Efficacy of hyaluronic acid and butyroyl glutathione in the management of glaucoma-related ocular surface disease: a prospective, interventional, double-blind, cross-over post market study

Introduction – To evaluate the efficacy of a novel eye drop formulation containing hyaluronic acid (0.2%) and butyroyl-glutathione (GSHC4, 0.4%) in glaucoma-associated ocular surface disease (G-OSD), and to explore putative mechanisms of action through in vitro assays of corneal epithelial wound healing and cytokine modulation under basal, inflammatory, and oxidative stress conditions. Methods – In this preliminary, hypothesis-generating, prospective, double-blind, cross-over study, 16 patients with glaucoma or ocular hypertension and coexisting dry eye symptoms were randomized to receive either HA alone or HA + GSH-C4 for 4 weeks, separated by a 1-week washout. Clinical endpoints included the Ocular Surface Disease Index (OSDI), FACES scale, tear film break-up time (TFBUT), Schirmer test, and NEI fluorescein staining. Tear cytokines were quantified at multiple timepoints. In vitro, human corneal epithelial cells underwent scratch-wound assays and cytokine profiling. Results – Fifteen of sixteen patients completed the study. HA + GSH-C4 significantly improved OSDI (p < 0.001), FACES scores (p = 0.012), TFBUT (p < 0.001), and NEI-SS (p < 0.001) compared with HA alone. No treatment-related adverse events were observed. Tear cytokine analysis revealed a reversible treatment-specific elevation of selected mediators (e.g., IFN-γ, IL-12p70) consistent with a controlled pro-repair response. The HA + GSH-C4 accelerated epithelial wound closure and selectively suppressed MCP-1 across all tested conditions. Discussion – The HA + GSH-C4 formulation improved G-OSD symptoms and ocular surface stability, accompanied by a dynamic cytokine response in tears. These findings support its clinical utility and suggest a dual mechanism involving barrier restoration and modulation of ocular surface immune responses.