Early Ocular-Surface Changes During Dupilumab Treatment According to Hyaluronic Acid Use: A Prospective Cohort Study

Background: Ocular-surface abnormalities are common in patients with moderate-to-severe atopic dermatitis and may predispose to dupilumab-associated ocular surface disease (DAOSD). We investigated early ocular-surface changes during dupilumab treatment and whether baseline-guided hyaluronic acid (HA) eye-drop use was associated with more favorable ocular outcomes. Methods: In this prospective single-center cohort study, patients with moderate-to-severe atopic dermatitis underwent ophthalmologic assessment before dupilumab initiation and after 4 months. HA 0.15% eye drops were prescribed to patients with at least one basal or reflex Schirmer value ≤15 mm and ocular symptoms. Ocular outcomes included tear break-up time (TBUT), basal and reflex Schirmer tests, meibography, and the Ocular Surface Disease Index (OSDI). Follow-up values were compared between HA users and non-users using baseline-adjusted models with false-discovery-rate correction. Results: Thirty-nine patients were included; 18 received HA eye drops and 21 did not. Twenty-seven patients (69.2%) had at least one baseline Schirmer value ≤15 mm. At 4 months, reflex Schirmer values were higher in HA users than in non-users after baseline adjustment (adjusted mean difference, 5.60 mm; 95% CI, 1.64-9.57; p = 0.007; q = 0.035). In the low-Schirmer subgroup, HA use was associated with higher reflex Schirmer (8.50 mm; 95% CI, 4.84-12.17; q < 0.001) and basal Schirmer values (5.07 mm; 95% CI, 1.41-8.73; q = 0.022). Among untreated patients with low baseline Schirmer values, reflex tear production decreased in eight of nine patients, despite OSDI scores remaining within the conventional normal range. Conclusions: HA supplementation at dupilumab initiation was associated with more favorable changes in tear production, particularly among patients with reduced baseline Schirmer measurements. Objective deterioration in tear production despite persistently low OSDI scores highlights the limitations of symptom-based assessment alone. These findings support baseline ophthalmologic evaluation and combined objective and symptom monitoring during dupilumab treatment. Larger controlled studies are needed to determine whether early, targeted HA eye-drop use can prevent clinically relevant dupilumab-associated ocular surface disease.