Department of Ophthalmology, Duke University, Durham, North Carolina.
Keystone Research, Ltd., Austin, Texas.
Ophthalmology. 2020 Dec;127(12):1627-1641. doi: 10.1016/j.ophtha.2020.06.018. Epub 2020 Jun 13.
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.
Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.
Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.
Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.
Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).
Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.
Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.
评估在原发性开角型青光眼（OAG）和高眼压症（OHT）患者中，初次和重复使用 10μg 和 15μg 比马前列素植入物的降眼压疗效和安全性。
随机、20 个月、多中心、受试者和疗效评估者双盲、平行分组、3 期临床研究。
每只眼均患有 OAG 或 OHT 的成年人，研究眼的下方房角开放，且研究眼基线眼压（小时 0；上午 8 点）在洗脱期后为 22-32mmHg。
研究眼于第 1 天接受比马前列素植入物 10μg（n=198）或 15μg（n=198）治疗，并在第 16 周和第 32 周进行重复治疗，或接受每日两次马来酸噻吗洛尔 0.5%滴眼剂（n=198）。每次就诊时均在小时 0 和 2 测量眼内压。
主要终点为眼压和第 12 周时的基线眼压变化。安全性测量指标包括治疗中出现的不良事件（TEAEs）和角膜内皮细胞密度（CECD）。
两种剂量的比马前列素植入物在每次给药后的降眼压效果均不劣于噻吗洛尔。在基线时，平均日间眼压为 24.0、24.2 和 23.9mmHg，在第 10μg 植入物、15μg 植入物和噻吗洛尔组中，分别为 16.5-17.2mmHg、16.5-17.0mmHg 和 17.1-17.5mmHg。与比马前列素植入物和噻吗洛尔相比，更感兴趣的角膜和炎症 TEAEs（例如，角膜内皮细胞丢失、虹膜炎）的发生率更高，且 15μg 剂量的发生率最高。重复治疗后角膜 TEAEs 的发生率增加；在固定的 16 周间隔进行 3 次治疗后，角膜内皮细胞损失≥20%的发生率为 10.2%（10μg 植入物）和 21.8%（15μg 植入物）。最佳矫正视力（BCVA）稳定；3 名接受植入物治疗的角膜 TEAEs 受试者在最后一次就诊时的 BCVA 损失超过 2 行。
两种剂量的比马前列素植入物均在第 12 周达到了非劣效于噻吗洛尔的主要终点。在 3 次给药 1 年后，大多数患者无需额外治疗即可控制眼压。与 15μg 剂量相比，10μg 植入物的风险效益评估更有利。正在进行的研究正在评估其他给药方案，以降低角膜内皮细胞丢失的风险。比马前列素植入物具有改善依从性和降低青光眼治疗负担的潜力。
