Oral citicoline as add-on therapy in open-angle glaucoma: a 12-month prospective, non-randomized comparative cohort study with multimodal microperimetric, structural and OCT angiography assessment

Background Lowering intraocular pressure (IOP) is the only proven treatment for glaucoma, yet many patients progress despite adequate IOP control. Evidence for citicoline, a candidate neuroprotectant, is inconclusive and relies mainly on perimetric and electrophysiological endpoints. We evaluated the association between add-on oral citicoline and functional, structural and vascular outcomes. Methods In this prospective, non-randomized, open-label cohort study, patients with progressing primary open-angle or normal-tension glaucoma on stable topical therapy were offered oral citicoline 500 mg twice daily; those who accepted and those who declined because of cost were followed for 12 months. Forty patients (40 eyes) per group were enrolled and all completed follow-up. The primary endpoint was the change in MP-3 microperimetric mean sensitivity. Secondary endpoints were fixation stability (BCEA, P1), visual field mean defect (MD), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, macular and peripapillary vessel density (VD) on OCT angiography, a post hoc responder analysis and safety. Results IOP did not differ between groups at 12 months ( p = 0.30) or over time (treatment × time, p = 0.68). Mean sensitivity changed by +1.7 ± 1.3 dB with citicoline and −0.4 ± 1.2 dB in controls (adjusted treatment × time, p < 0.001); BCEA and P1 improved only with citicoline ( p = 0.03 and 0.02). MD increased by 0.30 versus 0.82 dB/year ( p = 0.01), RNFL and GCC thinned by −0.55 versus −1.18 μm/year ( p = 0.01) and −0.42 versus −0.96 μm/year ( p = 0.02), and macular and peripapillary VD decreased less with citicoline ( p = 0.04 and 0.03); none of these secondary differences would survive correction for multiple testing, and structural and vascular differences were within test–retest variability. Responders (confirmed gain ≥1.5 dB without visual field progression) were 65.0% versus 22.5%. Adverse events were mild and transient (12.5%). Conclusion Add-on oral citicoline was associated with higher central retinal sensitivity and more stable fixation at 12 months with comparable IOP; secondary findings were small and exploratory. Because treatment was chosen by patients and assessments were unmasked, these findings describe an association, not efficacy; randomized, placebo-controlled trials are needed.