Dry eye disease (DED) is a prevalent ocular surface disorder traditionally attributed to tear film instability, inflammation, and loss of ocular surface homeostasis. Despite advances in anti-inflammatory therapies and a more sophisticated understanding of pathophysiology, response to treatment is often poor and inconsistent, suggesting additional underlying mechanisms are at play. Here we explore a possible primary role of neuropathy in driving the pathogenesis of DED. Corneal nerves provide afferent feedback through the sensory ophthalmic branch of the trigeminal nerve. This information generates an efferent output through motor nerves, parasympathetic nerves of cranial nerve VII, and the sympathetic nerves of the superior cervical ganglion. Disturbances to this circuit lead to tear film dysfunction, loss of homeostasis, corneal epithelial cell and ECM degradation, which may perpetuate a cycle of degeneration. Recognizing DED as a subclinical neuropathy may guide the development of novel therapeutic strategies focused on restoring corneal nerve integrity, extracellular matrix stability, and epithelial homeostasis.
Almaoui et al. (2026) studied this question.