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.