Kaur Prabhjit, Singh Sofia, Kaur Kirandeep, Mahesh Karthik Vinay, Tigari Basavaraj, Sehgal Vineet, Takkar Aastha, Mehta Sahil, Singh Ramandeep, Malhotra Samir
Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Ophthalmology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Neuroophthalmology. 2022 Aug 2;46(5):304-313. doi: 10.1080/01658107.2022.2100916. eCollection 2022.
Tuberculosis (TB) is a global health problem with the major brunt of disease occurring in developing countries. The cornerstone of treatment of TB is anti-tubercular therapy (ATT), which includes rifampicin, isoniazid, pyrazinamide and ethambutol. Because of emerging drug resistance, treatment failures, defaulters and increasing incidence of disseminated and extrapulmonary TB, the guidelines have been modified in some countries. Ethambutol is prescribed for longer times (in some cases >8 months) and hence the incidence of ethambutol-induced optic neuropathy (EtON) is expected to rise. The fundamental question which needs explanation is why only a small subset of patients on ethambutol are prone to develop loss of vision. This review focuses on available genetic studies which provide evidence that mitochondria are the likely substrates involved in the final pathway of reactive oxidative damage of the papillo-macular bundle. Genetic analysis of mitochondrial mutations encoding genes involved in oxidative phosphorylation pathways may help in isolating the subset of patients who are genetically susceptible. If the groups having high risk of developing EtON are recognised then prolonged duration of ethambutol treatment can be avoided in these susceptible individuals. A better understanding of the pathophysiology will also pave the way for the development of management strategies in this condition.
结核病是一个全球性的健康问题，疾病的主要负担发生在发展中国家。结核病治疗的基石是抗结核治疗（ATT），其中包括利福平、异烟肼、吡嗪酰胺和乙胺丁醇。由于新出现的耐药性、治疗失败、治疗中断以及播散性和肺外结核病发病率的增加，一些国家已对指南进行了修订。乙胺丁醇的使用时间延长（在某些情况下超过8个月），因此乙胺丁醇引起的视神经病变（EtON）的发病率预计会上升。需要解释的基本问题是，为什么使用乙胺丁醇的患者中只有一小部分容易出现视力丧失。本综述重点关注现有的遗传学研究，这些研究提供了证据，表明线粒体可能是参与视乳头黄斑束反应性氧化损伤最终途径的底物。对编码参与氧化磷酸化途径的基因的线粒体突变进行基因分析，可能有助于分离出具有遗传易感性的患者亚组。如果识别出发生EtON风险高的人群，那么在这些易感个体中可以避免延长乙胺丁醇治疗时间。更好地理解病理生理学也将为这种情况下管理策略的发展铺平道路。
