Citicoline as an Adjunct Therapy in Glaucoma: A Systematic Review of Clinical Outcomes and Safety

Background/Objectives: Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell loss and visual field deterioration despite adequate intraocular pressure control. Neuroprotective adjunct therapies have therefore been investigated, and citicoline has emerged as a potential candidate. We conducted a systematic review to summarize and critically appraise the evidence on the effects of citicoline, used as an adjunctive therapy, on visual function, functional vision, and quality of life in patients with glaucoma. Methods: A systematic literature search was performed in major electronic databases (PubMed, Scopus, and Web of Science) following PRISMA guidelines. Randomized and non-randomized clinical studies evaluating citicoline as adjunctive therapy in glaucoma were included. Outcomes of interest comprised visual function, electrophysiology, structural optical coherence tomography parameters, quality of life, and safety. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Results: Fifteen studies were included in this review, ten randomized controlled trials and five non-randomized clinical trials. Included studies showed heterogeneous designs and follow-up durations. Several studies reported improvements in electrophysiological responses, including retinal and post-retinal functional markers, and relative stabilization of selected visual field indices, with some studies reporting preservation of retinal nerve fiber layer and ganglion cell complex thickness under stable intraocular pressure. However, these surrogate outcomes were not consistently accompanied by improvements in visual acuity or patient-reported quality-of-life measures. Methodological limitations and endpoint variability reduced comparability across studies. Across oral, topical, and intramuscular routes of administration, citicoline was generally reported to have a favorable safety and tolerability profile. Conclusions: Current evidence suggests that citicoline may exert neurobiological effects compatible with neuroprotection in glaucoma, but the clinical significance of these findings remains uncertain. Available data are insufficient to support routine clinical recommendation. Well-designed randomized trials with standardized, patient-relevant outcomes are required to determine whether these effects translate into meaningful visual benefit.