The Genetics of Ethambutol-Induced Optic Neuropathy: A Narrative Review

ABSTRACT

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.

KEYWORDS:

• Tuberculosis
• ethambutol
• optic neuropathy
• mitochondria
• pharmacogenomics

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

Prabhjit Kaur: Conceptualisation, Writing-original draft, Writing-review and editing, Manuscript preparation, Data Curation, Formal Analysis

Sofia Singh: Data Curation and Formal Analysis

Kirandeep Kaur: Data Curation and Formal Analysis

Karthik Vinay Mahesh: Supervision, Visualisation and Validation

Basavraj Tigari: Visualisation and Validation

Vineet Sehgal: Visualisation and Validation

Aastha Takkar Kapila: Conceptualisation, Data Curation, Supervision, Visualisation and Validation

Sahil Mehta: Supervision, Visualisation and Validation

Ramandeep Singh: Supervision, Visualisation and Validation

Samir Malhotra: Supervision, Visualisation and Validation

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.