Retinal architecture and mfERG

Abstract

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.

Optical Coherence Tomography in Multiple Sclerosis

“…73 It has been shown that by modification of the MF-ERG test protocol it is possible to visualize an additional component of the MF-ERG, the optic nerve head component (ONHC), which is generated at the optic nerve head. 74 Recent work has shown a significantly increased number of abnormal ONHC responses in MS patients with a history of unilateral ON compared with normal subjects; ONHC abnormalities were also present (albeit reduced in number) in the fellow eyes of the same patients. 74 The number of abnormal ONHC responses appears to correlate strongly with RNFL thickness, so that a 10-µm reduction in RNFL thickness is associated with 6.8 additional abnormal ONHC responses (from 103 responses).…”

“…74 Recent work has shown a significantly increased number of abnormal ONHC responses in MS patients with a history of unilateral ON compared with normal subjects; ONHC abnormalities were also present (albeit reduced in number) in the fellow eyes of the same patients. 74 The number of abnormal ONHC responses appears to correlate strongly with RNFL thickness, so that a 10-µm reduction in RNFL thickness is associated with 6.8 additional abnormal ONHC responses (from 103 responses). 74 The relationship between the ONHC and other OCT parameters remains unclear at this time.…”

“…74 The number of abnormal ONHC responses appears to correlate strongly with RNFL thickness, so that a 10-µm reduction in RNFL thickness is associated with 6.8 additional abnormal ONHC responses (from 103 responses). 74 The relationship between the ONHC and other OCT parameters remains unclear at this time.…”

Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis

“…80 This was chosen for analysis because the normal ONHC response depends on the integrity of the RGC neuron, and is representative of the action potential as RGC axons traverse the lamina cribosa and conduction switches from unmyelinated to myelinated axons. This study found a significant reduction in ONHC responses in MS eyes with worse scores for LCLA.…”

Bilateral retinal pathology following a first-ever clinical episode of autoimmune optic neuritis

“…[11][12][13] Of interest, previous studies have found that the clinically unaffected contralateral eye may display some degree of dysfunction following unilateral ON. [14][15][16] Structural data to date are only available for the outer retina over 6 months after ON 17 or for the inner retina over 12 months. 18 Although a number of cross-sectional OCT studies in ON have been published, 8,19 longitudinal studies are still scarce.…”