Corneal neuropathy involves corneal nerve damage that disrupts ocular surface integrity, negatively impacting quality-of-life from pain and impaired vision. Any ocular or systemic condition that damages the trigeminal nerve can lead to corneal neuropathy. However, the condition currently does not have standardized diagnostic criteria or treatment protocols. The primary aim of this systematic review was to evaluate the efficacy and safety of interventions for treating corneal neuropathy. Randomized controlled trials (RCTs) that investigated corneal neuropathy treatments were eligible if the intervention(s) was compared to a placebo or active comparator. Comprehensive searches were conducted in Ovid MEDLINE, Ovid Embase and clinical trial registries from inception to July 2022. The Cochrane Risk-of-Bias 2 tool was used to assess study methodological quality. Certainty of the body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Overall, 20 RCTs were included. Evaluated interventions comprised regenerative therapies (n = 6 studies), dietary supplements (n = 4), anti-glycemic agents (n = 3), combination therapy (n = 3), supportive therapies (n = 2) and systemic pain pharmacotherapies (n = 2). Nine RCTs were judged at high risk of bias for most outcomes. Definitions for corneal neuropathy in the populations varied substantially across studies, consistent with lack of consensus on diagnostic criteria. A diverse range of outcomes were quantified, likely reflecting absence of an agreed core outcome set. There was insufficient evidence to draw definitive conclusions on the efficacy or safety of any intervention. There was low or very low certainty evidence for several neuroregenerative agents and dietary supplements for improving corneal nerve fiber length in corneal neuropathy due to dry eye disease and diabetes. Low or very low certainty evidence was found for neuroregenerative therapies and dietary supplements not altering corneal immune cell density. This review identifies a need to standardize the clinical definition of corneal neuropathy and define a minimum set of core outcome measures. Together, this will provide a foundation for improved phenotyping of clinical populations in studies, and improve the capacity to synthesize data to inform evidence-based care.

中文翻译：

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评估角膜神经病变治疗干预措施的有效性和安全性：系统评价


角膜神经病变涉及角膜神经损伤，破坏眼表完整性，因疼痛和视力受损而对生活质量产生负面影响。任何损害三叉神经的眼部或全身疾病都可能导致角膜神经病变。然而，该病目前没有标准化的诊断标准或治疗方案。本系统评价的主要目的是评估治疗角膜神经病变干预措施的有效性和安全性。如果将干预措施与安慰剂或活性比较剂进行比较，则研究角膜神经病变治疗的随机对照试验（RCT）是合格的。从开始到 2022 年 7 月，在 Ovid MEDLINE、Ovid Embase 和临床试验注册中心进行了全面检索。Cochrane 偏倚风险 2 工具用于评估研究方法学质量。使用建议评估、制定和评价分级（GRADE）方法对证据的确定性进行了评估。总体而言，纳入了 20 项随机对照试验。评估的干预措施包括再生疗法（n = 6项研究）、膳食补充剂（n = 4）、抗血糖药物（n = 3）、联合疗法（n = 3）、支持疗法（n = 2）和全身疼痛药物疗法（ n = 2）。九项随机对照试验的大多数结果被判定存在高偏倚风险。不同研究对人群中角膜神经病变的定义差异很大，这与诊断标准缺乏共识是一致的。对各种结果进行了量化，这可能反映出缺乏商定的核心成果集。没有足够的证据来对任何干预措施的有效性或安全性得出明确的结论。 对于几种神经再生剂和膳食补充剂可改善干眼病和糖尿病引起的角膜神经病的角膜神经纤维长度的证据质量较低或非常低。发现神经再生疗法和膳食补充剂不会改变角膜免疫细胞密度的低或极低确定性证据。本次综述确定需要标准化角膜神经病变的临床定义并定义一套最低限度的核心结果指标。总之，这将为改善研究中临床人群的表型分析奠定基础，并提高合成数据以告知循证护理的能力。