Neuropathic corneal pain is a recently defined condition that is often misdiagnosed and extremely difficult to treat. It is a condition in which corneal pain responds to normal, non-painful stimuli.1,2 This occurs when nociceptors of the cornea become dysfunctional. Persistent damage and inflammation results in acute nociceptor pain that can transition to chronic neuropathic pain, which is more difficult to manage.1-3 Increased hypersensitivity to repeated physiological or noxious stimuli develops.1-3 Central nerves in the brain become hypersensitized and detect pain independent of what is happening to the eye.4

Patients can progress to having symptoms of anxiety, depression and apathy.1 Neuropathic corneal pain has several features in common with conditions such as fibromyalgia and migraines since they share the same hypersensitivity to normal stimuli and the tendency to become chronic. 

Differential Challenges

Unfortunately, there are more questions than answers as to how to diagnose this affliction with certainty. Since impaired corneal nerve function is the hallmark observation, patients often experience a severe sensation of pain/irritation, burning, dryness and light sensitivity. Focal facial dystonia and blepharospasms are not uncommon.1 There are many known causes for neuropathic corneal pain, including chronic ocular surface disease, post-surgical complications, herpetic infection and toxic keratopathies. Overall, many triggers can lead to corneal nerve damage resulting in corneal neuropathy.4-6

As eyecare providers, our job is to decide whether the pain is a result of sensitized peripheral nociceptors or due to a central pain. Applying topical anesthetic can aid in this distinction. If the pain diminishes greatly or goes away entirely, the patient is experiencing peripheral sensitization.1,4 Applying a soft contact lens or moisture goggles may also neutralize any evaporative component of tear film dysfunction and decrease peripheral pain but not central sensitization.6 With confocal microscopy, direct evidence of nerve injury can be seen.1,3,4

Overall, consider neuropathic corneal pain any time a patient has symptoms that out-distance objective findings (“pain without stain/phantom cornea”).1,4-6 A complete eye examination investigating pain features (chronicity, intensity, systemic connections) is crucial. Use the Ocular Pain Assessment Survey to quantify pain and quality of life impact.1  


Individualized treatments should concentrate on restoring the ocular surface to minimize inflammation and avoid further nerve insult.1,3 A stepwise escalation therapy is recommended when a diagnosis is suspected, but once central corneal sensitization has occurred, invasive central pain pathway modulation is necessary.1,4 

Ocular surface treatment options (artificial tears, systemic and topical antibiotics for blepharitis, sclerals, cyclosporine, topical steroids) are used early in management.1,3 Neuro-regenerative therapies (autologous serum, nerve growth factor, fibronectin, amniotic membranes) are commonly relied upon. Systemic analgesics, antidepressives and antipsychotics are necessary especially with central sensitization of pain.1,3 Central pain modulation treatment when intractable also includes electrical stimulation, intrathecal infusions of analgesics, acupuncture and intravenous (IV) immunoglobulin.1,5 Vitamin B supplements and injection of botulinum toxin have been investigated and appear to also show some promise.1

I had a patient who had exhausted nearly all options for her neuropathic corneal pain and has recently started IV immunoglobulin treatment, which seems to help. This has been reported as a good therapeutic option for alleviating pain in various immune-mediated neurologic disorders, with minimal side effects.5 

Unfortunately, neuropathic pain continues to vex all who deal with it, and there is no one therapeutic approach for every patient. Let’s hope IV immunoglobulin might be an effective option. We welcome studies to help determine its efficacy and define appropriate protocols for using it for neuropathic corneal pain.

1. Rapuano C, Shovlin J. Herpes simplex virus dendritic epithelial keratitis. Accessed October 15, 2022.  

2. Herpes simplex—immunity serology. Public Health Ontario. Updated October 7, 2020. Accessed October 15, 2022.

3. Corey L, Spear PG: Infections with herpes simplex viruses. N Engl J Med. 1986;314:686-91.

4. Wang J, Cherlan DG, Goshe JM. Utility of HSV serology for chronic corneal pathology. Eye Contact Lens. 2020;46(3):190-3.