Optimizing hyaluronic acid therapy for dry eye disease: a systematic review, meta-analysis, and meta-regression by...

To evaluate the clinical efficacy of HA-based eye drops for the treatment of DED, stratified by concentration and comparator type, through a systematic review, meta-analysis, and meta-regression.

A comprehensive literature search was conducted across PubMed, Web of Science, Scopus, and the Cochrane Library, identifying 39 randomized controlled trials involving 3,469 patients. Outcomes included the OSDI, TBUT, Schirmer's test, and corneal staining. Subgroup analyses compared HA to placebo, inactive lubricants, active compounds, and HA-based combinations. HA concentration groups were analyzed separately (≤0.1%, 0.15-0.18%, 0.2-0.3%). Risk of bias and publication bias were assessed using the Cochrane tool and funnel plots. Certainty of evidence was evaluated using GRADE.

HA-based formulations showed significant improvements in symptoms, especially in the 0.15-0.18% subgroup (MD = -14.23; p < 0.001), with consistent benefits in Schirmer's test. Comparisons with placebo, other lubricants, and active agents showed that HA was associated with greater improvement in patient-reported symptoms (OSDI), while objective signs (TBUT and staining) showed variable and often non-significant results. Monotherapy with HA outperformed HA-based combinations in OSDI. The most consistent efficacy and tolerability were observed in intermediate HA concentrations. No significant publication bias was detected.

HA eye drops, particularly formulations within the 0.15-0.18% range, were associated with meaningful improvements in patient-reported symptoms and were generally well tolerated, supporting their use as a first-line option for mild-to-moderate DED within the limitations of formulation heterogeneity.