Serum Alpha-1-Antitrypsin and Folic Acid as Biomarkers for Glaucoma Risk

Introduction: Glaucoma remains a major cause of irreversible blindness, and many patients progress despite adequate intraocular pressure (IOP) control, suggesting contributions from systemic metabolic and inflammatory factors. This study investigated serum folic acid and α-1-antitrypsin (AAT) levels in glaucoma and non-glaucoma participants and examined their associations with global retinal nerve fiber layer (RNFL) integrity to clarify their potential relevance to glaucoma risk and pathophysiology. Methods: In this case–control study, 31 open-angle glaucoma (OAG) patients and 26 controls underwent comprehensive ophthalmic assessment, venous blood sampling, and OCT-based global RNFL measurement. Serum folate and AAT were quantified using chemiluminescent immunoassay and ELISA, respectively. Data normality was evaluated with the Shapiro–Wilk test, and correlations were analyzed using Spearman’s rank coefficient. Statistical analyses were conducted in Jamovi (version 2.5.5), with significance set at p < 0.05. Results: Glaucoma patients showed significantly higher IOP (p < 0.001), lower serum folic acid (p = 0.007), and higher AAT levels (p = 0.028) compared to controls. In the RNFL subgroup (n = 48), glaucoma was associated with reduced global RNFL thickness (p < 0.001), lower folic acid (p = 0.026), and higher AAT levels (p = 0.011). AAT correlated inversely with both folic acid (rs = –0.485, p < 0.001) and global RNFL thickness (rs = –0.386, p = 0.017), while glaucoma status correlated positively with AAT and negatively with folic acid levels. Conclusion: Glaucoma is associated with a distinct systemic biochemical pattern characterized by elevated AAT and reduced folate, alongside structural optic nerve damage. The relationship between AAT, folate and RNFL thickness suggests a potential interaction between inflammatory and metabolic pathways in glaucomatous neurodegeneration. These findings highlight AAT and folate as accessible systemic biomarkers warranting further longitudinal and mechanistic investigation.