Antibody-positive Optic Neuritis Research Articles

Evaluation of Steroid Pulse Therapy Responsiveness in Myelin-Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

Myelin-oligodendrocyte glycoprotein antibody-positive optic neuritis (MOGON) is usually responsive to the steroid, but, for some patients, steroid pulse therapy alone may be inadequate. This study aimed to investigate the factors predicting the response to steroid pulse therapy in MOGON. This study included 17 patients (24 eyes) with MOGON, who received single steroid pulse therapy as initial treatment. Best corrected visual acuity (BCVA) and mean deviation (MD) values after treatment were examined concerning findings at onset. No correlation was found between BCVA at onset and after treatment, but a correlation was observed between MD values at onset and after treatment (correlation coefficient 0.48, p=0.01, Spearman's rank correlation coefficient). Age, gender, duration from onset to treatment, magnetic resonance imaging findings, and optical coherence tomography findings did not affect visual function after treatment. Severe visual field impairment at onset may indicate that additional treatment may be necessary.

Analysis of the initial orbital MRI in aquaporin-4 antibody-positive optic neuritis (AQP4-ON): lesion location and lesion length can be predictive of visual prognosis.

Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3years. A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3mm) than in the recovery group (12.5 ± 5.3mm) (p = 0.001). AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term.

Successful Maintenance Therapy with Intravenous Immunoglobulin to Reduce Relapse Attacks and Steroid Dose in a Patient with Refractory Myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis.

A 25-year-old Japanese man developed visual disturbance with eye pain and was diagnosed with optic neuritis associated with anti-myelin oligodendrocyte glycoprotein antibodies. His symptoms improved temporarily after steroid therapy but chronically relapsed many times after tapering the steroid dose. He became highly steroid-dependent and was referred to our department for reconsideration of the treatment strategy. Maintenance intravenous immunoglobulin (IVIg) therapy successfully decreased the annual recurrence rate from 1.15 to 0.27 times/year and the maintenance dose of oral prednisolone from 35 to 5 mg/day. Maintenance IVIg therapy is a promising option for preventing disease relapse in such cases.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis

ABSTRACT In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

An Example of Interstitial Pneumonia Developed during Treatment of Anti-MOG Antibody Positive Optic Neuritis

An Example of Interstitial Pneumonia Developed during Treatment of Anti-MOG Antibody Positive Optic Neuritis

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.

Efficacy of Plasma Exchange Treatment for Demyelinating Optic Neuritis Associated with Various Serum Antibodies: A Prospective Cohort Study.

Introduction To evaluate the value of plasma exchange (PE) for patients with three subtypes of demyelinating optic neuritis (ON): aquaporin-4 (AQP4) antibody-positive ON (AQP4-ON), myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON (MOG-ON), and AQP4 and MOG double-antibody-seronegative ON (D-ON).MethodsA single-center prospective study compared the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at most severe onset, 1 day before intravenous high-dose methylprednisolone (IVMP) treatment, 1 day before PE treatment, after five-cycles of PE therapy, and at 1-, 3-, and 6-month follow-up visits. The proportions of eyes in each visual outcome category were also compared. Logistic regression and a receiver operating characteristic curve were used to analyze predicted factors for VA improvement.ResultsA total of 124 ON attacks of 122 patients were included. No significant differences were found in BCVA (P = 0.659) before and after PE therapy for 22 D-ON attacks, but VA improved in two of six MOG-ON patients. In 95 AQP4-ON patients suffering 96 attacks, the mean logMAR BCVA markedly improved and was steadily maintained after five-cycles of PE treatments (adjusted P < 0.001), with VA exhibiting a significantly increasing trend (adjusted P = 0.001) after PE treatment. The combination of the number of previous ON episodes and the time window to PE treatment showed accuracy of 74.7% for predicting an improvement in BCVA score ≥ 2 levels. In addition, a combination of logMAR VA before PE and the time window to PE treatment resulted in 83.4% accuracy in predicting whether VA would regain 1.0 logMAR.ConclusionPE therapy effectively improves visual outcomes for AQP4-ON patients, but offers limited value for D-ON patients. Early initiation greatly increases likelihood of achieving VA improvement.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00344-w.

Anti-Asialo GM1 Antibody-Positive Optic Neuritis and Optic Perineuritis in Chronic Inflammatory Demyelinating Polyneuropathy.

Anti-Asialo GM1 Antibody-Positive Optic Neuritis and Optic Perineuritis in Chronic Inflammatory Demyelinating Polyneuropathy.

Visual outcome of aquaporin-4 antibody-positive optic neuritis with maintenance therapy.

To assess the effect of maintenance therapy on visual outcomes in preventing recurrences one year after first onset in patients with aquaporin-4 antibody (AQP4Ab)-positive optic neuritis. Retrospective study. The medical charts of 56 patients with optic neuritis (22 with AQP4Ab-positive and 34 with AQP4Ab-negative) at Niigata University Medical and Dental Hospital were retrospectively analyzed. Clinical characteristics, including visual acuity and number of recurrences one year after first onset, were compared among patients who were AQP4Ab-positivie with and those without maintenance therapy such as oral prednisolone and azathioprine, as well as those who were AQP4Ab-negative. The mean ages were 49.3 and 45.2years in the AQP4Ab-positive and the AQP4Ab-negative groups. The female to male ratio was 21:1 and 18:16 in the two groups, respectively. Multiple between-group comparison showed a statistically significant difference in visual acuity one year after first onset between the AQP4Ab-positive without maintenance therapy group and the AQP4Ab-negative group (0.05 (median, same applies below) vs. 1.0, p < 0.01). There was also a statistically significant difference in the number of recurrences in the year after first onset between the AQP4Ab-positive with and without maintenance therapy groups (1 vs. 0, p < 0.01). This study demonstrates that patients with AQP4Ab-positive optic neuritis without maintenance therapy had the poorest visual acuity and the most recurrences one year after first onset. These results indicate that reducing the number of recurrences with maintenance therapy could improve the visual outcomes in patients with AQP4Ab-positive optic neuritis.

Clinical features and prognosis analysis of myelin oligodendrocyte glycoprotein antibody-positive optic neuritis

Objective: To investigate the clinical characteristics and prognosis of myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis (ON). Methods: The data of 39 patients with MOG antibody-positive ON in the Department of Neurology of Beijing Tongren Hospital, Capital Medical University from January 1, 2017 to October 31, 2019 were retrospectively collected. There were 25 males and 14 females, aged from 15 to 80 (40±16) years. According to the recurrence, the patients were divided into two groups: the recurrence group (n=12) and the non-recurrence group (n=27). The clinical manifestations, relapse-related factors, magnetic resonance imaging (MRI) manifestations, treatment and prognosis of the two groups were analyzed. Results: A total of 63 eyes were involved, including 30 cases of optic perineuritis (OPN), accounting for 47.6% (30/63). The number of attacks ranged from 1 to 9, among which 12 patients had more than 2 attacks. There were 37 eyes [58.7% (37/63)] with severe visual loss (SVL) at the time of onset, and 7 eyes [11.1% (7/63)] with SVL at the final follow-up. Forty-eight eyes [76.2% (48/63)] had optic disc edema. Forty seven eyes [74.6% (47/63)] showed long-segment disease on optic nerve MRI. One case was complicated with aseptic meningitis and encephalitis. The recurrence group was younger than the non-recurrence group [(28.5±9.8) years vs (43.3±16.4) years, P=0.001]. There were no statistically significant differences between the two groups in gender, bilateral onset, initial visual acuity, final visual acuity, optic disc edema, head and spinal cord lesions, and immunosuppressant (all P>0.05). All patients were treated with methylprednisolone (MP) pulse therapy during the acute attack, and 16 of them were additively treated with immunosuppressive agents; the pain was alleviated or relieved significantly after the application of glucocorticoids. Conclusions: MOG antibody-positive ON often occurred in both eyes at the same time, often manifesting as OPN, often accompanied by optic disc edema, and SVL at the beginning of the disease, but most of the visual recovery was good, might be associated with meningitis and encephalitis. MRI of the optic nerve showed that the lesions often manifested as long-segment lesions. Glucocorticoids could alleviate pain and promote the recovery of visual function.

Transient Tunnel Vision as Initial Presentation of Anti-MOG Antibody Positive Optic Neuritis.

Transient Tunnel Vision as Initial Presentation of Anti-MOG Antibody Positive Optic Neuritis.

A Case of Refractory Absence Epilepsy Precedes Anti-MOG Associated Optic Neuritis

Childhood absence epilepsy (CAE) is one of the most common forms of pediatric epilepsy. While most patients become seizure free with anti-epileptic drug therapy approximately 20% do not achieve seizure remission and are defined as having refractory CAE. Epilepsy is generally thought of as a grey matter disease but has also been associated with abnormal white matter. Optic neuritis (ON), on the other hand, is typically a white matter disorder characterized by inflammation and demyelination of the myelin sheath due to autoantibodies, such as the anti-myelin oligodendrocyte glycoprotein (MOG) antibody. We present the case of an 11-year-old female with refractory CAE who developed anti-MOG antibody positive ON. CAE and ON are not commonly co-morbid and to our knowledge their co-occurrence in a patient has not been previously described. However, in this case, the CAE and ON may be related as her seizures dramatically improved after initiating immunomodulatory treatments for the ON. This may indicate a relationship between ON (potentially specific to anti-MOG positive ON) and CAE, or may suggest that there is an inflammatory component to CAE and that immunomodulatory therapies may have a role in seizure control. Thus, in cases of treatment resistant absence epilepsy, an immune work up may be helpful.

網膜動脈分枝閉塞，前部虚血性視神経症，黄斑部漿液性網膜剥離，同側外転神経麻痺を合併した抗MOG抗体陽性視神経炎の1例

網膜動脈分枝閉塞，前部虚血性視神経症，黄斑部漿液性網膜剥離，同側外転神経麻痺を合併した抗MOG抗体陽性視神経炎の1例

Efficacy for the Annual Relapse Rate after the Immunosuppressive Therapy in Patients Associated with Anti-AQP4 or Anti-MOG Antibody-Positive Optic Neuritis.

Purpose Although oral prednisolone is the first-line treatment for preventing recurrent optic neuritis (ON) after the completion of acute-phase treatment, especially anti-aquaporin 4 (AQP4) antibody-positive ON, and anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON, some patients experience relapses. Immunosuppressants could be effective in reducing the recurrence rate for neuromyelitis optica spectrum disorder and MOG antibody-related diseases, but there have been few studies addressing this issue focusing on the changes in ophthalmic parameters. The objective of the study was to analyze the impact of off-label uses of immunosuppressants to reduce recurrent ON. Design Retrospective observational study, clinical case series. Methods We reviewed the medical charts of 11 cases (22 eyes) who underwent immunosuppressive therapy in Kobe University Hospital and compared the annualized relapse rate (ARR) before and after immunosuppressive therapy. We also evaluated the dosage of prednisolone, complications of immunosuppressants, and other visual functional ophthalmologic parameters. Results Eleven cases in total had AQP4 antibody (9 cases) and/or MOG antibody (3 cases). One case was double positive for these antibodies. Nine patients received azathioprine and two received mycophenolate mofetil as an initial immunosuppressive therapy. The median duration of immunosuppressant treatment was 2.8 years. The median ON ARR before immunosuppressive therapy was 0.33, and this decreased significantly to 0 after the therapy (p = 0.02). The dose of prednisolone was reduced from 17.8 ± 7.1 mg/day before to 5.8 ± 2.2 mg/day after immunosuppressive therapy (p < 0.01). Although two patients presented with mild elevation of liver enzymes and nausea, all patients were able to continue taking the immunosuppressants. Conclusions Immunosuppressants can potentially decrease relapses and steroid dosage in patients with anti-AQP4 or MOG antibody-positive ON without severe adverse events and the exacerbation of visual acuities.

Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan

To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. Multicenter cross-sectional, observational cohort study. A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. Antibody positivity, clinical and radiologic characteristics, and visual outcome. Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.

Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-positive optic neuritis

Objective: To investigate the clinical characteristics and prognosis of myelin oligodendrocyte glycoprotein(MOG) antibody-positive optic neuritis (MOG-ON). Methods: Retrospective case series study. A total of 65 patients diagnosed with MOG-ON at the Department of Ophthalmology of the Chinese People's Liberation Army General Hospital during January 2016 and October 2017 were selected. The patients underwent examinations including best corrected visual acuity (BCVA), fundus color photography, optical coherence tomography (OCT) and magnetic resonance imaging (MRI). The patients were tested for serum levels of antibodies for aquaporin 4 and MOG with a cell-based assay. The follow-up duration ranged from 14 to 217 months. Statistical analyses of patients' clinical features, neuroimaging features and prognosis were conducted. The independent-sample t test or Mann-Whitney U test for continuous variable data and the χ(2) test or Fisher exact test for classified variable data and rates were used. Results: There were 35 children (<18 years) and 30 adults (≥18 years) patients. Thirty-seven patients were female and 28 patients were male. The mean age of onset was (23±16) years (range of 3-61 years). There were 40 unilateral patients and 25 bilateral patients at the first onset. Fifty-five patients (84.6%) suffered from eye pain at the first onset and the incidence in children was significantly lower than that in adult [74.3% (26/35) and 96.7% (29/30), P=0.016]. Abnormal autoimmune antibodies were found in 13 patients (20.0%).And 47.8% (43/90) eyes had optic disc edema. Sixty percent (39/65) were recurrent optic neuritis and 73.8% (48/65) were bilateral diseases at final visit. Orbital MRI scans showed T(2) hyperintensity of optic nerve in 98.4% patients (62/63). Head MRI scans showed demyelinating lesions of the brain in 12/19 patients. Within 2 weeks of onset, 78.9%(71/90) of the affected eyes had BCVA ≤ 0.1. The visual impairment of the children and adult was serious, and there was no significant difference (P=0.650). After treatment with corticosteroid, visual acuity improved in all affect eyes. After the initial attack, 95.6%(86/90) of the affected eyes had BCVA ≥ 0.5. The children and adult had good visual recovery, and there was no significant difference (P=0.061). At the final visit, 86.7%(98/113) of the eyes had BCVA ≥ 0.5, the children had better visual recovery than adult [logarithm of the minimum angle of resolution, 0.10±0.35 vs. 0.32±0.53, t=-2.526, P=0.013].Three children (8.6%) were diagnosed with acute disseminated encephalomyelitis. The average thickness of peripapillary retinal nerve fiber layers (pRNFL) and macular ganglion cell-inner plexiform layers (mGCIPL) were (69.90±12.49) μm and (59.58±7.91) μm at least 6 months after optic neuritis attack. There were different degrees atrophy and not statistically different in pRNFL and mGCIPL between children and adult (P=0.606, 0.223). Conclusions: The clinical characteristics of MOG-ON are diverse. The children patients are more common and have better recovery of visual acuity. Additionally, some patients have demyelinating lesions in the brain. (Chin J Ophthalmol, 2019, 55: 174-179).

Clinical Characteristics and Pathogenesis of Anti-aquaporin-4 Antibody-positive Optic Neuritis

Clinical Characteristics and Pathogenesis of Anti-aquaporin-4 Antibody-positive Optic Neuritis

Clinical Characterizations of Anti-myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis

Clinical Characterizations of Anti-myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis

Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis In A Girl With Ulcerative Colitis

Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis In A Girl With Ulcerative Colitis

Clinical Characteristics of Anti-aquaporin 4 Antibody Positive Optic Neuritis in Japan

ABSTRACTTo investigate the clinical characteristics and the effectiveness of maintenance therapy of anti-AQP4 antibody positive optic neuritis in Japanese patients, medical records from 69 patients (103 eyes) were retrospective reviewed. The status of relapse in patients who received maintenance therapy following acute therapy was compared with that before maintenance therapy in patients who started maintenance therapy ≥6 months after acute therapy. In Japan, anti-AQP4 antibody positive optic neuritis was characterized by older onset age and poor visual outcome. The yearly rate and total number of relapses were lower when maintenance therapy was followed immediately after acute therapy.