Severe Optic Neuritis Research Articles

Efficacy and Safety of Inebilizumab, an Anti-CD19 Monoclonal Antibody, for the Treatment of Neuromyelitis Optica Spectrum Disorder: Based on the N-MOmentum Trial

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathic disease of the central nervous system characterized by severe optic neuritis and transverse myelitis. The antibody against aquaporin 4 (AQP4), a water channel mainly expressed in astrocytes, is specific to NMOSD and may be detected in >70% of all cases. Inebilizumab is a humanized IgG1 monoclonal antibody against CD19. Anti-AQP4 antibodies are produced by CD19-positive plasmablasts, and inebilizumab administration significantly reduces the number of CD19-positive B cells and has therapeutic effects on NMOSD. The efficacy and safety of inebilizumab have been verified in the N-MOmentum trial, an international double-blind, placebo-controlled phase II/III study, in which Japanese patients also participated. Inebilizumab was approved for the treatment of NMOSD with AQP4-IgG in Japan in March 2021. In this review, we summarize the efficacy and safety of inebilizumab in the treatment of NMOSD and, focus on findings from the primary and additional analyses of the N-MOmentum trial. These results suggest that inebilizumab is effective and safe in preventing the recurrence of NMOSD in populations with different backgrounds and that long-term treatment with inebilizumab is beneficial.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis.

Very late-onset neuromyelitis optica spectrum disorder-related optic neuritis is limited to a few case reports. To investigate the clinical features and visual prognosis of very late-onset neuromyelitis optica spectrum disorder-related optic neuritis. This study evaluated 22 patients with first-onset optic neuritis and fulfilled the 2015 diagnosis criteria for neuromyelitis optica spectrum disorders. The mean age at optic neuritis onset was 73.91 ± 4.71 (range: 70-82) years with a female predominance (81.8%; ratio: 4.5:1). Antinuclear antibody seropositivity and seronegativity were identified in 12 (55.5%) and 10 (45.5%) patients, respectively. Severe visual loss persisted in 19 (19/42, 45.3%) eyes at the last follow-up. Although patients with antinuclear antibody seropositivity had a significantly higher frequency of attacks (P = 0.015), but they had a longer median time to reach severe visual loss (37 vs. 26 months; log-rank test, P = 0.023). Multivariate logistic regression analysis revealed antinuclear antibody seropositivity (hazard ratio = 4.849, 95% confidence interval: 1.309-17.965, P = 0.018) as a good predictor of visual acuity improvement. Patients with very late-onset neuromyelitis optica spectrum disorder-related optic neuritis may develop severe optic neuritis, and those with antinuclear antibody seronegativity have a similar clinical presentation but worse outcome than those with seropositivity.

Poor Visual Outcome After First Attack in a Cohort of Patients With Myelin Oligodendrocyte Glycoprotein-Related Optic Neuritis.

Myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON) is typically a highly treatable condition that responds quickly to treatment with high doses of corticosteroids. We reviewed the cohort of patients with MOG-ON to identify patients who had poor visual outcome after the first attack despite rapid initiation of treatment. Records of all patients diagnosed with MOG-ON seen in a tertiary neuro-ophthalmology practice were reviewed to identify and describe those with poor visual recovery (final visual acuity of 20/200 or worse in at least one eye) after the first attack despite initiation of treatment within 1 week of symptoms onset. Two patients of 36 fulfilled inclusion criteria: both had bilateral severe optic neuritis at presentation, and both were seen within 7 days of symptoms onset and treated immediately with pulse doses of intravenous corticosteroids followed by very-slow oral taper. Plasma exchange (PLEX) was performed 2 weeks after symptoms onset in both patients because of poor response to steroids, followed by monthly intravenous immunoglobulin infusions. Despite the use of all available treatment modalities, final visual outcome was poor in both patients. In both patients, there was enhancement of intracanalicular portion of optic nerve in the worse-seeing eye. In this cohort of patients with MOG-ON, 2 (5.6%) had very poor visual outcome after the first attack despite immediate initiation of treatment with pulse doses of corticosteroids and subsequent treatment with PLEX. These cases highlight that despite immediate initiation and escalation of treatment, some patients with MOG-ON can have very poor visual outcomes after the initial attack that may be because of the involvement of the intracanalicular portion of the optic nerves.

NMOSD IgG Impact Retinal Cells in Murine Retinal Explants.

Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells. In this exploratory study, we analysed the response of mouse retinal explants to NMOSD immunoglobulins (IgG). Mouse retinal explants were treated with purified IgG from patient or control sera for one and three days. We characterized tissue response patterns through morphological changes, chemokine secretion, and complement expression. Mouse retinal explants exhibited a basic proinflammatory response ex vivo, modified by IgG addition. NMOSD IgG, unlike control IgG, increased gliosis and decreased chemokine release (CCL2, CCL3, CCL4, and CXCL-10). Complement component expression by retinal cells remained unaltered by either IgG fraction. We conclude that human NMOSD IgG can possibly bind in the mouse retina, altering the local cellular environment. This intraretinal stress may contribute to retinal degeneration independent of relapse activity in NMOSD, suggesting a primary retinopathy.

Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder

BackgroundStudies suggest that antinuclear antibodies (ANAs) may correlate with the long-term prognosis of Neuromyelitis optica spectrum disorder (NMOSD). In this study, we investigated ANAs in Chinese patients with NMOSD and their relationship with disease outcomes. MethodsWe retrospectively collected data from 525 patients diagnosed with NMOSD at West China Hospital between September 1, 2009, and October 1, 2021. Patients were classified into two groups: NMOSD with ANA (+) or without ANA (−). We compared the clinical characteristics, relapse rate, severe attacks, laboratory tests, Expanded Disability Status Scale (EDSS), and prognosis between the two groups. ResultsAmong the 525 NMOSD patients, those with ANA showed a higher frequency of AQP4-IgG (94.1% vs 79.3%, p < 0.001, false discovery rate (FDR) corrected p < 0.001), and anti-SSA (p < 0.001, FDR corrected p < 0.001), anti-SSB (p < 0.001, FDR corrected p < 0.001), anti-Ro52 antibodies (p < 0.001, FDR corrected p < 0.001), than those without ANA. ANA was detected in 403 patients during the acute phase. Patients with ANA (+) had higher EDSS scores in the acute stage (4.0 vs. 3.75, p = 0.013, FDR corrected p = 0.029) and at final follow-up (p = 0.032, FDR corrected p = 0.064). NMOSD patients with ANA (+) had a higher frequency of severe acute myelitis attack, severe acute myelitis and optic neuritis attack, motor and visual disability, compared to those with ANA (−) (42.1% vs. 27.8%, p = 0.001, FDR corrected p = 0.004, 19.3% vs. 10.3%, p = 0.004, FDR corrected p = 0.018, and 11.1% vs. 4.8%, p = 0.008, FDR corrected p = 0.022 respectively). The two groups had no significant difference in the annual recurrence rate (ARR). ConclusionANA may be associated with more severe disease activity and disability in NMOSD.

A Rare Case of Evans Syndrome Associated With Optic Neuritis: A Case Report

Purpose: To report a case of Evans Syndrome associated with severe optic neuritis. Case Report: HAF, male, 26 years old, diagnosed with Evans Syndrome at the age of nine, with a history of headache and right eye pain with worsening movement. Fifteen days after the initial condition, visual clouding and decreased visual acuity began. Ophthalmological examination revealed visual acuity of 20/200 in the right eye with progressive worsening as the condition progressed; and 20/20 in the left eye. Visual field with absolute scotomata in the right eye and relative and absolute scotomatous points in all quadrants of the left eye. Gluorescein angiography findings included optic disc attenuation, without hyperfluorescent lesions. Conclusion: Evans Syndrome is a pathology that is gradually expanding in the field of clinical research, which has allowed new concepts related to pathogenesis and association with other comorbid conditions. In this case, we report the association with unilateral Optic Neuritis, responsible for progressive visual loss. Such knowledge aggregates the scientific community and translates into the need for an early multidisciplinary approach.

Therapeutic efficacy and safety of plasmapheresis in elderly patients with neuromyelitis optica spectrum disorder: a single-center observational study

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating autoimmune disorder with cycles of escalating relapse. Rates of diagnosis in the elderly are increasing. Therapeutic decision-making is more challenging in elderly patients due to multiple comorbidities and high risk of drug-induced side effects. This retrospective study assessed the efficacy and safety of standard plasma exchange (PLEX) treatment in an elderly population with NMOSD. Seventy-six patients with NMOSD who received PLEX were apportioned to two groups as either elderly (⩾60 years, n = 26) or young (<60 years) at the time of the first procedure. Therapeutic response was judged according to functional recovery at 6 months, as reflected by Expanded Disability Status Scale (EDSS) and visual outcome scale (VOS) scores. The mean age of the 26 elderly patients was 67.7 ± 7.9 years (range 60-87 years); the population was predominantly female (88.5%). PLEX sessions were generally well tolerated among the elderly. Compared with the young patients, the elderly had significantly more comorbidities and concomitant medications. Twenty-four (96.0%) elderly patients showed functional improvement at 6 months after PLEX, of which 15 (60.0%) experienced moderate-to-marked improvement. Six months after the initial PLEX treatment, the patients overall experienced a significant improvement in EDSS and VOS scores. Logistic regression showed that severe optic neuritis attack was a significant independent prognostic factor associated with poor PLEX response. The groups were comparable regarding overall or serious adverse events. The rate of transient hypotension was significantly higher in the elderly compared with the young. PLEX is an effective and safe therapy for elderly patients with NMOSD and should be considered a treatment option during NMOSD attacks. In the elderly, preventive measures against hypotension are recommended before PLEX.

Identification of double-stranded DNA in the cerebrospinal fluid of patients with acute neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease of the central nervous system (CNS) characterized by severe myelitis and optic neuritis. Double-stranded DNA (dsDNA) is involved in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus. However, its role in NMOSD remains unclear. In this study, the concentration of dsDNA in the cerebrospinal fluid (CSF) was quantified in 23 patients with NMOSD and 16 patients with other neurological diseases (ONDs). CSF dsDNA levels in patients with NMOSD (median: 0.03 ng/µL) were significantly higher than those in patients with ONDs (median: 0.01 ng/μl). CSF dsDNA levels showed no significant difference before and after treatment. Elevation of CSF dsDNA levels may suggest its essential role in the augmentation of CNS inflammation in patients with NMOSD.

Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

From Darkness to Light: A Rare Case of Visual Recovery from Absent Light Perception to 20/20 in a Young Girl with Bilateral Optic Neuritis

Optic Neuritis is an ophthalmic emergency, characterized by sudden loss of vision, which needs immediate attention. Although steroids are the main stay of treatment, stringent diagnostic measures including an extensive serology workup and neuroimaging need to be done as to ascertain the etiology. This case report describes a young girl with bilateral severe optic neuritis, with denied perception of light in both eyes, and no systemic association. Immediate administration of methylprednisolone is the norm in such cases, and as per Optic Neuritis Treatment Trial, it is usually given for 3 days followed by oral prednisolone. In this patient, intravenous 1gram methylprednisolone was administered for 5 days, and then followed by oral prednisolone. The patient showed an excellent response with a complete recovery of vision to 20/20, which is an extremely rare phenomenon.

Longitudinal Retinal Changes in MOGAD.

Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. Eighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N=66 and HCs: N=103) and (2) Cirrus high-definition OCT (MOGAD: N=14 and HCs: N=36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified. At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HCs (p < 0.001). MOGAD-NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow-up up to 3 years), MOGAD-ON with ON within the last 6-12months before baseline exhibited greater pRNFL thinning than MOGAD-ON with an ON greater than 12months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort. Our study suggests the absence of attack-independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476-485.

Treatment outcomes of first-ever episode of severe optic neuritis

BackgroundSevere optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear. MethodsWe reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up. ResultsOf the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 – max 5.0) vs. 2.17 (min 1.3 – max 3.0); p=0.004). ConclusionIn our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.

Association of HLA DRB1-DQB1 Haplotypes with the Risk for Neuromyelitis Optica among South Indians.

Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder, mainly characterized by severe optic neuritis, transverse myelitis and the high levels of antibodies against NMO-immunoglobulin G (IgG) or aquaporin-4 (AQP4). HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are known to play a significant role in several autoimmune diseases including NMO. The rationale of the current case-control study is to explore the association of HLA-DRB1 and HLA-DQB1 alleles with the risk of NMO and its association with the clinical and serological markers. A total of 158 samples (38 NMO cases and 120-age and ethnicity matched controls) were genotyped for the HLA-DRB1 and HLA-DQB1 alleles by using PCR-SSP method. Our analysis showed significant association of HLA-DRB1*10 allele (OR 2.63, 95% CI: 1.18-5.83, p=0.02) with NMO whereas DRB1*14 showed protective role against NMO (OR 0.33: 95% CI: 0.11-0.94, p=0.043). HLA-DRB1*10 allele also showed significant association in patients with NMO-IgG positive antibody (OR 3.28: 95% CI: 1.42-7.5, p=0.006). There was no association of HLA DQB1 alleles with NMO and also with NMO-IgG antibody. Among the haplotypes groups, HLA-DRB1*10-DQB1*05 (OR 2.61, 95% CI: 1.11-6.1, p=0.03), HLA-DRB1*15-DQB1*03 (OR 4.5, 95% CI: 1.81-11.5, p=0.001) were strongly associated with the risk of NMO, whereas DRB1*14-DQB1*05 (OR 0.20, 95% CI: 0.060-0.721, p=0.008) showed negative association with NMO. From this study, it is concluded that the HLA-DRB1*10 and DRB1*10-DQB1*05 and HLA-DRB1*15-DQB1*03 haplotypes may influence the susceptibility to NMO among the South Indians. Additionally we found DRB1*14 allele and DRB1*14-DQB1*05 haplotype showed protective role for NMO.

Neuromyelitis optica spectrum: a case report

&lt;p class="abstract"&gt;Neuromyelitis optica (NMO) or Devic's disease is a rare inflammatory, demyelinating autoimmune disease of the central nervous system that primarily affects women, most commonly in their 30s and 40s. NMOSD has been linked to several different illnesses including autoimmune disorders. Recurrent bouts of optic neuritis, myelitis and brainstem disorders are caused by serum antibodies (Abs) against the aquaporin-4 (AQP4) water channel. No AQP4-Abs are detected in some patients with NMOSD symptoms, but Abs against myelin-oligodendrocyte-glycoprotein (MOG). The term MOG-encephalomyelitis is now commonly used to describe this clinical disorder. Long segments of inflammation in the spinal cord (myelitis), severe optic neuritis and bouts of persistent vomiting and hiccoughs are all characteristics symptoms. This was the case of 30 year old female who presented with a chief complaint of weakness of both lower limbs, unable to walk, tingling and numbness. Based on her MRI findings revealed that the patient was diagnosed with NMO spectrum. She was treated with immunosuppressants and corticosteroids.&lt;/p&gt;

Optic Neuritis in the Era of NMOSD and MOGAD: A Survey of Practice Patterns in Singapore.

The Optic Neuritis Treatment Trial was a landmark study with implications worldwide. In the advent of antibody testing for neuromyelitis optica spectrum disease (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), emerging concepts, such as routine antibody testing and management, remain controversial, resulting mostly from studies in White populations. We evaluate the practice patterns of optic neuritis investigation and management by neuro-ophthalmologists and neurologists in Singapore. 21-question online survey consisting of 4 clinical vignettes. The survey was sent to all Singapore Medical Council- registered ophthalmologists and neurologists who regularly manage patients with optic neuritis. Forty-two recipients (17 formally trained neuro-ophthalmol-ogists [100% response rate] and 25 neurologists) responded. Participants opted for routine testing of anti-aquaporin-4 antibodies (88.1% in mild optic neuritis and 97.6% in severe optic neuritis). Anti-MOG antibodies were frequently obtained (76.2% in mild and 88.1% in severe optic neuritis). Plasmapheresis was rapidly initiated (85.7%) in cases of nonresponse to intravenous steroids, even before obtaining anti-aquaporin-4 or anti-MOG serology results. In both NMOSD and MOGAD, oral mycophenolate mofetil was the preferred option if chronic immunosuppression was necessary. Steroids were given for a longer duration and tapered more gradually than in idiopathic optic neuritis cases. Serological testing for NMOSD and MOGAD is considered as a routine procedure in cases of optic neuritis in Singapore, possibly due to local epidemiological features of these conditions. Chronic oral immunosuppression is preferred for the long term, but further research is necessary to establish the efficacy and cost-effectiveness of these practices.

Hope for patients with neuromyelitis optica spectrum disorders - from mechanisms to trials.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory CNS disease that primarily manifests as relapsing episodes of severe optic neuritis and myelitis. Diagnosis of NMOSD is supported by the detection of IgG autoantibodies that target the aquaporin 4 (AQP4) water channel, which, in the CNS, is an astrocyte-specific protein. AQP4 antibody binding leads to AQP4 internalization, complement-dependent and antibody-dependent cellular cytotoxicity, and water channel dysfunction. Cumulative attack-related injury causes disability in NMOSD, so the prevention of attacks is expected to prevent disability accrual. Until recently, no regulator-approved therapies were available for NMOSD. Traditional immunosuppressant therapies, including mycophenolate mofetil, azathioprine and rituximab, were widely used but their benefits have not been assessed in controlled studies. In 2019 and 2020, five phase II and III randomized placebo-controlled trials of four mechanism-based therapies for NMOSD were published and demonstrated that all four effectively prolonged the time to first relapse. All four drugs were monoclonal antibodies: the complement C5 antibody eculizumab, the IL-6 receptor antibody satralizumab, the B cell-depleting antibody inebilizumab, which targets CD19, and rituximab, which targets CD20. We review the pathophysiology of NMOSD, the rationale for the development of these mechanism-based drugs, the methodology and outcomes of the five trials, and the implications of these findings for the treatment of NMOSD.

Clinicoradiological comparative study of Aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody associated disease (MOGAD): A prospective observational study and review of literature

Neuromyelitis Optica spectrum disorders (NMOSD) are autoimmune inflammatory central nervous system diseases. NMOSD patients typically have recurrent attacks of severe optic neuritis or/and myelitis with majority of them having autoantibodies against the aquaporin-4 (AQP4). In the recent past, a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations had been demonstrated. MOG-IgG antibody associated disease (MOGAD) is now considered as a disease entity in its own right, distinct from classic MS and from AQP4-IgG-positive NMOSD. Here, we compared the clinical, laboratory, radiological features and treatment outcomes of patients with Aquaporin-4-IgG seropositive NMOSD and MOGAD. Relatively younger age at onset, lesser number of relapses, better response to treatment and favorable clinical outcomes were found in MOGAD group in comparison to AQP4-IgG-positive NMOSD group.

The use of OCT in good visual acuity MOGAD and AQP4-NMOSD patients; with and without optic neuritis.

Myelin oligodendrocyte-antibody-associated disease (MOGAD) often presents with severe optic neuritis (ON) but tends to recover better than in aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-NMOSD). We measured OCT and VEP in MOGAD and AQP4-NMOSD eyes with good visual function, with or without previous ON episodes. Surprisingly, OCT and/or VEPs were abnormal in 84% MOGAD-ON versus 38% AQP4-NMOSD-ON eyes (p = 0.009) with good vision, compared with 18% and 17% respectively of eyes with no previous ON. A sub-group with macular OCT performed as part of a research study confirmed both retinal and macular defects in visually-recovered MOGAD eyes. These findings have implications for investigation and management of MOGAD patients.