nicotinamide-beta-riboside and Glaucoma

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells (RGCs), which leads to progressive visual field loss and may result in blindness. Currently, the only available treatment to avoid or delay progression in glaucoma patients is to decrease intraocular pressure (IOP). However, despite adequate IOP control, approximately 25% of the patients continue to progress. To delay or prevent optic nerve damage in glaucoma, two forms of vitamin B3, nicotinamide (NAM) and nicotinamide riboside (NR) are emerging as viable adjuvant therapies. These compounds are nicotinamide adenine dinucleotide (NAD) precursors. NAD is essential for proper cell functioning and is involved in several metabolic activities, including protection against reactive oxygen species, contribution to the performance of various enzymes, and maintenance of mitochondrial function. Due to its beneficial effects and to the evidence of the reduction of NAD bioavailability with aging, researchers are seeking ways to replenish the cellular NAD pool, by administrating its precursors (NAM and NR), believing that it will reduce the RGC vulnerability to external stressors, such as increased IOP. This article attempts to analyze the current knowledge regarding the use of NAM and NR for the prevention and/or treatment of glaucoma.

Topics: Glaucoma; Humans; NAD; Niacinamide; Pyridinium Compounds

Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo.. This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models.. Outcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups.. Chinese Clinical Trial Registry 1900021998.

Topics: Glaucoma; Glaucoma, Open-Angle; Humans; Multicenter Studies as Topic; Nerve Fibers; Neuroprotection; Niacinamide; Pyridinium Compounds; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Visual Fields