Mitochondrial Retinopathy

Johannes Birtel; Christina von Landenberg; Martin Gliem; Carla Gliem; Jens Reimann; Wolfram S Kunz; Philipp Herrmann; Christian Betz; Richard Caswell; Victoria Nesbitt; Cornelia Kornblum; Peter Charbel Issa

doi:10.1016/j.oret.2021.02.017

Mitochondrial Retinopathy

Standard

Mitochondrial Retinopathy. / Birtel, Johannes; von Landenberg, Christina; Gliem, Martin; Gliem, Carla; Reimann, Jens; Kunz, Wolfram S; Herrmann, Philipp; Betz, Christian; Caswell, Richard; Nesbitt, Victoria; Kornblum, Cornelia; Charbel Issa, Peter.

In: OPHTHALMOL RETINA, Vol. 6, No. 1, 01.2022, p. 65-79.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Birtel, J, von Landenberg, C, Gliem, M, Gliem, C, Reimann, J, Kunz, WS, Herrmann, P, Betz, C, Caswell, R, Nesbitt, V, Kornblum, C & Charbel Issa, P 2022, 'Mitochondrial Retinopathy', OPHTHALMOL RETINA, vol. 6, no. 1, pp. 65-79. https://doi.org/10.1016/j.oret.2021.02.017

APA

Birtel, J., von Landenberg, C., Gliem, M., Gliem, C., Reimann, J., Kunz, W. S., Herrmann, P., Betz, C., Caswell, R., Nesbitt, V., Kornblum, C., & Charbel Issa, P. (2022). Mitochondrial Retinopathy. OPHTHALMOL RETINA, 6(1), 65-79. https://doi.org/10.1016/j.oret.2021.02.017

Vancouver

Birtel J, von Landenberg C, Gliem M, Gliem C, Reimann J, Kunz WS et al. Mitochondrial Retinopathy. OPHTHALMOL RETINA. 2022 Jan;6(1):65-79. https://doi.org/10.1016/j.oret.2021.02.017

Bibtex

@article{15babd917ee544c2ad2e249ef757512d,

title = "Mitochondrial Retinopathy",

abstract = "PURPOSE: To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease.DESIGN: Retrospective case series.PARTICIPANTS: Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations.METHODS: Review of case notes, retinal imaging, electrophysiologic assessment, molecular genetic testing including protein modeling, and histologic analysis of muscle biopsy.MAIN OUTCOME MEASURES: Phenotypic characteristics of mitochondrial retinopathy.RESULTS: Genetic testing identified sporadic large-scale mitochondrial DNA deletions and variants in MT-TL1, MT-ATP6, MT-TK, MT-RNR1, or RRM2B. Based on retinal imaging, 3 phenotypes could be differentiated: type 1 with mild, focal pigmentary abnormalities; type 2 characterized by multifocal white-yellowish subretinal deposits and pigment changes limited to the posterior pole; and type 3 with widespread granular pigment alterations. Advanced type 2 and 3 retinopathy presented with chorioretinal atrophy that typically started in the peripapillary and paracentral areas with foveal sparing. Two patients exhibited a different phenotype: 1 revealed an occult retinopathy, and the patient with RRM2B-associated retinopathy showed no foveal sparing, no severe peripapillary involvement, and substantial photoreceptor atrophy before loss of the retinal pigment epithelium. Two patients with type 1 disease showed additional characteristics of mild macular telangiectasia type 2. Patients with type 1 and mild type 2 or 3 disease demonstrated good visual acuity and no symptoms associated with the retinopathy. In contrast, patients with advanced type 2 or 3 disease often reported vision problems in dim light conditions, reduced visual acuity, or both. Short-wavelength autofluorescence usually revealed a distinct pattern, and near-infrared autofluorescence may be severely reduced in type 3 disease. The retinal phenotype was key to suspecting mitochondrial disease in 11 patients, whereas 12 patients were diagnosed before retinal examination.CONCLUSIONS: Different types of mitochondrial retinopathy show characteristic features. Even in absence of visual symptoms, their recognition may facilitate the often challenging and delayed diagnosis of mitochondrial disease, in particular in patients with mild or nebulous multisystem disease.",

keywords = "Adolescent, Adult, Aged, Electroretinography, Female, Fluorescein Angiography/methods, Fundus Oculi, Humans, Male, Middle Aged, Mitochondrial Diseases/diagnosis, Retinal Degeneration/diagnosis, Retinal Pigment Epithelium/pathology, Retrospective Studies, Visual Acuity, Young Adult",

author = "Johannes Birtel and {von Landenberg}, Christina and Martin Gliem and Carla Gliem and Jens Reimann and Kunz, {Wolfram S} and Philipp Herrmann and Christian Betz and Richard Caswell and Victoria Nesbitt and Cornelia Kornblum and {Charbel Issa}, Peter",

year = "2022",

month = jan,

doi = "10.1016/j.oret.2021.02.017",

language = "English",

volume = "6",

pages = "65--79",

journal = "OPHTHALMOL RETINA",

issn = "2468-6530",

publisher = "Elsevier Inc.",

number = "1",

}

RIS

TY - JOUR

T1 - Mitochondrial Retinopathy

AU - Birtel, Johannes

AU - von Landenberg, Christina

AU - Gliem, Martin

AU - Gliem, Carla

AU - Reimann, Jens

AU - Kunz, Wolfram S

AU - Herrmann, Philipp

AU - Betz, Christian

AU - Caswell, Richard

AU - Nesbitt, Victoria

AU - Kornblum, Cornelia

AU - Charbel Issa, Peter

PY - 2022/1

Y1 - 2022/1

N2 - PURPOSE: To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease.DESIGN: Retrospective case series.PARTICIPANTS: Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations.METHODS: Review of case notes, retinal imaging, electrophysiologic assessment, molecular genetic testing including protein modeling, and histologic analysis of muscle biopsy.MAIN OUTCOME MEASURES: Phenotypic characteristics of mitochondrial retinopathy.RESULTS: Genetic testing identified sporadic large-scale mitochondrial DNA deletions and variants in MT-TL1, MT-ATP6, MT-TK, MT-RNR1, or RRM2B. Based on retinal imaging, 3 phenotypes could be differentiated: type 1 with mild, focal pigmentary abnormalities; type 2 characterized by multifocal white-yellowish subretinal deposits and pigment changes limited to the posterior pole; and type 3 with widespread granular pigment alterations. Advanced type 2 and 3 retinopathy presented with chorioretinal atrophy that typically started in the peripapillary and paracentral areas with foveal sparing. Two patients exhibited a different phenotype: 1 revealed an occult retinopathy, and the patient with RRM2B-associated retinopathy showed no foveal sparing, no severe peripapillary involvement, and substantial photoreceptor atrophy before loss of the retinal pigment epithelium. Two patients with type 1 disease showed additional characteristics of mild macular telangiectasia type 2. Patients with type 1 and mild type 2 or 3 disease demonstrated good visual acuity and no symptoms associated with the retinopathy. In contrast, patients with advanced type 2 or 3 disease often reported vision problems in dim light conditions, reduced visual acuity, or both. Short-wavelength autofluorescence usually revealed a distinct pattern, and near-infrared autofluorescence may be severely reduced in type 3 disease. The retinal phenotype was key to suspecting mitochondrial disease in 11 patients, whereas 12 patients were diagnosed before retinal examination.CONCLUSIONS: Different types of mitochondrial retinopathy show characteristic features. Even in absence of visual symptoms, their recognition may facilitate the often challenging and delayed diagnosis of mitochondrial disease, in particular in patients with mild or nebulous multisystem disease.

AB - PURPOSE: To report the retinal phenotype and the associated genetic and systemic findings in patients with mitochondrial disease.DESIGN: Retrospective case series.PARTICIPANTS: Twenty-three patients with retinopathy and mitochondrial disease, including chronic progressive external ophthalmoplegia (CPEO), maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Kearns-Sayre syndrome, neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, and other systemic manifestations.METHODS: Review of case notes, retinal imaging, electrophysiologic assessment, molecular genetic testing including protein modeling, and histologic analysis of muscle biopsy.MAIN OUTCOME MEASURES: Phenotypic characteristics of mitochondrial retinopathy.RESULTS: Genetic testing identified sporadic large-scale mitochondrial DNA deletions and variants in MT-TL1, MT-ATP6, MT-TK, MT-RNR1, or RRM2B. Based on retinal imaging, 3 phenotypes could be differentiated: type 1 with mild, focal pigmentary abnormalities; type 2 characterized by multifocal white-yellowish subretinal deposits and pigment changes limited to the posterior pole; and type 3 with widespread granular pigment alterations. Advanced type 2 and 3 retinopathy presented with chorioretinal atrophy that typically started in the peripapillary and paracentral areas with foveal sparing. Two patients exhibited a different phenotype: 1 revealed an occult retinopathy, and the patient with RRM2B-associated retinopathy showed no foveal sparing, no severe peripapillary involvement, and substantial photoreceptor atrophy before loss of the retinal pigment epithelium. Two patients with type 1 disease showed additional characteristics of mild macular telangiectasia type 2. Patients with type 1 and mild type 2 or 3 disease demonstrated good visual acuity and no symptoms associated with the retinopathy. In contrast, patients with advanced type 2 or 3 disease often reported vision problems in dim light conditions, reduced visual acuity, or both. Short-wavelength autofluorescence usually revealed a distinct pattern, and near-infrared autofluorescence may be severely reduced in type 3 disease. The retinal phenotype was key to suspecting mitochondrial disease in 11 patients, whereas 12 patients were diagnosed before retinal examination.CONCLUSIONS: Different types of mitochondrial retinopathy show characteristic features. Even in absence of visual symptoms, their recognition may facilitate the often challenging and delayed diagnosis of mitochondrial disease, in particular in patients with mild or nebulous multisystem disease.

KW - Adolescent

KW - Adult

KW - Aged

KW - Electroretinography

KW - Female

KW - Fluorescein Angiography/methods

KW - Fundus Oculi

KW - Humans

KW - Male

KW - Middle Aged

KW - Mitochondrial Diseases/diagnosis

KW - Retinal Degeneration/diagnosis

KW - Retinal Pigment Epithelium/pathology

KW - Retrospective Studies

KW - Visual Acuity

KW - Young Adult

U2 - 10.1016/j.oret.2021.02.017

DO - 10.1016/j.oret.2021.02.017

M3 - SCORING: Journal article

C2 - 34257060

VL - 6

SP - 65

EP - 79

JO - OPHTHALMOL RETINA

JF - OPHTHALMOL RETINA

SN - 2468-6530

IS - 1

ER -