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Young man with diabetes presents with progressive near visual loss
The dilated fundus exam revealed multiple telangiectasias surrounding both optic nerve heads.
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The patient, a 35-year-old man with diabetes, complained of 2 months of blurred vision in his left eye with near work. While working at a computer and reading for his job, he noted a left brow ache and pain at the back of his head. He denied problems with distance vision. He saw an optometrist 1.5 months previously but did not experience improvement with refraction.
 Isabel Balderas |  Tom Hsu, MD |
He had no ocular history and never required corrective lenses. His medical history was remarkable for diabetes mellitus, diagnosed 5 years ago. He had been on insulin for 3 years. His medications included insulin, lisinopril and Requip (ropinirole). He had no significant family history of ocular disease. He denied tobacco use and consumes alcohol only occasionally.
Examination
Distance visual acuity without correction was 20/20-2 in the right eye and 20/200 in the left eye. Vision was not improved at distance or near with refraction. Pupillary exam was normal. There was decreased color vision in the left eye and normal vision in the right eye, an abnormal Amsler grid in the left eye (Figure 1) and bilateral visual field defects on Humphrey SITA standard 24-2 threshold automated perimetry (Figures 2a, 2b).
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| Amsler grid test performed by the patient showing central visual defect when viewing the grid with his left eye | Humphrey SITA standard 24-2 threshold automated perimetry showing central defects in both eyes, the left eye demonstrating more extensive involvement. This test was administered at first visit. Images: Balderas IM, Hedges TR | |
Anterior segment examination was unremarkable. Fundus examination revealed multiple telangiectasias surrounding both optic nerve heads, but otherwise the retinas and nerves appeared normal (Figures 3a, 3b).
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| Color fundus photos of right and left eyes showing circumpapillary telangiectasias, central vascular tortuosity and abnormal nerve fiber layer appearance. | |
What is your diagnosis?
Multiple telangiectasias
Taking into consideration the patient’s history, physical examination and results of ancillary studies, a diagnosis of Leber’s hereditary optic neuropathy (LHON) was presumptively made. Other disease processes to consider in the differential diagnosis include toxic or metabolic optic neuropathy, a chiasmal lesion, optic neuritis or demyelinating disease, and psychogenic visual loss.
Toxic or metabolic optic neuropathy presents with painless, progressive, bilateral visual loss in a patient with a history of substance abuse, malnutrition or an exposure to either a medication or toxic substance that is known to cause optic nerve damage (eg, ethambutol, lead).
In the case of a compressive chiasmal lesion or demyelinating disease, one would expect to see characteristic brain CT scan or brain MRI findings along with systemic and/or neurologic findings.
This patient was sent for an MRI scan, which ruled out an intracranial lesion and demyelinating disease.
Discussion
Leber’s congenital optic neuropathy is a maternally inherited disease characterized by acute or subacute painless, rapidly progressive vision loss (usually 20/200 or worse). It most commonly affects young men aged 15 to 30 years and less commonly women in their 20s and 30s. It usually begins in one eye, with the fellow eye becoming involved within days to months of the first. Because the genetic defect is carried on mitochondrial DNA, approximately 50% to 70% of sons and 10% to 15% of daughters with mothers carrying the defective gene will manifest the disease. All female offspring are carriers, and none of the males can transmit the disease. In 1998, Wallace et al isolated the first mitochondrial DNA mutation associated with LHON. There are currently about 37 mutations that have been identified, and genetic testing is available for some of these mutations, particularly 11778, 14484 and 3460. The mutations affect proteins involved in the mitochondrial respiratory chain function causing the generation of reactive oxygen species that may be toxic to retinal ganglion cells.
In addition to visual loss, a centrocecal scotoma and impaired color vision may be noted. On clinical exam, one may appreciate vascular tortuosity of the central retinal vessels, circumpapillary telangiectatic microangiopathy and swelling of the retinal nerve fiber layer. Up to 20% of LHON cases have normal-appearing discs in the acute phase. Chronically, the papillomacular bundle degenerates, leaving a large centrocecal scotoma. Visual recovery seems to depend on the mutation that is present, but the majority of patients show no functional improvement, with many remaining legally blind.
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| Humphrey SITA standard 24-2 threshold automated perimetry performed 1 month after initial presentation. Notice progression or centrocecal scotoma when compared with the baseline test. | |
Management
To date, there is no intervention that has been shown to prevent, delay or reverse the onset and course of this disease. No treatment has been shown to improve final visual outcome. Because it is believed that reactive oxygen species may play a role in the pathogenesis of this disease, antioxidants (eg, coenzyme Q, vitamin C, vitamin E) are used in treatment. There are no large, randomized trials showing efficacy. In addition, neuroprotective medications used in the treatment of other neurodegenerative disorders have been tried (eg, memantine). Studies of monozygotic twins provide some anecdotal evidence that environmental factors such as smoking, alcohol and nutritional status may play some role in the disease.
Our patient was found to be heteroplasmic for the 11778 glycine to alanine mutation (the worst prognosis for visual outcome) and a wild-type allele. He was started on memantine, coenzyme Q10 and vitamins C and E. On his most recent visit, his best corrected visual acuity was 20/80 in the right eye and counting fingers vision in the left eye with bilateral centrocecal scotomas (Figures 4a, 4b).
For more information:
- Isabel M. Balderas, MD, and Thomas R. Hedges, 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 Isabel M. Balderas, MD, and Tom Hsu, MD. Drs. Balderas and Hsu 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. Balderas and Hsu have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.
References:
- Newman NJ. Leber’s hereditary optic neuropathy. Ophthalmol Clin North Am. 1991;4:431-447.
- Nikoskelainen EK, Huoponen K, et al. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology. 1996;10:504-514.
- Wallace DC, Singh G, et al. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242:1427-1430.
- Yen MY, Wang AG, Wei YH. Leber’s hereditary optic neuropathy: a multifactorial disease. Prog Retin Eye Res. 2006;25:381-396.