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Camiel Boon, Paul de Laat, Mirian Janssen, Jan Smeitink, Jan Keunen; Mitochondrial retinal dystrophy: genetic background, clinical classification, and systemic associations. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1365.
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To describe the spectrum of retinal abnormalities associated with the m.3243A>G mutation using multimodal imaging, and to analyze possible correlations with the systemic disease severity as well as mitochondrial heteroplasmy levels.
Patients underwent an extensive clinical examination, including visual acuity testing, indirect ophthalmoscopy, fundus photography, OCT, fundus autofluorescence, and Humphrey central visual field analysis. In selected cases, fluorescein angiography, Goldmann perimetry, multifocal ERG, full-field ERG, and EOG were performed. Heteroplasmy levels of the m.3243A>G mutation were measured in three different tissues, and the general disease severity was scored.
Twenty-five of 29 mutation carriers (86%) had evidence of retinal dystrophy. A remarkably broad systemic disease spectrum was found, from no systemic abnormalities to a variety of syndromes such as MELAS syndrome. The retinal changes could be classified into four stages according to the extent and severity of abnormalities. Six patients (21%) had stage 1 retinal dystrophy, characterized by very discrete pigmentary abnormalities that were better visible on fundus autofluorescence and fluorescein angiography. In early stage 2 disease (11 patients; 38%), one or a few yellowish or mildly pigmented deposits were seen in addition to discrete pigmentary changes. In advanced stage 2 disease, the pigmentary deposits encompassed the entire macula, and often also encircled the optic disc. Six patients (21%) had stage 3 retinal dystrophy, characterized by the appearance of one or more areas of well-delineated, profound chorioretinal ("geographic") atrophy outside the fovea. Marked loss of visual acuity occurred only in stage 4 retinal dystrophy (2 patients, 7%), when the fovea was also affected by profound chorioretinal atrophy. There was no correlation between the stage of retinal dystrophy and heteroplasmy levels or overall disease.
Mitochondrial retinal dystrophy associated with the m.3243A>G mutation has specific characteristics that can be categorized into four stages based on ophthalmoscopy and fundus autofluorescence imaging. The maternal inheritance pattern may be masked and the systemic disease associations may be highly variable. Therefore, a high index of suspicion and testing of the m.3243A>G mutation should be considered in patients with typical retinal abnormalities.
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