Background: Glaucoma is a progressive optic neuropathy, characterised by a complex pathophysiology, with mitochondrial dysfunction playing a significant role in the cellular damage and apoptosis of ganglion cells. Niacin is a precursor to several molecules acting as coenzymes in the mitochondrial production of ATP, in DNA repair and in the reduction of reactive oxygen species. The objective of this systematic review is to assess the impact of daily niacin intake on glaucoma. Methods: Case–control and cohort studies regarding niacin and glaucoma, indexed in PubMed, Web of Science, Cochrane and Scopus, were included. Other study methodologies, studies regarding niacin in other ocular disease or other nutrients in glaucoma were excluded. Bias was assessed using the Newcastle–Ottawa Scale. The study protocol was registered in the PROSPERO database (no. CRD42024578889). Results: Five case–control studies were included. In the pooled analysis, a significantly higher proportion of patients with high niacin consumption was found in the group without glaucoma compared to those with glaucoma as defined by ISGEO criteria (p-value < 0.00001; OR = 0.66, 95% CI 0.55–0.79) or as defined by retinal imaging (p-value = 0.02; OR = 0.63, 95% CI 0.43–0.94). Conclusions: Daily dietary intake of niacin is significantly lower in patients with glaucoma compared to the general population. Given different average daily intakes of niacin in these populations, different glaucoma definitions and several confounding variables which weaken the associations, large sample, standardised randomised controlled trials are needed to confirm the potential benefits of niacin in glaucoma.

Background/Objectives: Glaucoma is the primary cause of irreversible blindness worldwide, with enormous impact on quality of life and activities of daily living. Since one pathogenic mechanism of glaucoma is mitochondrial dysfunction at the retinal ganglion cell level, niacin has been proposed as an adjuvant treatment, with encouraging results. The objective of this prospective, non-randomized, single-arm clinical trial was to investigate the effect of oral supplementation with niacin on the quality of life of a cohort of glaucoma patients in Romania. Methods: Fifty-eight patients diagnosed with primary open angle glaucoma, under topical hypotensive treatment, were evaluated before and after a 6-month period of daily administration of 500 mg of oral niacinamide. Evaluation involved a complete ophthalmological exam and QoL quantification using the Glaucoma Quality of Life-15 (GQL-15) Questionnaire. Results: We found strong evidence that niacin supplementation for 6 months led to a statistically significant improvement in QoL scores among glaucoma patients (mean difference = −2.10, 95% CI: [−2.89, −1.32], p < 0.0001), including central and near vision (mean difference = −2.16, 95% CI: [−3.91, −0.4], p = 0.017), peripheral vision (mean difference = −2.66, 95% CI: [−0.23, −0.08], p < 0.001), and the glare and dark adaptation (mean difference = −5.24, 95% CI: [−0.33, −0.14], p < 0.001). In addition, B3 treatment resulted in a significant reduction in intraocular pressure in both eyes over 6 months (mean difference = 0.53, 95% CI: [0.21, 0.86] in the left eye and mean difference = 0.36, 95% CI: [0.04, 0.68] in the right eye), indicating potential clinical benefits. Conclusions: The observed GQL-15 score reductions suggest that B3 may be of benefit in glaucoma management. Further research with larger sample sizes and placebo-controlled designs is needed to confirm B3 potential impact on disease progression and quality of life. Trial Registration at clinicaltrials.gov: NCT07007260.

Background and Objectives: Primary open-angle glaucoma (POAG) is one of the leading ocular diseases leading to irreversible blindness and is often asymptomatic until advanced cases. While intraocular pressure reduction remains the cornerstone of treatment, neuroprotective strategies targeting retinal ganglion cell metabolism are actively investigated. Niacinamide (nicotinamide, vitamin B3), a precursor of NAD+, has shown neuroprotective potential in preclinical models. This exploratory study evaluated the short-term functional, structural, and electrophysiological effects of oral niacinamide supplementation in POAG. Materials and Methods: In this interventional study, patients with POAG received oral niacinamide 500 mg daily for six months. Visual field (VF) global and localized sensitivity (Mean Deviation [MD], Pattern Standard Deviation [PSD]), Optic Coherence Tomography (OCT)-derived peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), and Visual evoked potentials (VEP) latency parameters (P2 1.4 Hz, P100 1°, and P100 15′) were assessed at baseline and at six months. Because both eyes from some participants were included, primary longitudinal inference was based on clustered analyses using generalized estimating equations and linear mixed-effects models to account for inter-eye correlation. Eye-level paired analyses were used for exploratory comparison. Change–change relationships across modalities were explored using Spearman correlation. Results: After accounting for inter-eye correlation, no statistically significant change in MD was detected (mean ΔMD +0.43 dB; GEE p = 0.099; LME p = 0.101), and PSD remained stable. RNFL thickness showed a small decrease (−1.26 µm; GEE p = 0.046), while GCC did not change significantly. VEP P100 latencies remained stable, whereas P2 latency showed a small increase (+3.9 ms; GEE p = 0.039). Correlation analysis revealed a moderate association between changes in GCC and MD (ρ = 0.44), suggesting concordance between macular structural stability and global visual field performance. Conclusions: When inter-eye correlation is appropriately accounted for, six months of niacinamide supplementation in POAG is associated with overall functional, structural, and electrophysiological stability, without evidence of clinically meaningful improvement or progression. These findings support short-term safety and highlight the importance of clustered analytical approaches and macular-centered biomarkers in future glaucoma neuroprotection trials.