The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients

Pietroboni, Anna M.; Dell’Arti, Laura; Caprioli, Michela; Scarioni, Marta; Carandini, Tiziana; Arighi, Andrea; Ghezzi, Laura; Fumagalli, Giorgio; Riz, Milena A. De; Basilico, Paola; Colombi, A; Benatti, Eleonora; Triulzi, Fabio; Scarpini, Elio; Viola, Francesco; Galimberti, Daniela

doi:10.1177/1352458517740214

Cited by 40 publications

(32 citation statements)

References 28 publications

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“…In line with the results obtained from SyMRI we could not show a significant atrophy of the peripapillary RNFL in patients with recent MS onset. We confirmed that the peripapillary RNFL was of similar thickness in patients with recent clinical onset of MS and HC [ 40 ].…”

Section: Discussionsupporting

confidence: 79%

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers

et al. 2018

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BackgroundNeurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization.ObjectiveThis study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course.MethodsThis cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction.ResultsExcept for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400–2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration.ConclusionsIn clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

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Section: Discussionsupporting

confidence: 79%

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers

et al. 2018

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“…The complex of inner GCC and inner GCIP was significantly reduced in thickness in all MS subtypes, especially the inner GCC in the progressive subtypes (12.16 µm in PPMS and 12.79 µm in SPMS). Interestingly, in one of the most recent studies ( 37 ) it was presented that a loss of macular ganglion cells was not accompanied by a pRNFL thinning in newly diagnosed RRMS patients without previous history of ON, compared with HCs. They concluded that this finding suggests that the retinal damage might begin in the macular ganglion cell layer and is then spread to the axons.…”

Section: Discussionmentioning

confidence: 96%

The Temporal Retinal Nerve Fiber Layer Thickness Is the Most Important Optical Coherence Tomography Estimate in Multiple Sclerosis

et al. 2017

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BackgroundReduced peripapillary retinal nerve fiber layer (pRNFL) and combined ganglion cell and inner plexiform layer (GCIP) thicknesses as measured by optical coherence tomography (OCT) have been observed in multiple sclerosis (MS) patients. The purpose was to determine the most associative OCT measure to level of cognitive and physical disability in MS.MethodsData were collected from 546 MS patients and 175 healthy controls (HCs). We compared the average pRNFL, temporal pRNFL (T-pRNFL), overall inner ganglion cell/inner plexiform layer (GCIP), and the overall ganglion cell complex (GCC) including macular RNFL and GCIP thicknesses measurements in differentiating MS subtypes from HCs. The association between OCT measures, Expanded Disability Status Scale (EDSS), and Symbol Digit Modalities Test (SDMT) were assessed using generalized estimating equations models.ResultsBoth peripapillary and macular OCT measurements could differentiate all MS subtypes from HCs. The SDMT score was significantly associated with reduced thickness of all OCT measures, mostly in average pRNFL (0.14 µm, P = 0.001) and T-pRNFL (0.17 µm, P < 0.001). The EDSS score was significantly associated with reduced inner retinal layer thickness. The largest reduction was seen in T-pRNFL (−1.52 μm, P < 0.001) and inner GCC (−1.78 μm, P < 0.001).ConclusionThe T-pRNFL is highly sensitive and associated with level of both cognitive and physical disability.

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“…The second study analyzed non-optic neuritis eyes of the patients who were newly diagnosed with MS, with a mean disease duration of 9 months. 16 Again, authors found that GCIPL and mRNFL, but not pRNFL, were reduced in early MS patients compared to controls. Although temporal pRNFL segment was also similar between groups, there was a trend toward thinning.…”

Section: Discussionmentioning

confidence: 97%

“…Thinning of mGCIPL, but not pRNFL, was also found in two cross-sectional studies that studied CIS and early MS patients. 15,16 In the first study, GCIPL and nasal segment of mRNFL were reduced in non-optic neuritis eyes of CIS patients compared to HC eyes. 15 Furthermore, mGCIPL thinning was topographically more pronounced in the nasal and inferior segments, indicating a specific involvement of the papillomacular bundle.…”

Section: Discussionmentioning

confidence: 98%

Retinal degeneration is associated with brain volume reduction and prognosis in radiologically isolated syndrome

et al. 2018

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Background: The extent of neurodegeneration in the earliest stages of central nervous system (CNS) demyelination is not known. Optical coherence tomography (OCT) is a powerful tool to study neurodegeneration in demyelinating disorders. Objectives: To study neuroaxonal loss in the retina of individuals with radiologically isolated syndrome (RIS) and investigate whether OCT measurements are associated with brain volumetrics and clinical conversion to multiple sclerosis (MS). Methods: Subjects fulfilling the Okuda criteria for RIS ( n = 15 patients, 30 eyes) and age- and sex-matched healthy controls (HC) underwent spectral-domain OCT and magnetic resonance imaging for volumetric measurement of brain structures. Results: Macular ganglion cell-inner plexiform layer (mGCIPL), macular retinal nerve fiber layer (mRNFL), and temporal peripapillary RNFL (pRNFL) thickness; normalized total brain volume (nTBV); and normalized thalamic volume (nTV) were reduced in RIS compared to HC. mGCIPL, mRNFL, and pRNFL measurements were associated with nTBV, nTV, and normalized gray and white matter volumes in the RIS group. pRNFL was thinner in individuals with RIS who converted to MS in 5 years. Conclusions: Retinal neurodegeneration can be detected in the papillomacular region in the earliest stages of CNS demyelination and reflects global disease processes in the brain. OCT can be potentially useful for predicting prognosis in RIS.

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The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients

Abstract: mRNFL, mGCL, and mIPL are significantly reduced in MS patients without concomitant pRNFL thinning. These retinal changes show a significant association with cortical regions that are known to be important for visuospatial performance.

Cited by 40 publications

References 28 publications

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers

The Temporal Retinal Nerve Fiber Layer Thickness Is the Most Important Optical Coherence Tomography Estimate in Multiple Sclerosis

Retinal degeneration is associated with brain volume reduction and prognosis in radiologically isolated syndrome

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