Association Between Biologic Therapy and Ocular Adverse Events in Chronic Rhinosinusitis with Nasal Polyps

Introduction: Biologic therapies are increasingly used for chronic rhinosinusitis with nasal polyps (CRSwNP), but ocular adverse effects have been reported with related agents. This study evaluated whether biologic treatment for CRSwNP is associated with increased risk of adverse ocular outcomes compared with matched non-biologic controls.

Methods: Using the TriNetX database, a multicenter retrospective cohort study was performed. Adult patients with a history of CRSwNP either received or did not receive biologic therapy within 6 months of diagnosis. Biologics included dupilumab, omalizumab, mepolizumab, benralizumab, tezepelumab, and depemokimab. Patients with preexisting ocular outcomes within the year preceding the index event were excluded. Incidences of conjunctivitis, eyelid rosacea, blurred vision, keratitis, blepharitis, glaucoma, and ocular irritation (foreign body sensation, swelling/mass, redness/discharge of the eye and/or ocular pain) within 5 years of the index event were assessed. Propensity score matching (PSM) balanced demographics and comorbidities between cohorts, and risk ratios with 95% CIs were calculated with statistical significance defined as p< 0.05.

Results: After PSM, 2,720 patients were included in each cohort. Biologic use was associated with higher risk of conjunctivitis (p < 0.0001, RR 2.157 [1.77, 2.629]), glaucoma (p= 0.0059, RR 1.53 [1.127, 2.077]), blurred vision (p=0.0174, RR 1.468 [1.068, 2.018]), keratitis (p=0.0175, RR 1.9 [1.109, 3.257]), and ocular irritation (p=0.0452, RR 1.563 [1.006, 2.427]). No significant association was observed between biologic exposure and blepharitis (p=0.1826, RR 1.379 [0.858, 2.218]) or eyelid rosacea (p=0.3157, RR 1.4 [0.723, 2.71]).

Conclusions: Biologic therapy for CRSwNP was associated with increased risk of conjunctivitis, glaucoma, keratitis, and blurred vision, with a borderline increase in ocular irritation, while blepharitis and eyelid rosacea were not significant. These findings support counseling and symptom monitoring, and highlight the need for further mechanistic study and drug-specific risk stratification.