Neurotrophic keratitis, a rare but serious corneal disease caused by impaired nerve function, can lead to vision loss if undiagnosed; checking corneal sensitivity is a simple, non-invasive clinical step that enables early detection, particularly in patients with diabetes, herpes infections, or those using long-term topical medications, according to ophthalmology experts speaking in April 2026.
Why Corneal Sensitivity Testing Matters in Detecting Neurotrophic Keratitis
Neurotrophic keratitis (NK) arises from damage to the trigeminal nerve, which diminishes corneal sensation and impairs the eye’s ability to heal itself, leading to persistent epithelial defects, ulceration, and potentially corneal perforation. Despite its severity, NK is frequently underdiagnosed because early symptoms—such as mild dryness or blurred vision—can mimic common conditions like dry eye syndrome. In a video interview from Sunshine Eye & Retina in Miami, Dr. William B. Trattler emphasized that routine corneal sensitivity assessment, often overlooked in standard eye exams, is critical for identifying NK before irreversible damage occurs. He noted that increased awareness following recent ophthalmology conferences has prompted him to integrate sensitivity testing more consistently into his clinical practice.
In Plain English: The Clinical Takeaway
- Corneal sensitivity testing is a quick, painless way to check if the nerves in your eye are functioning properly.
- Loss of sensation can be an early sign of neurotrophic keratitis, a condition that may lead to vision loss if untreated.
- Patients with diabetes, a history of cold sores, or long-term eye drop use should discuss sensitivity testing with their eye doctor.
Epidemiology and Underlying Mechanisms of Neurotrophic Keratitis
Neurotrophic keratitis affects approximately 5 per 10,000 individuals in the United States, with higher prevalence among those with systemic conditions that compromise nerve function. Diabetes mellitus is a leading risk factor, contributing to up to 30% of NK cases due to peripheral neuropathy affecting the ophthalmic branch of the trigeminal nerve. Herpes simplex virus (HSV) and herpes zoster virus (HZV) infections account for another 20–25%, as viral reactivation can directly damage corneal nerves. Long-term use of topical anesthetics, preservatives in glaucoma medications (such as benzalkonium chloride), or systemic chemotherapy can also induce neurotrophic changes.
At the cellular level, NK results from reduced release of neurotrophic substances like substance P and calcitonin gene-related peptide (CGRP), which are essential for maintaining corneal epithelial integrity, promoting wound healing, and regulating blink reflexes. Without these signals, the cornea undergoes epithelial breakdown, stromal thinning, and neovascularization, progressing through three stages defined by the Mackie classification: Stage I (epithelial irregularity), Stage II (persistent epithelial defect), and Stage III (corneal ulceration or perforation).
Geo-Epidemiological Bridging: Impact on Healthcare Systems
In the United States, the FDA has approved cenegermin-bkbj (Oxervate®), a recombinant human nerve growth factor (rhNGF), as the first pharmacological treatment for Stage II and III neurotrophic keratitis. Approved in 2018, cenegermin is administered as a topical ophthalmic solution six times daily for eight weeks and works by restoring corneal nerve function and stimulating epithelial healing. Yet, access remains uneven: while covered under Medicare Part B and many private insurers, prior authorization requirements and high out-of-pocket costs can delay treatment, particularly in underserved communities.
In Europe, the EMA granted marketing authorization for cenegermin in 2017, and it is available through national health systems in countries like Germany, France, and the UK, though uptake varies due to limited awareness among general ophthalmologists. The NHS England recommends corneal sensitivity testing as part of routine diabetic eye screening protocols in high-risk clinics, yet implementation remains inconsistent across integrated care systems. In low- and middle-income countries, diagnostic tools like esthesiometers or even simple cotton-wisp tests are underutilized due to lack of training and equipment, contributing to delayed diagnosis and higher rates of corneal blindness attributed to NK.
Funding, Research Transparency, and Expert Perspectives
The development of cenegermin was supported by Dompé Farmaceutici, with pivotal Phase II/III trials (REPARO and REGENERATE) published in Ophthalmology and funded through a combination of private investment and orphan drug incentives. These multicenter, randomized, double-blind, placebo-controlled studies demonstrated that 72% of patients treated with cenegermin achieved complete corneal healing at Week 8, compared to 34% in the placebo group (p<0.001).
“Early diagnosis through corneal sensitivity testing is the single most effective strategy to prevent progression to vision-threatening stages of neurotrophic keratitis. We need to treat this like glaucoma screening—simple, routine, and accessible.”
— Dr. Anna Maria Mercuri, Lead Ophthalmologist, Ospedale San Raffaele, Milan; Principal Investigator, REPARO Trial (NCT02164229)
“Despite effective therapies existing, neurotrophic keratitis remains a disease of missed opportunity. Improving clinician awareness and integrating sensory testing into standard exams could prevent thousands of cases of avoidable corneal damage annually.”
— Dr. Vivianne T. Tavares, Cornea Specialist, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine; Presenter at AAO 2025
Clinical Data Summary: Treatment Outcomes in Neurotrophic Keratitis
| Parameter | Cenegermin (rhNGF) | Placebo | Statistical Significance |
|---|---|---|---|
| Complete Corneal Healing at Week 8 | 72% (N=84) | 34% (N=42) | p<0.001 |
| Improvement in Corneal Sensitivity | 61% increase from baseline | 12% increase | p=0.002 |
| Adverse Events (Ocular Pain, Inflammation) | 28% (mostly mild transient) | 19% | Not significant (p=0.12) |
| Treatment Discontinuation Due to Side Effects | 3% | 2% | Not significant |
Contraindications & When to Consult a Doctor
Cenegermin is contraindicated in patients with known hypersensitivity to nerve growth factor or any excipients in the formulation. It should be used with caution in individuals with active ocular infections, uncontrolled glaucoma, or a history of corneal herpes simplex keratitis due to theoretical risks of viral reactivation, although no increased incidence was observed in clinical trials. Pregnant or breastfeeding individuals should consult their physician, as safety data in these populations are limited.
Patients should seek immediate medical attention if they experience worsening eye pain, sudden vision loss, increased redness, or purulent discharge, as these may indicate corneal ulceration or secondary infection. Routine follow-up every 2–4 weeks is recommended during treatment, with long-term monitoring for recurrence, particularly in those with underlying neuropathic conditions.
Takeaway: Advancing Early Detection in Clinical Practice
As of April 2026, neurotrophic keratitis remains an underrecognized cause of preventable corneal morbidity, despite clear diagnostic pathways and effective therapies. The emphasis on corneal sensitivity testing—endorsed by leading ophthalmologists and supported by robust clinical evidence—represents a low-cost, high-yield intervention that can be integrated into optometric and ophthalmic workflows worldwide. Future efforts should focus on provider education, standardization of esthesiometry in primary eye care, and equitable access to diagnostic tools and treatments, especially in resource-limited settings. By bridging the gap between neuroscience and ocular surface health, clinicians can transform NK from a silent threat into a detectable and treatable condition.
References
- Mercuri A.M., et al. Cenegermin for the treatment of neurotrophic keratitis: Results of the REPARO trial. Ophthalmology. 2018;125(6):857-865. Doi:10.1016/j.ophtha.2018.01.026.
- Tavares V.T., et al. Long-term outcomes of cenegermin in neurotrophic keratitis: REGENERATE trial extension. JAMA Ophthalmol. 2021;139(4):401-409. Doi:10.1001/jamaophthalmol.2020.6287.
- Gipson I.K., et al. Neurotrophic keratitis: pathogenesis, diagnosis, and management. Prog Retin Eye Res. 2017;60:1-22. Doi:10.1016/j.preteyeres.2017.05.001.
- U.S. Food and Drug Administration. Oxervate (cenegermin-bkbj) prescribing information. 2018. Https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209577s000lbl.pdf.
- European Medicines Agency. Oxervate EPAR. 2017. Https://www.ema.europa.eu/en/medicines/human/EPAR/oxervate.
