Flora Hui1, Jessica Tang1,2, Pete A Williams3, Myra B McGuinness1, Xavier Hadoux1, Robert J Casson4, Michael Coote1,2, Ian A Trounce1,2, Keith R Martin1,2,5, Peter van Wijngaarden1,2, Jonathan G Crowston1,2,6,7. 1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. 2. Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia. 3. Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden. 4. Ophthalmic Research Laboratories, Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia. 5. Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. 6. Centre for Vision Research, Duke-NUS Medical School, Singapore, Singapore. 7. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Abstract
IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS: Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS:PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS:Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.
RCT Entities:
IMPORTANCE: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+ , is low in serum of glaucomapatients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in humanglaucoma is unknown. BACKGROUND: To examine the effects of nicotinamide on inner retinal function in glaucoma, in participants receiving concurrent glaucoma therapy. DESIGN: Crossover, double-masked, randomized clinical trial. Participants recruited from two tertiary care centres. PARTICIPANTS: Fifty-seven participants, diagnosed and treated for glaucoma. METHODS:Participants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6 weeks of 1.5 g/day then 6 weeks of 3.0 g/day followed by crossover without washout. Visual function measured using electroretinography and perimetry. MAIN OUTCOME MEASURES: Change in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). RESULTS: PhNR Vmax improved beyond 95% coefficient of repeatability in 23% of participants following nicotinamide vs 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (P = .02) on nicotinamide and 5.2% [-4.2%, 14.6%], (P = .27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (P = .002) following nicotinamide, 3.6% [-3.4%, 10.5%], (P = .30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1 dB on nicotinamide and fewer deteriorating (4%) compared to placebo (P = .02). CONCLUSIONS:Nicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.
Authors: James R Tribble; Flora Hui; Melissa Jöe; Katharina Bell; Vicki Chrysostomou; Jonathan G Crowston; Pete A Williams Journal: Cells Date: 2021-02-01 Impact factor: 6.600
Authors: Xian Zhang; Nan Zhang; Micah A Chrenek; Preston E Girardot; Jiaxing Wang; Jana T Sellers; Eldon E Geisert; Charles Brenner; John M Nickerson; Jeffrey H Boatright; Ying Li Journal: Pharmaceutics Date: 2021-06-16 Impact factor: 6.321