Patient-Reported Symptoms, Ocular Surface Manifestations, and Risk Factors in Dupilumab-Associated Ocular Surface Disease: A Case-Control Study

Abstract

Purpose: Dupilumab-associated ocular surface disease (DAOSD) is a reported side effect with several manifestations and uncertain risk factors. This study uses objective assessments and a patient-reported questionnaire to evaluate ocular surface disease (OSD) in Dupilumab-treated patients. Methods: A case-control study, at ULS São João, Porto, Portugal, included 58 Dupilumab-treated adults categorized by the DAOSD Questionnaire. Cases (Group A, n=40) had ≥3 symptoms or ≥1 severe symptom, while controls (Group B, n=18) had <3 symptoms without daily impact. Ocular surface parameters were assessed including eye redness score, non-invasive break-up time (NIBUT), tear meniscus thickness, tear film stability evaluation (TFSE®), and tear osmolarity. The Ocular Surface Disease Index (OSDI) classified symptom severity. Results: Group A had significantly higher tear osmolarity (303.43±7.61 vs. 293.31±5.11 mOsm/L, p<0.001) and eye redness (2.00(1.00) vs. 1.00(1.00) points, p=0.036). TFSE® values were higher (252.76±3.30 vs. 138.74±3.43 points, p=0.094), while NIBUT was lower (1.00(4.00) vs. 6.50(10.00) s, p=0.078). Conjunctivitis was more frequent in Group A (57.50% vs. 33.33%, p=0.089), followed by posterior blepharitis (40.00% vs. 5.56%, p=0.008). OSDI scores had significantly different mean in Group A (27.32±20.24 vs. 2.11±3.24 points, p<0.001), with 37.5% exhibiting severe disease classification. Conclusion: DAOSD is associated with increased symptom burden. The DAOSD questionnaire correlated with OSDI scores and ocular surface changes, supporting its role in early detection and referral for ophthalmological management.