Mitochondrial A3243G mutation results in corneal
Mathieu F. Bakhoum
Eugenia C. White
Jesse D. Sengillo
Marcelle M. Morcos
K. Bailey Freund
Henry D. Perry
Stephen H. Tsang
Received: 31 October 2017 / Revised: 7 January 2018 / Accepted: 17 January 2018 /Published online: 29 January 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
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 exam-
ination were primarily mild to rare guttata. Specular biomicroscopy displayed mainly polymegathism associated with guttata.
The average endothelial cell count was 2358 ± 456 cells per mm
, the average endothelial cell size was 442 ± 103 μm
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’sopacity.
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.
Keywords Mitochondrial diseases
Endothelial corneal dystrophy
Graefe's Archive for Clinical and Experimental Ophthalmology (2018) 256:583–588
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s00417-018-3914-z) contains supplementary
material, which is available to authorized users.
* Stephen H. Tsang
Jonas Children’s Vision Care, and Bernard & Shirlee Brown
Glaucoma Laboratory, Columbia University, New York, NY, USA
Department of Ophthalmology, College of Physicians and Surgeons,
Columbia University, New York, NY, USA
Department of Ophthalmology, Nassau University Medical Center,
East Meadow, NY, USA
Stein Eye Institute, Department of Ophthalmology, David Geffen
School of Medicine at UCLA, Los Angeles, CA, USA
Vitreous Retina Macula Consultants of New York, New York, NY,
Ophthalmic Consultants of Long Island, Long Island, NY, USA
Greater Los Angeles Veterans Affairs Healthcare System, Los
Angeles, CA, USA
Departments of Pathology & Cell Biology, Institute of Human
Nutrition, College of Physicians and Surgeons, Columbia University,
New York, NY, USA
New York, USA