  • Promote wound healing

Defects or injuries to the nerves can affect the cornea negatively, and one common result is neurotrophic keratitis (NK).

Neurotrophic keratitis can be serious, but it is often underdiagnosed in patients with underlying disorders or other comorbidities. In this article, we’ll help you understand the critical aspects of neurotrophic keratitis, including the following:

  • Neurotrophic keratitis causes
  • The role of nerves in neurotrophic keratitis cases
  • Diagnosis of neurotrophic keratitis
  • Available medications and treatments for neurotrophic keratitis  

Understanding the symptoms or stages of the disease helps with early diagnosis and treatment to save your eyesight.  

What is Neurotrophic Keratitis?

Neurotrophic keratitis is also known as neuroparalytic keratitis or neurotrophic keratopathy. It’s a degenerative disease leading to epithelial breakdown of the cornea (clear front part of the eye).1

The prevalence of NK is estimated at less than 5 per 10,000 people.2 Clinical presentation of NK ranges from subtle corneal surface irregularities to corneal melting and perforation.

The condition has three different stages according to the Mackie classification:

  • Mild (stage 1)
  • Moderate (stage 2)
  • Severe (stage 3)

As the disease advances, the cornea becomes opaque. Corneal opacities (COs) are one of the top five causes of blindness, with infectious keratitis being the major culprit.3 

Infectious keratitis (IK) is when an infection occurs on the corneal ulcer. IK can be caused by a wide range of bacteria, fungi, viruses, and parasites. According to the World Health Organization (WHO), blindness caused by corneal opacity affects about 1.9 million people worldwide.4 

What Causes Neurotrophic Keratitis

Damage or injury to the 5th cranial nerve (trigeminal nerve) is the common cause of neurotrophic keratitis. The trigeminal nerve (CN V) is the largest of all cranial nerves and has three branches:

  • Ophthalmic nerve
  • Maxillary nerve
  • Mandibular nerve

The ophthalmic nerve is responsible for the sensory innervation of the cornea. Any damage to this nerve will lead to loss of corneal sensation and impaired lacrimal reflexes.

Nerve damage can be due to:

  • Long-term use of contact lenses
  • Herpetic keratitis (Herpes simplex keratitis)
  • Previous corneal surgery
  • Chemical and physical burns
  • Intracranial space occupying masses like meningioma or aneurysms 
  • Excessive use of topical agents with benzalkonium chloride (BAK), diclofenac sodium, timolol, and sulfacetamide.
  • Underlying conditions like diabetes and multiple sclerosis. 
  • Congenital disorders (Mobius syndrome, Riley-Day syndrome, familial corneal hypesthesia, etc.)

Any corneal disease compromising innervation to the corneal epithelium results in neurotrophic keratopathy.

Why are Corneal Nerves Important?

The cornea has numerous nerves⁠—approximately 7,000 nociceptors per square millimeter. The dense innervation makes the cornea 100 times more sensitive than the conjunctiva and 300 to 600 times more sensitive than the skin.12

The functions of corneal nerves include:

  • Sensing stimuli. Detecting pain, touch, and temperature changes
  • Corneal reflexes. The rapid eye blink that happens when anything touches the surface of your eye
  • Eye lubrication. The reflex arcs that control lacrimation (tearing) rely on sensory input from the ocular surface to keep the tear film intact
  • Wound healing. TRPV1+ sensory nerves are closely involved in the wound repair process of the cornea by balancing the inflammatory response

The amount of corneal nerves dedicated to reacting to different stimuli varies:

  • 70% of the nerves help convey sharp and sustained pain in response to chemical, heat, or mechanical stimuli to the cornea
  • 20% convey acute sharp pain in response to mechanical trauma or contact
  • 10% are cold receptors that respond to dry eyes due to exposure to cold air or solution

Symptoms of Neurotrophic Keratitis

Early signs and symptoms include:

  • Stinging, burning, or irritation in your eyes
  • Blurry or fluctuating vision
  • Eye discharge (mucus)
  • Sensitivity to light (photophobia)
  • Redness
  • A foreign body sensation in your eye(s)
  • Discomfort when wearing contact lenses

As the diseases advance, patients get more complications such as:

  • Decreased corneal sensitivity
  • Sensory nerve damage
  • Impaired healing
  • Corneal ulceration (ulcers with rolled edges)
  • Neovascularization (formation of new blood vessels)  
  • Corneal melting and perforation (open injury) 
  • Vision loss  

Stages of Neurotrophic Keratitis

Due to the lack of corneal sensation, patients with neurotrophic keratitis rarely have symptoms to report. Eye doctors classify the stage of disease based on presenting symptoms. 

Here is the Mackie classification of corneal damage:5

Stage 1 (Mild)

In stage 1, there is minimal damage to the cornea. People present with dry or cloudy epithelium.

The dryness is due to decreased tear break-up time and increased viscosity of the tear mucus. Staining with fluorescein or Rose Bengal helps detect damage to the corneal epithelial cells and conjunctiva.

Without diagnosis and treatment, there is more epithelium scarring, leading to neurotrophic keratitis’s progression to stage 2.

Stage 2 (Moderate)

Stage 2 is characterized by recurrent or persistent corneal epithelial defects (PED). Reduced wound healing further decreases corneal innervation.

Other consequences include:

  • Loosening of epithelial wall
  • Folding of Descemet’s membrane
  • Anterior chamber inflammation
  • The affected areas of the epithelium form oval or circular shapes with smooth folded edges.  

Stage 3 (Severe)

In stage 3, the disease is advanced with reduced corneal sensation. The stroma cells become edematous (swollen with fluid accumulation).

A corneal ulcer develops, and the stroma melts, causing corneal perforation.6 Patients with stage 3 neurotrophic keratitis should be hospitalized for specialized care.

How is Neurotrophic Keratitis Diagnosed?

Neurotrophic keratopathy is made based on history and eye exam findings. In all cases, a common finding is decreased corneal sensation.

Below are some of the diagnostic procedures for NK:

  • History evaluation. Taking a detailed patient’s ocular, medical, and surgical history
  • Corneal surface examination. Staining with fluorescein, lissamine green, or Rose Bengal to highlight epithelial changes
  • Corneal sensitivity evaluation. Using handheld devices like a Cochet-Bonnet contact aesthesiometer or CRCERT-Belmonte non-contact aesthesiometer. 
  • Schirmer test. To assess tear production and TBUT test to evaluate tear break-up time which decreases following a reduction in corneal sensitivity
  • Slit-lamp test. Used to magnify the eye’s features and allows the ophthalmologist to see any notable corneal changes
  • Confocal microscopy (IVCM). A noninvasive procedure used to magnify the eye’s structures at the cell level
  • Immunofluorescence. To rule out herpes simplex or herpes zoster infection
  • Fundus exam. To check for diabetic retinopathy and pan-retinal photocoagulation scars that may be associated with NK

Some conditions share the same symptoms as NK. Some of the differential diagnoses to rule out include the following:

  • Dry eye disease
  • Bacterial keratitis
  • Herpes zoster and simplex virus
  • Corneal mucous plaques
  • Sjögren’s syndrome
  • Postoperative corneal melt
  • Blepharitis
  • Keratopathy (exposure or ultraviolet)
  • Corneal limbal stem cell deficiency

Medications for Neurotrophic Keratitis

Treatment of neurotrophic keratitis mandates a team effort from specialists like corneal specialists, neurologists, ophthalmologists, and surgeons.7 Although the clinical diagnosis may be made without difficulty, management of neurotrophic keratitis can be quite challenging. The earlier you start medication, the better as you halt disease progression.

Below are common medications used for neurotrophic keratitis:

  • Oxervate. First FDA-approved treatment for neurotrophic keratitis; makes or sustains your eye’s nerve cells
  • Artificial tears. Keeps the cornea moist and clean; avoid products that contain preservatives as they may cause anatomical and physiological changes in the corneal epithelium
  • Oral doxycycline or tetracycline. Administered to prevent inflammation and excess mucus formation; may be taken with other medications
  • Routine medication: Eye drops, ointments, and artificial tears in all stages act as lubricants
  • Treat underlying conditions: Managing underlying conditions like herpes, diabetes, and other ocular surface disease helps reduce the impact on the existing neurotrophic keratitis
  • Topical insulin. Effective in repairing the damaged epithelium
  • Regenerating matrix agent (RGTA). Applied topically to encourage wound healing and repair
  • Cyanoacrylate and fibrin glue. Management of acute corneal perforations (up to 3 mm in diameter)8 

What is the First Line Treatment for Keratitis?

The first line of treatment for keratitis is fortified antibiotic administration.9 Fortified topical antibiotics prevent infections from developing in the affected eye. 

These antibiotics are prepared by mixing artificial tears or a saline solution (salt solution) with a recommended antibiotic. A common antibiotic for severe keratitis is fortified tobramycin.

Use fortified antibiotics as instructed by your doctor. Excessive use can harm your corneal epithelium and compromise the healing process.

What Other Treatments Are Available for Neurotrophic Keratitis?

Other treatment options for neurotrophic keratitis include the following:

  • Dietary supplements. Vitamin C supplements can slow down collagen degradation. On the other hand, formulations containing sodium hyaluronate, vitamin B6 taurine, and vitamin B12 can promote corneal wound healing.
  • Therapeutic soft contact lenses. To protect against infections and promote healing. Studies have shown that overnight wearing of scleral lenses can promote epithelial healing.
  • Cenegermin (Oxervate™). Topical medication for NK containing recombinant human nerve growth factor (NGF). Oxervate promotes corneal healing with 70% efficacy.10 It’s only used for adults with moderate to severe NK (administered six times daily for eight weeks).
  • Corneal neurotization surgery. It involves grafting the supraorbital or supratrochlear nerve onto the neurotrophic cornea. 
  • Partial or total tarsorrhaphy. It involves slightly sewing the eyelids to reduce the space between the top and bottom lid. It helps protect the cornea and encourage wound healing.
  • Amniotic membrane transplantation. Instead of tarsorrhaphy, you can undergo amniotic membrane transplantation to treat severe corneal neurotrophic ulcers.11 The most common procedure of amniotic membrane transplantation is Prokera (BioTissue).


  • Neurotrophic keratitis is a degenerative disorder resulting from loss of corneal sensation, breakdown of the epithelial lining with decreased wound healing.
  • Common causes of NK are long-term use of contact lenses, history of corneal surgery, chemical and physical burns, herpes keratitis, and underlying conditions.
  • Your eye doctor will subject you to various tests to make a proper diagnosis and the severity of the disease and administer treatment. 
  • Topical medications such as ointments, lubricants, and artificial tears are common treatments in mild and moderate NK.  
  • Other modes of treatment include conjunctival flap, use of cyanoacrylate glue, therapeutic contact lenses, and amniotic membrane transplantation. 
  • Advanced cases may require surgical interventions, corneal neurotization, or partial or total tarsorrhaphy.  
  • To avoid complications like permanent corneal scarring and blindness, you must start treatment early. 
Updated on  April 30, 2024
12 sources cited
Updated on  April 30, 2024
  1. Neurotrophic Keratitis.” National Organization for Rare Disorder (NORD), 2019.
  2. Neurotrophic Keratitis.” National Library of Medicine, 2023.
  3. Aguas et al. “Infectious keratitis: A review.” National Center for Biotechnology Information (NCBI), 2022.
  4. Shaheen et al. “Corneal Nerves in Health and Disease.” National Center for Biotechnology Information (NCBI), 2014.
  5. Diagnosing and Treating Neurotrophic Keratopathy.” American Academy of Ophthalmology (AAO), 2008.
  6. Dana et al. “Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy.” BMC Ophthalmology, 2021.
  7. Neurotrophic Keratitis.” American Academy of Ophthalmology (AAO), 2022. 
  8. Tissue Adhesives for Repair of Corneal Perforations.” American Academy of Ophthalmology (AAO), 2007.
  9. Austin et al. “Update on the Management of Infectious Keratitis.” National Center for Biotechnology Information (NCBI), 2017. 
  10. FDA approves first drug for neurotrophic keratitis, a rare eye disease.” Food and Drug Administration (FDA), 2018.
  11. Chen et al. “Amniotic membrane transplantation for severe neurotrophic corneal ulcers.”  British Journal of Ophthalmology (BMJ).
  12. Yang et al. “Corneal Innervation and Sensation: The Eye and Beyond.” National Center for Biotechnology Information (NCBI), 2018. 
The information provided on VisionCenter.org should not be used in place of actual information provided by a doctor or a specialist.