{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:04:27Z","timestamp":1780639467404,"version":"3.54.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifteen of sixteen patients completed the study. HA + GSH-C4 significantly improved OSDI (p &amp;lt; 0.001), FACES scores (p = 0.012), TFBUT (p &amp;lt; 0.001), and NEI-SS (p &amp;lt; 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-\u03b3, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1780815","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:38:12Z","timestamp":1780637892000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"17","author":[{"given":"Gabriele","family":"Gallo Afflitto","sequence":"first","affiliation":[{"name":"Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]},{"name":"Moorfields Eye Hospital NHS Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialaura","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Petrone","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Chirico","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Martucci","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Minutolo","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Aiello","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Garaci","sequence":"additional","affiliation":[{"name":"Casa di cura San Raffaele","place":["Sulmona, L\u2019Aquila, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Matteucci","sequence":"additional","affiliation":[{"name":"Microbiology and Clinical Microbiology, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Nucci","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Experimental Medicine, University of Rome Tor Vergata","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/jcbfm.2013.236","article-title":"Pyroptotic neuronal cell death mediated by the AIM2 inflammasome","volume":"34","author":"Adamczak","year":"2014","journal-title":"J. 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