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

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.

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.

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.

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.