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Mathieu Bakhoum, Kevin Bubel, Michael Reinsbach, John Alexander, Marcelle Morcos, K Bailey Freund, David Sarraf, Henry Perry, Stephen H Tsang; Endothelial corneal dystrophy is penetrant in mitochondrial disorders. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2915. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Mitochondrial disorders can have a spectrum of ocular manifestations, mainly pigmentary retinopathy, macular dystrophy, ptosis, and ophthalmoplegia. We had previously shown that a point mutation in the mitochondrial genome, A3243G, results in endothelial corneal dystrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients with mitochondrial diseases to assess for the presence of corneal endothelial dystrophy.
We performed an observational clinical study to identify endothelial corneal abnormalities in patients diagnosed with mitochondrial disorders. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Corneal examination using slit-lamp examination and specular microscopy were performed. The results of genetic testing were also recorded. Patients who were diagnosed based on clinical examination were genetically tested for the mitochondrial mutations using pyrosequencing, a sensitive method that detects low heteroplasmy.
Seven patients (three male and four female participants), with different ethnic backgrounds met the inclusion criteria. Mitochondrial disorders in these patients were maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), neuropathy, ataxia, and retinitis pigmentosa (NARP) and Kearns Sayre syndrome. Their ages ranged from 27 to 63 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed polymegathism. The average endothelial cell count was 2234 +/- 471 cells/mm2, the average endothelial cell size was 468 +/- 107 μm2 and the average central corneal thickness was 550 +/- 29 um. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 41.5 ± 3.8%. The average COV was significantly higher than predicted for the patients' age.
This study is the first comprehensive report of anterior segment complications, specifically corneal endothelial dystrophy, associated with the mitochondrial disorders. This corneal dystrophy is mainly associated with polymegathism along with mild guttata and polymorphism, while maintaining appropriate corneal thickness. The findings of corneal endothelial cell polymegathism may be potentially used as a biomarker of mitochondrial disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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