Neuroimaging changes in the pregeniculate visual pathway and chiasmal enlargement in Leber hereditary optic neuropathy.

PURPOSE: To describe the pattern of MRI changes in the pregeniculate visual pathway in Leber hereditary optic neuropathy (LHON). METHOD: This retrospective observational study enrolled 60 patients with LHON between January 2015 and December 2021. The abnormal MRI features seen in the pregeniculate visual pathway were investigated, and then correlated with the causative mitochondrial DNA (mtDNA) mutation, the distribution of the MRI lesions and the duration of vision loss. RESULT: The cohort included 48 (80%) males and 53 (88%) had bilateral vision loss. The median age of onset was 17.0 years (range 4.0-58.0). 28 (47%) patients had the m.11778G>A mutation. 34 (57%) patients had T2 hyperintensity (HS) in the pregeniculate visual pathway and 13 (22%) patients with chiasmal enlargement. 20 patients (71%) carrying the m.11778G>A mutation had T2 HS, significantly more than the 14 patients (44%) with T2 HS in the other LHON mutation groups (p=0.039). Furthermore, significantly more patients in the m.11778G>A group (16 patients (57%)) had T2 HS in optic chiasm (OCh)/optic tract (OTr) than the other LHON mutation groups (7 patients (22%), p=0.005). Optic chiasmal enlargement was more common in patients with vision loss duration <3 months compared with those ≥3 months (p=0.028). CONCLUSION: T2 HS in the pregeniculate visual pathway is a frequent finding in LHON. Signal changes in the OCh/OTr and chiasmal enlargement, in particular within the first 3 months of visual loss, were more commonly seen in patients carrying the m.11778G>A mtDNA mutation, which may be of diagnostic significance.

Human subcortical pathways automatically detect collision trajectory without attention and awareness.

Detecting imminent collisions is essential for survival. Here, we used high-resolution fMRI at 7 Tesla to investigate the role of attention and consciousness for detecting collision trajectory in human subcortical pathways. Healthy participants can precisely discriminate collision from near-miss trajectory of an approaching object, with pupil size change reflecting collision sensitivity. Subcortical pathways from the superior colliculus (SC) to the ventromedial pulvinar (vmPul) and ventral tegmental area (VTA) exhibited collision-sensitive responses even when participants were not paying attention to the looming stimuli. For hemianopic patients with unilateral lesions of the geniculostriate pathway, the ipsilesional SC and VTA showed significant activation to collision stimuli in their scotoma. Furthermore, stronger SC responses predicted better behavioral performance in collision detection even in the absence of awareness. Therefore, human tectofugal pathways could automatically detect collision trajectories without the observers' attention to and awareness of looming stimuli, supporting "blindsight" detection of impending visual threats.

Clinical characteristics of radiation-induced optic neuropathy: A single-center retrospective study.

Purpose: To observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION). Methods: We retrospectively reviewed the clinical data of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021. Results: The latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 â€‹± â€‹30.48) months. Optic disc pallor and optic disc edema were found in 27.0% (10/37) and 8.1% (3/37) of the eyes, respectively, within 2 months. After treatment, the best corrected visual acuity (BCVA) was restored in 24.6% (17/69) of the eyes and the final BCVA improved in 13.0% (9/69) of the eyes. An 82.5% (33/40) of the eyes with magnetic resonance imaging (MRI) showed enhancement of the affected optic nerve, mostly (69.7%) in the intracranial segment, and 36.4% (12/33) of the eyes with expansion and T2-high signals also showed enhancement of the affected optic nerve. The superior retinal nerve fiber layer (RNFL) and the outer circle superior quadrant (OS) of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened significantly during the first two months and the inner circle temporal quadrant (IT) of the ILM-RPE layer thickened significantly from the third to sixth month. The RNFL thinned significantly after 6 months except for the temporal quadrant, and the average inner circle superior quadrant (IS) and outer circle of the ILM-RPE layer thinned significantly after 6 months. There was no significant difference between hyperbaric oxygen therapy (HBOT) and high-dose intravenous methylprednisolone (IVMP) therapy in improving BCVA recovery or final BCVA (P â€‹> â€‹0.05). Conclusions: The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning during the first month, thickening from the third to sixth month, and thinning after 6 months. There was a discrete region of enhancement of the optic nerve, often with expansion and high-T2 signals on MRI. HBOT and high-dose IVMP therapy were hardly effective for treating RION in the non-acute stage.

Glial autoantibody prevalence in Chinese optic neuritis with onset after age 45: clinical factors for diagnosis.

Purpose: As glial autoantibody testing is not yet available in some areas of the world, an alternative approach is to use clinical indicators to predict which subtypes of middle-aged and elderly-onset optic neuritis (ON) have manifested. Method: This study was a single-center hospital-based retrospective cohort study. Middle-aged and elderly-onset ON patients (age > 45 years) who had experienced the first episode of ON were included in this cohort. Single- and multi-parametric diagnostic factors for middle-aged and elderly-onset myelin oligodendrocyte glycoprotein immunoglobulin-associated ON (MOG-ON) and aquaporin-4 immunoglobulin-related ON (AQP4-ON) were calculated. Results: From January 2016 to January 2020, there were 81 patients with middle-aged and elderly-onset ON, including 32 (39.5%) AQP4-ON cases, 19 (23.5%) MOG-ON cases, and 30 (37.0%) Seronegative-ON cases. Bilateral involvement (47.4%, P = 0.025) was most common in the MOG-ON group. The presence of other concomitant autoimmune antibodies (65.6%, P = 0.014) and prior neurological history (37.5%, P = 0.001) were more common in the AQP4-ON group. The MOG-ON group had the best follow-up best-corrected visual acuity (BCVA) (89.5% ≤ 1.0 LogMAR, P = 0.001). The most sensitive diagnostic factors for middle-aged and elderly-onset MOG-ON were 'follow-up VA ≤ 0.1 logMAR' (sensitivity 0.89), 'bilateral involvement or follow-up VA ≤ 0.1 logMAR' (sensitivity 0.95), 'bilateral involvement or without neurological history' (sensitivity 1.00), and 'follow-up VA ≤ 0.1 logMAR or without neurological history' (sensitivity 1.00), and the most specific factor was 'bilateral involvement' (specificity 0.81). The most sensitive diagnostic factors for middle-aged and elderly-onset AQP4-ON were 'unilateral involvement' (sensitivity 0.88), 'unilateral involvement or neurological history' (sensitivity 0.91), and 'unilateral involvement or other autoimmune antibodies' (sensitivity 1.00), and the most specific factor was neurological history (specificity 0.98). Conclusion: Based on our cohort study of middle-aged and elderly-onset ON, MOG-ON is less prevalent than AQP4-ON and Seronegative-ON. Using multiple combined parameters improves the sensitivity and negative predictive value for diagnosing middle-aged and elderly-onset MOG-ON and AQP4-ON. These combined parameters can help physicians identify and treat middle-aged and elderly-onset ON early when glial autoantibody status is not available.

Upregulation of C-X-C motif chemokine 12 in the spinal cord alleviated the symptoms of experimental autoimmune encephalomyelitis in Lewis rats.

Background: C-X-C motif chemokine 12 (CXCL12) is a chemokine that performs many functions. Studies have shown that CXCL12 can aggravate inflammatory symptoms in the central nervous system (CNS). Evidence also indicates that CXCL12 can promote the repair of myelin sheaths in the CNS in experimental autoimmune encephalomyelitis (EAE). Here, we investigated the function of CXCL12 in CNS inflammation by upregulating CXCL12 in the spinal cord and subsequently inducing EAE. Materials and methods: CXCL12 upregulation in the spinal cords of Lewis rats was induced by the injection of adeno-associated virus 9 (AAV9)/eGFP-P2A-CXCL12 after intrathecal catheter implantation. Twenty-one days after AAV injection, EAE was induced and clinical score was collected; Immunofluorescence staining, WB and LFB-PAS staining were used to evaluate the effect of CXCL12 upregulation. In the in vitro study, oligodendrocyte precursor cells (OPCs) were harvested, cultured with CXCL12 and AMD3100, and subjected to immunofluorescence staining for functional assessment. Results: CXCL12 was upregulated in the lumbar enlargement of the spinal cord by AAV injection. In each stage of EAE, upregulation of CXCL12 significantly alleviated clinical scores by inhibiting leukocyte infiltration and promoting remyelination. In contrast, the addition of AMD3100, which is a CXCR4 antagonist, inhibited the effect of CXCL12. In vitro, 10 ng/ml CXCL12 promoted the differentiation of OPCs into oligodendrocytes. Conclusion: AAV-mediated upregulation of CXCL12 in the CNS can alleviate the clinical signs and symptoms of EAE and significantly decrease the infiltration of leukocytes in the peak stage of EAE. CXCL12 can promote the maturation and differentiation of OPCs into oligodendrocytes in vitro. These data indicate that CXCL12 effectively promotes remyelination in the spinal cord and decreases the signs and symptoms of EAE.

ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Prevalence of refractive error among Chinese preschool children: The Changsha children eye study.

Purpose: We aimed to investigate the refractive status and prevalence of refractive error, as well as its characteristics in Chinese preschool children aged 1-6 years old. Methods: A population-based cross-sectional study-Changsha Children Eye Study (CCES) was conducted. The prevalence of refractive errors among children aged 1-6 years old from 18 community health service centers was surveyed. A handheld child vision screener, Suowei, was used for examination. Results: A total of 43,105 preschool children were included. The mean spherical equivalent (SE) was 0.42 ± 1.05 D for the right eyes. The mean astigmatism (diopter of cylinder, DC) was -0.83 ± 1.02 D for the right eyes. The magnitude of refractive error was lower in older children, indicating the ongoing of the emmetropization during the 1-6-year-old children. The prevalence of myopia (SE ≤ -1.00 D), hyperopia (SE ≥ +2.00 D) and astigmatism (DC ≥1.50 D) was 2.94, 13.8 and 17.6%, respectively. The prevalence of myopia decreased with the increase of age between the six age groups (P < 0.001). The prevalence of hyperopia was lower in 5-6 years old, whereas, the prevalence of myopia was slightly higher at this period of time. With-the-rule (WTR) astigmatism (+ cylinder axis 90° ± 15°) was the most prevalent type of astigmatism than against-the-rule (ATR) astigmatism (+ cylinder axis 180° ± 15°) and oblique (OBL) astigmatism (X 2 = 209.5, P < 0.001). The binary logistic regression model showed that older age and suffering astigmatism were independently associated with the development of myopia. In addition, there was no significant gender difference in the prevalence of myopia, emmetropia, and hyperopia. Conclusions: Our population-based cross-sectional study investigated the prevalence of myopia, hyperopia, and astigmatism in preschool children aged 1-6 years old. The distribution of the refractive error was disperse in the younger group and gradually turned more centralized in older group. Similar to hyperopia, with age increased, the prevalence of myopia was lower in preschool children younger than 5 years old and then slightly increased at 5-6 years, which may indicate an early sign of myopia in school-age children. Therefore, we emphasize that more attention should be given to the children at this age.

MOG antibody prevalence in adult optic neuritis and clinical predictive factors for diagnosis: A Chinese cohort study.

OBJECTIVE: Because AQP4/MOG antibody testing is not available in some parts of the world and there are often delays in obtaining results, it is particularly important to use clinical factors to predict the subtypes of adult optic neuritis (ON). METHODS: This was a single-center retrospective cohort study. RESULTS: The final analysis included 249 adult patients presenting with the first ON attack during January 2016 to January 2020. These included 109 (43.8%) AQP4-ON cases, 49 (19.7%) MOG-ON cases, and 91 (36.5%) Seronegative-ON cases. The proportion of optic disk swelling (ODS) and bilateral involvement in MOG-ON group was significantly higher than in the other two subgroups (P = 0.029, 0.001). The MOG-ON group had the best follow-up BCVA (P = 0.003). To predict adult AQP4-ON, unilateral involvement (sensitivity 0.88, NPV 0.77) was the most sensitivity predictors, while neurological history (specificity 0.96, PPV 0.65) and concomitant other autoimmune antibodies (specificity 0.76, PPV 0.65) were the most specific predictors. Using the parallel test 'unilateral or other autoimmune antibodies' increased sensitivity to 0.95, with an optimal NPV of 0.88. To predict adult MOG-ON, the most sensitive clinical characteristics were ODS (sensitivity 0.79, NPV 0.88), and follow-up VA ≤0.1logMAR (sensitivity 0.78, NPV 0.92), whereas the most specific values were prior neurological history or bilateral involvement, with specificities of 0.92 and 0.82, respectively. The sensitivity increased to 0.94, 0.97, and 0.97 when using the parallel clinical factors of 'bilateral or ODS or relapse', 'bilateral or ODS or follow-up VA ≤0.1logMAR', and 'ODS or follow-up VA ≤0.1logMAR', and the corresponding NPV (0.94, 0.97 vs 0.98). CONCLUSION: The proportion of MOG-ON (19.7%) was less than that of AQP4-ON and Seronegative-ON. Moreover, MOG-ON had a better prognosis and was more likely to be associated with ODS or bilateral involvement. The use of parallel clinical parameters improved the sensitivity for the diagnosis of adult MOG-ON and AQP4-ON.

Serial analyses of clinical spectra and outcomes in Chinese women with pregnancy-induced optic neuritis.

Objective: This study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON). Methods: We analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019. Results: A total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths. Conclusion: The significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

Leber's hereditary optic neuropathy companied with multiple-related diseases.

Objective: To elucidate the clinical, radiologic characteristics of Leber's hereditary optic neuropathy (LHON) associated with the other diseases. Materials and methods: Clinical data were retrospectively collected from hospitalized patients with LHON associated with the other diseases at the Neuro-Ophthalmology Department at the Chinese People's Liberation Army General Hospital (PLAGH) from December 2014 to October 2018. Results: A total of 13 patients, 24 eyes (10 men and 3 women; mean age, 30.69 ± 12.76 years) with LHON mitochondrial DNA (mtDNA) mutations, were included in the cohort. 14502(5)11778(4)11778 &11696(1)12811(1)11696(1)3460(1). One patient was positive for aquaporin-4 antibody (AQP4-Ab), and two were positive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab). Three patients were associated with idiopathic optic neuritis (ON). Two patients were with compression optic neuropathy. Three patients were with the central nervous system (CNS) diseases. One patient was with proliferative diabetic retinopathy (PDR) and one with idiopathic orbital inflammatory syndrome (IOIS). At the onset, visual acuity (VA) in eighteen eyes was below 0.1, one eye was 0.5, five eyes were above 0.5, while VA in sixteen eyes was below a 0.1 outcome, three eyes experienced moderate vision loss. MRI images showed T2 lesions and enhancement in nine patients who received corticosteroids treatment; additional immune modulators treatment was performed on two patients. None of the patients had relapse during the follow-up time. Conclusion: Leber's hereditary optic neuropathy can be accompanied with multiple-related diseases, especially different subtypes of ON, which were also exhibited with IOIS and compression optic neuropathy for the first time in this cohort. This condition may be a distinct entity with an unusual clinical and therapeutic profile.

Clinical Characteristics of Methanol-Induced Optic Neuropathy: Correlation between Aetiology and Clinical Findings.

Purpose: To show the clinical characteristics, identify the magnetic resonance imaging (MRI) and optical coherence tomography (OCT) features, and observe the visual outcome of methanol-induced optic neuropathy. Methods: Clinical data were retrospectively collected from in-patients diagnosed with methanol-induced optic neuropathy in the Neuro-Ophthalmology Department of the Chinese People's Liberation Army General Hospital from January 2016 to January 2021. Results: Eight patients were included in this study. The exposure time was 6-34 h for ingestion, 3-4 months for inhalation, and more than ten years for skin absorption. All patients demonstrated bilateral acute visual impairment. Seven of eight patients had other accompanying systemic symptoms. Seven of eight patients demonstrated optic nerve lesions in MRI, and five presented with a hyperintense T2 signal in a "central" type. OCT showed the macular ganglion cell layer and inner plexiform layer (mGCL-IPL) thinning before the peripapillary retinal nerve fiber layer (pRNFL) thinning. The visual improvement was achieved transiently for seven of eight patients after treatment. One patient with a mitochondrial DNA mutation maintained a bilateral no-light perception (NLP) from the onset to the last visit. All patients had poor visual prognoses, with either light perception or NLP. Conclusions: Methanol-induced optic neuropathy is a rare bilateral optic neuropathy with a poor visual outcome. A centrally hyperintense T2 signal of the optic nerve is common in methanol-induced optic neuropathy. The thinning of the mGCL-IPL is more sensitive than that of the pRNFL for early diagnosis. A mitochondrial genetic defect may be a predisposing factor for methanol-induced optic neuropathy.

Update on glial antibody-mediated optic neuritis.

Optic neuritis (ON) refers to inflammatory demyelinating lesions of the optic nerve, which can cause acute or subacute vision loss and is a major cause of vision loss in young adults. Much of our understanding of typical ON is from the Optic Neuritis Treatment Trial. Glial autoantibodies to aquaporin-4 immunoglobulin (AQP4-IgG) and myelin oligodendrocyte glycoprotein immunoglobulin (MOG-IgG) are recently established biomarkers of ON that have revolutionized our understanding of atypical ON. The detection of glial antibodies is helpful in the diagnosis, treatment, and follow-up of patients with different types of ON. AQP4-IgG and MOG-IgG screening is strongly recommended for patients with atypical ON. Research on the pathogenesis of NMOSD and MOGAD will promote the development and marketing of targeted immunotherapies. The application of new and efficient drugs, such as the selective complement C5 inhibitor, IL-6 receptor inhibitor, B cell-depleting agents, and drugs against other monoclonal antibodies, provides additional medical evidence. This review provides information on the diagnosis and management of glial antibody-mediated ON.

Longitudinal Changes in Refractive Error Among Preschool Children Aged 1-6 Years: The Changsha Children Eye Study.

Purpose: To investigate the longitudinal changes in refractive error of preschool children and explore the factors related to these changes and the timing of intervention. Methods: The refractive data of preschool children aged 1-6 years were collected from 16 community Health Service Centers in Changsha during April 2016 to July 2019 for the retrospective cohort study. The refractive data of each participant was measured with a hand-held vision screener without cycloplegia. A follow-up for all the included participants was performed. The spherical equivalent change was calculated, subsequently, an analysis of risk factors related to the change was performed. Results: Four thousand nine hundred twenty-one cases were included in the study with the follow-up for 1-2 years. The refractive status was found smoothly changed in 67.8% of children. The overall initial SE was 0.62 ± 1.13 D, and the average SE change was -0.20 ± 1.23 D per year. However, profound myopic shift was observed in 32.2% of children. The change of SE in 3-year-old group is most overt. The proportions of 1-6 years old who showed moderate and severe myopic shift (SE change ≥-1.00 D) were 21.6, 18.9, 28.2, 25.5, 13.4, and 10%, respectively. At the first visit, the younger children with greater hyperopic state exhibited more noticeable myopic shift, no significant difference was found in gender. Conclusion: The shift from hyperopia to myopia in preschool children is smooth, with -0.20D change on average per year. We suggest that an optometry screening should start at 3-year-old to track children's refractive status. We recommend that preschool children whose SE changes more than -1.00 D per year go to the ophthalmology department for further examination. Our study also found that at the first visit, the younger the child is and the more positive initial SE is, the degree of shift of myopia is greater.

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). METHODS: A 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. RESULTS: A 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. CONCLUSION: PE 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.

Incidence of neuromyelitis optica spectrum disorders in China: a large cohort study using claim data.

OBJECTIVES: Population-based studies estimating the incidence of neuromyelitis optica spectrum disorders (NMOSDs) in Asia are limited, and the relationship between latitude and incidence has been scarcely investigated. We aimed to estimate the incidence of NMOSDs in Chinese adults and explore their relationship to latitude. DESIGN: Cohort study based on data from the Urban Employee Basic Medical Insurance in China. PARTICIPANTS: 177 million people were followed from 2016 to 2017 in 20 provinces. PRIMARY OUTCOME MEASURES: The incidence rate was estimated by Poisson distribution and reported as age-adjusted and sex-adjusted rates using the standard population. RESULTS: There were 1313 incident NMOSD cases, with an overall incidence of 0.41 (95% CIs: 0.39 to 0.43) per 100 000 person-years. The incidence in females was higher, with a female-to-male IRR of 4.52. The incidence increased with age, peaking at 55-64 years in females and 65-74 years in males and then decreasing thereafter. The female-to-male IRRs were higher in those <55 years. The association between latitude and incidence was not statistically significant. CONCLUSIONS: The incidence of NMOSD in Chinese adults was 0.41 per 100 000 person-years. There is no latitude gradient observed. Sex and age influence the risk of NMOSD, suggesting the role of genetic, hormonal and other related factors in the pathophysiology.

Vision Prognosis and Associated Factors of Optic Neuritis in Dependence of Glial Autoimmune Antibodies.

PURPOSE: To assess the visual prognosis of optic neuritis (ON) in dependence of the glial autoimmune antibody status and associated factors. DESIGN: Longitudinal observational cohort study. METHODS: Patients with ON and measurements of serum concentrations of glial autoantibodies were consecutively and longitudinally examined with a minimal follow-up of 3 months. Patients with multiple sclerosis and double seronegative results were excluded. RESULTS: The study included 529 patients (aquaporin-4 immunoglobulin [AQP4-IgG] seropositive, n = 291; myelin oligodendrocyte glycoprotein immunoglobulin [MOG-IgG] seropositive, n = 112; double-seronegative, n = 126) with 1022 ON episodes (AQP4-IgG seropositive, n = 550; MOG-IgG seropositive, n=254; double-seronegative, n = 218). Prevalence of severe vision loss (best-corrected visual acuity [BCVA] ≤20/200 at the end of follow-up) was higher (P < .001) in the AQP4-IgG group (236/550; 42.9%) than in the seronegative group (68/218; 31.2%) and in the MOG-IgG group (15/254; 5.9%). Prevalence of good vision recovery (BCVA≥20/40) was higher (P < .001) in the MOG-IgG group (229/254; 90.2%) than in the seronegative group (111/218; 50.9%) and in the AQP4-IgG group (236/550; 42.9%). In multivariable logistic analysis, higher prevalence of severe vision loss was associated with AQP4-IgG seropositivity (odds ratio [OR] 1.66; 95% CI 1.14, 2.43; P = .008), male sex (OR 1.97, 95% CI 1.33, 2.93; P < .001), age at ON onset >45 years (OR 1.93, 95% CI 1.35, 2.77; P < .001), nadir vision ≤20/200 (OR 14.11, 95% CI 6.54, 36.93; P < .001), and higher number of recurrences (OR 1.35, 95% CI 1.14, 1.61; P = .001). Higher prevalence of good vision outcome was associated with MOG-IgG seropositivity (OR 8.13, 95% CI 4.82, 14.2; P < .001), age at ON onset <18 years (OR 1.78, 95% CI 1.18, 2.71; P = .006), nadir visual acuity ≥20/40 (OR 4.03; 95% CI 1.45, 14.37; P = .015), and lower number of recurrences (OR 0.60; 95% CI 0.50, 0.72; P < .001). CONCLUSION: Severe vision loss (prevalence in the AQP4-IgG group, MOG-IgG group, and seronegative group: 42.9%, 5.9%, and 31.2%, respectively) was associated with AQP4-IgG seropositivity, male gender, older age at onset, worse nadir vision, and higher number of recurrences.

Efficacy and safety of monoclonal antibodies in neuromyelitis optica spectrum disorders: A survival meta-analysis of randomized controlled trials.

Background: Monoclonal antibodies such as rituximab (RTX), eculizumab, inebilizumab, satralizumab, and tocilizumab have been found to be effective therapies for neuromyelitis optica spectrum disease â€‹(NMOSD) in several clinical randomized controlled trials. Objective: The purpose of this meta-analysis of randomized controlled trials was to assess the efficacy and safety of monoclonal antibodies in the treatment of NMOSD. Methods: We searched the following databases for relevant English language literature from the establishment of the database to June 2021: PubMed, Embase, Cohorane Library, the Central Register of Controlled Trials (CENTRAL), and Web of Science. Randomized controlled trials of monoclonal antibodies were the targets of the review. Results: We included seven trials containing 775 patients (485 in the monoclonal antibody group and 290 in the control group). Patients in the monoclonal group (HR 0.24, 95% CI: 0.14 to 0.40, P â€‹< â€‹0.00001), as well as patients with seropositive AQP4-IgG (HR 0.18, 95% CI: 0.11 to 0.29, P â€‹< â€‹0.00001), both had a higher free recurrence rate than that in the control group. In the first year (HR 0.25, 95% CI: 0.09 to 0.71, P â€‹= â€‹0.009) and the second year (HR 0.32, 95% CI: 0.13 to 0.81, P â€‹= â€‹0.02), no relapses were documented. The average changes of the expanded disability status scale (EDSS) score decreased by 0.29 (95% CI: -0.09 to 0.51, P â€‹= â€‹0.005). Upper respiratory tract infection (OR 1.52, 95% CI: 0.76 to 3.04, P â€‹= â€‹0.24), urinary tract infection(OR 0.79, 95% CI: 0.51 to 1.21, P â€‹= â€‹0.27), and headache (OR 1.30, 95% CI: 0.78 to 2.17, P â€‹= â€‹0.31) were three most frequent adverse reactions. Conclusions: Monoclonal antibodies are particularly effective treatments in avoiding recurrence for NMOSD patients, according to this meta-analysis. The associated adverse responses are not significantly different from those seen with traditional immunosuppressants.

Clinical predictive factors for diagnosis of MOG-IgG and AQP4-IgG related paediatric optic neuritis: a Chinese cohort study.

BACKGROUND: Different glial-autoantibodies-related paediatric optic neuritis (ON) are associated with different clinical characteristics and prognosis that require different treatments. Because glial autoantibody detection is not available in some parts of the world and there is often a delay in obtaining results, clinical factors that can be used to predict the subtype of paediatric ON are needed. METHODS: This was a single-centre retrospective cohort study. Children who presented with their first ON attack and with complete clinical data were included in the analysis. Single and multiple parameters for predicting paediatric myelin oligodendrocyte glycoprotein immunoglobin-associated ON (MOG-ON) and aquaporin-4 immunoglobin-related ON (AQP4-ON) were calculated. RESULTS: 78 paediatric patients had their first ON attack from January 2016 to December 2019, of whom 69 were included in the final analysis, including 33 MOG-ON cases, 17 AQP4-ON cases and 19 Seronegative-ON cases. For predicting paediatric MOG-ON, the most sensitive predictors were 'male or optic disc swelling (ODS) or bilateral' (sensitivity 0.97 (95% CI 0.82 to 1.00)) and 'follow-up visual acuity (VA) ≤0.1 logMAR or ODS' (sensitivity 0.97 (95% CI 0.82 to 1.00)), and the most specific factor was 'Age ≤11 y and simultaneous CNS involvement' (specificity 0.97 (95% CI 0.84 to 1.00)). For predicting paediatric AQP4-ON, the most sensitive predictor was 'Female or without ODS' (sensitivity 1.00 (95% CI 0.77 to 1.00)), and the most specific factors were Neurological history (sensitivity 0.94 (95% CI 0.83 to 0.98)) and follow-up VA >1.0 logMAR (sensitivity 0.96 (95% CI 0.86 to 0.99)). CONCLUSION: According to our data from a Chinese paediatric cohort, using multiple parameters increases the sensitivity and specificity of diagnosing paediatric MOG-ON and AQP4-ON. These can assist clinicians in diagnosing and treating paediatric ON when glial autoantibody status is not available.