Impact of presbyopia treatment pilocarpine hydrochloride 1.25% on night-driving performance

Patients prescribed pilocarpine ophthalmic solution are advised to be cautious when driving at night, but studies evaluating the effects of pilocarpine hydrochloride ophthalmic solution 1.25% (pilo), approved to treat presbyopia, on driving at night are lacking. This double-masked, crossover, phase 3b study evaluated night-driving performance with pilo or the placebo once daily. Forty-three adults (40–55 years) with presbyopia impacting daily activities and mesopic, high-contrast, binocular distance-corrected near vision 6/12–6/30 were randomised to bilateral treatment with pilo followed by placebo or placebo followed by pilo (with a ≥7-day washout between interventions). Night-driving performance was evaluated at twilight at a closed-circuit course. Primary efficacy endpoint: overall composite night-driving performance Z score at the end of the 7–14-day intervention period, 1 hour post-instillation. Pilo was considered non-inferior if the lower limit of the 95% confidence interval (CI) for the least squares mean difference (LSMD, pilo minus placebo) was &gt;–0.25. Other efficacy endpoints: individual components of the night-driving performance test (hazard avoidance rate; road sign recognition rate and distance; pedestrians recognition distance; overall driving and lane-keeping times) and night-driving experience questionnaire. Safety included treatment-emergent adverse events (TEAEs). The mean overall composite Z scores were −0.121 (pilo) and 0.118 (placebo). The LSMD (pilo minus placebo) was −0.224 (95% CI, −0.346, −0.103), with 3 of the 7 individual tasks being significantly better with the placebo. The questionnaire did not reveal significant differences between pilo and the placebo. There were no serious or severe TEAEs and no TEAE-related discontinuations. The most common ocular TEAEs were headache and visual impairment with pilo (both 27.9%), and dry eye (7.0%) with the placebo. The overall performance of night driving was inferior with pilo, compared with placebo. The study findings are consistent with the current class labelling and provide evidence to inform regulators and assist clinicians considering prescribing pilo to adults who seek treatment of presbyopia symptoms and drive at night. <b>ClinicalTrials.gov identifier:</b> NCT04837482.处方毛果芸香碱滴眼液（pilocarpine ophthalmic solution）的患者被建议在夜间驾驶时保持谨慎，但目前尚缺乏针对获批用于治疗老视（presbyopia）的1.25%盐酸毛果芸香碱滴眼液（以下简称pilo）对夜间驾驶影响的评估研究。本项双盲（double-masked）、交叉设计（crossover design）的3b期临床试验（phase 3b study）评估了每日一次给药的pilo与安慰剂对夜间驾驶表现的影响。共纳入43名年龄40~55岁、因老视影响日常活动且暗适应（mesopic）状态下高对比度双眼经屈光矫正的近视力为6/12~6/30的成人受试者，随机分为两组：一组先接受双侧眼pilo给药，随后接受安慰剂给药；另一组先接受安慰剂给药，随后接受双侧眼pilo给药，两次干预之间设置≥7天的洗脱期（washout period）。研究在黄昏时段的闭路驾驶赛道上评估受试者的夜间驾驶表现。主要疗效终点为干预7~14天后、滴眼后1小时的整体复合夜间驾驶表现Z评分。若最小二乘均数差（least squares mean difference, LSMD，pilo组减安慰剂组）的95%置信区间（confidence interval, CI）下限大于-0.25，则认为pilo具有非劣效性。其他疗效终点包括夜间驾驶测试的各项分项指标（危险规避率、道路标志识别率与识别距离、行人识别距离、整体驾驶与车道保持时长）以及夜间驾驶体验问卷。安全性评估指标为治疗期间出现的不良事件（treatment-emergent adverse events, TEAEs）。结果显示，pilo组与安慰剂组的平均整体复合Z评分分别为-0.121与0.118；最小二乘均数差（pilo组减安慰剂组）为-0.224（95%CI：-0.346~-0.103），安慰剂组在7项分项任务中有3项表现显著更优。夜间驾驶体验问卷未显示两组间存在显著差异。本研究未发生严重或重度治疗期间出现的不良事件，亦无与不良事件相关的受试者脱落病例。pilo组最常见的眼部不良事件为头痛与视力损害（发生率均为27.9%），安慰剂组则为干眼（发生率7.0%）。相较于安慰剂组，pilo组的整体夜间驾驶表现更差。本研究结果与当前的药品分类标签一致，可为监管机构提供决策依据，并帮助临床医生考量为寻求老视症状治疗且存在夜间驾驶需求的成人开具pilo处方。临床试验注册号（ClinicalTrials.gov）：NCT04837482。