Grand Rounds

Linezolid, an oxazolidinone-class antibiotic increasingly utilized for multidrug-resistant tuberculosis (MDR-TB) and gram-positive infections, carries an underrecognized risk of toxic optic neuropathy (LON). Its mechanism of ocular toxicity is rooted in off-target binding to mitochondrial 16S rRNA, resulting in mitochondrial dysfunction analogous to Leber's Hereditary Optic Neuropathy (LHON). We present a case of bilateral, painless visual loss with cecocentral scotoma and dyschromatopsia developing after prolonged linezolid and tedizolid therapy. Multimodal imaging was unremarkable aside from progressive ganglion cell-inner plexiform layer thinning and visual evoked potentials revealing prolonged latencies and decreased amplitude bilaterally. A systematic review of reported LON cases identifies treatment duration exceeding 28 days and daily doses ≥600 mg as the primary risk factors, with complete visual recovery achieved in only 66.7% of cases following drug cessation. We compare LON with tacrolimus-induced optic neuropathy (TION), highlighting key mechanistic, imaging, and prognostic differences. While LON reflects pure mitochondrial toxicity, TION involves a mixed ischemic, demyelinating, and axonal mechanism. VEP serve as critical imaging tools for diagnosis of optic neuropathies and differentiation from functional vision loss. Early recognition of LON and prompt drug discontinuation are essential for visual recovery. Baseline and serial ophthalmic monitoring should be standard of care for all patients receiving extended linezolid therapy. Good history taking and multidisciplinary care are essential for prevention and management of toxic optic neuropathies.

Presentation Date: 04/30/2026
Issue Date: 05/01/2026