Aim — to develop an algorithm to guide neuroprotective therapy in railway workers undergoing long-term follow-up for primary open-angle glaucoma (POAG) judging from the efficacy of sequential administration of intravenous dosage form of Mexidol and oral tablets. Material and methods. All sorts of JSC Russian Railways employees with stage I—III POAG and well-controlled intraocular pressure were enrolled. Mexidol was first to be administered intravenously by a dropper in a day hospital (250 mg daily for 5 days) and then taken orally at home (125 mg t.i.d. for 3 months). A comprehensive ophthalmic examination with high-technology control was performed in all patients at their first, second, and third follow-up visits. Results. Data from 58 patients (96 eyes) were analyzed. Statistically significant improvements in perimetry and optical coherence tomography results were only obtained at a third visit, i.e. at the end of the course of Mexidol tablets. The treatment effect was most pronounced in stage I—II patients. Conclusion. The results suggest that combination therapy with intravenous and oral Mexidol received sequentially as well as long-term (3-month) administration of Mexidol tablets can both be recommended in POAG patients. It has been also found that neuroprotective therapy with Mexidol performs best for early stages of the disease.