结核病是由结核分枝杆菌(Mtb)引起的空气传播疾病,可以表现为肺部和肺外疾病,包括眼结核(OTB)。OTB的准确诊断和快速最佳治疗开始面临许多挑战,加上缺乏标准化治疗方案,这导致OTB结果不确定。这项研究的目的是总结现有的诊断方法和最近发现的可能有助于建立OTB诊断的生物标志物。抗结核治疗(ATT)方案的选择,和治疗监测。关键词眼结核,结核病,分枝杆菌,生物标志物,分子诊断,多组学,蛋白质组学,基因组学,转录组学,代谢组学,在PubMed和MEDLINE数据库上搜索T淋巴细胞谱。包含至少一个关键字的文章和书籍,并进行相关性筛选。纳入研究没有时间限制。更多的重点放在最近的出版物上,这些出版物提供了有关发病机理的新信息,诊断,或OTB的治疗。我们排除了不是用英语写的摘要和文章。在确定的文章中引用的参考文献用于进一步补充搜索。我们发现10项研究评估了干扰素-γ释放试验(IGRA)的敏感性和特异性,和6项研究评估了结核菌素皮肤试验(TST)在OTB患者中的应用。IGRA(Sp=71-100%,Se=36-100%)比TST(Sp=51.1-85.7%;Se=70.9-98.5%)具有更好的总体敏感性和特异性。对于核酸扩增试验(NAAT),我们发现了7项针对不同Mtb靶标的单重聚合酶链反应(PCR)的研究,基于DNA的多重PCR的7项研究,1基于mRNA的多重PCR研究,关于不同Mtb靶标的环介导等温扩增(LAMP)测定的4项研究,关于GeneXpert测定的3项研究,1项关于GeneXpertUltra测定的研究和1项关于MTBDRplus测定OTB的研究。特异性总体上得到了提高,但对于NAAT来说,灵敏度是高度可变的(不包括单重PCR,Sp=50-100%;Se=10.5-98%),与IGRA相比。我们还发现了3项转录组学研究,6蛋白质组学研究,关于刺激测定的2项研究,1关于OTB患者眼内蛋白分析的研究和1关于T淋巴细胞谱分析的研究。除1项研究外,所有研究都评估了新颖,以前未被发现的生物标志物。只有1项研究通过大型独立队列进行了外部验证。通过多组学方法发现未来的治疗诊断标记对于加深对OTB的病理生理学理解至关重要。这些结合起来可能会导致迅速,优化和个性化的治疗方案,以调节OTB的异质性机制。最终,这些研究可以改善OTB目前繁琐的诊断和管理.
Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.