Optic nerve head component responses of the multifocal electroretinogram in MS

Frohman, Teresa C.; Beh, Shin C.; Saidha, Shiv; Schnurman, Zane; Conger, Darrel; Conger, Amy; Ratchford, John N.; López, Carmen Vázquez; Galetta, Steven; Calabresi, Peter A.; Balcer, Laura J.; Green, Ari J.; Frohman, Elliot M.

doi:10.1212/wnl.0b013e31829e6faa

Cited by 11 publications

(14 citation statements)

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“…[101][102][103][104] The optic nerve head component responses of multifocal ERG may also emerge as a useful tool in the assessment of optic neuritis. 105 …”

Section: Research Protocolmentioning

confidence: 99%

The investigation of acute optic neuritis: a review and proposed protocol

et al. 2014

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| Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course. Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward. Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena. To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis. In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.

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“…[101][102][103][104] The optic nerve head component responses of multifocal ERG may also emerge as a useful tool in the assessment of optic neuritis. 105 …”

Section: Research Protocolmentioning

confidence: 99%

The investigation of acute optic neuritis: a review and proposed protocol

et al. 2014

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“…For mfERG assessments, a scaled hexagonal array with a pattern-reversal stimulus was used to provoke responses that can be collected as corneal signals by an electrode placed within a contact lens. 22 Eyes were anesthetized with proparacaine and then dilated with tropicamide and phenylephrine. We then used Burian-Allen bipolar contact lens electrodes for mfERG recordings.…”

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“…Binary stimulation was performed in the context of pseudorandom sequences (so-called m-sequence stimulation) as previously reported. 15,22,23 Eye fixation was confirmed via the use of a fundus camera.…”

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“…In contrast to the 8 segments used for mfERG responses, here we used 16 segments. 22 The acquisition at the amplifier level for the single channel of data was a gain of 20 K, low-cutoff filter at 10 Hz, high-cutoff filter at 300 Hz, and the notch filter in the out position. To parse out the ONHC, a novel stimulus protocol has been developed that applies global flash stimuli that are interleaved at specific intervals between the multifocal stimuli, thereby enhancing the ONHC potential and the inner retinal response.…”

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confidence: 99%

“…To parse out the ONHC, a novel stimulus protocol has been developed that applies global flash stimuli that are interleaved at specific intervals between the multifocal stimuli, thereby enhancing the ONHC potential and the inner retinal response. 15,22,23 ONHC analysis and rating. The VERIS 6.3 software was used for both recording and documenting abnormalities of ONHC responses.…”

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Retinal architecture and mfERG

et al. 2014

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Objective: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. Methods:We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n 5 18), patients with multiple sclerosis (MS) (n 5 18), and those with glaucoma (n 5 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potentialinduced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography.Results: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p , 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p , 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p , 0.0001). Regarding average RNFL thickness, for each 10-mm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p 5 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p , 0.0001). Conclusion:Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular. Neurology ® 2014;82:1888-1896 GLOSSARY AON 5 acute optic neuritis; CI 5 confidence interval; GEE 5 generalized estimating equation; ICC 5 intraclass correlation coefficient; mfERG 5 multifocal electroretinography; mfVEP 5 multifocal visual-evoked potential; MS 5 multiple sclerosis; OCT 5 optical coherence tomography; ONHC 5 optic nerve head component; RGC 5 retinal ganglion cell; RNFL 5 retinal nerve fiber layer.The eye has been proposed as a "window" into the CNS. High-precision techniques have evolved and are accelerating scientific discovery, particularly regarding protective and restorative neurotherapeutic effects. [1][2][3][4] Whereas spectral-domain optical coherence tomography (OCT) has been of great utility in precisely characterizing the topography of retinal architecture, multifocal electroretinography (mfERG) is a technique that can yield information on discrete functional responses within the retina, following a stimulus with precisely defined characteristics. [5][6][7][8][9][10][11][12][13][14][15] The retinal ganglion cell (RGC) contribution to the global retinal response is small, thereby limiting the utility of this technique for the purpose of examining retinal mechanisms of axonal and neuronal degeneration. 16*These authors contributed equally to these investigations as senior authors.

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Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics

et al. 2017

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IMPORTANCE A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments.OBJECTIVE To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. DESIGN, SETTING, AND PARTICIPANTSThe case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). MAIN OUTCOMES AND MEASURESAssociation of pupillary response characteristics with alterations in retinal architecture. RESULTSOf 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). CONCLUSIONS AND RELEVANCEIn this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

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Optic nerve head component responses of the multifocal electroretinogram in MS

Cited by 11 publications

References 7 publications

The investigation of acute optic neuritis: a review and proposed protocol

The investigation of acute optic neuritis: a review and proposed protocol

Retinal architecture and mfERG

Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics

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