<![CDATA[Linezolid remains a key component in drug-resistant tuberculosis (DR-TB) regimens but is associated with toxic optic neuropathy (TON). Although mitochondrial dysfunction has been implicated in linezolid-induced neurotoxicity, the contribution of mitochondrial DNA (mtDNA) variants remains uncertain, with limited data from Indonesian populations. This study aimed to evaluate clinical risk factors and mitochondrial DNA polymorphisms associated with linezolid-related TON in DR-TB patients. This cross-sectional analytical study was conducted at Dr. Mohammad Hoesin Hospital in Palembang from January to March 2025 and involved 51 DR-TB patients receiving linezolid therapy, selected through consecutive sampling. Demographic and clinical data were collected, and mtDNA polymorphisms (G3010A and A2706G) were examined using PCR-RFLP, chosen based on previous studies linking these variants to linezolid toxicity in Asian and African populations. TON was identified in 22 of 51 patients (43.1%) based on standardized ophthalmological criteria. Diabetes mellitus (PR=2.078, 95% CI=1.191–3.624, p=0.03) and treatment regimen (PR=12.469, 95% CI=1.821–85.398, p=0.00) demonstrated statistically significant associations with TON, whereas age (p=0.635), sex (PR=0.713, 95% CI=0.384–1.322, p=0.29), HIV status (PR=1.600, 95% CI=0.672–3.809, p=0.40), and DR-TB type (PR=1.438, 95% CI=0.735–2.812, p=0.28) were not associated. All subjects had a wild-type genotype for G3010A and a mutant-type genotype for A2706G, precluding any association analysis for these variants. In conclusion, diabetes mellitus and individual treatment regimens were associated with linezolid-induced TON in this study. In contrast, the investigated mtDNA polymorphisms (G3010A and A2706G) showed no variability; thus, no relationship could be evaluated. Larger prospective studies with expanded genetic markers and multivariate adjustment are warranted to characterize susceptibility factors for linezolid-associated TON better.]]>
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