Lin Jonathan B, Harris James M, Baldwin George, Goss Deborah, Margeta Milica A
Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, USA.
Eye (Lond). 2024 Dec;38(18):3418-3428. doi: 10.1038/s41433-024-03342-4. Epub 2024 Sep 16.
Topical therapies targeting Rho-associated protein kinase (ROCK) signalling, including netarsudil (Rhopressa®) and ripasudil (Glanatec®), have become widely adopted as part of standard clinical practice to lower intraocular pressure (IOP) in patients with ocular hypertension or glaucoma. Given the pleiotropic roles of ROCK signalling, ROCK inhibition has the potential to cause unintended ocular side effects beyond IOP lowering in other substructures of the eye, both beneficial and deleterious. Additional experience and observation of patients treated with this class of medications have uncovered both new side effects not reported in the initial clinical trials, as well as potential benefits that have inspired off-label uses and that have been the topic of numerous clinical studies, case series, case reports, and translational studies. Here, we performed a comprehensive systematic review and identified 170 studies describing ocular effects of ROCK inhibition. In addition to describing well-established ocular effects associated with inhibition of ROCK signalling, such as conjunctival hyperaemia, corneal verticillata, and reticular corneal epithelial oedema, we also highlight other effects, such as corneal haemorrhages, changes in corneal contour, anterior subcapsular opacities, contact dermatitis, punctal stenosis, and eyelid wound dehiscence, which have been described in case series and case reports. Finally, we evaluated studies describing potential novel applications of ROCK inhibition for treating disorders affecting the cornea, the retina, and the optic nerve, finding strong evidence in support of a beneficial effect of ROCK inhibitors on corneal oedema due to corneal endothelial cell dysfunction. The other potential applications require further research.
靶向Rho相关蛋白激酶（ROCK）信号通路的局部疗法，包括奈他地尔（Rhopressa®）和ripasudil（Glanatec®），已被广泛应用于临床实践，作为降低高眼压症或青光眼患者眼压的标准治疗方案的一部分。鉴于ROCK信号通路具有多种作用，抑制ROCK可能会在降低眼压之外，对眼部其他亚结构产生意外的眼部副作用，这些副作用既有有益的，也有有害的。对使用这类药物治疗的患者的更多经验和观察发现了一些最初临床试验中未报告的新副作用，以及激发了超说明书使用且成为众多临床研究、病例系列、病例报告和转化研究主题的潜在益处。在此，我们进行了一项全面的系统评价，确定了170项描述ROCK抑制眼部效应的研究。除了描述与抑制ROCK信号通路相关的既定眼部效应，如结膜充血、角膜涡状浑浊和网状角膜上皮水肿外，我们还强调了其他效应，如角膜出血、角膜轮廓改变、前囊下混浊、接触性皮炎、泪点狭窄和眼睑伤口裂开，这些效应已在病例系列和病例报告中有所描述。最后，我们评估了描述ROCK抑制在治疗影响角膜、视网膜和视神经疾病方面潜在新应用的研究，发现有力证据支持ROCK抑制剂对角膜内皮细胞功能障碍引起的角膜水肿具有有益作用。其他潜在应用需要进一步研究。
