Importance Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial function and energy production may enhance retinal ganglion cell survival in animal models of glaucoma, but there is scant information on its effectiveness in a clinical setting.

Objective To test the hypothesis that a combination of nicotinamide and pyruvate can improve retinal ganglion cell function in human glaucoma as measured with standard automated perimetry.

Design, Setting, and Participants In this phase 2, randomized, double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients were assessed for eligibility. Of these, 42 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized. A total of 32 completed the study and were included in the final analysis. The mean (SD) age was 64.6 (9.8) years. Twenty-one participants (66%) were female. Participant race and ethnicity data were collected via self-report to ensure the distribution reflected that observed in clinical practice in the US but are not reported here to protect patient privacy. Recruitment took place in April 2019 and patients were monitored through December 2020. Data were analyzed from January to May 2021.

Interventions Ascending oral doses of nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) vs placebo (2:1 randomization).

Main Outcomes and Measures Number of visual field test locations improving beyond normal variability in the study eye. Secondary end points were the rates of change of visual field global indices (mean deviation [MD], pattern standard deviation [PSD], and visual field index [VFI]).

Results Twenty-two of 29 participants (76%) randomized to the intervention group and 12 of 13 participants (92%) randomized to placebo received their allocation, and 32 participants (32 eyes; ratio 21:11) completed the study (21 from the intervention group and 11 from the placebo group). Median (IQR) follow-up time was 2.2 (2.0-2.4) months. No serious adverse events were reported during the study. The number of improving test locations was significantly higher in the treatment group than in the placebo group (median [IQR], 15 [6-25] vs 7 [6-11]; P = .005). Rates of change of PSD suggested improvement with treatment compared with placebo (median, −0.06 vs 0.02 dB per week; 95% CI, 0.02 to 0.24; P = .02) but not MD (0.04 vs −0.002 dB per week; 95% CI, −0.27 to 0.09; P = .35) or VFI (0.09 vs −0.02% per week; 95% CI, −0.53 to 0.36; P = .71).

Conclusions and Relevance A combination of nicotinamide and pyruvate yielded significant short-term improvement in visual function, supporting prior experimental research suggesting a role for these agents in neuroprotection for individuals with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression.

Trial Registration ClinicalTrials.gov Identifier: NCT03797469

重要性 尽管眼压 (IOP) 显着降低，但开角型青光眼可能会继续恶化。临床前研究表明，增强线粒体功能和能量产生可能会增强青光眼动物模型中视网膜神经节细胞的存活，但关于其在临床环境中有效性的信息很少。

目的 检验烟酰胺和丙酮酸盐的组合可以改善人类青光眼视网膜神经节细胞功能的假设，如标准自动视野计所测量。

设计、设置和参与者 在这个 2 期、随机、双盲、安慰剂对照的临床试验中，在一个学术机构中，对 197 名患者进行了资格评估。其中，42 名接受过治疗的开角型青光眼患者和至少 1 只眼中度视野缺损的患者被随机分组​​。共有 32 人完成了研究并被纳入最终分析。平均 (SD) 年龄为 64.6 (9.8) 岁。21 名参与者 (66%) 是女性。参与者的种族和种族数据是通过自我报告收集的，以确保分布反映在美国临床实践中观察到的情况，但此处未报告以保护患者隐私。招募于 2019 年 4 月进行，患者监测持续到 2020 年 12 月。分析了 2021 年 1 月至 2021 年 5 月的数据。

干预 烟酰胺（1000 至 3000 毫克）和丙酮酸（1500 至 3000 毫克）与安慰剂（2:1 随机化）的口服剂量递增。

主要成果和措施 研究眼中超出正常变异性的视野测试位置的数量。次要终点是视野整体指数（平均偏差 [MD]、模式标准偏差 [PSD] 和视野指数 [VFI]）的变化率。

结果 随机分配到干预组的 29 名参与者中有 22 名 (76%) 和随机分配到安慰剂组的 13 名参与者中的 12 名 (92%) 接受了分配，32 名参与者（32 只眼；比例 21:11）完成了研究（21 名来自干预组和安慰剂组 11 人）。中位 (IQR) 随访时间为 2.2 (2.0-2.4) 个月。研究期间没有报告严重的不良事件。治疗组改善测试位置的数量明显高于安慰剂组（中位数 [IQR]，15 [6-25] 对比 7 [6-11]；P  = .005）。与安慰剂相比，PSD 的变化率表明治疗有所改善（中位数，每周 −0.06 vs 0.02 dB；95% CI，0.02 至 0.24；P  = .02）但不是 MD（每周 0.04 vs −0.002 dB；95%置信区间，-0.27 至 0.09；P  = .35) 或 VFI（每周 0.09 与 −0.02%；95% CI，−0.53 至 0.36；P  = .71）。

结论和相关性 烟酰胺和丙酮酸盐的组合在视觉功能方面产生了显着的短期改善，支持先前的实验研究表明这些药物在青光眼患者的神经保护中的作用并证实需要长期研究以确定它们在减缓中的有用性进展。

试验注册 ClinicalTrials.gov 标识符：NCT03797469