Aim: To identify and analyze the key clinical, structural, and functional factors influencing the progression of glaucomatous optic neuropathy after antiglaucoma surgical intervention in patients with POAG, as well as to determine their prognostic value for optimizing postoperative patient management. Materials and Methods: A retrospective observational cohort study included 56 patients (56 operated eyes) with primary open‑angle glaucoma who underwent unilateral antiglaucoma surgery and were followed dynamically in the postoperative period. Based on follow‑up results, patients were divided into two groups: with postoperative disease progression (n = 20) and without progression (n = 36). Results: Postoperative disease progression was not associated with age, sex, axial length, or phacomorphic syndrome. Besides, disease progression was significantly associated with elevated plasma LOX1 concentration (≥ 80.1 pg/mL), reduced neuroretinal rim area (< 0.7 mm²), and elevated preoperative IOP (> 25 mmHg). In multivariate logistic regression analysis, reduced neuroretinal rim area < 0.7 mm² (OR = 12.9; 95% CI: 3.4–49.1; p < 0.05) and preoperative IOP > 25 mmHg (OR = 7.6; 95% CI: 1.9–29.4; p < 0.05) remained independent predictors of postoperative disease progression, while plasma LOX1 showed moderate discriminative performance (AUC = 0.664). Conclusions: Postoperative progression of glaucomatous optic neuropathy in patients with primary open‑angle glaucoma is determined by a combination of structural, biomechanical, and systemic vascular‑related factors. Preoperative IOP, neuroretinal rim morphology, and plasma LOX1 levels have prognostic significance and should be considered for postoperative risk stratification and individualized follow‑up.