Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography

Barboni, Piero; Carbonelli, Michele; Savini, Giacomo; Ramos, Carolina do Val Ferreira; Carta, Arturo; Berezovsky, Adriana; Salomão, Solange Rios; Carelli, Valerio; Sadun, Alfredo A.

doi:10.1016/j.ophtha.2009.07.026

Cited by 188 publications

(137 citation statements)

References 14 publications

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“…The optic nerve may appear elevated (pseudo-swelling), and teleangiectatic vessels may be evident in approximately 50% of patients. The OCT findings of LHON demonstrate an interesting sequence of RNFL involvement [85]. In a recent study, a significant increase of RNFL thickness was noted in the temporal and inferior quadrants in the presymptomatic state to disease onset.…”

Section: Leber's Hereditary Optic Neuropathymentioning

confidence: 86%

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

et al. 2011

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Summary: Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal nerve fiber layer (RNFL), a structure which is principally composed of ganglion cell axons that form the optic nerves, chiasm, and optic tracts. Since retinal axons are nonmyelinated until they penetrate the lamina cribrosa, the RNFL is an ideal structure (no other central nervous system tract has this unique arrangement) for visualizing the processes of neurodegeneration, neuroprotection and, potentially, even neuro-repair. OCT is capable of providing high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and permits objective analysis of the RNFL (axons) as well as ganglion cells and other neurons in the macula. In a systematic OCT examination of multiple sclerosis (MS) patients, RNFL thickness and macular volumes are reduced when compared to disease-free controls.Conspicuously, these changes, which signify disorganization of retinal structural architecture, occur over time even in the absence of a history of acute demyelinating optic neuritis. RNFL axonal loss in MS is most severe in those eyes with a corresponding reduction in low-contrast letter acuity (a sensitive vision test involving the perception of gray letters on a white background) and in those patients who exhibit the greatest magnitude of brain atrophy, as measured by validated magnetic resonance imaging techniques. These unique structure-function correlations make the anterior visual pathway an ideal model for investigating the effects of standard and novel therapies that target axonal and neuronal degeneration. We provide an overview of the physics of OCT, its unique properties as a non-invasive imaging technique, and its potential applications toward understanding mechanisms of brain tissue injury in MS, other optic neuropathies, and neurologic disorders.

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Section: Leber's Hereditary Optic Neuropathymentioning

confidence: 86%

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

et al. 2011

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“…The optic neuropathy of familial dysautonomia closely resembles that seen in mitochondrial optic neuropathies such as Leber hereditary optic neuropathy (15,19), autosomal dominant optic atrophy (20), and tobacco/alcoholic (21), Cuban epidemic (22), B 12 deficiency, and drug-related optic neuropathies (23). Pathological studies in Leber hereditary optic neuropathy and dominant optic atrophy have shown relatively preservation of melanopsin-containing ganglion cells in spite of extensive loss of the predominantly small midget/ parvocellular P-ganglion cells (17,24).…”

Section: Discussionmentioning

confidence: 98%

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Mendoza‐Santiesteban

Palma

Hedges

et al. 2017

Journal of Neuropathology &Amp; Experimental Neurology

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Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition.

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“…7 Moreover, in some neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, the RNFL thinning has been demonstrated with OCT, even in patients without visual loss. 4,5 Considering neurodegenerative ataxias, such as Friedreich's ataxia, alterations in the afferent OCT in SCA-3 G Alvarez et al visual pathway, expressed by a reduction of the RNFL thickness in the OCT can be ascertained.…”

Section: Discussionmentioning

confidence: 99%

Optical coherence tomography findings in spinocerebellar ataxia-3

Álvarez

Rey

Sánchez-Dalmau

et al. 2013

Eye

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Purpose To report optical coherence tomography (OCT) findings in order to detect subclinical alterations of the afferent visual pathways in spinocerebellar ataxia 3 (SCA-3). Patients and methods Nine genetically confirmed patients (18 eyes) were evaluated with a complete ophthalmologic examination including visual acuity, colour vision, visual field test, and retinal nerve fibre layer (RNFL) and macular thickness with OCT Cirrus HD. A neurological examination was performed and the Scale for the Assessment and Rating of Ataxia (SARA score) was determined in all patients. Results The mean RNFL thickness was 77.39 microns, standard deviation (SD) was ± 5.93. In 15 eyes (83.33%), the mean RNFL thickness was lower than the population average considering age and sex. In 10 cases, there was a reduction of the RNFL thickness in the superior sector, eight in the inferior and four in the nasal. Temporal sector RNFL thickness was preserved in all eyes. RNFL thickness was inversely correlated to SARA score (r ¼ À 0.64, P ¼ 0.012). The mean macular thickness was 252.61 microns, SD±22.80, being inferior respecting average population in only two eyes (11.11%). In four patients, (eight eyes) OCT studies were performed during a mean follow-up of 14.25 months, and in five eyes (62.50%) there was a mild trend to a RNFL thickness decrease in this period. Conclusion A mild and progressive decrease in RNFL thickness can be observed in SCA-3 patients. A negative correlation exists between an anatomic marker (RNFL thickness) and a clinical severity scale (SARA score); thus, RNFL thickness could be considered as a promising biomarker of the disease.

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Natural History of Leber's Hereditary Optic Neuropathy: Longitudinal Analysis of the Retinal Nerve Fiber Layer by Optical Coherence Tomography

Cited by 188 publications

References 14 publications

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Optical coherence tomography findings in spinocerebellar ataxia-3

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