Kolko Miriam, Tatham Andrew J, Lim Kin Sheng, Wells Anthony P, Shiu Michael, Uy Harvey S, Sarkisian Steven R, Ho Quoc, Jiao Jenny, Kim Kimmie, Goodkin Margot L, Bejanian Marina, Robinson Michael R, Paauw James D
From the Department of Drug Design and Pharmacology (M.K.), University of Copenhagen, Copenhagen, Denmark; Department of Ophthalmology (M.K.), Copenhagen University Hospital, Rigshopitalet, Glostrup, Denmark.
Ophthalmology Department (A.J.T.), Princess Alexandra Eye Pavilion, Edinburgh, United Kingdom.
Am J Ophthalmol. 2025 Apr;272:19-37. doi: 10.1016/j.ajo.2024.12.026. Epub 2025 Jan 10.
To evaluate the intraocular pressure (IOP)-lowering effect and safety of up to 2 bimatoprost implant administrations versus selective laser trabeculoplasty (SLT).
Phase 3 (Stage 2), randomized, 24-month, multicenter, patient- and efficacy evaluator-masked, paired-eye clinical trial (NCT02507687).
Patients (n = 183) with open-angle glaucoma or ocular hypertension inadequately managed with topical IOP-lowering medication for reasons other than efficacy.
Patients received a single 360° SLT procedure in 1 eye and 10-µg bimatoprost implant administration in the contralateral eye. Initially, implant-treated eyes received a second implant at week 16 if safety criteria were met. After a protocol amendment, implant-treated eyes were retreated with flexible scheduling if IOP was >17 mm Hg and safety criteria were met.
The primary efficacy variable was IOP change from baseline, with primary timepoints at weeks 4, 12, and 24. Safety measures included treatment-emergent adverse events (TEAEs) and ocular safety measures.
Mean (±SE) baseline IOP (mm Hg) was 25.2 ± 0.22 and 25.1 ± 0.22 in implant- and SLT-treated eyes, respectively. Least-squares mean (±SE) IOP reduction from baseline (mm Hg) for eyes treated with up to 2 implants versus SLT was 6.8 ± 0.28 versus 6.2 ± 0.28 at week 4, 6.9 ± 0.30 versus 6.4 ± 0.30 at week 12, and 6.9 ± 0.27 versus 6.5 ± 0.28 at week 24. The probability of not having required nonstudy (rescue) IOP-lowering treatment at days 360 and 720, respectively, was 67.5% and 50.2% for implant-treated eyes versus 68.7% and 60.6% for SLT-treated eyes. The most common ocular TEAE in both implant- and SLT-treated eyes was increased IOP attributed to wearing off of efficacy. Mean (±SE) percentage change in corneal endothelial cell density from baseline at month 24 was -6.2 ± 1.13% in implant-treated eyes (-7.9 ± 2.04% with fixed readministration; -5.2 ± 1.35% with flexible readministration) versus -3.1 ± 0.43% in SLT-treated eyes.
The bimatoprost implant demonstrated statistical and clinical noninferiority to SLT in IOP reduction from baseline at weeks 4, 12, and 24. In subgroup analysis, patients with flexible implant readministration met the same criteria. Both the implant and SLT demonstrated sustained (2-year) IOP lowering in many eyes. A flexible administration schedule improved the safety profile of the implant over the fixed administration schedule.
评估最多两次使用比马前列素植入剂与选择性激光小梁成形术（SLT）降低眼压（IOP）的效果及安全性。
3期（第2阶段）、随机、24个月、多中心、患者及疗效评估者双盲、双眼配对的临床试验（NCT02507687）。
因除疗效外的其他原因，使用局部降眼压药物治疗效果不佳的开角型青光眼或高眼压症患者（n = 183）。
患者一只眼睛接受单次360° SLT手术，对侧眼睛接受10μg比马前列素植入剂治疗。最初，如果符合安全标准，植入剂治疗的眼睛在第16周接受第二次植入。方案修订后，如果眼压>17 mmHg且符合安全标准，植入剂治疗的眼睛可灵活安排再次治疗。
主要疗效变量是眼压相对于基线的变化，主要时间点为第4、12和24周。安全指标包括治疗中出现的不良事件（TEAE）和眼部安全指标。
植入剂治疗组和SLT治疗组眼睛的平均（±SE）基线眼压（mmHg）分别为25.2±0.22和25.1±0.22。在第4周，最多接受2次植入剂治疗的眼睛与接受SLT治疗的眼睛相比，眼压相对于基线的最小二乘均值（±SE）降低分别为6.8±0.28和6.2±0.28；第12周时分别为6.9±0.30和6.4±0.30；第24周时分别为6.9±0.27和6.5±0.28。在第360天和720天，植入剂治疗组眼睛分别有67.5%和50.2%的患者无需接受非研究（挽救）性降眼压治疗，而SLT治疗组眼睛分别为68.7%和60.6%。植入剂治疗组和SLT治疗组眼睛最常见的眼部TEAE均为因疗效消退导致的眼压升高。在第24个月时，植入剂治疗组眼睛角膜内皮细胞密度相对于基线的平均（±SE）百分比变化为-6.2±1.13%（固定再次给药组为-7.9±2.04%；灵活再次给药组为-5.2±1.35%），而SLT治疗组眼睛为-3.1±0.43%。
在第4、12和第24周时，比马前列素植入剂在降低眼压方面相对于基线水平在统计学和临床上均不劣于SLT。在亚组分析中，灵活再次使用植入剂的患者也符合相同标准。植入剂和SLT在许多眼睛中均显示出持续（2年）降低眼压的效果。与固定给药方案相比，灵活给药方案改善了植入剂的安全性。
