The aim of the study was to investigate annual structural and functional results, and their correlation with inheritance pattern of retinitis pigmentosa (RP) patients who were treated with Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs). This prospective, sequential, open-label phase-3 clinical study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology, between April 2019 and May 2020. The study included 34 eyes from 32 retinitis pigmentosa patients of various genotypes who were enrolled in the stem cells clinical trial. The patients were followed for 12 months after the WJ-MSCs transplantation into subtenon space and evaluated with consecutive examinations. Genetic mutations were investigated using a retinitis pigmentosa panel sequencing method consisting of 90 genes. All patients underwent a complete routine ophthalmic examination with best corrected visual acuity, optical coherence tomography angiography, visual field, and full-field electroretinography. Quantitative data obtained from baseline (T0), 6th month (T1), and 12th month (T2) examinations were compared. According to timepoints at T0, T1, and T2: The mean outer retinal thickness was 100.3 μm, 119.1 μm, and 118.0 μm, respectively (p = 0.01; T0 < T1, T2). The mean horizontal ellipsoid zone width were 2.65 mm, 2.70 mm, and 2.69 mm respectively (p = 0.01; T0 < T1, T2). The mean best corrected visual acuity (BCVA) were 70.5 letters, 80.6 letters, and 79.9 letters, respectively (p = 0.01; T0 < T1, T2). The mean fundus perimetry deviation index (FPDI) was 8.0%, 11.4%, and 11.6%, respectively (p = 0.01; T0 < T1, T2). The mean full-field flicker ERG parameters at T0, T1, and T2: amplitudes were 2.4 mV, 5.0 mV, and 4.6 mV, respectively (p = 0.01; T0 < T1, T2). Implicit time were 43.3 ms, 37.9 ms, and 38.6 ms, respectively (p = 0.01; T0 > T1, T2). According to inheritance pattern, BCVA, FPDI, ERG amplitude, and implicit time data improved significantly in autosomal dominant (AD) and in autosomal recessive (AR) RP at 1 year follow-up (pAD = 0.01, pAR = 0.01; pAD = pAR > pX-linked). No ocular or systemic adverse events related to the surgical methods and/or WJ-MSCs were observed during the 1 year follow-up period. Subtenon transplantation of WJ-MSCs was found to be effective and safe in the treatment of RP during the first year, similar to the sixth month’s results. In autosomal dominant and autosomal recessive inheritance of RP, regardless of the genetic mutations, subtenon administration of WJ-MSCs can be considered an effective and safe option without any adverse effect for slowing or stopping the disease progression. ClinicalTrials.gov, NCT04224207 . Registered 8 January 2020

中文翻译：

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沃顿商学院胶体间充质干细胞治疗色素性视网膜炎：1 年结果的前瞻性分析。

该研究的目的是调查接受沃顿胶源间充质干细胞（WJ-MSCs）治疗的色素性视网膜炎（RP）患者的年度结构和功能结果及其与遗传模式的相关性。这项前瞻性、序贯、开放标签的 3 期临床研究于 2019 年 4 月至 2020 年 5 月在安卡拉大学医学院眼科进行。该研究纳入了来自 32 名不同基因型视网膜色素变性患者的 34 只眼睛干细胞临床试验。WJ-MSCs移植到眼球筋膜下间隙后对患者进行12个月的随访，并通过连续检查进行评估。使用由 90 个基因组成的视网膜色素变性面板测序方法对基因突变进行了研究。所有患者均接受了完整的常规眼科检查，包括最佳矫正视力、光学相干断层扫描血管造影、视野和全视野视网膜电图检查。比较从基线 (T0)、第 6 个月 (T1) 和第 12 个月 (T2) 检查获得的定量数据。根据 T0、T1 和 T2 的时间点：平均外层视网膜厚度分别为 100.3 μm、119.1 μm 和 118.0 μm（p = 0.01；T0 < T1、T2）。平均水平椭球区宽度分别为 2.65 毫米、2.70 毫米和 2.69 毫米（p = 0.01；T0 < T1、T2）。平均最佳矫正视力 (BCVA) 分别为 70.5 个字母、80.6 个字母和 79.9 个字母（p = 0.01；T0 < T1、T2）。平均眼底视野偏差指数 (FPDI) 分别为 8.0%、11.4% 和 11.6%（p = 0.01；T0 < T1、T2）。T0、T1 和 T2 处的平均全场闪烁 ERG 参数：幅度分别为 2.4 mV、5.0 mV 和 4.6 mV（p = 0.01；T0 < T1、T2）。隐式时间分别为 43.3 ms、37.9 ms 和 38.6 ms（p = 0.01；T0 > T1、T2）。根据遗传模式，常染色体显性 (AD) 和常染色体隐性 (AR) RP 在 1 年随访时 BCVA、FPDI、ERG 幅度和隐式时间数据显着改善（pAD = 0.01，pAR = 0.01；pAD = pAR > pX 连接）。在 1 年随访期间，未观察到与手术方法和/或 WJ-MSC 相关的眼部或全身不良事件。研究发现，WJ-MSCs 腱鞘下移植在治疗 RP 的第一年是有效且安全的，与第六个月的结果相似。在常染色体显性和常染色体隐性遗传的RP中，无论基因突变如何，WJ-MSCs的筋膜下给药都可以被认为是一种有效且安全的选择，对减缓或阻止疾病进展没有任何不利影响。ClinicalTrials.gov，NCT04224207。2020 年 1 月 8 日注册