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.