Atlas of Ophthalmology

Bilateral Linezolid-associated Toxic Optic Neuropathy (Colour Photography, VEP, OCT)

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Patient: 63 years of age, male, BCVA 0.6 at OD, 01 at OS; IOP 15/15 mmHg. General Medical History: in 06/2011 acute myeloic leucemia (AML M4) with 126.000 leucocytes, coronary heart disease, cranial MRI without lesions, Hb 9.3 g/dl. In 10/2011 beginn of systemic therapy with Adriamycin, Cytrarabin, and Mitoxatron. In 11/2011 due to thrombophlebitis and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli antibiotic therapy with meropenem (Meronem®, vancomycin und linezolid (Zyvoxid®) over three weeks. Ocular Medical History: in 01/2012 fast reduction of VA at OS after systemic therapy over three weeks with meropenem (Meronem®, vancomycin und linezolid (Zyvoxid®). Main Complaint: reduction of VA in OS. Findings: 1) Colour Photography: bilateral optic nerve atrophy (OS>OD). 2) VEP: decreased amplitudes und prolonged latencies. 3) OCT: decreased retinal nerve fiber layer thickness. Discussion: It was reported (1,2), that antibiotic therapy with Linezolid (Zyvoxid®) can cause optic nerve atrophy. Linezolid, an oxazolidinone, used against infections with methicillin resistant staphylococcus aureus (MRSA) may lead to progressive, potentially irreversible neuropathies of the optic nerve especially in long-time application. Linezolid is part of the oxazolidinone class of antibiotics that inhibit bacterial protein synthesis by binding to the 70S ribosomal initiation complex. Although this complex is not present in mammalian cells, a study has demonstrated reduced mitochondrial respiratory chain enzyme activity in a patient receiving linezolid therapy who developed optic neuropathy, suggesting that mammalian mitochondria are vulnerable. Linezolid-induced toxic optic neuropathy may be similar to the respiratory chain dysfunction observed in mitochondrial optic neuropathies (e.g., Leber hereditary optic neuropathy). Coadministration of ciprofloxacin or rifampicin may potentiate the toxicity of linezolid. In general the functions of the eye can be disturbed by pharmaceutical agents via various mechanisms. Especially antimicrobial agents can produce ocular adverse drug reactions. The complexity of ocular adverse drug reactions underlines the need for a close interdisciplinary cooperation to optimize drug safety of antimicrobial agents. Literature: (1) Huber M, Stahlmann R. The eye as target of adverse ocular drug reactions. Focus on systemic antiinfective therapy. Med Monatsschr Pharm. 2012 Dec;35(12):436-42; quiz 443-4. (2) Joshi L, Taylor SR, Large O, Yacoub S, Lightman S.A case of optic neuropathy after short-term linezolid use in a patient with acute lymphocytic leukemia. Clin Infect Dis. 2009 Apr 1;48(7):e73-4.

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