Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, USA.
Department of Ophthalmology & Vision Science, School of Medicine, University of California Davis, Davis, California, USA.
Transl Vis Sci Technol. 2022 Sep 1;11(9):2. doi: 10.1167/tvst.11.9.2.
The purpose of this study was to evaluate the tolerability and efficacy of topical rho-kinase inhibitor ripasudil in the treatment of primary corneal endothelial degeneration (PCED) in dogs.
Twenty-one eyes of 12 client-owned, PCED-affected dogs received topical ripasudil 4 times daily. Ophthalmic examination, ultrasonic pachymetry (USP), Fourier-domain optical coherence tomography (FD-OCT), and in vivo confocal microscopy were performed at baseline and 1, 3, 6, and 12 months. Effects of treatment on corneal thickness, corneal edema extent, and endothelial cell density (ECD) were evaluated by repeated-measures ANOVA or Friedman test. Individual eyes were classified as improved, progressed, or stable at 12 months using clinical response criteria. Kaplan-Meier curves and log-rank test were used to compare ripasudil-treated eyes to age-, breed/size-, and disease stage-matched historical controls.
During treatment, 12 dogs developed conjunctival hyperemia, 4 demonstrated reticular bullous epithelial edema, and 2 developed corneal stromal hemorrhage. No adverse event necessitated permanent cessation of ripasudil. Central corneal thickness measured by USP significantly progressed from baseline to 12 months. Corneal thickness by FD-OCT, ECD, and edema extent did not differ over time. Considered individually, 5 eyes improved, 8 remained stable, and 8 progressed. The log-rank test found less edema progression in ripasudil-treated eyes compared to historical controls.
Ripasudil was well-tolerated in PCED-affected dogs. Response to therapy varied; 62% of eyes showed improved or stable disease whereas 38% progressed. Ripasudil-treated eyes progressed more slowly than historical controls.
Topical ripasudil offered a therapeutic benefit in a subset of patients using a canine model of endothelial degeneration, which may guide future trials in humans.
本研究旨在评估局部 Rho 激酶抑制剂 ripasudil 治疗犬原发性角膜内皮变性（PCED）的耐受性和疗效。
21 只患 PCED 的犬 12 只患眼接受 ripasudil 滴眼，每日 4 次。在基线和 1、3、6 和 12 个月时进行眼科检查、超声角膜测厚术（USP）、傅里叶域光学相干断层扫描（FD-OCT）和共焦显微镜检查。采用重复测量方差分析或 Friedman 检验评估治疗对角膜厚度、角膜水肿程度和内皮细胞密度（ECD）的影响。根据临床反应标准，将个体患眼在 12 个月时分为改善、进展或稳定。采用 Kaplan-Meier 曲线和对数秩检验比较 ripasudil 治疗眼与年龄、品种/大小和疾病阶段匹配的历史对照眼。
在治疗期间，12 只犬出现结膜充血，4 只出现网状大疱性上皮水肿，2 只出现角膜基质出血。无不良事件需要永久停止 ripasudil 治疗。USP 测量的中央角膜厚度从基线到 12 个月显著进展。FD-OCT、ECD 和水肿程度的角膜厚度随时间无差异。个别来看，5 只眼改善，8 只眼稳定，8 只眼进展。对数秩检验发现，与历史对照相比，ripasudil 治疗眼的水肿进展较少。
ripasudil 在 PCED 患犬中耐受性良好。治疗反应各不相同；62%的眼表现出疾病改善或稳定，而 38%的眼进展。与历史对照相比，ripasudil 治疗眼的进展速度较慢。
胡晓琳
