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Year : 2006  |  Volume : 54  |  Issue : 3  |  Page : 218-219

Leber's hereditary optic neuropathy masquerading as ethambutol- Induced optic neuropathy in a young male

1 Hindu Rao Hospital, Department of Ophthalmology, Delhi, India
2 Department of Neurology, G. B. Pant Hospital, New Delhi, India

Correspondence Address:
Debashish Chowdhury
Department of Neurology, G. B. Pant Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.27091

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How to cite this article:
Chowdhury B, Nagpaul A K, Chowdhury D. Leber's hereditary optic neuropathy masquerading as ethambutol- Induced optic neuropathy in a young male. Indian J Ophthalmol 2006;54:218-9

How to cite this URL:
Chowdhury B, Nagpaul A K, Chowdhury D. Leber's hereditary optic neuropathy masquerading as ethambutol- Induced optic neuropathy in a young male. Indian J Ophthalmol [serial online] 2006 [cited 2023 Dec 6];54:218-9. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?2006/54/3/218/27091

Dear Editor,

We read with interest, the article by Verma et al ,[1] regarding molecular characterization in two Indian families with Leber's hereditary optic neuropathy (LHON). We wish to share our experience of a case of LHON which posed a diagnostic challenge. A 32 year old male presented with acute onset of painless, progressive diminution of vision involving both eyes, since 5 days. The patient was a known case of pulmonary tuberculosis receiving INH (300 mg/day), rifampicin (450 mg/day), pyrazinamide (1 gm/day) and ethambutol (800 mg/day), since the past 4 months. There was no other significant past, personal and family history. His vision was 20/60 (right eye) and 20/120 (left eye) and color vision was defective. Intraocular pressure, pupils, anterior chamber, iris and vitreous were normal. There was no relative afferent pupillary defect. Fundus showed bilateral hyperemic discs. Ethambutol- induced optic neuropathy was considered and the patient was asked to stop ethambutol. His vision continued to deteriorate further (right eye 20/120, left eye 20/200). After 2 weeks, fundus showed bilateral disc edema with blurred margins and a single disc hemorrhage in left eye [Figure - 1]. Venous pulsations were seen in both eyes. Visual field showed bilateral central scotomas. His neurological examination was normal. His complete blood count, routine biochemistry, serum B12, calcium, phosphorus, angiotensin- converting enzyme, cerebrospinal fluid and magnetic resonance imaging (MRI) of brain were normal. VDRL was non-reactive. A pattern- reversal VEP showed prolonged P100 latency in both eyes. MRI of optic nerves and orbit showed bilateral, thinned out optic nerves without any plaque. Fasting blood lactate was high. The mutation G11778A in the mitochondrial gene MTND4 was identified in the patient. Thus, a diagnosis of LHON was made.

Ethambutol toxicity causing optic neuropathy is a well recognized complication of anti-tubercular therapy. Color vision is usually affected early. This was seen in our case. Also, the central scotomas and disc hyperemia, disc edema and splinter hemorrhages in the disc have been reported, though the rest of the fundus remains normal in most cases. It is a rare occurrence in the dose of 15 mg/kg/day, although it is unpredictable and it is recommended that all patients should have a thorough eye check up prior to starting ethambutol.[2] Our patient's weight being 52 kg, was at a marginally higher dose of 15.38 mg/kg/day and did not have any prior eye check up. Although it is usually believed that optic neuritis is reversible over a period of time after stopping the drug, experience from previously published Indian data suggest that only 42.2% achieved a visual recovery of better than 20/200 after an average follow-up of 8.3 ± 2.1 months, after stoppage of the drug.[2] By two weeks, the clinical picture in our patient was more like a demyelinating optic neuropathy with significant decrease in vision, abnormal VEP and a fundus picture suggestive of papillitis. Our patient did not have any neurological symptoms or signs. Radiologically also, there was no demyelination either in brain or in optic nerves. The other differential diagnoses like nutritional amblyopia, Lyme's disease, sarcoidosis, diabetic papillitis and syphilitic optic neuropathy were ruled out. Finally, genetic analysis clinched the diagnosis in favor of LHON. Identification of one of the three major primary pathogenic mutations establishes the diagnosis, even in the absence of a family history.[1]

Bilateral simultaneous papillitis is seen in 50% of patients of LHON.[3] Fundus examination characteristically shows a triad of signs: circumpapillary telangiectatic microangiopathy, pseudoedema and absence of leakage on fluorescein angiography.[3] However, these fundus changes may be absent or minimal in some cases, as seen in our case. The incidence of the mt DNA 11718 mutation is high in patients with acute optic nerve disease without family history, as seen in our patient.[4] Ethambutol has rarely been identified as the triggering agent in LHON patients.[4] Both ethambutol and LHON mutation can affect oxidative phosphorylation through impairment of mitochondrial function. It is possible that ethambutol acted as the triggering factor for visual loss in our patient. To the best of our knowledge, this is the third case study highlighting the association of ethambutol- related optic neuropathy and LHON.

  References Top

Verma IC, Bijarnia S, Saxena R, Kohli S, Puri RD, Thomas E, et al . Leber's hereditary optic neuropathy with molecular characterization in two Indian families. Indian J Ophthalmol 2005;53:167-71.  Back to cited text no. 1
Kumar A, Sandramouli S, Verma L, Tewari HK, Khosla PK. Ocular ethambutol toxicity: Is it reversible? J Clin Neuroophthalmol 1993;13:15-7.  Back to cited text no. 2
Carelli V, Ross-Cisneros FN, Sudan AA. Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res 2004;23:53-89.  Back to cited text no. 3
Dotti MT, Plewnia K, Cardaioli E, Manneschi L, Rufa A, Alema G, et al . A case of ethambutol induced neuropathy harboring the primary mitochondrial LHON mutation at 11778nt. J Neurol 1998;245:302-3.  Back to cited text no. 4


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