Effects Of A Tear Substitute Containing Hyaluronic Acid 0.2% With Or Without Hydrocortisone 0.001% On Sign/Symptoms Of Dry Eye Disease And Tear Cortisol Levels: A Prospective, Randomized, Double-Masked, Controlled Clinical Trial

This study aimed at (i) comparing the effects of HA 0.2% + hydrocortisone 0.001% versus HA 0.2% on DED signs and symptoms in patients with mild-to-moderate dry eye disease (DED), and (ii) quantifying tear cortisol levels before and after the two treatments.

Single-center, spontaneous, randomized, double-masked controlled clinical trial conducted at the Complex Ophthalmology Unit, University Hospital of Cagliari (Cagliari, Italy).

Patients with mild-to-moderate DED were randomized 1:1 to receive eye drops containing HA 0.2% + hydrocortisone 0.001% (group 1) or HA 0.2% alone (group 2) and were evaluated at baseline, day 15 and day 45. Outcomes included ocular surface disease index (OSDI) score, corneal and conjunctival staining (NEI score), tear breakup time (TBUT), Schirmer test and intraocular pressure. Tear samples were collected at a fixed time (10:00 am) using standard Schirmer strips. Tear cortisol was quantified by HPLC–mass spectrometry. The injected aliquot corresponded to 5 mm of a diluted strip, standardized to 10 μL tear load. Mixed-effects models accounted for inter-eye correlation. Between-group comparisons used ANCOVA mixed models adjusted for baseline.

Overall, 38 patients (51.2±18.1 years) were included. OSDI score improved in group 1 at day 45 (from 25 [19–31] to 12 [10–22]; p=0.002) but not in group 2. TBUT increased from 4 (4–6) to 7 (5–8) seconds at day 45 (p=0.036) but not in group 2. Corneal/conjunctival staining and Schirmer test showed no between-group differences. Tear cortisol decreased significantly in group 1 (from 1.9 [1.8–2.1] to 1.1 [0.7–1.7] and 1.1 [0.4–1.6] pg/µl, respectively at day 15 and 45 [both p<0.001]), while no changes were detected in group 2. A significant difference was observed for tear cortisol reduction between the two groups after 15 days (p=0.025) and 45 days (p=0.009). Cortisol levels were significantly associated with TBUT changes (β = −1.25, p=0.046).

HA 0.2% supplemented with low-dose hydrocortisone (0.001%) produced a significant reduction in tear cortisol levels and improved ocular discomfort symptoms as well as tear film stability in patients with mild-to-moderate DED. It is possible to speculate that supplementation with hydrocortisone eye drops could support the restoration of a state of functional para-inflammation that is crucial for the maintenance of ocular surface homeostasis.