Mathieu F Bakhoum1,2,3, Wei-Pu Wu1,2, Eugenia C White1, Jesse D Sengillo1,2, Christian Sanfilippo4, Marcelle M Morcos3, K Bailey Freund2,5, Henry D Perry3,6, David Sarraf4,7, Stephen H Tsang8,9,10,11. 1. Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Columbia University, New York, NY, USA. 2. Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. 3. Department of Ophthalmology, Nassau University Medical Center, East Meadow, NY, USA. 4. Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 5. Vitreous Retina Macula Consultants of New York, New York, NY, USA. 6. Ophthalmic Consultants of Long Island, Long Island, NY, USA. 7. Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA. 8. Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, Columbia University, New York, NY, USA. sht2@cumc.columbia.edu. 9. Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. sht2@cumc.columbia.edu. 10. Departments of Pathology & Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA. sht2@cumc.columbia.edu. 11. , New York, USA. sht2@cumc.columbia.edu.
Abstract
PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities. METHODS: We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing. RESULTS: Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 μm2 and the average central corneal thickness (CCT) was 551 ± 33 μm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.
PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern macular dystrophy and concentric perifoveal atrophy. Given the high metabolic demand of corneal endothelial cells, we performed specular biomicroscopy analysis in patients harboring the mitochondrial DNA point mutation A3243G to assess for the associated presence of corneal endothelial abnormalities. METHODS: We present a case series with participants from two institutions. Patients diagnosed with macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal examination and specular biomicroscopy were performed. Corneal endothelial cell count, cell size and polymegathism, and central corneal thickness were assessed. Patients diagnosed with MIDD or MELAS based on clinical history and examination were genetically tested for the mitochondrial DNA point mutation A3243G using pyrosequencing. RESULTS: Five patients (two male and three female participants) from five different families, and with different ethnic backgrounds, met the inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial changes observed using slit-lamp examination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata. The average endothelial cell count was 2358 ± 456 cells per mm2, the average endothelial cell size was 442 ± 103 μm2 and the average central corneal thickness (CCT) was 551 ± 33 μm. These values were similar to that of the average population. The average coefficient of variation (COV), an index of heterogeneity in cell size, was 42.0 ± 4.1%. When compared to the average population, the average COV was significantly higher than predicted for the patients' age. None of the patients had signs of corneal edema. One patient had a pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point mutation A3243G, corneal endothelial polymegathism is present. This is mainly associated with mild guttata. The findings of corneal endothelial cell polymegathism may be a biomarker of mitochondrial disease, specifically in patients with the mitochondrial DNA A3243G mutation.
Authors: J M van den Ouweland; H H Lemkes; W Ruitenbeek; L A Sandkuijl; M F de Vijlder; P A Struyvenberg; J J van de Kamp; J A Maassen Journal: Nat Genet Date: 1992-08 Impact factor: 38.330
Authors: Stephan Ong Tone; Viridiana Kocaba; Myriam Böhm; Adam Wylegala; Tomas L White; Ula V Jurkunas Journal: Prog Retin Eye Res Date: 2020-05-08 Impact factor: 21.198