ESCRS 2026: When "dry eye” isn’t dry eye: a case-based look at corneal neuropathic pain

In a case-based presentation, the patient reports severe ocular burning, aching, and light sensitivity. She has been treated for dry eye disease for years, yet her symptoms remain disabling, and the ocular surface examination does not seem severe enough to explain them. The problem may not simply be that the dry eye has been undertreated. The problem may be that dry eye is not the whole diagnosis.

That was the central message of a case-based presentation by Anat Galor, MD, MSPH, of the Miami VA Healthcare System and Bascom Palmer Eye Institute, University of Miami, Miami, at the 2026 annual meeting of the European Society of Cataract and Refractive Surgeons in London.

Galor emphasized that chronic ocular pain can arise from several overlapping mechanisms. Nociceptive pain is driven primarily by factors on the ocular surface or in the environment that irritate normally functioning sensory nerves. In contrast, pain related to somatosensory nervous system dysfunction may involve peripheral corneal nerves, central pathways, autonomic pathways, or all three. This may result from neuropathic mechanisms, in which there is a lesion or disease affecting the somatosensory nervous system, or nociplastic mechanisms, in which pain processing becomes altered without ongoing tissue injury or a lesion or disease of the somatosensory system sufficient to explain symptom severity.

For clinicians, the challenge is therefore to resist simply labeling ocular pain as dry eye disease. Instead, the goal is to determine what is generating and maintaining the patient's pain. It may be dry eye disease, but it may not.

When the symptoms and signs do not match

The first clue may come from listening carefully to how patients describe what they feel.

The term dryness may be used to describe a patient's symptoms, but patients often use other words that can provide clues to the origin of their pain. Grittiness and foreign-body sensation are often associated with nociceptive processes, whereas burning, tingling, electric-like or stabbing pain, and pain triggered by normally innocuous stimuli such as wind or light may point toward an abnormal sensory system. Thus, listening carefully to the words patients use to describe their pain is important.

Another clue is when symptom severity seems markedly out of proportion to ocular surface findings. Abnormal corneal sensitivity, whether reduced or increased, can indicate dysfunction at the level of the corneal nerves. Persistence of pain after topical anesthetic can suggest that although the pain is perceived at the ocular surface, it is not generated entirely there. Because topical anesthetic reduces peripheral corneal input, substantial residual pain raises suspicion that central pain pathways are also contributing. Pain outside the ocular surface, such as pain with light touch of the surrounding skin, is another clue that the pain may not originate solely at the ocular surface. However, no single finding establishes the source of pain, and testing must be interpreted within the patient's broader clinical picture.

A patient who had more than dry eye

Galor illustrated the problem with the case of a 50-year-old woman with longstanding, severe bilateral ocular and periocular pain. Her medical history itself offered important clues: she had chronic inflammatory demyelinating polyneuropathy, chronic migraine, trigeminal neuralgia, and biopsy-confirmed Sjögren's disease.

Her ocular symptoms were profound. Her Ocular Surface Disease Index score was 71, and she described constant pain that reached 9 on a 10-point scale. Yet years of conventional dry-eye treatment, including preservative-free artificial tears and topical loteprednol, provided only modest relief.

The examination did not reveal ocular surface disease of a magnitude that could readily account for that degree of pain. Instead, several findings began to build a different story.

She reported prominent burning and pain provoked by light and wind. Corneal sensation testing demonstrated hypersensitivity, and in vivo confocal microscopy revealed abnormal-appearing corneal nerves. Her pain persisted despite topical anesthesia. She also had cutaneous allodynia over the face, greater on the right than the left, in the V1 and V2 trigeminal distributions.

Taken together with the history and symptom pattern, these findings supported dysfunction within the sensory nervous system. There was another layer. The patient's score on the COMPASS-31 questionnaire, which assesses autonomic symptoms, was 37, above the referenced normal cutoff of 28.5. This suggested that autonomic dysfunction might also be contributing to her broader pain phenotype.

The result was not a choice between Sjögren's disease and neuropathic pain. She could have both. Inflammation associated with Sjögren's disease and other ocular surface abnormalities could continue to provide nociceptive input, while peripheral nerve dysfunction, central amplification, and autonomic abnormalities could independently magnify or sustain pain. That distinction helps explain why simply escalating traditional dry-eye therapy may fail in some patients.

Treat the mechanism, not just the label

That change in diagnosis has practical consequences. If ongoing ocular surface inflammation or tear dysfunction is present, it should still be treated. But when peripheral corneal nerve abnormalities appear to contribute, therapies directed toward the corneal nerves can also be considered. Blood-derived products such as autologous serum tears and platelet-rich plasma are of particular interest. Other topical approaches include naltrexone, which has biologic rationale and early safety data, although clinical evidence for efficacy in corneal neuropathic pain remains limited.

New therapies are also beginning to emerge. Urcosimod, formerly OK-101, is an investigational topical therapy being developed specifically for neuropathic corneal pain and is moving into a global Phase 3 program. Another approach, the ETX-4143 ocular cooling device, targets the region of the long ciliary nerves with a single brief cooling treatment.

However, when central mechanisms predominate, topical therapy alone is unlikely to be sufficient. Oral neuromodulatory medications used for other neuropathic pain conditions may be considered. Other strategies may include transcutaneous electrical nerve stimulation, approaches directed at emotional contributors and coping mechanisms, and reducing environmental triggers, for example with FL-41 tinted lenses. Treatment therefore needs to be personalized according to what is identified in the history and examination.

The eye-body connection

Galor also emphasized that ocular symptoms should not be interpreted in isolation from the rest of the body, particularly in patients with autoimmune disease and systemic pain. That concept was highlighted in a study by Galor and colleagues involving 1,541 individuals who met classification criteria for Sjögren's disease.¹ The investigators found substantial heterogeneity in both ocular symptoms and signs. Approximately half of patients had reduced tear production, but roughly one-third reported significant spontaneous or evoked ocular pain.

More importantly, different ocular presentations tracked with different systemic manifestations. Patients who described grittiness or scratchiness, blurred vision, and reduced tear production were more likely to report oral dryness. In contrast, burning or stinging, discomfort in low-humidity environments, and relatively normal tear production and ocular surface staining were more closely associated with pain outside the eye.

In other words, even among patients who unquestionably had Sjögren's disease, not all ocular symptoms appeared to arise through the same mechanism. Some clustered with traditional glandular dysfunction and tear deficiency; others clustered with a broader pain phenotype.

This observation supports a broader principle that runs throughout Galor's work: the eye can provide clues to what is occurring elsewhere in the nervous system and the body.

Moving beyond dry eye

The goal, then, is not to replace dry eye disease with neuropathic corneal pain as another one-size-fits-all diagnosis. It is to stop assuming that every patient with ocular discomfort has the same disease.

A patient may have tear deficiency, ocular surface inflammation, peripheral nerve injury, central sensitization, autonomic dysfunction, systemic pain amplification, or several of these simultaneously. Environmental exposures and psychological and systemic factors can further influence how pain is experienced and maintained.

For the patient in Galor's case, the key clinical step was recognizing that the severity and character of her pain could not be explained by ocular surface findings alone. That recognition opens a much broader therapeutic landscape.

For clinicians faced with a patient whose dry eye remains severe despite appropriate therapy, Galor's message was to reconsider the mechanism: examine the ocular surface but also listen to the symptom descriptors; ask about wind and light sensitivity; assess corneal sensation and the response to topical anesthetic; look for cutaneous allodynia and systemic pain conditions; and, evaluate the health of the corneal nerves. Only then can treatment be directed at the particular combination of nociceptive, peripheral neuropathic, central, and autonomic mechanisms operating in that patient.

The objective is not simply to find a stronger dry-eye treatment. It is to find each patient's therapeutic “Goldilocks” by identifying what is actually driving the pain. In this patient, targeting multiple contributors, including ocular surface inflammation with topical cyclosporine, corneal nerve abnormalities with autologous serum tears, neuromodulation with a vagal nerve stimulator, emotional contributors through positive coping strategies, and environmental triggers with FL-41 tinted lenses, gradually led to improvement in her pain.

Reference
1. Baeza DC, Sanchez V, Goldhardt R, et al. The eye as a window to oral and pain symptoms in Sjögren's disease. Br J Ophthalmol. 2025;109:982-9. doi:10.1136/bjo-2024-326748.