Association of Inflammatory and Ischemic Markers with Posterior Segment Parameters in Pseudoexfoliation Syndrome and Glaucoma

<b>Objective:</b> This study aimed to investigate the structural, vascular, and biochemical alterations in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PXG) and to evaluate the associations between serum biomarkers, the retinal nerve fiber layer (RNFL), choroidal thickness (CT), and vessel density (VD) in these groups. <b>Methods:</b> All subjects underwent spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) to assess RNFL thickness, CT, and VD. Serum levels of inflammatory and oxidative stress biomarkers-including malondialdehyde (MDA), glutathione (GSH), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), galectin-3, and SCUBE-1-were analyzed, and regression and ROC curve analyses were performed to evaluate predictive value and diagnostic performance. <b>Results:</b> A total of 80 patients were included and are listed as follows: 25 controls, 30 with PES, and 25 with PXG. There were no significant differences among groups in terms of age or gender. RNFL thickness, CT, and VD were significantly reduced in the PXG group compared to the PES and control groups (<i>p</i> < 0.001). PXG patients showed the most pronounced reductions in both peripapillary and macular CT, as well as superficial and deep VD. Serum iNOS, SCUBE-1, galectin-3, and MDA levels were significantly elevated in PXG, while GSH levels were lower (<i>p</i> < 0.001); NO levels showed no significant differences. In the PES and PXG groups, several ocular parameters correlated significantly with serum biomarkers, particularly iNOS, MDA, and GSH. Regression analysis in PXG patients identified iNOS and MDA as significant predictors of RNFL thickness and VD. ROC analysis demonstrated that MDA and GSH exhibited the highest diagnostic accuracy among the tested biomarkers for distinguishing PXG patients from controls. <b>Conclusions:</b> PXG is associated with significant structural, vascular, and biochemical alterations, including reduced RNFL thickness, choroidal thinning, and decreased VD. Altered serum levels of MDA and GSH were significantly associated with these ocular changes and demonstrated the highest diagnostic accuracy among the biomarkers evaluated. These findings support their potential utility as non-invasive biomarkers for distinguishing PXG from PES and healthy controls and for monitoring disease progression.