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Decreased vision in a patient with miliary tuberculosis
Visual field testing showed bitemporal superior defects.
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A 52-year-old man was referred to the New England Eye Center for progressive bilateral visual loss over the course of 2 months. His medical history was significant for acute myelogenous leukemia, which was treated with chemotherapy 10 months before presentation. After the treatment, he developed miliary tuberculosis and had been treated with oral anti- tuberculosis medications for the previous 8 months. He was recently hospitalized for drainage of paraspinal and pleural tubercular abscesses. His medical history was also remarkable for hypertension and atrial fibrillation. He was on multiple medications including isoniazid (INH), rifampin, ethambutol, pyrazinamide, streptomycin, vitamin B6, folate, metoprolol and amiodarone. He wore reading glasses and denied any history of ocular trauma or surgery. Family history was not contributory. He worked as a mechanic, and he did not smoke or drink.
| Shazia Ahmed | My Hanh T. Nguyen |
Examination
Best corrected visual acuity was 20/60 in both eyes. Both pupils were sluggish to react from 5 mm to 3 mm. He recognized 8/10 Ishihara color plates with the right eye and 5/10 with the left. Visual field testing showed bitemporal superior defects apparently respecting midline (Figures 1a and 1b). IOP was 20 mm Hg in both eyes.
Slit lamp exam revealed trace nuclear sclerosis in both eyes. Dilated fundus examination showed optic discs with moderate cupping. Disc margins appeared sharp with healthy neuroretinal rims (Figures 2a and 2b). Optical coherence tomography of nerve fiber layers showed normal thicknesses and contours (Figure 3).
| Humphrey visual field (30-2) of both eyes showing bitemporal superior quadrantanopia apparently respecting midline. | |
| Fundus photographs of both eyes showing normal fundi. Both discs are symmetric and have moderate cupping and healthy rims. Images: Yamamoto I, Hedges TR | Optical coherence tomography of the nerve fiber layers of both eyes (top, right eye; bottom, left eye) showing normal thicknesses except for slight thinning of the nasal quadrant in the left eye. | |
What is your diagnosis?
Bitemporal visual field defects
In this patient with bitemporal visual field defects, chiasmal lesions should be ruled out. Given our patient’s presentation of miliary tuberculosis and recent history of abscess collection elsewhere, an abscess involving the chiasm or chiasmal tuberculoma was a possibility. Common tumors in adults affecting the chiasm include pituitary adenoma, parasellar meningioma and craniopharyngioma. Internal carotid aneurysm, sarcoidosis, third ventricle dilation from an intracranial tumor blocking the aqueduct and chiasmal contusions from trauma may give such visual field defects. In this patient, an MRI was performed immediately and was normal.
Another possible cause of dyschromatopsia and visual field loss is toxic optic neuropathy from anti-tuberculosis medications including ethambutol and isoniazid.
Discussion
Toxic optic neuropathy from ethambutol was suspected in this patient. Out of all anti-tuberculosis medications, ethambutol is by far the most common cause of toxic optic neuropathy, followed by isoniazid. The exact pathophysiology is unknown. However, early animal models have shown histological changes in the optic nerve and chiasm. Multifocal ERG has also shown bilateral reduction of retinal responses in the macula indicating retinal pathology.
Ethambutol toxicity is dose and duration dependent. With doses of more than 35 mg/kg/day, up to 18% of patients develop optic neuropathy. The incidence decreases to 5% to 6% with doses of 25 mg/kg/day and further decreases to less than 1% for doses of 15 mg/kg/day. Optic neuropathy has been reported with doses as low as 12 mg/kg/day. Ethambutol toxicity develops, on average, 3 to 5 months after starting the therapy, but initial presentation can range from 1.5 to 12 months. Patients typically present with bilateral decreased vision with dyschromatopsia. Loss of color vision may be the earliest sign of toxicity. Blue-yellow color loss is the most common. Visual fields show bilateral centrocecal scotomas or bitemporal defects.
Treatment of ethambutol toxicity involves immediate withdrawal of the drug from the anti-tuberculosis regimen. It usually takes at least 2 months to recover from the damage. Extent of recovery is variable. A recent study showed prolonged visual decline after 1 to 2 years follow-up. Ethambutol toxicity may also lead to permanent visual loss with optic atrophy.
For initial tuberculosis therapy, starting with 15 mg/kg per day is recommended to minimize toxicity. If a patient has had prior tuberculosis therapy, then starting with 25 mg/kg/day for 60 days followed by 15 mg/kg/day is recommended. Since ethambutol is excreted through the renal system, use of the drug in patients with renal insufficiency requires extra caution.
Isoniazid is almost always used concomitantly with ethambutol as part of the anti-tuberculosis treatment regimen. The major neuronal toxicity of isoniazid is peripheral neuropathy, but it can rarely cause optic neuropathy as well.
A few case reports have described optic disc swelling in association with isoniazid optic nerve toxicity. If there is no improvement in optic neuropathy after the discontinuation of ethambutol for 3 months, isoniazid should be discontinued as well.
Our patient noticed visual changes after 6 months of using anti-tuberculosis medications. He was taking ethambutol at a dose of 22 mg/kg/day. The ethambutol was promptly discontinued, and the patient is currently being closely monitored.
For more information:
- Izumi Yamamoto, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com.
- Edited by Shazia Ahmed, MD, and My Hanh T. Nguyen, MD. Drs. Ahmed and Nguyen can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; Web site: www.neec.com. Drs. Ahmed and Nguyen have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
- Behbehani RS, Affel EL, Sergott RC, Savino PJ. Multifocal ERG in ethambutol associated visual loss. Br J Ophthalmol. 2005;89(8):976-982.
- Chan RY, Kwok AK. Ocular toxicity of ethambutol. Hong Kong Med J. 2006;12(1):56-60.
- Kumar A, Sandramouli S, et al. Ocular ethambutol toxicity: Is it reversible? J Clin Neuroophthalmol. 1993;13(1):15-17.
- Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol toxicity. Mayo Clin Proc. 2003;78(11):1409-1411.
- Merino P, Pelaez C, et al. Severe toxic optic neuropathy and isoniazid. Infectious Dis in Clin Practice. 1996;279-281.