Long‐Term Ocular Outcomes of Dupilumab in Atopic Dermatitis: Results From the BioDay Registry

BACKGROUND: Dupilumab-associated ocular surface disease (DAOSD) is the most reported side effect in dupilumab-treated atopic dermatitis (AD) patients. We investigated the effect of long-term dupilumab treatment on ocular surface disease (OSD), conjunctival goblet cells (GCs), and tear fluid dupilumab levels and proteins. METHODS: This prospective study included moderate-to-severe AD patients at the University Medical Center Utrecht, the Netherlands. Patients initiating dupilumab between February 2020-October 2022 were eligible to participate in scheduled ophthalmological examinations alongside routine dermatological examinations at baseline, week 28, and last follow-up (≥ 2 years). OSD severity was assessed using the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score, with DAOSD defined as a ≥ 3-point increase from baseline. Conjunctival GC quantity and function were assessed with impression cytology. Dupilumab levels and proteins were measured in tear fluid. RESULTS: Forty-four patients were included. OSD was present in 90.9% (n = 40/44) of patients at all visits. DAOSD occurred in 22.7% (n = 10/44) of patients; 40.0% (n = 4/10) persisted or newly developed at last follow-up. Tear break-up time decreased while tear production increased. Tear fluid dupilumab levels and AD-related inflammatory proteins decreased over time. Conjunctival GCs decreased at last follow-up compared to baseline. Mucin5AC (MUC5AC) production in CK19-CD45-MUC5AC + cells decreased at week 28 and remained stable at last follow-up. CONCLUSION: OSD remained common during long-term dupilumab treatment in AD patients. Some patients developed worsening of OSD compatible with DAOSD, including delayed onset, highlighting the need for continued awareness of ocular side effects among clinicians. Reduced MUC5AC production and declining AD-related inflammatory proteins in tear fluid suggest changes in conjunctival homeostasis and ocular inflammation.