Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

Raz, Noa; Hallak, Michal; Ben‐Hur, Tamir; Levin, Netta

doi:10.3791/51107

Cited by 8 publications

(7 citation statements)

References 23 publications

(17 reference statements)

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“… 34 , 35 , 47 , 48 The full spectrum of psychophysiological testing has not yet been exploited, possibly dynamic visual tests are a step in this direction, suitable for quantitative, longitudinal readouts. 49 Finally lactate can be elevated for a number of reasons we have discussed in detail. 14 In the current cohort there was no clinical evidence to suggest an inclusion bias to the high lactate group due to systemic infection, muscle atrophy, or deconditioning.…”

Section: Discussionmentioning

confidence: 99%

Visual pathway neurodegeneration winged by mitochondrial dysfunction

Petzold

Nijland

Balk

et al. 2014

Ann Clin Transl Neurol

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ObjectivesTo test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis.MethodsA single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry.ResultsThe visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport.InterpretationThis study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

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Section: Discussionmentioning

confidence: 99%

Visual pathway neurodegeneration winged by mitochondrial dysfunction

Petzold

Nijland

Balk

et al. 2014

Ann Clin Transl Neurol

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“…The majority of ON lesions, therefore, are left with residual demyelination which may persist for years, leading to significantly slower conduction along the demyelinated part of the optic nerve . While the slower conduction per se does not represent a problem in the everyday visual environment, it can make some of the tasks requiring fast visual processing challenging . In addition, it is believed that permanent demyelination can make axons more vulnerable to damage and may potentially cause axonal degeneration .…”

Section: Introductionmentioning

confidence: 99%

Afferent visual pathways in multiple sclerosis: a review

Graham

Klistorner

2016

Clinical Exper Ophthalmology

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Multiple sclerosis (MS) is a disease of the central nervous system that involves inflammation and demyelination at multiple sites and causes a wide variety of clinical presentations with variable neurological deficits. The visual pathways are frequently involved with either visual or motor dysfunction. Optic neuritis (ON) is one the most common and best characterized presentations of the disease, but there are many other manifestations depending on the site of the lesion. Eyes that have never had ON show slow progressive loss of axons and retinal ganglion cells. Previously unrecognized optic radiation lesions may be associated with residual latency delays on visual evoked potentials. Both anterograde and retrograde degeneration may occur along the visual pathway. This review covers the features of MS in the anterior and posterior visual system and describes advances that have been made with newer techniques such as retinal optical coherence tomography (OCT), magnetic resonance imaging (MRI) with diffusion tensor imaging and probabilistic tractography (DTI) and multifocal visual evoked potentials (mfVEPs). We report on the inter-relationship between these measures of structure and function, and how they may be used as biomarkers for the disease.

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“…The role of psychophysical tests in ON and MS is expanding due to the temporal effect exerted by demyelination. Other tests of the dynamic visual system include the object-from-motion and number-from-motion tests presented by Raz et al [1][2][3] and the CFF test, which is of some diagnostic value in the field of ON and MS [5][6][7][8] but rather unspecific as it seemingly depends on visual acuity [22]. We did not include CFF as an end point.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Various static visual tests are involved in the clinical evaluation of ON. The value of dynamic visual tests is becoming recognized due to the effect on the temporal aspects of the visual system exerted by demyelination [1][2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Sensitive Assessment of Acute Optic Neuritis by a New, Digital Flicker Test

et al. 2019

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Background: The Aulhorn flicker test (AFT) previously showed promise in diagnosing acute optic neuritis (ON) albeit with suboptimal sensitivity. A new, digitalized version of the AFT (the DFT) has not previously been examined in acute ON. Objectives: To examine the sensitivity, specificity and reproducibility of the DFT in acute ON. Method: The DFT assesses the subjective brightness of a flickering field (1-60 Hz). In normal subjects, brightness enhancement occurs at intermediate frequencies, whereas in acute ON darkness enhancement (DE) is hypothesized. AFT and DFT measurements were obtained in acute ON patients (≤31 days from first symptom) with DE as a quantitative covariate. Reproducibility of the DFT end point was assessed in the form of an intraclass correlation. Results: 30 untreated first-time acute ON patients and 55 healthy controls were examined. AFT and DFT were performed 12.7 days (range: 4-30) following ON onset. The DFT showed a sensitivity of 0.93 (95% CI = 0.78-0.99) to a specificity of 0.96 (95% CI = 0.87-1.00). The AFT showed a sensitivity of 0.76 (95% CI = 0.56-0.90) to a specificity of 1.00 (95% CI = 0.93-1.00). No significant correlation was shown between DFT and visual acuity. The intraclass correlation of the DFT end point in healthy subjects was 0.84. Conclusions: We present a new DFT in acute ON displaying a high specificity of 0.96 and a sensitivity of 0.93. Our study indicates the DFT to be an accurate and easy-to-use tool in diagnosing acute ON, which may be especially helpful in atypical cases.

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Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

Cited by 8 publications

References 23 publications

Visual pathway neurodegeneration winged by mitochondrial dysfunction

Visual pathway neurodegeneration winged by mitochondrial dysfunction

Afferent visual pathways in multiple sclerosis: a review

Sensitive Assessment of Acute Optic Neuritis by a New, Digital Flicker Test

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