Purpose

Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD) and assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease.

Methods

The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix.

Results

105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies.

Conclusions

This is the first systematic review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events were noted. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features that develop in patients.

中文翻译：

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评估角膜缘干细胞缺陷动物模型的临床转化相关性：系统评价

目的

动物模型对于阐明病理生理机制和评估新疗法至关重要。该系统评价确定了开发或调整角膜缘干细胞缺乏症 (LSCD) 动物模型的研究，并评估了它们的报告质量，总结了它们的关键特征，并确定了它们与人类疾病的临床转化相关性。

方法

该协议是前瞻性注册的 (PROSPERO CRD42020203937)。在 PubMed、Ovid EMBASE 和 Web of Science 中进行了搜索。两位作者筛选引文，提取数据，使用 ARRIVE 指南评估合格研究的报告质量，并使用自定义矩阵判断每个模型的临床转化相关性。

结果

纳入了 105 项研究。兔子是最常见的动物物种。总体而言，97% 的研究将 LSCD 概括为临床病因，但 62% 的研究没有提供足够的方法学细节来实现模型的独立再现。很少报告不良事件和/或排除动物（20%）。大约四分之一的研究没有产生预期的 LSCD 严重程度；34% 提供的信息不足以评估疾病诱导的保真度。在 13% 的研究中进行了 LSCD 诱导的辅助诊断确认。

结论

这是第一个评估 LSCD 动物模型的报告质量和临床转化相关性的系统评价。LSCD 模型随着时间的推移而演变，导致动物特征、实验程序和不良事件的报告出现变化。在大多数研究中，LSCD 的验证是通过临床试验进行的。更新的辅助技术将增强诊断验证。由于大多数研究试图评估 LSCD 的新疗法，动物模型应该理想地概括患者身上出现的所有特征。