When the eyes and nose collide: The shared pathways of rhinoconjunctivitis

Although allergic rhinoconjunctivitis (ARC) is highly prevalent and involves both nasal and ocular symptoms, the mechanisms proposed to connect these responses remain poorly integrated, limiting a comprehensive understanding of the disease. Multiple anatomic, neural, and immunologic pathways have been proposed to explain the nasal-ocular interactions in ARC, yet these mechanisms remain dispersed across the literature without a recent unifying analysis. This review brings together current evidence to clarify the pathways that drive the rhinoconjunctivitis response. Specifically, anatomic connections, including the nasolacrimal duct and shared venous drainage, allow for the physical movement of antigens and mediators between the sites. Furthermore, the shared trigeminal and autonomic neural pathways allow for a rapid reflex response between the eye and nose after allergen triggers. Immune mediators, including histamine and eosinophilic proteins, can also diffuse both locally and systemically to promote cross-tissue inflammation. This appraisal takes a novel approach by exploring an aspect of ARC often mentioned but widely underappreciated in the literature, which is the bilateral responses after unilateral allergen challenges, which reflect complex integrated neural and inflammatory responses. Moreover, these integrated mechanisms provide a rationale for cross-site therapeutic effects, including improved ocular symptoms with intranasal corticosteroid use. Although anatomic, neural, and immunologic pathways have been described, the precise interactions underlying bilateral and cross-site responses are still largely underdefined, representing a major gap in the literature, particularly in terms of ocular allergy research. By clarifying these interconnected pathways, researchers may inform more effective treatment strategies resulting in better patient outcomes.