Severe Dupilumab-Associated Ocular Surface Disease: Multicenter Experience and Management Considerations

Purpose: To evaluate severe dupilumab-associated ocular surface disease (DAOSD) and identify clinical features, risk factors, and outcomes associated with delayed ophthalmologic referral. Methods: A multicenter retrospective case series of 13 patients (26 eyes) with severe DAOSD presenting to tertiary centers between January 2014 and April 2026 was conducted. Clinical findings were analyzed alongside a focused review of current evidence on pathophysiology, diagnosis, and management. Results: Initial ocular symptoms were frequently mild and nonspecific, most commonly redness and pruritus (13/13, 100%), followed by blurred vision with tearing (3/13, 23.1%), eye pain (2/13, 15.4%), and mucoid discharge (2/13, 15.4%), contributing to delayed referral. Symptom onset ranged from 0 to 37 months after dupilumab initiation (mean 11.7 months). At presentation, advanced disease manifestations included limbitis (3/13, 23.1%), conjunctivalization with corneal neovascularization (3/13, 23.1%), limbal stem cell deficiency (2/13, 15.4%), and cicatricial conjunctivitis (1/13, 7.7%). Preexisting atopic ocular disease was present in 6/13 patients (46.2%). Management included lubrication, topical corticosteroids, calcineurin inhibitors, and scleral lenses. Dupilumab was discontinued in 7/13 patients (53.8%). Clinical stabilization was achieved in 12/13 patients (92.3%) over a mean follow-up of 21.4 ± 20.3 months. Conclusions: Severe DAOSD may be underrecognized, as mild early symptoms can delay referral and allow progression to advanced, vision-threatening complications. Preexisting ocular surface disease identifies a high-risk subgroup. Early ophthalmologic evaluation and timely referral are essential to prevent irreversible ocular surface damage and vision loss.