Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy
Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy
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DOI：
10.1056/nejmoa1712770
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发表时间：
2018-03-15
影响因子：
158.5
通讯作者：
Hamuro, Junji
中科院分区：
文献类型：
--
作者：
Kinoshita, Shigeru;Koizumi, Noriko;Hamuro, Junji
角膜内皮细胞（CEC）疾病，如Fuchs角膜内皮营养不良，诱导异常角膜水合作用，导致角膜混浊和视力丧失，称为大泡性角膜病。我们调查是否注射培养的人CEC补充rho相关蛋白激酶（ROCK）抑制剂进入前房可以增加CEC density. METHODS我们进行了一个不受控制的，单组研究，涉及11人谁收到了大泡性角膜病变的诊断，并没有检测到CEC。从供体角膜培养人CEC;向总共1 × 10（6）个传代细胞中补充ROCK抑制剂（最终体积，300 μ l），并注射到选择用于治疗的眼睛的前房中。手术后，患者被放置在俯卧位3小时。主要结果是角膜透明度的恢复，在细胞注射后24周，中央角膜的CEC密度超过500个细胞/平方毫米。次要结果是角膜厚度小于630 μ m，并且在细胞注射后24周，最佳矫正视力的改善相当于Landolt C视力表上的两行或更多。（范围，947至2833）（100%; 95%置信区间[CI]，72至100），其中10只的CEC密度超过1000个细胞/平方毫米。角膜厚度小于630 μ m 11只治疗眼中有10只达到了489 ~ 640（91%; 95%CI，59 - 100），11只治疗眼中有9只记录到最佳矫正视力改善两行或更多（82%; 95%CI，48 - 98）.结论：在11名大泡性角膜病变患者中，注射补充有ROCK抑制剂的人CEC后，24周后CEC密度增加。
BACKGROUNDCorneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.METHODSWe performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1x10(6) passaged cells were supplemented with a ROCK inhibitor (final volume, 300 mu l) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 mu m and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection.RESULTSAt 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 mu m (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98).CONCLUSIONSInjection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy.