Evaluation of Inner Retinal Layers in Patients with Multiple Sclerosis or Neuromyelitis Optica Using Optical Coherence Tomography

Fernandes, Danilo B.; Raza, Ali; Nogueira, Rafael G.F.; Wang, Diane; Callegaro, Dagoberto; Hood, Donald C.; Monteiro, Mário Luiz Ribeiro

doi:10.1016/j.ophtha.2012.07.066

Cited by 120 publications

(97 citation statements)

References 37 publications

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“…Damage to optic nerves in NMO is associated with retinal injury, including thinning of the inner retinal layers (IRLs) and axonal damage (20). Therefore, we also evaluated optic nerve involvement in recipients of encephalitogenic Th17-polarized AQP4-specific T cells by serial OCT.…”

Section: Aqp4-specific T Cells From Aqp4mentioning

confidence: 99%

Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4

Sagan

Winger

Cruz-Herranz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor T cells targeting them caused CNS autoimmune disease in recipient mice. In contrast, robust proliferation was observed following immunization of AQP4-deficient (AQP4 , but not WT, mice induced paralysis in recipient WT and B-cell-deficient mice. AQP4-specific Th17-polarized cells induced more severe disease than Th1-polarized cells. Clinical signs were associated with opticospinal infiltrates of T cells and monocytes. Fluorescent-labeled donor T cells were detected in CNS lesions. Visual system involvement was evident by changes in optical coherence tomography. Fine mapping of AQP4 p201-220 and p135-153 epitopes identified peptides within p201-220 but not p135-153, which induced clinical disease in 40% of WT mice by direct immunization. Our results provide a foundation to evaluate how AQP4-specific T cells contribute to AQP4-targeted CNS autoimmunity (ATCA) and suggest that pathogenic AQP4-specific T-cell responses are normally restrained by central tolerance, which may be relevant to understanding development of AQP4-reactive T cells in NMO.is a rare, disabling, and sometimes fatal CNS autoimmune inflammatory demyelinating disease that causes attacks of paralysis and visual loss (1). Immunologic, epidemiologic, and pathologic evidence suggests T cells have an important role in the etiology of NMO (1-3). Pathogenic aquaporin-4 (AQP4)-specific antibodies in NMO serum are predominantly IgG1, a T-cell-dependent IgG subclass (4), and T-cell-mediated CNS inflammation permits CNS entry of those antibodies (5, 6). NMO susceptibility is associated with allelic MHC II genes, in particular HLA-DR17 (DRB1*0301) in certain populations (7). AQP4-specific T cells have been identified in patients (8, 9), and T cells specific for dominant AQP4 epitopes exhibit Th17 polarization (8). It is therefore important to understand factors that control development and regulate the expression of AQP4-specific T cells in NMO.One cannot feasibly test whether AQP4-reactive T cells participate directly in CNS inflammation in NMO patients. Animal models can permit in vivo evaluation of the role of AQP4-specific T cells in CNS autoimmunity. Although multiple AQP4 T-cell epitopes have been identified in WT mice and rats (10-13), attempts to create AQP4-targeted experimental NMO ("ENMO") with clinical manifestations of CNS autoimmune disease by either direct immunization of those determinants or adoptive transfer of T cells targeting them have been unsuccessful (11-13).Recently, it was observed that immunization of AQP4-deficient (AQP4 −/− ) mice with AQP4 peptide (p) 135-153 elicited T-cell proliferation and that those T cells induced mild clinical disease in 70% of recipient WT mice (14...

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Section: Aqp4-specific T Cells From Aqp4mentioning

confidence: 99%

Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4

Sagan

Winger

Cruz-Herranz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Oberwahrenbrock et al 20 reported that eyes of MS patients without a previous ON showed a significant reduction of RNFL thickness compared with healthy controls. Fernandes et al 21 showed that RNFL thickness was significantly reduced in patients with MS, either with or without ON. Similarly, in our study, RNFL was significantly thinner in MS patients than controls and in MS group, the difference in RNFL between eyes with or without ON was not significant.…”

Section: Discussionmentioning

confidence: 99%

Decreased Ocular Pulse Amplitude and Retinal Nerve Fibre Layer in Multiple Sclerosis

Çetin¹,

Erdoǧan

Acer³

et al. 2013

Neuro-Ophthalmology

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This study was conducted to assess ocular pulse amplitude and retinal nerve fibre layer in patients with multiple sclerosis and their correlation with disease duration and with severity. Retinal nerve fibre layer thickness was measured by Heidelberg Retinal Tomography II (HRT-II; Heidelberg Engineering, Dossenheim, Germany) and ocular pulse amplitude was measured by dynamic contour tonometry (Ziemer Ophthalmic Systems, Port, Switzerland) in 37 multiple sclerosis patients and 72 age-and gender-matched controls. Ocular pulse amplitude was significantly reduced and retinal nerve fibre layer was significantly thinner in temporal, superotemporal, and nasal sectors in patients with multiple sclerosis regardless of having an optic neuritis attack. The retinal nerve fibre layer was thinner in eyes with a previous optic neuritis attack compared with the eyes without an attack, but the difference was not significant. Ocular pulse amplitude showed a positive correlation with visual evoked potential amplitude and a negative correlation with visual evoked potential latency. Retinal nerve fibre layer thickness showed a significant negative correlation with the disease duration but not with visually evoked potential, disease severity, nor previous optic neuritis. These findings indicate that the process of degeneration starts in the early period of the disease, as our study group is composed of earlymiddle-stage multiple sclerosis patients, and is independent of relapses.

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“…[7][8][9] In addition, it has been suggested that OCT can help differentiate demyelinating diseases, and OCT findings can be long-term prognostic factors on the basis of the severity of axonal loss. 10,11 OPN has been reported as a type of idiopathic orbital inflammatory disease and the diagnosis of OPN is most commonly based on the magnetic resonance image findings, along with the clinical characteristics. 2,12 Neuro imaging in OPN patient typically shows a characteristic pattern of enhancement around the optic nerve, like tram-track on axial views and doughnut on coronal views.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Retinal Nerve Fiber Layer in Patients with Idiopathic Optic Perineuritis using Optical Coherence Tomography

Byon

Jung

Choi

et al. 2014

Neuro-Ophthalmology

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The aim of this study was to assess the effect of idiopathic Optic perineuritis on the retinal nerve fiber layer, and determine the ability of optical coherence tomography to evaluate retinal nerve fiber loss after idiopathic Optic perineuritis. Four patients were assessed in this study. In all cases, average retinal nerve fiber layer was significantly thinner in the affected eye in comparison with the normal reference value and with the value for the contralateral normal eye at 12 months after the onset of optic perineuritis. Our study revealed that retinal nerve fiber layer loss occurs in idiopathic optic nerve sheath inflammation.

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Evaluation of Inner Retinal Layers in Patients with Multiple Sclerosis or Neuromyelitis Optica Using Optical Coherence Tomography

Cited by 120 publications

References 37 publications

Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4

Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4

Decreased Ocular Pulse Amplitude and Retinal Nerve Fibre Layer in Multiple Sclerosis

Evaluation of Retinal Nerve Fiber Layer in Patients with Idiopathic Optic Perineuritis using Optical Coherence Tomography

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