Functional Assessment of Outer and Middle Macular Layers in Multiple Sclerosis.

Lucia Ziccardi,Vincenzo Parisi,Doriana Landi,Benedetto Falsini,Andrzej Grzybowski,Diego Centonze,Girolama Alessandra Marfia,Maria Albanese,Laura Boffa,Lucilla Barbano,Carolina Gabri Nicoletti

doi:10.3390/jcm9113766

Abstract

The involvement of macular preganglionic elements’ function, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without optic neuritis (ON) (MS-noON Group) and 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery (between 0.2 and 1 LogMAR) of BCVA, (MS-ON-P Group). In the latter Group, Sd-OCT macular volumes and thicknesses of whole and inner and outer retina were measured. MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs), were measured from concentric rings (R) with increasing foveal eccentricity: 0–5° (R1), 5–10° (R2), 10–15° (R3), 15–20° (R4), 20–25° (R5), and from retinal sectors (superior, nasal, inferior and temporal) between 0–15° and 0–25°. In the MS-ON-P Group, mean mfERG RADs detected from R1 (0–5°) and from the central nasal sector (0–15°) were significantly reduced (p < 0.01) with respect to those of the Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. All Sd-OCT measurements, apart from the inner retina macular volume in the central 1 mm, were significantly reduced in MS-ON-P patients compared to Controls. The functional impairment in the MS-ON-P Group was associated but not correlated with structural changes of the outer and inner retinal layers in corresponding retinal Areas and Sectors. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.

Highlights

Multiple sclerosis (MS) is a neurodegenerative disease, characterized by chronic demyelination of the central nervous system, which can result in visual system involvement including retrobulbar optic neuritis (ON) [1].The ON event is followed by secondary neurodegenerative processes for retrograde trans-synaptic degeneration [2] that involve retinal ganglion cells (RGCs) and their axons [3] forming the innermost retinal layers (IML)
The function of preganglionic elements can be assessed by electroretinogram (ERG) recordings [8] that, with its variants, allow us to study the bioelectrical activity of photoreceptor and bipolar cells from the whole retina by Full-field ERG (Ff-ERG) [9], from the central retina by focal ERG (F-ERG) [10] and from multiple localized retinal areas by multifocal ERG [11]
Eighty-eight relapsing remitting (RR) multiple sclerosis (MS) patients were enrolled at the Visual Neurophysiology and Neurophthalmology Research Unit, IRCCS- Fondazione Bietti referred by the Multiple Sclerosis center of the Tor Vergata University Hospital in Rome, between September 2016 and 20 October 2020

Summary

Introduction

Multiple sclerosis (MS) is a neurodegenerative disease, characterized by chronic demyelination of the central nervous system, which can result in visual system involvement including retrobulbar optic neuritis (ON) [1].The ON event is followed by secondary neurodegenerative processes for retrograde trans-synaptic degeneration [2] that involve retinal ganglion cells (RGCs) and their axons [3] forming the innermost retinal layers (IML). It is a debated topic to understand whether the neurodegenerative mechanisms occurring in MS, could involve retinal structures beyond the IML towards the preganglionic elements (i.e., photoceptors, bipolar cells) located in the outer and in middle retinal (O-MR) layers. The function of preganglionic elements can be assessed by electroretinogram (ERG) recordings [8] that, with its variants, allow us to study the bioelectrical activity of photoreceptor and bipolar cells from the whole retina by Full-field ERG (Ff-ERG) [9], from the central retina by focal ERG (F-ERG) [10] and from multiple localized retinal areas by multifocal ERG (mfERG) [11]. A “kernel analysis” applied to mfERG responses can be used to assess nonlinear functions of the visual system mainly originating from selected populations of photoreceptors and bipolar cells [12,13,14]

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