Department of Ophthalmology, Royal Victoria Infirmary and University of Newcastle, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK.
York Health Economics Consortium, Enterprise House, Innovation Way, University of York, York, YO10 5NQ, UK.
Ocul Surf. 2021 Apr;20:48-61. doi: 10.1016/j.jtos.2020.12.008. Epub 2021 Jan 4.
This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown.
A protocol was registered with PROSPERO (CRD42017081117). Searches were conducted in 14 databases and 6 conference websites. Two reviewers independently selected studies, conducted data extraction and assessed risk of bias. One reviewer extracted individual patient data (IPD); a second checked extracted data. Data were assessed to determine the feasibility of statistical analysis, with Bayesian synthesis used to estimate improvement achieved by different treatments.
Fifty-two studies were eligible for inclusion (1113 eyes); 41 studies (716 eyes) reported IPD. No evidence was identified on cost-effectiveness. This SR was unable to confirm that any of the types of ex vivo cultured stem cell transplants identified for LSCD treatment were statistically superior when assessed against the outcomes of interest.
We believe this SR is the first to include IPD analysis of LSCD data. There is no evidence for the superiority of any method of limbal stem cell transplant. Confirmation of the safety and efficacy of this treatment modality is challenging due to heterogeneity within and between the studies identified. Therefore, recommendations for future research are proposed.
本系统评价（SR）评估了细胞疗法治疗角膜缘干细胞缺乏症（LSCD）的疗效、安全性和成本效益，LSCD 是一种威胁视力的孤儿病，最常与严重的化学或热烧伤有关。LSCD 传统上通过移植角膜缘组织进行治疗。1997 年，一种新的治疗方法，即培养的角膜缘上皮自体移植物，被用于治疗单侧 LSCD。在双侧疾病的情况下，已使用培养的自体口腔黏膜干细胞。不同培养组织程序的相对疗效尚不清楚。
该方案已在 PROSPERO（CRD42017081117）中注册。在 14 个数据库和 6 个会议网站上进行了检索。两名评审员独立选择研究，进行数据提取和评估偏倚风险。一名评审员提取个体患者数据（IPD）；第二名评审员检查提取的数据。评估数据以确定统计分析的可行性，使用贝叶斯综合估计不同治疗方法所取得的改善程度。
52 项研究符合纳入标准（1113 只眼）；41 项研究（716 只眼）报告了 IPD。没有关于成本效益的证据。本 SR 无法确认在评估关注结局时，任何一种已确定用于 LSCD 治疗的体外培养干细胞移植类型在统计学上具有优势。
我们认为这是首次包括 LSCD 数据 IPD 分析的 SR。没有任何一种角膜缘干细胞移植方法具有优越性的证据。由于所确定的研究之间存在异质性，因此，确认这种治疗方式的安全性和疗效具有挑战性。因此，提出了对未来研究的建议。
