A neurotrophic ulcer is an open wound on the cornea that forms because the nerve supply to the eye’s surface has been damaged or destroyed. The cornea is the most densely innervated tissue in the human body, and when those sensory nerves stop working properly, the surface loses its ability to heal, produce adequate tears, and even trigger the protective blink reflex. The result is a degenerative condition called neurotrophic keratopathy, which can progress from subtle surface drying all the way to ulceration and, in the worst cases, perforation of the cornea itself. Understanding what disrupts corneal nerves, how to recognize the problem early, and what treatments exist at each stage can make the difference between preserving vision and losing it.
Why the Cornea Depends on Its Nerves
Most people think of nerves as wiring that lets you feel pain. Corneal nerves do that, but they also perform a second, less obvious job: they release growth and repair factors that keep the surface cells healthy and cycling normally. When you blink, that reflex is triggered partly by corneal nerve signaling. When your eye waters in response to wind or dust, corneal nerves are behind that too. Remove or damage those nerves and the surface starts to break down, not because something is attacking it, but because the maintenance system has gone offline.1PubMed Central. Neurotrophic keratopathy: Update in diagnosis and management This is why neurotrophic ulcers are so tricky: the cornea looks like it has an infection or an injury, but the root cause is a failure of nerve-driven healing rather than an external assault.
What Damages Corneal Nerves
The sensory nerves reaching the cornea travel through a branch of the trigeminal nerve, the large nerve that supplies feeling to most of your face. Anything that injures this pathway, from the brainstem all the way to the corneal surface, can set the stage for a neurotrophic ulcer. The causes fall into a few broad categories.
Herpes simplex and herpes zoster (shingles) infections are among the most common culprits. These viruses live inside nerve tissue and can destroy corneal nerve fibers during active flare-ups or through repeated episodes of inflammation.2PubMed Central. Neurotrophic keratitis: current challenges and future prospects Chemical burns to the eye surface are another major cause, wiping out nerve endings along with the epithelial cells they support. Corneal and refractive surgeries, including LASIK, sever nerve fibers when the tissue is cut; most people recover full sensation over months, but a small percentage do not.
Diabetes deserves special attention. Chronic high blood sugar gradually damages small nerve fibers throughout the body, and the cornea is no exception. Diabetic corneal neuropathy is common but underdiagnosed, in part because many people with diabetes do not report eye pain or dryness until significant surface damage has already occurred.3PubMed Central. Diabetic Corneal Neuropathy Neurosurgical procedures that compress or cut the trigeminal nerve, such as operations for acoustic neuromas or trigeminal neuralgia, can also cause immediate and profound loss of corneal sensation. Less frequent causes include multiple sclerosis, certain autoimmune conditions like rheumatoid arthritis, and congenital insensitivity to pain.4PubMed Central. Diagnosis and management of neurotrophic keratitis
In a case series of patients with systemic-disease-related neurotrophic keratopathy treated with recombinant nerve growth factor, post-neuroma surgery accounted for the largest share of cases, followed by diabetes, with smaller contributions from rheumatoid arthritis, trauma, prior eye surgery, atopic disease, and Graves’ disease.5PubMed Central. Neurotrophic Keratopathy in Systemic Diseases: A Case Series on Patients Treated With rh-NGF The common thread across all of these is damage to trigeminal innervation, regardless of where along the nerve the injury happens.
How It Is Diagnosed and Staged
One of the biggest challenges with neurotrophic keratopathy is that reduced corneal sensation often goes unnoticed by the patient. If your cornea cannot feel pain properly, you may not realize that something is wrong until your vision starts to blur or your eye looks red for weeks on end. Clinicians test corneal sensitivity using an esthesiometer, a device that touches or presses against the corneal surface to measure how much stimulus it takes before you feel something. Newer disposable versions of this tool are being developed to improve accuracy and ease of use in the clinic.6PubMed. New disposable esthesiometer (KeraSenseⓇ) to improve diagnosis and management of neurotrophic keratitis
Alongside sensitivity testing, doctors look at tear film stability, the height of the tear meniscus along the lower lid, and the degree of surface staining with fluorescein dye.7PubMed Central. Detection of Subclinical Neurotrophic Keratopathy by Non-Contact Esthesiometry These measurements help distinguish neurotrophic keratopathy from garden-variety dry eye, which can look similar on the surface.
Once the diagnosis is established, the condition is classified using the Mackie staging system, which divides neurotrophic keratopathy into three stages based on severity.8PubMed. In vivo microscopic and optical coherence tomography classification of neurotrophic keratopathy Stage 1 involves superficial irregularity and dryness of the corneal surface but no open wound. Stage 2 features a persistent epithelial defect, meaning a patch of the surface layer has broken down and will not close on its own. Stage 3 is a full-thickness ulcer with stromal melting, carrying a real risk of perforation. In one clinical study, eyes presenting for treatment were roughly equally divided among all three stages, suggesting that many people arrive at the clinic only after the disease has already progressed significantly.9PubMed. Neurotrophic keratitis: Frequency, etiologies, clinical management and outcomes
Conservative and Early Treatment
Treatment is guided by stage. At Stage 1, the goal is to protect the fragile corneal surface and support whatever healing capacity remains. Preservative-free lubricating drops, gels, and ointments are the first line, often used frequently throughout the day. Punctal plugs, tiny devices inserted into the tear drainage channels, can help keep natural and artificial tears on the eye longer. Importantly, any eye drops containing preservatives should be removed from the regimen, because preservatives themselves are mildly toxic to an already compromised surface.10Cornea. Neurotrophic Keratopathy: Current Concepts, Management, and Emerging Treatments
If the surface breaks down into a persistent epithelial defect (Stage 2), more aggressive intervention is needed. Autologous serum eye drops, made from your own blood and containing a natural mix of growth factors, have shown encouraging results. In one study comparing autologous serum drops to amniotic membrane transplantation in eyes with neurotrophic corneal ulcers, about 70% of eyes treated with serum drops healed completely over roughly six months of follow-up, and visual acuity improved in 90% of treated eyes.11PubMed. A comparison of the efficacy of autologous serum eye drops with amniotic membrane transplantation in neurotrophic keratitis Therapeutic contact lenses, which act as a bandage shielding the defect from the mechanical scrubbing of the eyelid, are another common step at this stage.
Cenegermin and Nerve Growth Factor
The arrival of cenegermin (marketed as Oxervate) represented a genuine shift in how neurotrophic keratopathy is treated. This is a topical eye drop containing a recombinant form of human nerve growth factor (NGF), a protein the corneal nerves normally release to keep the surface cells dividing and repairing. By supplying it externally, the drop effectively substitutes for what the damaged nerves can no longer provide.12PubMed Central. A Novel Treatment for Neurotrophic Corneal Ulcer Using Topical Cenegermin (OXERVATEâ„¢) Containing Recombinant Human Nerve Growth Factor Clinical trials showed it could heal persistent epithelial defects that had resisted conventional therapy, restoring corneal integrity even in moderate-to-severe cases.
The catch is cost. A health technology assessment conducted for the UK’s NICE found that the company’s economic model for cenegermin had serious structural problems, including questionable assumptions about lifetime treatment effects and ongoing costs after healing. An independent analysis produced a cost-effectiveness figure well above standard thresholds, and the committee concluded that cenegermin could not be recommended at the proposed price.13PubMed Central. Cenegermin for Treating Neurotrophic Keratitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal In other health systems, including the United States, cenegermin is available but often requires prior authorization and can carry a steep out-of-pocket price. For patients with moderate-to-severe disease who have not responded to lubricants, serum drops, or contact lenses, the drug remains one of the few treatments that directly targets the underlying problem rather than just protecting the surface.
Surgical Options
When medical therapy cannot hold the line, or when a Stage 3 ulcer threatens perforation, surgery enters the picture. Two of the most commonly compared procedures for persistent epithelial defects are tarsorrhaphy (partially stitching the eyelids together to shield the cornea) and amniotic membrane transplantation (placing a patch of donated amniotic membrane over the wound to promote healing).
A prospective study of 60 patients found that tarsorrhaphy produced faster healing, with a mean time of about 10 days compared to roughly 18 days for amniotic membrane transplantation.14PubMed Central. A comparative study of tarsorrhaphy and amniotic membrane transplantation in the healing of persistent corneal epithelial defects However, a separate comparative study found that amniotic membrane transplantation achieved a somewhat higher overall healing rate (about 86% versus 70%), though the difference was not statistically significant, and tarsorrhaphy was associated with more corneal scarring.15PubMed Central. Amniotic Membrane Transplantation versus Tarsorrhaphy for the Treatment of Persistent Corneal Epithelial Defects: A Comparative Study in a Tertiary Eye Care Facility in Riyadh, Saudi Arabia In practice, the choice often depends on the urgency of the situation: tarsorrhaphy is quick and can be done at the bedside, while amniotic membrane transplantation may leave the cornea in better cosmetic and optical shape afterward.
Corneal Neurotization
For patients whose corneal nerves are permanently destroyed, the most ambitious treatment option is corneal neurotization, a microsurgical technique that reroutes a healthy sensory nerve from elsewhere (often the supraorbital or supratrochlear nerve above the eyebrow, or a sural nerve graft from the leg) to the cornea. The goal is not just to heal the current ulcer but to restore actual sensation to the corneal surface, addressing the root cause rather than managing its downstream effects.16PubMed Central. Corneal neurotization for the treatment of neurotrophic keratopathy
Results have been promising. In one series using sural nerve grafts, corneal sensation improved significantly in all quadrants of the cornea by one year after surgery, with early improvement detectable in most patients by three months and in over 80% by six months.17PLoS ONE. Clinical outcomes of corneal neurotization using sural nerve graft in neurotrophic keratopathy Studies consistently show improvements in epithelial integrity and overall ocular surface health after the procedure. Younger patients tend to recover faster and more completely, which makes sense given that nerve regeneration slows with age.18American Journal of Ophthalmology Case Reports. Minimally invasive corneal neurotization for neurotrophic keratopathy: The potential effect of age, denervation chronicity and lesion location The procedure can be done through a direct nerve transfer or an indirect nerve graft, with comparable long-term outcomes reported for both approaches. This is still a relatively specialized surgery, available mainly at academic centers, but its ability to permanently restore sensation makes it a significant option for people with severe, recurrent disease.
Matrix Regenerating Agents
An emerging class of topical treatment targets the extracellular matrix, the scaffolding between cells that helps organize healing. Matrix regenerating agents (RGTA) are synthetic molecules that mimic natural sugar-protein complexes in the tissue, essentially providing a temporary framework for new cells to grow across. In a small study of 11 patients with neurotrophic ulcers that had not responded to standard treatment, RGTA eye drops achieved complete corneal healing in about 73% of cases over an average of roughly nine weeks. The ulcer area shrank significantly within the first week and continued to decrease steadily over the following weeks.19Investigative Ophthalmology & Visual Science. Topical Treatment with a New Matrix Therapy Agent (RGTA) for the Treatment of Corneal Neurotrophic Ulcers Individual case reports have echoed these findings, with some patients experiencing dramatic recovery of visual function.20PubMed Central. Matrix Regenerating Agent (RGTA) in a Neurotrophic Corneal Ulcer RGTA is not yet a mainstream first-line therapy, but it offers another tool when conventional drops and growth factors have not worked.
Preventing Neurotrophic Ulcers
Prevention starts with recognizing who is at risk. If you have diabetes, a history of herpes simplex or zoster eye infections, or have undergone neurosurgery or extensive corneal surgery, your corneal nerves may be compromised even if your eyes feel fine. Routine screening for reduced corneal sensation in these groups can catch the problem before it progresses to an open wound.
For people already diagnosed with early-stage neurotrophic keratopathy, the most important preventive step is rigorous surface protection. That means using preservative-free artificial tears consistently, avoiding contact-lens wear that could stress the fragile epithelium, and stopping any eye drops that contain preservatives. Punctal occlusion can be added to maximize the tear film.10Cornea. Neurotrophic Keratopathy: Current Concepts, Management, and Emerging Treatments Environmental factors matter too: dry air, wind, and prolonged screen time all accelerate tear evaporation and can push a vulnerable cornea past its tipping point. Moisture-chamber glasses, which create a small humid environment around the eye, are a low-tech option that some patients find helpful.
Prompt treatment of herpes flare-ups is critical for anyone with a history of herpetic eye disease, since each recurrence inflicts additional nerve damage. Long-term antiviral prophylaxis may be worth discussing with an ophthalmologist if flare-ups are frequent. For people with diabetes, improved blood sugar control has been associated with slower progression of small-fiber neuropathy throughout the body, and the cornea is part of that picture.
Quality of Life and the Burden of Living With It
Neurotrophic keratopathy is sometimes treated as a niche condition, but its impact on daily life is real and measurable. A utility analysis found that the condition significantly reduces quality of life regardless of the patient’s visual acuity or disease severity. What drove the lowest quality-of-life scores were difficulty performing everyday tasks and a sense of dependence on others, rather than the degree of vision loss per se.21PubMed. Impact of neurotrophic keratopathy on quality of life: a utility analysis
Qualitative research paints a more detailed picture. When patients were asked to describe their experience, the most commonly reported symptoms included redness, sensitivity to light, general eye discomfort, dry eye, and blurred vision. The most frequently cited life impacts were frustration, difficulty driving, trouble reading, and an underlying worry about going blind.22PubMed Central. Development of the neurotrophic keratopathy questionnaire: qualitative research The fear of vision loss was reported by nearly half of participants, even among those whose current vision was relatively preserved.
Paradoxically, patients with neurotrophic keratopathy can also experience significant ocular pain despite having reduced corneal sensation. In a study of patients with graft-versus-host disease, those who also had neurotrophic keratopathy reported higher pain intensity, more burning, and greater light sensitivity than those without it.23Investigative Ophthalmology & Visual Science. Impact of Neurotrophic Keratopathy on Eye Pain and Quality-of-Life-Related Parameters in Patients with Ocular Graft-Versus-Host Disease This seems counterintuitive for a condition defined by nerve damage, but it reflects the fact that dysfunctional nerves can generate abnormal pain signals even as they fail to perform their normal protective and healing roles. Patients who are told their condition involves “reduced sensation” sometimes feel dismissed when they report that their eye hurts, which adds to the psychological burden.
Neurotrophic Keratopathy in Children
Though far less common than in adults, neurotrophic keratopathy does occur in children. The causes include both congenital conditions (such as congenital insensitivity to pain or Goldenhar syndrome) and acquired injuries from trauma, surgery, or infection. Children present unique challenges because they may be unable to describe symptoms, their compliance with frequent drop regimens is harder to maintain, and amblyopia (lazy eye) from prolonged corneal opacity can permanently affect visual development if not addressed quickly.24PubMed. Neurotrophic Keratopathy in Pediatric Patients
Treatment follows the same general ladder as in adults: lubrication, antibiotics to prevent secondary infection, serum drops, and, if needed, corneal neurotization. The surgical reinnervation approach has gained particular attention in pediatric cases because children’s nerves have a greater capacity for regeneration, meaning the long-term payoff of restoring sensation may be even greater than in adults. Still, published experience remains limited, and most of the evidence comes from small case series rather than controlled trials.
When Neurotrophic Ulcers Are Mistaken for Something Else
One of the practical dangers of neurotrophic keratopathy is misdiagnosis. A non-healing corneal ulcer can easily be attributed to dry eye disease, recurrent erosion syndrome, or a smoldering infection, especially if no one checks corneal sensation. Dry eye is by far the most common look-alike: both conditions cause surface staining, blurred vision, and discomfort. The key distinguishing feature is reduced or absent corneal sensation, which is not a feature of ordinary dry eye. If a clinician treats a neurotrophic ulcer as simple dry eye, the patient may spend months on standard lubricants without improvement, during which the ulcer can progress to stromal melting.
Infectious keratitis is another common misdiagnosis. Because the surface breakdown in neurotrophic keratopathy creates an entry point for bacteria, a neurotrophic ulcer can become secondarily infected, and at that point the infection may take center stage while the underlying nerve damage goes unrecognized. Antibiotics will clear the infection, but if the neurotrophic component is not addressed, the cycle of breakdown and infection repeats. The take-home point for anyone with a corneal ulcer that refuses to heal despite appropriate treatment: ask whether corneal sensation has been tested. It is a simple exam that can redirect the entire management plan.
Exposure keratopathy, which occurs when the eyelids do not close fully (from Bell’s palsy, thyroid eye disease, or post-surgical lid changes), can also mimic neurotrophic disease. In exposure cases, the cornea dries out because it is physically uncovered, not because the nerves are damaged. However, the two conditions can coexist: someone who has had neurosurgery may have both a trigeminal nerve injury reducing sensation and a facial nerve injury preventing full lid closure, creating a double threat to the corneal surface. Recognizing overlap is important because treating only one component will leave the other free to cause continued damage.