Nicotinamide, Vitamin B3 Exposure and Inner Retinal Function in Glaucomatous Neurodegeneration: A Systematic Review and Meta-Analysis of Randomised Trials and Longitudinal Cohorts

Abstract

Background: Glaucoma is a neurodegeneration of the optic nerve in which retinal ganglion cell axons fail metabolically before they die. Nicotinamide, the amide form of vitamin B3, is the most advanced candidate neuroprotectant in this disease, but its clinical evidence has never been pooled.

Objective: To determine whether nicotinamide supplementation improves inner retinal function in glaucoma, whether higher vitamin B3 exposure is associated with lower glaucoma risk, and whether vitamin B3 deficiency is demonstrable in patients.

Methods: PubMed/MEDLINE was searched with four pre-specified queries. Randomised and observational studies of vitamin B3 exposure in glaucoma or ocular hypertension were eligible, appraised with RoB 2.0 and ROBINS-E. Outcomes were pooled as Hedges' g or log-ratios using DerSimonian-Laird random-effects models.

Results: Fifteen studies (19 reports) were included; 11 pooled. Across all three existing trials, all on continued pressure-lowering therapy, nicotinamide improved inner retinal function (Hedges' g 0.41, 95% CI 0.14 to 0.69). On identical constructs, absolute photopic negative response amplitude replicated (g 0.33, 0.03 to 0.63) but the b-wave-normalised ratio did not (g 0.11, −0.37 to 0.58), so selective ganglion cell rescue was not shown. Visual field mean deviation was null in all trials. Highest versus lowest vitamin B3 exposure gave a pooled odds or hazard ratio of 0.44 (0.33 to 0.59), and each extra mg/day of dietary niacin 0.94 (0.92 to 0.97). Plasma nicotinamide was lower in glaucoma (g 0.70, 0.29 to 1.11) but dietary intake was not. All outcomes were GRADE low or very low.

Conclusion: Nicotinamide improved inner retinal amplitude in every randomised trial to date, but not visual field; selective ganglion cell rescue remains unproven. Trial doses exceeded dietary quartile differences fifty-fold, so observational and interventional findings describe different interventions.