Randomized Single-Masked Study of Preservative-Free Versus Preserved Hyaluronic Acid in Dry Eye Disease
In brief
Preservative-free hyaluronic acid reduced dry-eye symptoms more than preserved drops
In a 6-month randomized trial of 47 patients, symptom scores fell more with preservative-free hyaluronic acid, and about 40% reached normal scores compared with none using benzalkonium chloride-preserved drops. Both treatments improved dry-eye symptoms and signs, but several clinical measures did not differ between groups at the final visit; the small trial leaves the long-term advantage uncertain.
- Journal
- Translational vision science & technology (Q1)
- Published
- 2 November 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Radu Bucsan, Jacqueline Chua, Li Chi, Dan Deleanu, Madalina Totir, Ruxandra Coroleuca, et al.
- PMID
- 42986170
- DOI
- 10.1167/tvst.15.11.6
Why clinicians should know about it
- Picked for Ophthalmology (top studies of the week, 8 November 2026): Randomized comparison of dry-eye treatments and symptoms
Abstract
PURPOSE: To compare the effects of preservative-free hyaluronic acid (PF HA) versus benzalkonium chloride-preserved hyaluronic acid (BAK HA) on symptoms and signs of dry eye disease (DED) using identical formulations except for preservative content. METHODS: In this randomized, single-masked, 6-month trial, 47 patients with DED were randomized to receive PF HA or BAK HA. The primary outcome was the change in Ocular Surface Disease Index (OSDI) score from baseline to month 6. Secondary outcomes included non-invasive tear break-up time (NIBUT), Schirmer I test, fluorescein tear break-up time (TBUT), fluorescein corneal staining (FCS), lissamine green conjunctival staining (LCS), best-corrected visual acuity (BCVA), and instillation frequency. Continuous and ordinal outcomes were analyzed using linear mixed-effects and mixed-effects ordinal logistic regression models, respectively. RESULTS: Forty-three patients completed the study. PF HA produced a greater OSDI score reduction than BAK HA (adjusted change, -14.36 vs. -9.42; P = 0.001), and ∼40% of PF HA-treated patients achieved normal OSDI scores at the final visit, compared with none in the BAK HA group. At the final visit, no significant between-group differences were observed for NIBUT, Schirmer I, TBUT, BCVA, FCS, or LCS. PF HA showed more favorable longitudinal changes in symptoms and selected signs, including OSDI (P < 0.001), NIBUT (P = 0.017), FCS (P = 0.002), and LCS (P < 0.001), indicating a treatment-by-time effect. PF HA was associated with lower instillation frequency (P < 0.001). CONCLUSIONS: Both formulations improved DED signs and symptoms. PF HA provided greater symptomatic relief and showed more favorable longitudinal changes. TRANSLATIONAL RELEVANCE: These findings support the translation of experimental knowledge regarding preservative-induced ocular surface toxicity into evidence-based therapeutic decisions for long-term patient care.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.