On this episode of Inside Intrepid, Jake Lang, OD, FAAO, president of the Intrepid Eye Society and optometrist at Associated Eye Care, sits down with Selina McGee, OD, FAAO, of Bespoke Vision in Edmond, Oklahoma, and Damon Dierker, OD, FAAO, of Eye Surgeons of Indiana to work through four conditions most likely to be misdiagnosed as dry eye—and the clinical signals that give each one away.
Dry eye masqueraders
Dry eye is the most convenient diagnosis on the ocular surface. When a patient stops responding, most clinicians reach for another treatment. Drs. Lang, McGee, and Dierker argue for the opposite move: pause, step back, and ask, “What did I miss?”
The conversation covers conjunctivochalasis, superior limbic keratoconjunctivitis, palpebral conjunctiva pathology, and neurotrophic keratitis—each capable of mimicking dry eye closely enough to stay undetected through multiple visits. Dr. McGee explained that NK patients typically look terrible and their osmolarity is normal
Fast facts: Neurotrophic keratitis
- NK is classified as an orphan disease with an estimated prevalence of 1.6 to 5 per 10,000; stage 1 is the stage most commonly misidentified as dry eye.1
- Central corneal staining—not inferior—with normal or near-normal osmolarity needs to be investigated further to rule out NK.
- Persistent photophobia is nerve-mediated. It usually does not resolve with cyclosporine, lifitegrast, or any anti-inflammatory dry eye therapy.
- Risk factors include diabetes mellitus, herpetic keratitis, prior ocular surgery (ex., scleral buckles and glaucoma), and chemical injury.1
- Cenegermin (OXERVATE, Dompé) is the only FDA-approved therapy targeting corneal nerve regeneration.
NK: The dry eye masquerader with the highest stakes
In the REPARO trial evaluating cenegermin, 74% of treated patients achieved complete corneal healing at 8 weeks versus 19.6% with vehicle.2 The patient looks bad. The cornea stains centrally, the eye is inflamed, and they are wearing sunglasses indoors. Standard dry eye metrics do not explain it.
Osmolarity is the key differentiator. A patient with NK presents with a cornea that looks severely compromised but osmolarity that reads normal or near-normal. That mismatch is the signal to stop and reconsider.
Photophobia is the flag most clinicians attribute to the surface. Persistent, debilitating photophobia that does not improve with anti-inflammatory therapy is nerve-mediated—the underlying nerve damage usually does not respond to cyclosporine or lifitegrast.
Risk factor history closes the differential. Diabetic patients, those with prior herpetic keratitis, or anyone with a history of ocular or refractive surgery—all carry elevated baseline NK risk.1 Diabetic patients are frequently routed to retina, and the cornea is ignored in the process.
Diagnostic testing to confirm the NK diagnosis
Corneal esthesiometry is the definitive test. The Cochet-Bonnet esthesiometer quantitatively measures sensitivity at the central cornea and distinguishes nerve dysfunction from surface disease.
It is not yet in every clinic, but the clinical case for adding it is straightforward: when presentation and osmolarity point to NK, some form of esthesiometry confirms it before you commit to an 8-week course of OXERVATE.
Central staining plus normal osmolarity plus persistent photophobia plus a risk factor in the history equals a nerve workup, not another drop. Dr. Dierker noted that in his experience, persistent photophobia (with an unremarkable clinical exam) is almost always a nerve issue.
Key takeaways
- A cornea that looks terrible with normal osmolarity is an NK patient until proven otherwise.
- Staining patterns are diagnostic: inferior staining points to dry eye and exposure; central staining points to nerve dysfunction.
- Persistent photophobia that does not respond to anti-inflammatory therapy is a nerve symptom, not a surface symptom.
- Diabetic patients, post-surgical patients, and patients with a herpetic history carry elevated NK risk—screen proactively, not after treatment failure.
- When a patient stops responding to dry eye treatment, go back to the first visit and ask whether you are solving the original chief complaint.
Conclusion
Watch the full conversation with Dr. Lang, Dr. McGee, and Dr. Dierker for their approach to conjunctivochalasis, superior limbic keratoconjunctivitis (SLK), and palpebral conjunctiva pathology—and the exam techniques that surface each one before treatment fails.
For more on identifying and managing NK in clinical practice, read The History of Advancements in Neurotrophic Keratitis on Eyes On Eyecare.
