Allergic conjunctivitis: phenotype, pathophysiology, innate immune pathways, and treatment

Abstract

Allergic conjunctivitis (AC) is an inflammatory disorder of the ocular surface caused by allergic reactions to environmental substances. It presents with symptoms such as itching, redness of the eye, excessive tearing, and swelling/irritation in the eyes and eyelids. While many AC episodes occur on their own and go away, some forms of this disease are present in a chronic fashion or have the potential to cause serious loss of vision. In recent years, AC has been viewed as primarily an episodic irritative condition to a mucosal inflammatory condition in which the ocular surface provides an environment for the initiation and perpetuation of local immune responses. The molecular basis of AC represents a phase-linked inflammatory cascade: an immediate (minutes) mediator-driven response followed by a late (6–12 hours) cytokine/chemokine-driven cellular recruitment phase that can sustain symptoms and, in severe phenotypes, contribute to tissue remodeling. The initial response is due to the activation of mast cells via IgE-dependent pathways, producing the early phase response. The sustained response seen in the late phase of the disease is mediated by the action of lipid mediators and cytokines/chemokines involved in the recruitment of eosinophils and Th2-associated leukocytes. This narrative review synthesizes evidence on epithelial “alarmins” (TSLP, IL-33, IL-25) as upstream signals that may amplify type-2 inflammation in a phenotype-dependent manner, particularly in more severe or chronic disease, alongside established IgE/mast-cell biology. Further, we discuss neuroimmune mechanisms implicated in histamine-independent itch and symptom persistence, while noting that their clinical contribution likely varies across AC phenotypes. Finally, we will discuss how the mechanistic pathways relate to current limitations and to developing new therapeutic approaches.

Keywords

allergic conjunctivitis / inflammation / Th2 response / alarmins / therapeutics

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