Importance: Retinal ganglion cells endure significant metabolic stress with ageing and glaucoma-related stressors. Injured cells require increased energy for repair but maintain capacity to recover function despite periods of functional loss. Nicotinamide, a precursor of redox co-factor and metabolite, NAD₊, is low in serum of patients with primary open-angle glaucoma and its supplementation provides robust protection of retinal ganglion cells by targeting mitochondrial health in glaucoma models. However, the potential of nicotinamide to improve retinal ganglion cell function in humans with glaucoma is yet unknown. Objective: To determine whether nicotinamide supplementation taken in conjunction with conventional IOP-lowering therapy leads to early improvement in retinal ganglion cell function in people with glaucoma. Design: Crossover, double-masked, randomized clinical trial conducted between October 2017 to January 2019. Setting: Study participants recruited from two tertiary care centers in Melbourne, Australia. Participants: Adults diagnosed and treated for primary glaucoma. Ninety-four participants assessed for study eligibility. Intervention: Participants randomized to first receive oral placebo or nicotinamide and reviewed six-weekly. Accelerated dosing method utilized; participants commenced 6-week course of 1.5 grams/day followed by 6 weeks of 3.0 grams/day. After 12 weeks, participants crossed over to other intervention for 12 weeks without washout. At each visit, visual function measured using full-field flash electroretinography and white-on-white perimetry. Main outcome measures: Primary endpoint was change in inner retinal function determined a-priori as change in photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio). Results: Fifty-seven participants (65.5±10.0 years, 39% female) enrolled. PhNR Vmax improved beyond 95% coefficient of repeatability (COR) in 23% of participants following 12 weeks of nicotinamide versus 9% on placebo. Conversely, PhNR Vmax deteriorated in 9% on placebo and 7% on nicotinamide. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [-4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved on average by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide and 3.6% [-3.4%, 10.5%], (p=0.30) on placebo. A concomitant trend for improved visual field mean deviation was observed with 27% improving ≥1dB on nicotinamide and fewer deteriorating ≥1dB (4%) compared to placebo (p=0.02). Moderate correlation was observed between PhNR and visual field change with treatment. Participants demonstrated excellent treatment adherence rates (>94%) and nicotinamide was well tolerated with minimal side effects. Conclusions and Relevance: Nicotinamide supplementation can improve inner retinal function in patients receiving concurrent IOP-lowering glaucoma therapy. Further studies are underway to elucidate the effects of long-term nicotinamide supplementation on glaucoma progression.

中文翻译：

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青光眼对烟酰胺（维生素B3）补充的反应后视网膜内部功能的改善：交叉临床随机试验

重要性：视网膜神经节细胞在衰老和青光眼相关的应激源下会承受明显的代谢应激。受伤的细胞需要增加能量进行修复，但是尽管功能丧失了一段时间，但仍保持恢复功能的能力。烟酰胺，氧化还原辅助因子和代谢物的前体，NAD ₊，是原发性开角型青光眼患者的低血清，其补充可通过靶向青光眼模型中的线粒体健康为视网膜神经节细胞提供强大的保护。然而，烟酰胺改善青光眼患者视网膜神经节细胞功能的潜力尚不清楚。目的：确定烟酰胺与传统的降低眼压的疗法联合使用是否可导致青光眼患者视网膜神经节细胞功能的早期改善。设计：2017年10月至2019年1月进行的交叉，双掩蔽，随机临床试验。背景：研究参与者来自澳大利亚墨尔本的两个三级护理中心。参与者：诊断为原发性青光眼并接受治疗的成年人。九十四名参与者评估了研究资格。介入：随机分组的参与者首先接受口服安慰剂或烟酰胺治疗，并每六周检查一次。采用加速加药方法；参与者开始1.5克/天的6周疗程，然后是3.0克/天的6周疗程。12周后，参与者交叉接受其他干预12周，而不会出现冲洗现象。每次访视时，使用全场闪光视网膜电图和白光/白光视野术测量视觉功能。主要结局指标：主要终点是内部视网膜功能的变化，确定为先验，视光阴性反应（PhNR）参数的变化为：饱和PhNR振幅（Vmax），PhNR / b波振幅比（Vmax比）。结果：57名参与者（65.5±10.0岁，女性39％）被纳入研究。烟酰胺治疗12周后，PhNR Vmax改善了23％的参与者的重复性系数（COR）超过95％，而安慰剂为9％。相反，在安慰剂上，PhNR Vmax下降了9％，在烟酰胺上，下降了7％。总体而言，烟酰胺Vmax改善了14.8％[95％CI：2.8％，26.9％]，（p = 0.02），安慰剂则改善了5.2％[-4.2％，14.6％]，（p = 0.27）。烟酰胺治疗后，Vmax比平均改善了12.6％[5.0％，20.2％]（p = 0.002），安慰剂组改善了3.6％[-3.4％，10.5％]（p = 0.30）。与安慰剂相比，观察到了改善视野平均偏差的趋势，其中烟酰胺改善≥1dB的比例为27％，恶化≥1dB（4％）的比例较少（p = 0.02）。在治疗中，PhNR与视野变化之间存在中等相关性。参与者表现出极好的治疗依从率（> 94％）和烟酰胺具有良好的耐受性，且副作用极小。结论和相关性：烟酰胺补充可以改善并发眼压降低青光眼的患者的内部视网膜功能。正在进行进一步的研究以阐明长期补充烟酰胺对青光眼进展的影响。