# An Exploratory Study of Six-Month Niacinamide Supplementation on Macular Structure and Electrophysiology in Primary Open-Angle Glaucoma

## TL;DR

This study explores the effects of six months of niacinamide supplementation on eye health in people with primary open-angle glaucoma, finding no significant changes in vision or structure.

## Contribution

The study introduces a novel clustered analytical approach to assess niacinamide's effects in glaucoma, emphasizing macular biomarkers.

## Key findings

- Niacinamide supplementation showed no significant improvement in visual field sensitivity or retinal nerve fiber layer thickness.
- VEP P2 latency increased slightly, but P100 latencies remained stable.
- GCC changes correlated with visual field performance, suggesting structural-functional relationships.

## Abstract

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.