Early biochemical and microvascular alterations in asymmetric nonglaucomatous pseudoexfoliation syndrome: a multimodal aqueous humor, serum, OCTA, and CVI analysis.

PURPOSE: To evaluate serum and aqueous humor levels of hypoxia-inducible factor-1 alpha (HIF-1α), growth differentiation factor-15 (GDF-15), and fatty acid-binding protein-4 (FABP-4) in asymmetric nonglaucomatous pseudoexfoliation syndrome (PEX). METHODS: This cross-sectional comparative study included 153 eyes of 102 participants. Fifty-one asymmetric PEX patients contributed both PEX-positive (PEX+) and fellow PEX-negative (PEX-) eyes, while 51 eyes of age-matched cataract patients without PEX served as controls. Serum and aqueous humor samples were collected immediately before cataract surgery and analyzed for HIF-1α, GDF-15, and FABP-4 levels. Optical coherence tomography angiography (OCTA)-derived peripapillary vascular parameters (whole radial peripapillary capillaries vessel density [WRPC], inside disc radial peripapillary capillaries vessel density [IDRPC], peripapillary radial peripapillary capillaries vessel density [PPRPC]), peripapillary retinal nerve fiber layer (pRNFL) thickness, and choroidal vascularity index (CVI) measurements were evaluated. RESULTS: Serum HIF-1α, GDF-15, and FABP-4 levels were significantly higher in PEX patients compared with controls (all p<0.05). Aqueous HIF-1α levels were significantly elevated in both groups. PEX+ eyes demonstrated significantly higher aqueous FABP-4 levels compared with both controls and fellow PEX- eyes. OCTA analysis revealed significantly reduced WRPC, IDRPC, PPRPC, CVI, and pRNFL values in PEX+ eyes. Fellow PEX- eyes also exhibited significant microvascular and choroidal alterations compared with control cataract patients. CONCLUSION: Among the evaluated biomarkers, aqueous FABP-4 may be more closely associated with clinically affected eyes and microvascular impairment.