Optical coherence tomography as a possible tool to monitor and predict disease progression in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

Shinkai, Akihiro; Shinmei, Yasuhiro; Hirooka, Kiriko; Tagawa, Yoshiaki; Nakamura, Kayoko; Chin, Shinki; Ishida, Susumu

doi:10.1016/j.mito.2020.11.003

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…An older study presents fundus photography and ERG data from 26 individuals with genetically confirmed MELAS diagnosis [ 50 ]. The investigators identified paramacular RPE atrophy in 10 of 26 patients (38%), and found decreased ERG response amplitude, increased latency, or both in 7 of 8 patients who underwent electrodiagnostic evaluation (88%) A more recent study performed OCT imaging on 10 affected individuals and 5 healthy controls [ 58 ]. The investigators found lower GCL thickness among MELAS patients compared to controls (after adjusting for prior episodes of transient homonymous hemianopia potentially accounting for direct retinal disease involvement).…”

Section: Resultsmentioning

confidence: 99%

Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review

et al. 2022

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Introduction Cerebral Small Vessel Disease (CSVD), a progressive degenerative disorder of small caliber cerebral vessels, represents a major contributor to stroke and vascular dementia incidence worldwide. We sought to conduct a systematic review of the role of retinal biomarkers in diagnosis and characterization of CSVD. Methods We conducted a systematic review of MEDLINE, PubMed, Scopus, the Cochrane Library Database, and Web of Science. We identified studies of sporadic CSVD (including CSVD not otherwise specified, Cerebral Amyloid Angiopathy, and Hypertensive Arteriopathy) and the most common familial CSVD disorders (including CADASIL, Fabry disease, and MELAS). Included studies used one or more of the following tools: visual fields assessment, fundus photography, Optical Coherence Tomography and OCT Angiography, Fluorescein Angiography, Electroretinography, and Visual Evoked Potentials. Results We identified 48 studies of retinal biomarkers in CSVD, including 9147 cases and 12276 controls. Abnormalities in retinal vessel diameter (11 reports, n = 11391 participants), increased retinal vessel tortuosity (11 reports, n = 617 participants), decreased vessel fractal dimension (5 reports, n = 1597 participants) and decreased retinal nerve fiber layer thickness (5 reports, n = 4509 participants) were the biomarkers most frequently associated with CSVD. We identified no reports conducting longitudinal retinal evaluations of CSVD, or systematically evaluating diagnostic performance. Conclusion Multiple retinal biomarkers were associated with CSVD or its validated neuroimaging biomarkers. However, existing evidence is limited by several shortcomings, chiefly small sample size and unstandardized approaches to both biomarkers’ capture and CSVD characterization. Additional larger studies will be required to definitively determine whether retinal biomarkers could be successfully incorporated in future research efforts and clinical practice.

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Section: Resultsmentioning

confidence: 99%

Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review

et al. 2022

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“…MELAS-like retinal anomalies detected on fundoscopy and fundus autofluorescence (FAF) imaging, further support this theory [ 13 , 14 ]. Moreover, OCT reduction of GCL is an already described finding within MELAS retinal assessment [ 15 ]. Based on the constellation of clinical symptoms in our patient and the results of the investigations performed, we diagnosed an ischemic optic neuropathy in a middle-aged woman harbouring MELAS classic mutation, possibly secondary to a stroke-like event affecting the optic nerve.…”

Section: Discussionmentioning

confidence: 99%

Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation

et al. 2023

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Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON). Case presentation Here we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms. Conclusions Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.

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“…Stroke-like episodes may be precipitated by acute illness, surgery, and medications (including sodium valproate), leading to cerebral dysfunction accompanied by migraine-like prodromes, acute confusional states and focal seizures. Posterior brain regions are typically involved in the stroke-like episodes, potentially leading to homonymous visual field defects and detectable thinning of the ganglion cell complex layer on OCT, due to trans-synaptic retrograde degeneration of the RGC [ 77 ]. Other reported visual symptoms include cortical blindness, visual anosognosia (Anton syndrome), prosopagnosia, and regional geographic disorientation.…”

Section: Retrochiasmal Vision Lossmentioning

confidence: 99%

Mitochondria and the eye—manifestations of mitochondrial diseases and their management

Chen

Harvey

Gilhooley

et al. 2023

Eye

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Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue, mitochondrial diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well as deficiencies of the retrochiasmal visual pathway. With the wider availability of genetic testing in clinical practice, it is now recognised that genotype-phenotype correlations in mitochondrial diseases can be imprecise: many classic syndromes can be associated with multiple genes and genetic variants, and the same genetic variant can have multiple clinical presentations, including subclinical ophthalmic manifestations in individuals who are otherwise asymptomatic. Previously considered rare diseases with no effective treatments, considerable progress has been made in our understanding of mitochondrial diseases with new therapies emerging, in particular, gene therapy for inherited optic neuropathies.

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Optical coherence tomography as a possible tool to monitor and predict disease progression in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

Cited by 6 publications

References 24 publications

Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review

Retinal biomarkers of Cerebral Small Vessel Disease: A systematic review

Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation

Mitochondria and the eye—manifestations of mitochondrial diseases and their management

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