Tan Nicholas E, Patnaik Jennifer L, McWilliams Sara, Seibold Leonard K, Kahook Malik Y
Sue-Anschutz Rodgers Eye Center at the University of Colorado, Aurora, CO, USA.
Clin Ophthalmol. 2024 Dec 21;18:3893-3901. doi: 10.2147/OPTH.S496420. eCollection 2024.
To evaluate the safety and efficacy of sublingual methazolamide in patients with open-angle glaucoma (OAG) and inform future trial design.
Fourteen participants (28 eyes) aged 50 to 90 years with bilateral OAG and intraocular pressure (IOP) between 18 and 35 mmHg after medication washout were included. Participants were randomized to receive either 25 mg or 50 mg of sublingual methazolamide once daily for one week, followed by twice-daily administration during the second week. The primary outcome was change in IOP from baseline to days 7 and 14. Secondary outcomes included changes in serum methazolamide levels, serum electrolytes, urine pH and electrolytes, and side effects.
After randomization, exclusion, and two dropouts, four patients in the 25 mg group and ten in the 50 mg group completed the study in full. Both doses of sublingual methazolamide resulted in significant reductions in IOP from the post-washout baseline at all follow-up points (all p < 0.05). Lowest mean IOPs were recorded 8 hours post-dose; after a week of daily dosing, the 25 mg and 50 mg groups achieved reductions of 6.6 mmHg (-26.5%) and 4.2 mmHg (-19.3%), respectively (both p < 0.001). Twice-daily dosing resulted in significantly lower morning IOPs compared to once-daily in each group (p = 0.05 for 25 mg; p = 0.003 for 50 mg). Serum methazolamide levels correlated with dose amount and frequency. Serum electrolyte levels were stable throughout, while urinary pH and urinary electrolytes fluctuated based on time since last dose. Side effects of mild headaches and/or fatigue were reported by 3 out of 14 (21.4%) participants, with no serious adverse events.
Sublingual methazolamide demonstrated effective IOP reduction with a favorable safety profile. Twice-daily dosing may offer more sustained IOP control. These findings support further investigation into sublingual methazolamide as an alternative glaucoma treatment.
评估舌下含服醋甲唑胺治疗开角型青光眼（OAG）患者的安全性和有效性，并为未来的试验设计提供参考。
纳入14名年龄在50至90岁之间的双侧OAG患者（28只眼），在药物洗脱后眼压（IOP）为18至35 mmHg。参与者被随机分为每日一次接受25 mg或50 mg舌下含服醋甲唑胺，为期一周，随后在第二周改为每日两次给药。主要结局是从基线到第7天和第14天的IOP变化。次要结局包括血清醋甲唑胺水平、血清电解质、尿液pH值和电解质的变化以及副作用。
随机分组、排除和两名退出者后，25 mg组有4名患者和50 mg组有10名患者完成了整个研究。两种剂量的舌下含服醋甲唑胺在所有随访点均导致IOP从洗脱后基线显著降低（所有p < 0.05）。最低平均IOP在给药后8小时记录；每日给药一周后，25 mg组和50 mg组的IOP分别降低了6.6 mmHg（-26.5%）和4.2 mmHg（-19.3%）（均p < 0.001）。与每组每日一次给药相比，每日两次给药导致早晨IOP显著降低（25 mg组p = 0.05；50 mg组p = 0.003）。血清醋甲唑胺水平与剂量和频率相关。血清电解质水平在整个过程中保持稳定，而尿液pH值和尿液电解质根据上次给药后的时间波动。14名参与者中有3名（21.4%）报告有轻度头痛和/或疲劳的副作用，无严重不良事件。
舌下含服醋甲唑胺显示出有效的IOP降低且安全性良好。每日两次给药可能提供更持久的IOP控制。这些发现支持进一步研究舌下含服醋甲唑胺作为青光眼的替代治疗方法。
