Fibrosis-Associated Fluid Biomarkers for Predicting Surgical Outcomes in Glaucoma Surgery: A Systematic Review

Glaucoma surgery is an effective treatment for advanced glaucoma, but fibrosis-induced bleb failure complicates its success. Understanding fibrosis and its modulation is essential for improving outcomes. This systematic review aims to provide an overview of biomarkers in aqueous humor, Tenon, and tear fluid associated with fibrosis and glaucoma surgery outcomes.

A systematic search was conducted in Embase and MEDLINE databases for articles on biomarkers in aqueous humor (AH) tear fluid (TF) and Tenon (TN) in relation to fibrosis and failure of glaucoma surgery. Articles published until December 5th, 2025, were included. The snowball method identified additional relevant studies, leading to a total of 20 articles.

353 biomarkers have been studied in relation to failed glaucoma surgery. MCP-1, TGF-β, VEGF, IFN-γ, MMP-3, SPARC, IL-1, IL-2, IL-6, IL-8, IL-10, and IL-18 in AH, TF and TN showed significant associations with glaucoma surgery outcomes. Overall, failure was more frequently associated with increased levels of pro-inflammatory biomarkers and decreased levels of anti-inflammatory biomarkers. High variability was found between observed biomarkers linked to fibrosis and glaucoma surgery failure due to inconsistencies across studies and differences between AH, TF and TN.

Further research, as well as standardized protocols, are essential to establish reliable biomarkers and develop targeted therapies to improve glaucoma surgery success.