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Neurotrophic keratitis

Neurotrophic keratitis of the eye, pink, inflamed cornea.

What is neurotrophic keratitis?

Neurotrophic keratitis (NK) is when the cornea loses its ability to sense pain due to nerve damage. The cornea depends on sensation to function and heal properly, so NK can threaten your vision. It can lead to erosion, thinning and even perforation (a break through all the layers) of the cornea.

The cornea is the transparent membrane at the front of the eye. Its nerve endings are connected to the trigeminal nerve (also called the fifth cranial nerve). Damage to this nerve can cause this loss of sensation and affect the health of the surface of the cornea.

Causes of neurotrophic keratitis

The trigeminal nerve is the fifth and largest of 12 cranial nerves that leave the brainstem at the bottom of the brain. It has three branches and handles pain and touch signals from the face and the eye. Its ophthalmic branch processes the signal from the cornea.

A healthy cornea is very sensitive. It depends on sensation to trigger tear production and blinking so it can stay hydrated and clean. Sensory impulses from the cornea also help regulate its ability to regenerate and heal.

Damage anywhere along the path of the trigeminal nerve can cause neurotrophic keratitis.

This nerve is also part of an important system called the lacrimal functional unit (LFU). The LFU contains other nerves that are activated by the cornea’s sensory signals. They send signals from the brainstem to control blinking, produce the tear film and initiate healing. 

Therefore, damage to any part of the LFU can result in neurotrophic keratitis. It’s important for your eyecare provider to find out where in the LFU the problem started.

Damage to the cornea

The eyelids, lacrimal glands and the entire surface of the eye are all also part of the LFU. Many types of disease or trauma can affect them and lead to corneal damage. Depending on its severity, it can result in nerve damage and neurotrophic keratitis.

  • Herpes keratitis – Herpes simplex (also a cause of cold sores) and herpes zoster (also a cause of chickenpox and shingles) can be dormant in the body. Stress on the body such as a fever, use of steroid medication or psychological stress can activate the virus. The virus travels through the trigeminal nerve from the brain to the eye and causes damage in the process.

  • Corneal dystrophies – In these inherited disorders, deposits build up in the cornea that can affect the function of the nerve endings. Of all the dystrophies, the lattice and granular types are most likely to cause NK.

  • Topical anesthesia abuse – Drugs such as cocaine can be instilled in the eye, causing it to become numb. Anesthetic drops, sometimes prescribed after welder’s flash or a scratch of the eye, can be used for too long. Over time, these anesthetics can end up injuring the corneal nerves, resulting in infections and NK.

  • Contact lens overwear – Sleeping in, not cleaning or not replacing contact lenses when you are supposed to can inflame the cornea, eventually resulting in NK. 

  • Eye surgery – Corneal transplant and vision correction surgery such as LASIK and PRK can damage the surface and nerve endings. Surgery of other parts of the eye, such as cataract surgery, can also cause damage to the corneal nerves. 

  • Corneal burns – Injuries from hot liquids or chemicals can cause permanent damage to the nerves of the cornea and the cells that help maintain its surface (called limbal stem cells).

  • Preservatives in eyedrops – Long-term use of eyedrops containing preservatives can cause NK. A common preservative that is toxic to the cornea called benzalkonium chloride (BAK) can result in damage when used over long periods of time.

  • Eye medications – Certain topical medications reduce the ability of the corneal nerves to sense pain, leading to NK. These include timolol and betaxolol (glaucoma beta blockers), sulfacetamide (an antibiotic) and ketorolac and diclofenac sodium (NSAIDs). These medications are generally safe to use, and your eye doctor will be on the lookout for any side effects, should they occur.

  • Chronic inflammation – Inflammation of the eyelids caused by rosacea or other skin conditions, severe constant allergies, immune conditions and dry eye can cause NK.

  • Toxic exposure – The industrial chemicals hydrogen sulfide and carbon disulfide can damage the corneal nerves. Agents such as pepper spray can also cause this damage.

Damage to the trigeminal nerve

Trauma and disease that aren't related to the cornea can also damage the trigeminal nerve. For example, ocular surgery, a stroke or a tumor could impact its ability to function. This can lead to neurotrophic keratitis if the cornea loses too much sensation.

  • Neurosurgery – Surgery for trigeminal neuralgia — a condition where the trigeminal nerve produces signals for no apparent reason, and people experience pain in the face, eye, orbit and other parts of the head — can help with pain but often causes a loss of sensation to the cornea. Depending on the type of surgery, the likelihood of NK may vary, but all types of surgery have some risks.

  • Orbital and acoustic neuroma surgery – Orbital surgery such as scleral buckle procedures and others can damage the trigeminal nerve and other parts of the LFU. Acoustic neuromas are noncancerous tumors that grow on the main nerve connecting the inner ear to the brain. This nerve affects balance and hearing and sits very close to the trigeminal nerve. Surgery on this nerve can damage the trigeminal nerve.

  • Retinal surgery – Surgeries to the retina for retinal detachment or diabetic retinopathy can affect the trigeminal nerve and the LFU.

  • Stroke – When the part of the brain called the dorsolateral medulla has a stroke, it can damage the trigeminal nerve's center (the ganglion).

  • Face trauma – Injury of the bones and soft tissue around the eyes can injure different parts of the LFU.

  • Aneurysm – The trigeminal nerve travels through a space behind the eye called the cavernous sinus. An important artery (the carotid) that brings blood to the head and eye also travels through the cavernous sinus. When the carotid artery develops an outpouching (aneurysm), this swelling can press on and damage the trigeminal nerve. 

  • Systemic diseases – Multiple sclerosis, diabetes, leprosy and vitamin A deficiency all affect the nerves of the body and result in neuropathy. This is when the peripheral nerves malfunction, causing numbness and weakness.

  • Tumor – An acoustic neuroma can press on the trigeminal nerve, and other types of tumors can develop inside or on top of the trigeminal nerve itself. It is possible that trigeminal neuralgia — sharp shooting pains from the eye and face — is the first symptom of such a tumor and that NK develops later.

  • Congenital syndromes (present at birth) – Very rarely, the trigeminal does not develop normally, and a baby will be born with NK. A number of uncommon syndromes are associated with NK: dysautonomia, Mobius syndrome, Goldenhar-Gorlin syndrome, Riley-Day syndrome, familial corneal hypesthesia, and Congenital Insensitivity to Pain with Anhidrosis.

Other causes

NK doesn't always result directly from damage to the cornea or the trigeminal nerve. It may be related to other nerves within the LFU or to age-related corneal nerve changes.

  • Adie’s pupilThe pupil stays dilated even in bright light. This is caused by damage to the ciliary nerve right behind the eyeball that regulates pupil size and our ability to focus on close objects. Damage to this nerve can cause NK as well.

  • Age – NK becomes more common as we get older. One study found that NK is diagnosed at an average age of 68 years.

Stages of neurotrophic keratitis

Neurotrophic keratitis can range from mild — with people barely noticing they have a problem — to severe. Severe NK can cause devastating vision loss and the risk of losing the eye from corneal thinning or infection. The severity can be divided into three stages (called the “Mackie” classification system):

  • Stage 1 – The cornea gets slightly swollen and cloudy, with small erosions on the surface.

  • Stage 2 – The cornea's surface erodes off, creating a corneal ulcer. This ulcer is called a persistent epithelial defect (PED) if it doesn’t heal in two weeks.

  • Stage 3 – The corneal ulcer erodes deeper into the cornea, leading to the possibility of a full-thickness hole in the cornea (a perforation). 

Each stage has different levels of treatment and urgency. Patients with stage 1 should not wait longer than a few weeks before seeing a doctor. Patients with stage 2 should see a doctor within a day. Stage 3 is an emergency that requires immediate care, as corneal perforation can lead to rapid blindness and loss of the whole eyeball.


Complications depend on the stage of NK. Because of the numbness of the eye, people usually don’t feel discomfort from the corneal damage. The doctor will need to look for other signs and symptoms, including:

  • Blurry vision

  • Small erosions of the cornea

  • A cloudy and grayish appearance of the cornea

  • Scratch (abrasion) of the cornea

  • Corneal ulcer

  • Corneal infection 

  • Corneal inflammation

  • Perforation of the cornea

  • Infection of the inside of the eye (endophthalmitis)

  • Loss of the eye

NK can be a sign of other diseases, including a brain tumor, stroke or aneurysm. In these cases, it is very important that you work with your eye doctor and other specialists to get to the bottom of what may have caused your NK.


Corneal sensitivity testing

The level of numbing of the cornea is called corneal sensitivity. It can be evaluated by the eye doctor pressing a cotton-tipped applicator or a small piece of dental floss on the cornea. Because NK is most often localized in one eye only, the sensitivity on one side is compared to the other.

Sometimes, the exact amount of sensitivity needs to be measured. In these cases, the doctor can use a special device called an esthesiometer, or they might stimulate the nerve endings with capsaicin or heat. However, most clinics do not have these methods available. 

Slit-lamp and dilated fundus exam

A slit-lamp (also called a biomicroscope) allows the doctor to look at the surface and front of the eye and detect diseases of the eyelids, cornea and iris. This allows the detection of dry eye, pupillary abnormalities and other signs of NK. This part of the exam also detects underlying causes of NK, such as cataract or LASIK surgery. 

The slit-lamp exam is also essential in determining the stage of NK. It allows the doctor to evaluate whether there is an ulcer or even a perforation of the cornea.

A dilated fundus exam provides the doctor with a good view deeper inside the eye at the retina and optic nerve. These structures can be damaged when a tumor or aneurysm causes NK. Laser treatment of the retina and scleral buckle procedures for retinal detachment can also be causes of NK. They can be detected in this way.

Dry eye testing

NK and dry eye disease are intertwined conditions. Your doctor can detect dry eye by testing your tear production, tear stability, dry eye inflammation and tear salt concentration. Corneal and conjunctival staining tests can also detect scratches on the eye caused by dry eye.

Confocal microscopy

This test allows a direct look at the shape, size and number of corneal nerves. In NK, the size of the corneal nerves increases while the number decreases. This can be reversed with treatment.


Artificial tears and ointments

Artificial tears, gels and ointments are the first line of treatment for stage-1 NK. This treatment needs to be done many times a day, so doctors recommend using only preservative-free products. Some preservatives (such as BAK) can further damage the cornea and worsen NK. 

Punctal occlusion

Tears leave the surface of the eye by evaporation and through two drainage channels — one in each eyelid. These channels deposit tears into the back of the nose after every blink. 

The openings of these channels (called puncta) can be closed off (punctal occlusion) so the eye’s tear film can become thicker. This allows the cornea to heal faster. However, punctal occlusion may not be a good idea when NK is associated with a lot of inflammation. The inflammatory molecules in the tear film will not be able to drain from the surface.

Contact lenses

Contact lenses provide protection that allows epithelium cells to move from the edge of the cornea to the area that is eroded or damaged. 

  • Soft lenses – Soft contact lenses are called bandage contact lenses when used to help protect and heal the cornea. The Food and Drug Administration has only approved certain contact lens brands to be used this way. Patients are asked to sleep with the lens in while the cornea is healing. This can increase the risk of corneal infection, so antibiotic eye drops are often prescribed for anyone wearing a bandage lens.

  • Scleral lenses – These lenses are large and rigid. The edge rests on the white part of the eye (sclera), trapping a layer of tears behind the lens. This layer of tears protects the surface from eyelid blinking and allows the cornea to heal and stay healthy. Scleral lenses are custom designed for an individual eye by a contact lens specialist. They are usually covered by medical insurance.

Amniotic membranes

Researchers have found that part of the placenta and umbilical cord — the amnion — can heal injured tissue. This tissue is donated and used to heal eye ulcers and other diseases of the eye’s surface. It is thoroughly tested to make sure it’s safe. Then it is prepared for storage by freeze drying or a more advanced process called cryopreservation. 

The doctor will place the membrane on the cornea, similar to placing a contact lens on the eye. It is left on your eye for two to seven days. The amniotic membrane is thought to reduce inflammation, new blood vessel growth and scarring. It also helps epithelium cells move to the area of damage/ulceration.


Botox, or botulinum toxin, causes muscle paralysis. When injected into the upper eyelid, it can cause it to droop over the damaged or ulcerated cornea, protecting and helping it heal. Botox leaves muscles paralyzed for up to six months and cannot be reversed.

Vitamin C

Ascorbic acid (vitamin C) is present in high concentrations in the corneal epithelium. It helps epithelial stem cells grow better and promotes the healing of erosions. The recommended dose is 1 gram per day.


Doxycycline and tetracycline are medications that reduce the risk of melting the middle layer of the cornea. This is called corneal melt and can lead to perforation of the cornea and even loss of the whole eye. Other medications that work similarly to tetracyclines are N-acetylcysteine and medroxyprogesterone.


Steroid eye drops can reduce inflammation. But in the case of NK, they may slow down the healing of the ulcer and can even cause a corneal melt. 

Autologous serum tears

Autologous serum tears (AST) are isolated from our own blood. Both the red and white blood cells are removed, leaving blood serum that is diluted into 20% or 50%. ASTs contain growth factors and antioxidants that stop cell death (apoptosis) and help cells grow and move around on the cornea. They can help close a persistent epithelial defect and help grow back nerves in the cornea.

Platelet-rich plasma

PRP is similar to AST except with a higher concentration of blood platelets. Platelets cause blood to coagulate and also make factors that help damaged tissue to heal. 


Insulin, which is used to treat diabetes mellitus, can heal neurotrophic ulcers when applied as an eyedrop. One study showed it took an average of one month to fully heal the cornea.


Oxervate (cenegermin) is a recombinant human growth factor. It was approved by the FDA in 2018 for use in all stages (1-3) of NK. A drop is placed in the eye six times a day for eight weeks. In clinical trials, 72% of patients using the medication had their NK healed. One year later, 80% of these patients were still free of NK. 


This procedure is done for stages 2 and 3 of NK. It joins the upper and lower eyelid together, allowing the damaged cornea to heal. The cornea is usually not completely covered, so vision is still possible. 

Tarsorrhaphy is preferred over patching the eye shut because it allows more oxygen to the surface of the eye and reduces the risk of infection. Over 80% of patients with NK heal after they receive this procedure. A tarsorrhaphy can be removed once the eye has healed.

Corneal neurotization

This is one of the most exciting surgical procedures developed over recent years. It is used for severe stages of NK that did not heal with other therapies.

  • Direct neurotization – A part of a functioning trigeminal nerve is surgically connected to the eye that has NK. The most recent technique is called minimally invasive direct corneal neurotization. It is done through an almost invisible incision. 

  • Indirect neurotization – A nerve is transplanted from somewhere else in the body and used to connect a functioning trigeminal nerve to the eye with NK. This technique is highly advanced and requires a surgeon who is experienced with connecting nerves.

Matrix regenerating agents

Cacicol is a type of matrix-regenerating agent that has been used to heal neurotrophic ulcers. These agents contain molecules that are similar in structure to the natural components of the cornea but cannot be broken down as easily. These molecules will settle into the ulcer and provide a framework for healing cells to settle in the cornea and repair it. 

Cyanoacrylate glue

Corneal perforation is an emergency. It can be treated by applying cyanoacrylate glue — the same as superglue — to the leaking hole in the cornea. A contact lens will be placed on top of the perforated cornea. Once the leak is sealed, the cornea can start healing. Fibrin glue made from blood is also sometimes used. It has the advantage of being less toxic to the cornea than cyanoacrylate.

When to see an eye doctor

It’s important to have eye exams on a regular basis, even if you aren’t at a higher risk for neurotrophic keratitis. The American Optometric Association recommends yearly comprehensive eye exams for everyone beginning at age 6. 

However, if you do have a risk factor or if you have blurred vision together with a loss of sensation in or around your eye, seek out care as soon as possible.

Structure and function of the external eye and cornea. In External disease and cornea. BCSC Basic and Clinical Science Course Book 8. American Academy of Ophthalmology. 2020–2021. 

Post-herpes neurotrophic keratopathy: Aetiopathogenesis, clinical signs and current therapies. Archivos de la Sociedad Española de Oftalmología (English Edition). April 2019.

Topical anesthetic abuse keratopathy. EyeWiki. American Academy of Ophthalmology. Accessed August 2023.

Neurotrophic keratitis secondary to long-duration contact lens wearing Modern Optometry. July/August 2022.

Neurotrophic keratitis. National organization of rare diseases (NORD). Accessed August 2023

Chemical eye injury: pathophysiology, assessment, and management. Eye. November 2020.

Neurotrophic keratitis: current challenges and future prospects. Eye and Brain. June 2018.

Neurotrophic keratopathy after retinal detachment surgery combined with endo laser photocoagulation. Retinal Cases & Brief Reports. 2021.

Neurotrophic keratitis. StatPearls [Internet]. April 2023.

Neurotrophic keratitis. EyeWiki. American Academy of Ophthalmology. Accessed August 2023.

Diagnosing and treating neurotrophic keratopathy. EyeNet Magazine. American Academy of Ophthalmology. November 2023.

Case Series: Management of neurotrophic keratitis from familial dysautonomia. Optometry and Vision Science. August 2018.

Adie syndrome. National organization of rare diseases (NORD). Accessed August 2023.

Characterization of hydrogen sulfide toxicity to human corneal stromal fibroblasts. Annals of the New York Academy of Sciences. November 2020.

Clinical analysis of cavernous sinus anatomy, pathologies, diagnostics, surgical management and complications – Comprehensive review. Annals of Anatomy - Anatomischer Anzeiger. January 2023.

Neurotrophic keratopathy in the United States: An intelligent research in sight registry analysis. Ophthalmology. November 2022.

Corneal esthesiometry. EyeWiki. American Academy of Ophthalmology. Accessed August 2023.

Corneal neurotization—Indications, surgical techniques and outcomes Journal of Clinical Medicine. March 2023.

Commentary: Tarsorrhaphy: A stitch in time Indian Journal of Ophthalmology. January 2020.

Topical recombinant human nerve growth factor (cenegermin) for neurotrophic keratopathy: A multicenter randomized vehicle-controlled pivotal trial Ophthalmology. January 2020.

Efficacy of autologous serum gel in neurotrophic persistent corneal epithelial defects combined with lagophthalmos. Ophthalmology and Therapy. September 2022.

Autologous and allogenic serum tears. EyeWiki. American Academy of Ophthalmology. Accessed August 2023.

Amniotic membrane transplant. EyeWiki. American Academy of Ophthalmology. October 2023.

Topical insulin for refractory persistent corneal epithelial defects. European Journal of Ophthalmology. September 2020.

Effect of autologous platelet-rich plasma drops in the treatment of ocular surface disease. Clinical Ophthalmology. December 2022.

Clinical efficacy of platelet-rich plasma in the treatment of neurotrophic corneal ulcer. Journal of Ophthalmology. June 2018.

New pharmacological approaches for the treatment of neurotrophic keratitis. Frontiers in Pharmacology. March 2022.

Tissue adhesives for the management of corneal perforations and challenging corneal conditions. Clinical Ophthalmology. January 2023.

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