Reduced conjunctival goblet cells and altered tear film stability predispose atopic dermatitis patients to develop dupilumab-associated ocular surface disease and show a Th1/innate immune response in tear fluid

BACKGROUND: Atopic dermatitis (AD) is often associated with ocular surface disease (OSD). Dupilumab, an IL-4Rα inhibitor, is an effective treatment for AD but it sometimes induces dupilumab-associated OSD (DAOSD). DAOSD may associate with a paucity of conjunctival goblet cells or altered immune response; however, the mechanism remains undetermined. Therefore, we aimed to identify ophthalmological alterations and to explore the potential mechanisms of DAOSD in AD patients receiving dupilumab. METHODS: We conducted a prospective, single-arm, observational study with 50 moderate-to-severe AD patients receiving dupilumab for 24 weeks. We performed ophthalmological evaluations, conjunctival impression cytology analysis, and tear fluid profiling at baseline, weeks 4, 12, and 24. RESULTS: Clinical severity scores of AD indicated significant improvement with dupilumab. At baseline, 18% of patients already exhibited OSD. During the study period, DAOSD ever occurred in 46% of patients, and it was mild and controllable by topical anti-inflammatory drops. AD patients with reduced conjunctival goblet cells at baseline had significantly a lower level of BDNF and higher levels of VEGF-A, PDGF-BB, and MCP-1 in tears. Patients with DAOSD had higher residual AD severity at weeks 12 and 24. Elevated levels of IL-9, IL-16, and GM-CSF in tears were specific for new onset DAOSD, indicating a shift toward Th1/9 and innate immune activation. CONCLUSIONS: DAOSD is common but transient in AD patients receiving dupilumab. Its underlying mechanisms may involve pre-existing goblet cell deficiency, changes in tear composition, and an altered inflammatory profile. Timely ophthalmic intervention may mitigate the damage and symptoms associated with related complications.