The Efficacy of Nicotinamide in Maintaining Mean Deviation in Glaucoma: A Systematic Review

Glaucoma is a major cause of blindness worldwide and is characterized by progressive retinal ganglion cell loss and visual field deterioration. Although intraocular pressure reduction remains the cornerstone of management, disease progression may occur despite optimal treatment. Nicotinamide, a precursor to nicotinamide adenine dinucleotide, has emerged as a potential neuroprotective therapy due to its role in mitochondrial function and cellular energy metabolism. This systematic review evaluated the efficacy of nicotinamide in preserving visual field mean deviation (MD) in adults with glaucoma, alongside its safety profile and broader ophthalmological outcomes. This systematic review was conducted in accordance with the PRISMA guidelines. MEDLINE, Embase, ClinicalTrials.gov, and the Cochrane Library were searched in March 2026. Randomized controlled trials (RCTs) involving adults with glaucoma receiving nicotinamide-containing interventions and reporting MD outcomes were included. Data extraction and risk of bias assessment using the Risk of Bias 2 tool were performed independently by two reviewers. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Due to heterogeneity in study design, interventions, follow-up duration, and outcome reporting, meta-analysis was not feasible, and findings were synthesized narratively. Three phase II RCTs involving 152 participants met the inclusion criteria. None of the studies demonstrated a statistically significant improvement in MD following nicotinamide therapy. One crossover study showed nonsignificant improvements in MD with nicotinamide, with a mean improvement of +0.10 dB compared to placebo over 24 weeks. However, all studies met their primary outcomes. Two crossover trials reported significant improvements in electroretinography parameters, and a parallel-arm study reported a significantly greater number of improved visual field test locations. No serious adverse events were reported. Overall certainty of evidence was low due to small sample sizes, short follow-up durations, and methodological limitations. Current evidence does not support nicotinamide for improving MD in adults with glaucoma in clinical practice. Although preliminary findings suggest potential neuroprotective effects, the evidence remains limited and hypothesis-generating. Larger, adequately powered phase III trials with longer follow-up are required before nicotinamide's neuroprotective efficacy can be determined with validity.