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Patient experiences vision loss in Indonesia
Patient also had blurred vision in both eyes and photophobia.
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A previously healthy 19-year-old college student was referred to the New England Eye Center for evaluation after returning from Indonesia where she had studied abroad and suffered a severe illness requiring hospitalization. She had blurred vision in both eyes, photophobia and a blind spot in the center of her vision. Her ocular history was notable only for congenital coloboma in her right eye, and she was on no medications. She had never smoked cigarettes or used drugs, and she drank beer and liquor occasionally with friends.
Examination
On presentation, visual acuity was 20/30-1 in the right eye and 20/15-1 in the left eye. The right pupil was irregular, but both pupils were reactive and there was no afferent defect. The patient recognized all Ishihara color plates with both eyes. She had saccadic pursuit movement, but saccades were accurate and vestibulo-ocular responses appeared normal. There was an inferonasal iris coloboma and an inferior chorioretinal defect with a tilted optic disc associated with mild peripapillary atrophy (Figure 1a). In the left eye there was trace segmental pallor of the optic disc temporally (Figure 1b).
Visual field testing (Humphrey 10-2) showed mild central depression in both eyes (Figures 1c and 1d). OCT of the optic nerve head showed preserved retinal nerve fiber layer (RNFL) in both eyes (Figure 1e). Ganglion cell analysis appeared grossly normal in the right eye, but there was segmental thinning in the region of the papillomacular bundle in the left eye (Figure 1f).
Images: Klein K, Hedges TR
What is your diagnosis?
Vision loss
The differential diagnosis of bilateral blurred vision, photophobia and central scotoma in a young woman with mild optic disc pallor includes nutritional optic neuropathy, toxic optic neuropathy, inherited optic neuropathy, optic neuritis, compressive optic neuropathy and retinopathy.
Differential diagnosis
Nutritional optic neuropathy can result from chronic deficiency in B vitamins and folic acid from special diets, anorexia nervosa and gastric bypass surgery. A variety of toxins can cause optic neuropathy, including methanol and ethylene glycol acutely, and ethambutol and linezolid after months of use. Inherited optic neuropathies include Leber’s hereditary optic neuropathy, which results from mutations in mitochondrial DNA and typically affects men between the ages of 10 years and 30 years. It can occur in women and typically presents with acute, severe, painless, sequential vision loss or central visual field impairment. Autosomal dominant optic atrophy usually results in vision loss during the first decade of life, central scotomas and temporal optic disc pallor. Demyelinating optic neuritis is common in young women, but typically presents unilaterally and with pain. Similarly, sarcoid, syphilis, tuberculosis, lymphoma and leukemia can cause an infiltrative optic neuropathy with progressive vision loss, but these typically present without pain. Compressive optic neuropathy can result from an optic pathway glioma, resulting in unilateral or bilateral visual field defects and optic disc pallor. Various retinopathies, such as multiple evanescent white dot syndrome, can present with an enlarged blind spot and photopsias, and cone dystrophy can result in a gradual decline in vision, color discrimination and photophobia.
More history
The night before symptom onset, the patient was out with other international students studying in Indonesia, drinking various alcoholic beverages from multiple street vendors. In addition to the mixed drinks, she consumed chocolates filled with liquor (of note, she was the only one to eat these chocolates and the only student to get sick). When she returned to her host family’s home later that evening, her friends noted she had difficulty walking. The next morning, she slept the entire day and had multiple episodes of emesis. The following day, she was somnolent and in respiratory distress. She was brought immediately to the local hospital where she became apneic and required resuscitation and intubation. An arterial blood gas revealed profound metabolic acidosis, with a pH of 6.79. No crystals were seen in the urine to suggest ethylene glycol poisoning, and a blood methanol level was elevated at 0.6 (normal is less than 0.02). She was diagnosed with methyl alcohol poisoning. She was started on intravenous ethanol, Solu-Medrol, sodium bicarbonate and vitamin B12. She required renal dialysis for the metabolic acidosis.
When she was extubated the following day, she had bilateral blurred vision, photophobia and a blind spot in her vision. A hospital ophthalmologist found no specific abnormalities. In addition to the visual symptoms, she had weakness of the extremities, a shuffling gait, decreased volume of speech and micrographia. MRI of the brain demonstrated hyperintense lesions on T2 imaging involving the basal ganglia bilaterally, consistent with acute hemorrhage, and hyperintensity of the cerebral cortex consistent with hypoxic injury (Figure 2).
After being hospitalized for more than 1 week, she returned home. She was seen at the New England Eye Center 3 weeks later.
Follow-up
The patient was seen 7 months after initial presentation and was getting ready to return to college. She had been in intensive physical therapy and felt almost back to normal, although her speech continued to be somewhat quiet, and she still had some trouble with balance. She felt her vision was almost back to normal, and her exam was unchanged. Although the RNFL measurements were normal, ganglion cell analysis showed bilateral segmental defects in the area of the papillomacular bundles on both sides (Figure 3a). Furthermore, corresponding nasal macula scans demonstrated inner nuclear layer microcysts in the right eye (Figure 3b) and left eye (Figure 3c).
Discussion
Methanol, also known as wood alcohol, is used in antifreezes, photocopying fluids, perfumes and illegal spirits. As little as 10 mL (8 g) of 100% methanol can cause blindness after oral consumption. In Southeast Asia, most cases of methanol poisoning result from adulterated liquor in local drinks. Formic acid, or formate, is the metabolite of methanol that is responsible for visual impairment. Formate interferes with the mitochondrial respiratory chain by inhibiting cytochrome c oxidase.
The first symptoms of intoxication appear 4 or more hours after ingestion and commonly include nausea, vomiting, headache, vertigo, confusion, respiratory distress and coma. The first ophthalmic symptoms typically appear later (at 6 to 48 hours), and the severity varies widely. Vision loss is usually painless and progressive, and can range from minor decreases in acuity to no light perception. Dyschromatopsia, photophobia and visual field defects in the form of dense central scotomas are common. Ophthalmic signs include nonreactive, dilated pupils, optic disc edema, hyperemia and disc hemorrhages acutely, and optic atrophy and pallor chronically. General and visual prognosis is most dependent on the severity of acidosis rather than the blood methanol level. The most common toxic effect of methanol in the central nervous system is necrosis of the putamen, causing rapid-onset Parkinsonism. It is believed that the putamen is differentially affected due to its high metabolic demand and susceptibility to ischemia.
Van Buren first described microcysts of the retinal inner nuclear layer in experimental traumatic optic neuropathy in 1963. Since that time, microcystic inner nuclear layer abnormalities have been described in a variety of disease states, including multiple sclerosis, neuromyelitis optica, hereditary optic neuropathies, compressive optic pathway diseases and glaucoma. Various theories have been put forth to explain these cystic changes, including transsynaptic retrograde degeneration, subclinical inflammation in the inner nuclear layer, autoantibodies and mitochondrial dysfunction.
The findings from this case suggest that retinal ganglion cell loss may be a more sensitive indicator of optic neuropathy than RNFL thickness. The relative sparing of the optic nerve in this case demonstrates the evolution of methanol toxicity with early segmental ganglion cell involvement and preservation of the RNFL. Further, the development of inner nuclear layer microcysts at follow-up supports that these are non-specific and may signify preferential loss of small caliber axons of the papillomacular bundle, which are rich in mitochondria and most vulnerable in energy-depleted states.
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- For more information:
- Kendra Klein, 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; website: www.neec.com.
- Edited by Kristen E. Dunbar, MD, and Kendra Klein, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St, Box 450, Boston, MA 02111; website: www. neec.com.