Hypoxia and growth factor profiling in high myopia: linking HIF-1α suppression and PDGF-BB activation to structural degeneration.

Introduction: High myopia is associated with structural and molecular changes in the eye, particularly involving hypoxia-responsive and fibrotic mediators. Growing evidence points to a subset of growth factors as central mediators of these alterations. Among these, our findings identify HIF-1α and PDGF-BB as key contributors to the progression of myopia. Methods: This cross-sectional study included 88 Caucasian patients undergoing cataract surgery, categorized into control, low myopia, and high myopia groups based on axial length. Clinical assessments involved interferometric axial length measurement, swept-source OCT for choroidal thickness, and maculopathy classification following IMI guidelines. Aqueous humor samples were collected intraoperatively and analyzed using multiplex Quantibody arrays to quantify HIF-1α, VEGF, HGF, PDGF-BB, IL-6, and IL-17. Statistical analyses included Kruskal-Wallis tests with Bonferroni correction and correlation analyses to explore associations between molecular profiles and clinical severity. Results: Patients with high myopia exhibited significantly reduced choroidal thickness and increased axial length ( Discussion: For the first time, this study identifies significant alterations in HIF-1α and PDGF-BB levels in high myopia, with consistent correlations to key clinical parameters such as axial length, choroidal thickness, and maculopathy severity. These findings indicate an association suggesting a shift from adaptive hypoxia signaling toward fibrotic remodeling in high myopia. The suppression of HIF-1α and upregulation of PDGF-BB suggest a molecular imbalance that may be associated with structural degeneration. The integration of clinical imaging and aqueous humor profiling supports the potential of HIF-1α and PDGF-BB as biomarkers and therapeutic targets in pathological myopia.