Kaufman Paul L
a Department of Ophthalmology and Visual Sciences , University of Wisconsin , Madison , WI , USA.
Expert Opin Pharmacother. 2017 Mar;18(4):433-444. doi: 10.1080/14656566.2017.1293654. Epub 2017 Feb 20.
Intraocular pressure (IOP)-lowering has been demonstrated to slow the progression or onset of visual field loss in open-angle glaucoma (OAG) or ocular hypertension (OHT). Pharmacological lowering of IOP is the most common initial intervention in patients with OAG or OHT, however, many patients will require more than one therapy to achieve target IOP. Latanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α analog for the reduction of IOP. Areas covered: Current knowledge concerning the mechanism of action of latanoprostene bunod is presented. Additionally, clinical safety and efficacy data from published Phase 1 (KRONUS), Phase 2 (VOYAGER, CONSTELLATION) and Phase 3 (APOLLO, LUNAR, JUPITER) studies are reviewed. Expert opinion: Latanoprostene bunod is a dual mechanism, dual pathway molecule, consisting of latanoprost acid, which is known to enhance uveoscleral (unconventional) outflow by upregulating matrix metalloproteinase expression and remodeling of the ciliary muscle's extracellular matrix, linked to an NO-donating moiety, which enhances trabecular meshwork/Schlemm's canal (conventional) outflow by inducing cytoskeletal relaxation via the soluble guanylyl cyclase-cyclic guanosine monophosphate (sGC-cGMP) signaling pathway. Latanoprostene bunod 0.024% solution applied topically once daily appears more effective in reducing IOP in OHT and OAG subjects than either latanoprost or timolol, with a side effect profile similar to that of latanoprost.
眼压降低已被证明可减缓开角型青光眼(OAG)或高眼压症(OHT)患者视野缺损的进展或发病。药物降低眼压是OAG或OHT患者最常见的初始干预措施,然而,许多患者需要不止一种治疗方法才能达到目标眼压。比马前列素氨丁三醇是一种新型的释放一氧化氮(NO)的前列腺素F2α类似物,用于降低眼压。涵盖领域:介绍了关于比马前列素氨丁三醇作用机制的当前知识。此外,还回顾了已发表的1期(KRONUS)、2期(VOYAGER、CONSTELLATION)和3期(APOLLO、LUNAR、JUPITER)研究的临床安全性和疗效数据。专家意见:比马前列素氨丁三醇是一种双机制、双途径分子,由比马前列素酸组成,已知其通过上调基质金属蛋白酶表达和重塑睫状肌细胞外基质来增强葡萄膜巩膜(非常规)流出,与一个释放NO的部分相连,该部分通过可溶性鸟苷酸环化酶 - 环磷酸鸟苷(sGC - cGMP)信号通路诱导细胞骨架松弛,从而增强小梁网/施莱姆管(常规)流出。0.024%的比马前列素氨丁三醇溶液每日一次局部应用,在降低OHT和OAG患者眼压方面似乎比拉坦前列素或噻吗洛尔更有效,且副作用与拉坦前列素相似。