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Anthony G Robson, Shiying Li, Magella Marie Neveu, Zheng Q Yin, Graham E Holder; The electrophysiological characteristics and monitoring of ethambutol toxicity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6213.
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To describe and monitor the electrophysiological and ophthalmic characteristics of ethambutol optic neuropathy (EON).
Thirty patients (median age 59 years; range 30-86 years) being treated with ethambutol for tuberculosis, and with a clinical diagnosis of presumed EON, were identified from the Department of Electrophysiology database at Moorfields Eye Hospital. All had undergone pattern reversal and flash visual evoked potential (PVEP; FVEP), and pattern and full-field electroretinogram (PERG; ERG) testing. Serial data were available in 7 cases monitored over periods of up to 3 years following cessation of ethambutol. The case notes were reviewed and the available clinical data compared with the electrophysiological findings.
Patients presented with blurred vision or reduced visual acuity (VA; median logMAR 0.8; range 0 to 3). PVEPs were delayed in 33 of 45 eyes with a detectable response (median peak time 130ms; range 117-175ms) and were subnormal in 18 eyes including 5 without delay. Comparison between eyes revealed a high degree of inter-ocular symmetry of PVEP peak times (slope = 0.92, r2=0.87) and amplitudes (slope= 0.70, r2= 0.68). Pattern ERG P50 component, a measure of macular function, was normal in 45 of 56 eyes and mildly reduced (<33%) in 11 eyes; the N95:P50 ratio was subnormal in 21 of 56 eyes, indicating retinal ganglion cell dysfunction. ERGs were mildly abnormal in 3 patients including two with normal PERG and one case with mild bilateral P50 reduction. The VEP timing and PERG P50 parameters did not correlate with VA. Eleven of 14 eyes showed improvement in VA following cessation of ethambutol (median improvement logMAR 0.5). Pattern VEP timing improved bilaterally in 9 eyes of 7 patients (by 4 to 46ms) including 4 eyes that normalised; PVEP returned in 3 eyes with previously undetectable PVEPs, including 2 with normal N95 components at baseline.
Ethambutol use may be associated with severe optic nerve and retinal ganglion cell dysfunction. Severe PVEP abnormalities may resolve following cessation of ethambutol and the need for early diagnosis is stressed.
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