Citicoline Associated With Better Retinal Sensitivity in Glaucoma Cohort

In a prospective, non-randomized, open-label cohort study published in Frontiers in Neuroscience, researchers observed that add-on oral citicoline was associated with higher central retinal sensitivity and more stable fixation in patients with progressing open-angle glaucoma. The primary finding indicated that mean sensitivity on MP-3 microperimetry changed by +1.7 dB in the citicoline group, compared to -0.4 dB in the control group, a difference that remained significant after adjustment for time. These results suggest a potential neuroprotective association, though the study design limits causal interpretation.

The research addresses a persistent clinical challenge in glaucoma management: while lowering intraocular pressure (IOP) is the only proven treatment, many patients continue to experience disease progression despite adequate IOP control. Citicoline, a candidate neuroprotectant, has previously shown inconclusive evidence in trials relying mainly on perimetric and electrophysiological endpoints. This study aimed to clarify the association between add-on oral citicoline and a broader range of outcomes, including functional, structural, and vascular measures. The investigators offered oral citicoline at a dose of 500 mg twice daily to patients with progressing primary open-angle or normal-tension glaucoma who were already on stable topical therapy.

The study enrolled 80 patients, with 40 patients (40 eyes) in the citicoline group and 40 patients (40 eyes) in the control group. All participants completed the 12-month follow-up. The control group consisted of patients who declined the citicoline treatment due to cost. This non-randomized design means that treatment assignment was not random, and the groups may differ in ways beyond the intervention. The primary endpoint was the change in MP-3 microperimetric mean sensitivity, a measure of central retinal function. Secondary endpoints included fixation stability, visual field mean defect, retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness, and macular and peripapillary vessel density on optical coherence tomography angiography.

At 12 months, intraocular pressure did not differ between the two groups, with a p-value of 0.30, and there was no significant treatment-by-time interaction for IOP (p = 0.68). This indicates that the observed differences in retinal sensitivity were not driven by changes in eye pressure. The primary outcome, mean sensitivity, improved significantly in the citicoline group compared to controls, with an adjusted treatment-by-time p-value of less than 0.001. Fixation stability measures, specifically BCEA and P1, also improved only in the citicoline group, with p-values of 0.03 and 0.02, respectively. These functional improvements suggest that citicoline may support the stability of central vision in patients with glaucoma.

Secondary structural and vascular outcomes showed trends favoring the citicoline group, but the authors noted that none of these differences would survive correction for multiple testing. Visual field mean defect increased by 0.30 dB per year in the citicoline group versus 0.82 dB per year in controls (p = 0.01). RNFL thickness decreased by -0.55 μm per year in the citicoline group compared to -1.18 μm per year in controls (p = 0.01), and GCC thickness decreased by -0.42 μm per year versus -0.96 μm per year (p = 0.02). Macular and peripapillary vessel density decreased less in the citicoline group (p = 0.04 and 0.03, respectively). However, the authors emphasized that these structural and vascular differences were within the range of test-retest variability, limiting their clinical significance.

A post hoc responder analysis defined responders as patients with a confirmed gain of at least 1.5 dB in sensitivity without visual field progression. The proportion of responders was 65.0% in the citicoline group versus 22.5% in the control group. This substantial difference in responder rates further supports the association between citicoline and functional stability. Safety data indicated that adverse events were mild and transient, occurring in 12.5% of the citicoline group. No serious adverse events were reported, suggesting that the add-on therapy was well-tolerated over the 12-month period.

The study has several important limitations that must be considered when interpreting the results. First, the non-randomized, open-label design means that treatment was chosen by patients, and assessments were unmasked. This introduces the potential for bias, as both patients and investigators knew which group each participant was in. Second, the control group consisted of patients who declined treatment due to cost, which may differ from a placebo-controlled group in terms of motivation, health status, or other factors. The authors explicitly state that these findings describe an association, not efficacy, and that randomized, placebo-controlled trials are needed to confirm the neuroprotective effects of citicoline.

Despite these limitations, the study provides valuable insights into the potential role of citicoline in glaucoma management. The observed improvements in central retinal sensitivity and fixation stability, along with the higher responder rate, suggest that citicoline may offer additional benefits beyond IOP control. The consistent trends in structural and vascular outcomes, although not statistically robust after correction for multiple testing, align with the functional findings. The mild and transient nature of adverse events further supports the safety profile of the treatment.

Subject of Research: 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

Article Title: 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

Article References: Menna, F., Lupo, S., Pinelli, C., De Luca, L., Baldascino, A., Vingolo, E. M., & Meduri, A. (2026). 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. Frontiers in Neuroscience, 20, Article 2004530. https://doi.org/10.3389/fnins.2026.2004530

Image Credits: AI Generated

DOI: 10.3389/fnins.2026.2004530

Keywords: Oral, citicoline, add-on, therapy, open-angle, glaucoma, month, prospective, non-randomized, comparative, cohort, multimodal