Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis Research Articles

Isolated myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in adults: The importance of age of onset and prognosis-related radiological features

BackgroundMyelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) exhibits phenotypic diversity and it varies by age. However, less is known about whether the manifestations of isolated MOG antibody-associated optic neuritis (iMOG-ON) vary across different age groups. We aimed to investigate the clinical and prognostic features of iMOG-ON in young and middle-aged adult patients. MethodsPatients with iMOG-ON were enrolled in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University between January 2018 and October 2021. Medical records were reviewed to obtain clinical data and orbital MRI images of adult patients with iMOG-ON. Multivariate linear regression analysis was performed to investigate the associations between final best-corrected visual acuity (BCVA) in logMAR and clinical characteristics. ResultsBased on the age of onset, 70 patients were divided into 2 groups: 38 young (< 46 years; female/male = 0.76:1) and 32 middle-aged (≥ 46 years; female/male = 5.56:1) adults. There were statistical differences in both the female-to-male ratio and frequencies of contrast enhancement of the optic nerve sheaths and surrounding orbital tissues between both groups (p = 0.001, p = 0.004, respectively). The average follow-up periods were 28.04 ± 11.22 months. The median final BCVA was 0 (0 - 0.50) logMAR and 0.5 (0.3 - 1.0) logMAR in the young and middle-aged patients, respectively (p = 0.000). The multivariate linear regression analysis indicated significant positive relationships between final BCVA and age of onset (p = 0.038, 95 % CI: 0.020 - 0.728), sex (p = 0.030, 95 % CI: -0.793 - -0.042), BCVA at nadir (p = 0.000, 95 % CI: 0.164 - 0.386), and numbers of segments of optic nerve lesions (p = 0.009, 95 % CI: 0.068 - 0.450) with a coefficient of determination (R2) of 0.359 after adjusting for prior attacks of ON, time intervals between sudden-onset vision loss and administration of intravenous methylprednisolone, and corticosteroid dosages. The worst final BCVA was observed in afflicted eyes with lesions extending across three segments of the optic nerve. ConclusionCompared to young adults with iMOG-ON, the middle-aged patients tended to have a female predominance, higher frequencies of perineural enhancement, and worse visual outcomes. In addition to age of onset, visual recovery may also be influenced by patient's sex, BCVA at nadir, and lengths of longitudinally expansive lesions of the optic nerve to a certain extent.

A Case of Retinal Edema in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

Purpose: To report a case of retinal edema and retinal hemorrhage in myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG) positive optic neuritis.Case summary: A 49-year-old male visited the clinic due to decreased vision and eye pain in the left eye after 2 times of right eye and 1 time of left eye optic neuritis. The patient presented with eyelid swelling and retinal hemorrhage as well as optic disc swelling of the left eye. Optical coherence tomography (OCT) showed parafoveal intraretinal fluid. The patient received the intravenous high-dose steroids and the immune globulin therapy. He was then put on maintenance oral steroids and immunosuppressive agents. After the treatment, the best corrected visual acuity of left eye was improved to 0.2. Retinal hemorrhage and retinal edema of the left eye decreased, and optic nerve pale in both eyes was observed. OCT showed overall atrophy of the retinal nerve fiber layer in both eyes.Conclusions: Some patient with MOG-IgG positive optic neuritis will have eyelid swelling or retinal edema that is necessary to be differentiated from eyelid inflammatory disorder or macular disease such as diabetic retinopathy. Thus, clinician should consider MOG-IgG positive optic neuritis in patients with retinal edema when accompanied by eye pain with severe vision loss or repeated disc swelling. When diagnosed with MOG-IgG positive optic neuritis, a combined treatment of relatively long-term steroid treatment and immunosuppressants may be required.

Subclinical damage to the contralateral eye in unilateral optic neuritis: A longitudinal study.

Early detection of subclinical injuries can lead to a correct diagnosis and help control the advancement of the condition. This study aims to investigate the presence of subclinical damage and silent progression to the contralateral eye's visual function and structure in patients experiencing their first episode of unilateral optic neuritis (ON). Fifty patients with first-onset unilateral ON were enrolled in this study. Based on etiology, they were classified as having neuromyelitis optica spectrum disorder-related ON (NMOSD-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), idiopathic ON (IDON), or multiple sclerosis-related ON (MS-ON). These cases were followed up for one year to determine whether there was any silent progression of visual function and structure in the contralateral non-ON (NON) eye. A gender- and age-matched healthy control (HC) group was included to compare the differences in visual function and structure between the patients with NON eyes and the HC group. Within two weeks of onset, best-corrected visual acuity (BCVA; P=0.008), mean deviation (MD) of the visual field (VF) (P=0.001), and peripapillary retinal nerve fiber layer (pRNFL; P=0.019) thickness were significantly worse in the NMOSD-NON patients than those in the HC group, while there were no differences in the pRNFL and the ganglion cell-inner plexiform layer (GCIPL) thicknesses and quadrant thicknesses (P > 0.05) of the groups. IDON-NON only showed subclinical damage in VF (P=0.001) and temporal pRNFL (P=0.042), while the BCVA, VF, and optic nerve structure (pRNFL, GCIPL) of the MOG-NON patients showed no subclinical damage (P > 0.05). In addition, the one-year follow-up of each NON eye type showed that there was no silent progression in NMOSD-NON, MOG-NON, or IDON-NON. A pairwise comparison of the different types of NON eyes revealed no statistical differences (P > 0.05). Among the patients with unilateral ON, NMOSD-NON and IDON-NON resulted in subclinical damage to the visual function and structure of the contralateral eye within two weeks of onset, whereas MOG-NON did not show any subclinical damage to visual function or structure. Furthermore, these subclinical damages did not show any silent progression during the one-year follow-up period.

Different immunological mechanisms between AQP4 antibody-positive and MOG antibody-positive optic neuritis based on RNA sequencing analysis of whole blood.

To compare the different immunological mechanisms between aquaporin 4 antibody-associated optic neuritis (AQP4-ON) and myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) based on RNA sequencing (RNA-seq) of whole blood. Whole blood was collected from seven healthy volunteers, 6 patients with AQP4-ON and 8 patients with MOG-ON, and used for RNA-seq analysis. An examination of immune cell infiltration was performed using the CIBERSORTx algorithm to identify infiltrated immune cells. RNA-seq analysis showed that the inflammatory signaling was mainly activated by TLR2, TLR5, TLR8 and TLR10 in AQP4-ON patients, while which was mainly activated by TLR1, TLR2, TLR4, TLR5 and TLR8 in MOG-ON patients. Biological function identification of differentially expressed genes (DEGs) based on Gene Ontology (GO) term and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, as well as Disease Ontology (DO) analysis, showed that the inflammation in AQP4-ON was likely mediated by damage-associated molecular pattern (DAMP), while which in MOG-ON was likely mediated by pathogen-associated molecular pattern (PAMP). Analysis of immune cell infiltration showed that the proportion of immune cell infiltration was related to patients' vision. The infiltration ratios of monocytes (rs=0.69, P=0.006) and M0 macrophages (rs=0.66, P=0.01) were positively correlated with the BCVA (LogMAR), and the infiltration ratio of neutrophils was negatively correlated with the BCVA (LogMAR) (rs=0.65, P=0.01). This study reveals different immunological mechanisms between AQP4-ON and MOG-ON based on transcriptomics analysis of patients' whole blood, which may expand the current knowledge regarding optic neuritis.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis Mimicking Pituitary Apoplexy With Bitemporal Field Loss.

Miller, Matthew J. BA; Charoenkijkajorn, Chaow MD; Pakravan, Mohammad MD; Mortensen, Peter W. MD; Chen, John J. MD, PhD; Lee, Andrew G. MDEditor(s): Avery, Robert DO; Golnik, Karl C. MD; Froment, Caroline MD, PhD; Wang, An-Guor MD Author Information

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis and myelitis in COVID-19: a case report and a review of the literature

BackgroundOur case explored the spectrum of autoimmune and infectious neurological complications of Coronavirus Disease 2019. In addition, we also reviewed and discussed clinical features, neuroimaging, CSF findings, and outcomes in patients with COVID-19-associated Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD) CNS inflammatory disorder.Case presentationHere we presented a case of post-Coronavirus Disease 2019 infection Myelin Oligodendrocyte Glycoprotein Antibody Disorder in a 41-year-old male who presented with gait instability, urinary retention, and confusion. Workup done in hospital showed transverse myelitis in cervical spine region and left optic neuritis. Laboratory findings showed Myelin Oligodendrocyte Glycoprotein-IgG antibodies were positive in serum (1:100), suggestive of post-COVID Myelin Oligodendrocyte Glycoprotein Antibody Disorder.ConclusionTo our knowledge, this is the first comprehensive case report and the literature review that includes the clinical features, neuroimaging, CSF findings, and outcomes in COVID-19-associated Myelin Oligodendrocyte Glycoprotein Antibody Disorder.

Delayed Visual Improvement in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis

Bilateral involvement and severe visual impairment can occur in the acute phase of pediatric myelin oligodendrocyte glycoprotein (MOG) antibody–associated optic neuritis (ON), but few patients have residual severe vision loss. 1 Giacomini T. Foiadelli T. Annovazzi P. et al. Pediatric optic neuritis and anti MOG antibodies: a cohort of Italian patients. Mult Scler Relat Disord. 2019; 39: 101917 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Limited data exist regarding the prognosis of refractory pediatric MOG antibody–associated ON. We present the case of an adolescent with severe MOG antibody–associated ON followed by delayed but significant improvement.

Structural and functional markers of optic nerve damage in myelin oligodendrocyte glycoprotein antibody-associated optic neuritis.

BackgroundOptic neuritis (ON) occurs in immune-mediated disorders including multiple sclerosis (MS), aquaporin-4 antibody-positive (AQP4) neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination (MOGAD). Accurate determination of aetiology is critical for appropriate treatment and prognostication.ObjectiveTo evaluate demyelination and axonal loss in MOG-ON to facilitate differentiation from MS-ON and AQP4-ON.Methods15 MOGAD patients with previous ON (25 eyes) underwent multifocal visual evoked potential (mfVEP) recordings and optical coherence tomography scans. Comparison was made to previously reported MS patients (n = 67, 69 eyes) and AQP4-NMOSD patients (n = 15, 23 eyes) with prior ON and healthy controls (n = 37, 74 eyes).ResultsMOG-ON patients had less retinal nerve fibre layer (RNFL) loss than AQP4-ON patients (p < 0.05) and less mfVEP latency prolongation than MS-ON patients (p < 0.01). Number of ON episodes in MOGAD was associated with reduced RNFL thickness (global, p = 0.07; temporal, p < 0.001) and mfVEP amplitude (p < 0.001). There was no abnormality in non-ON eyes.ConclusionsOur study demonstrated a distinct pattern of damage in MOG-ON compared to AQP4-ON and MS-ON. ON in MOGAD produces less axonal loss than AQP4-NMOSD. Damage accumulates with relapses, supporting the role of maintenance immunosuppression to induce remission. Compared to MS, MOGAD causes less demyelination.

Comparative analysis of immunosuppressive therapies for myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: a cohort study

AimsThe optimal immunosuppressive therapy (IST) in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) remains uncertain. This study aimed to observe the disease course of MOG-ON and evaluate the...

Alterations in the Retinal Vascular Network and Structure in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis: A Longitudinal OCTA Study

ABSTRACT Purpose To investigate the longitudinal microstructural and microvascular changes in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) without new attacks. Methods We included 20 eyes of 12 MOG-ON patients without new attacks during the follow-up and 24 eyes of 12 age- and sex-matched healthy controls. Results The BCVA, retinal vessels and structure were significantly lower in MOG-ON eyes than in healthy eyes(all P < .05). In MOG-ON eyes, the BCVA (p = .408) and mean deviation (p = .854) were not significantly decreased at the follow-up visit. However, there were small, significant decreases in parafoveal vessel density (p = .026), peripapillary vessel density (p = .008), and RNFL thickness (p = .03), but not GCIPL thickness (p = .107). Conclusions Ongoing deterioration was observed in RNFL thickness and parafoveal and peripapillary vessel density, but not GCIPL thinning, in MOG-ON eyes without a new attack of ON.

Markedly Elevated Serum Level of T-Helper Cell 17-Related Cytokines/Chemokines in Acute Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.

Purpose: The purpose of this study was to examine the differences in immunopathogenesis based on the cytokine/chemokine profiles in myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-positive and -negative groups.Methods: We measured the levels of T-helper cell 17 (Th17) cell-related cytokines/chemokines in 74 serum samples, which were divided into four groups: healthy control (HC) group (n = 15), idiopathic demyelinating optic neuritis (IDON) group (n = 20), aquaporin 4 (AQP4)-IgG-positive optic neuritis (ON) group (n = 18), and MOG-IgG positive-ON group (n = 21). Serum IL17, IL21, IL28, IL31, CXCL1, CXCL2, CCL2, CCL11, CCL20, and LT-α were detected.Results: The serum of the MOG-IgG-positive ON patients showed an obvious elevation of Th17 cell-related cytokines/chemokines compared with that of all the MOG-IgG-negative ON patients. Serum IL17 and IL21 were significantly higher in the ON patients with MOG-IgG positive than in all the other three groups. The serum levels of IL28, IL31, CXCL1, and CCL11 were higher in the ON patients with MOG-IgG positive than in the HC group and the IDON group. The serum concentration of CCL2, CXCL2, and CCL20 in the MOG-IgG-positive and AQP4-IgG-positive group is higher than that of the HC group. No difference in serum LT-α level was found among the four groups. Adjusted multiple regression analyses showed a positive association of IL17 and IL21 levels with the serum concentration of MOG-IgG in the ON patients.Conclusion: The elevated serum level of Th17 cell-related cytokine/chemokines may play an important role in the pathogenesis of MOG-IgG-positive demyelinating ON.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis in Canada.

To describe clinical characteristics of Canadian patients with myelin-oligodendrocyte glycoprotein immunoglobulin-G optic neuritis (MOG-IgG ON). Retrospective observational case series of MOG-IgG seropositive patients with ON referred to tertiary neuro-ophthalmology practices. Outcome measures included clinical characteristics, radiologic findings, and visual outcomes. Forty-six eyes of 30 patients were included. Twenty-three (76.7%) were women, mean onset age was 40.7 years (range 16-77), and most were Caucasian. Seventeen (56.7%) presented with their first ON episode. Sixteen (53.3%) had bilateral eye involvement. Isolated ON without associated neurological symptoms occurred in 90.0%. In 22 patients with acute ON (seen within 1 month of onset), presenting mean visual acuity (VA) was 20/258 (logMAR 1.11), mean deviation (MD) on Humphrey visual fields was -16.90 ± 10.83 dB, and peripapillary retinal nerve fiber layer (RNFL) thickness on ocular coherence tomography (OCT) was 164.23 ± 46.53 um. Orbital magnetic resonance imaging (MRI) within 1 month of symptom onset for 19 patients demonstrated orbital optic nerve enhancement in 11 (57.9%) and perineural enhancement in 11 (57.9%). Brain MRI was normal in 28 (93.3%) patients. Twenty out of 22 patients with acute presentation were treated with high-dose glucocorticoids and 5 with plasma exchange in addition to corticosteroids. Long-term immunosuppression was utilized in 9 (30%) out of all 30 patients. Final VA was 20/30 (logMAR 0.18), MD was -7.17 ± 8.85 dB, and RNFL thickness was 72.15 ± 20.16 um. MOG-IgG ON in Canada has a variable presentation with most patients having substantial initial vision loss with good recovery. This is the largest characterization of the disease in Canada to date.

Differences in Clinical Features of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis in White and Asian Race

To determine whether clinical features and visual outcomes of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) differ between White and Asian subjects. Multicenter retrospective cohort. This was a multicenter study of 153 subjects who were White or Asian with a history of adult-onset (age 18 years or older) optic neuritis (ON) and positive MOG-IgG serology by cell-based assay. Subjects were enrolled from 2 unpublished cohorts (January 2017-November 2019) and 9 published cohorts with case-level data available (2012-2018). Subjects with alternative etiologies of demyelinating disease and positive or lack of aquaporin-4-IgG serology result were excluded. The main outcome measurements were clinical features and final visual outcomes. Of the 153 subjects who were White (n= 80) or Asian (n= 73) included in the study, 93 (61%) were women, mean age of onset was 40.8 ± 14.9 years, and median follow-up was 35.2months (range: 1-432months); all of these characteristics were similar between White and Asian subjects. White subjects were more likely to have recurrent ON (57 [71%] vs 20 [27%]; P= .001) and extra-optic nerve manifestations (35 [44%] vs 8 [11%]; P= .001). Optic disc swelling, neuroimaging findings, presenting visual acuity (VA), treatment, and final VA did not differ according to subjects' race. Despite the high prevalence of severe visual loss (<20/200) during nadir, most subjects had good recovery of VA (>20/40) at final examination (51/77 [66%] White subjects vs 52/70 [74%] Asian subjects). White subjects with MOG-ON were more likely to have recurrent disease and extra-optic nerve manifestations. Visual outcomes were similar between White and Asian subjects.

Clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis in children

Objective: To investigate the clinical characteristics, treatment and prognosis of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) in pediatric patients. Methods: Clinical data, laboratory examination, the initial best corrected visual acuity (BCVA), fundus, neuroelectrophysiological results, MRI imaging, treatment and prognosis of children diagnosed with MOG-ON from 2016 to 2019 were retrospectively analyzed. Results: A total of 29 eyes from 16 children were involved, with a male/female ratio of 1∶1, onset age of (7.0±2.9) years. Seven of 16 patients had prodromal infection, with a unilateral/bilateral ratio of 3∶13, and 2 cases had recurrent optic neuritis. Before treatment, BCVA of 19 eyes (65.5%) was ≤0.1, among them, 4 had no sense of light, 5 had light sense, 5 with sense of hands in front of eyes, and 5 with sense of fingers in front of eyes. There were 10 eyes (34.5%) with BCVA of 0.1-0.5. After treatment, there were 4 eyes (13.8%), 5 eyes (17.2%) and 20 eyes (69.0%) in groups with BCVA of 0.1-0.5, 0.5-1.0, and>1.0, respectively. Twelve of 16 patients had optic papillitis in fundus examination during acute phase. The latency was prolonged and the amplitude was decreased in P100 wave of all the children. Thirteen out of 16 children showed swelling and thickening of optic nerve in MRI T2WI. MRI images exhibited intracranial demyelinating lesions in 12 of 16 children and long segment spinal cord lesions in 3 of 16 children. Thirteen of 16 patients showed effective results after intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) treatment. There was no relapse after administration of mycophenolate mofetil in 2 recurrent children. No progression after administration of rituximab was found in 1 child with corticosteroid insensitivity. The average follow-up time was (16±9) months and no recurrence occurred. Ten of 16 patients had full recovery, 4 had significant improvement, and 2 showed no significant improvement. Conclusions: There is no significant gender difference in the incidence of pediatric MOG-ON. Bilateral involvement and severe visual impairment are common in acute phase. Most patients have good response to IVMP combined with IVIG treatment and hence have a good prognosis. Only a few of them have neurological sequelae.

Unfavorable Structural and Functional Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis.

Recurrent optic neuritis (rON) associated with myelin oligodendrocyte glycoprotein (MOG)-specific antibodies has been initially reported to show a better clinical outcome than aquaporin-4 (AQP4)-seropositive ON in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterize clinical and neuroimaging findings in severe cases of MOG antibody-positive and AQP4 antibody-negative bilateral rON. Three male adults with rON (ages 18, 44, and 63 years) were evaluated with optical coherence tomography (OCT), MRI, cerebrospinal fluid (CSF), and serological studies. All patients experienced >7 relapses of ON with severe reduction of visual acuity and partial response to steroid treatment. Optic nerves were affected bilaterally, although unilateral relapses were more frequent than simultaneous bilateral recurrences. Patients were MOG-seropositive but repeatedly tested negative for AQP4 antibodies. OCT showed severe thinning of the peripapillary retinal nerve fiber layer. On MRI, contrast-enhancing lesions extended over more than half the length of the optic nerve. CSF analyses during ON episodes were normal. Severe visual deficits accumulated over time in 2 of 3 patients, despite immunosuppressive therapy. MOG-seropositive and AQP4-seronegative rON may be associated with an aggressive disease course and poor functional and structural outcomes. In contrast to previous reports, the severity and pattern of retinal and optic nerve damage closely resembled phenotypes commonly observed in AQP4-seropositive rON without fulfilling current diagnostic criteria for NMOSD.