Neuromyelitis optica spectrum disorder (NMOSD) is a kind of demyelinating disease of central nervous system which mainly affect optic nerve and spinal cord. Because of its serious blindness and disability, how to effectively prevent relapse has become the focus of ophthalmologists. With the deep understanding of the pathogenesis and the progress of scientific and technological means, more and more monoclonal antibodies(mAb) continue to enter clinical trials. B cell surface antigen CD20 blocker, rituximab, has become a first-line drug for the treatment of NMOSD. CD19 blocker, inebilizumab, can reduce the recurrence and disability of NMOSD patients. The addition of interleukin 6 receptor blocker, satralizumab, and complement C5 inhibitor, eculizumab, reduce the recurrence. Some mAbs such as natalizumab and alemtuzumab may not be effective for the treatment of NMOSD. The expansion of mAb treatment indications and the launch of new drugs still require more clinical trials which are large-scale and international cooperation. At the same time, its potential adverse events and cost issues cannot be ignored.
ObjectiveTo observe the changes of serum cytokines in patients with neuromyelitis optic neuromyelitis optic spectrum disorder (NMOSD) associated optic neuritis (NMOSD-ON) before and after intravenous methylprednisolone pulse (IVMP) treatment. MethodsA prospective clinical study. From November 2020 to December 2021, 24 NMOSD-ON patients who visited the Neuro-Ophthalmology Clinic of Beijing Tongren Hospital Affiliated to Capital Medical University were included. Among them, 9 patients were male; 15 patients were female. According to the detection results of aquaporin 4 (AQP4) immunoglobulin G (IgG) antibody (AQP4-IgG) in peripheral blood, the patients were divided into AQP4-lgG positive group and AQP4-lgG negative group, which were 10 and 14 cases respectively. Twenty healthy volunteers were selected as control group. Age (F=0.639) and sex (χ2=2.373) composition ratio of the three groups were compared, the difference were not statistically significant (P=0.504, 0.333). All patients were treated with 500 mg/d or 1 000 mg/d IVMP. Peripheral venous blood of all subjects, and quantitatively analyze interferon-gamma (IFN-γ), interleukin (IL)- 4, IL-31, IL-33, IL-17A, IL-6, IL-21, IL-23, IL-10, tumor necrosis factor (TNF)-α level in serum with Luminex FLEX MAP 3D liquid-phase suspension chip detection system were collected. The differences among groups were analyzed by one-way ANOVA and Kruskal Wallis H test. ResultsBefore IVMP treatment, serum IL-17A concentrations in AQP4-lgG positive group, AQP4-lgG negative group and control group were 2.39, 2.17 and 1.97 pg/ml, respectively. TNF-α concentrations were 5.60, 4.17 and 5.89 pg/ml, respectively. Compared with control group, serum IL-17A concentration in AQP4-IgG positive group was increased, while TNF-α concentration in AQP4-IgG negative group was decreased, with statistical significance (H=12.720, 10.900; P=0.040, 0.039). The levels of IL-17A, IL-6 and other cytokines did not change significantly. After IVMP treatment, serum IL-6 in AQP4-lgG positive group and AQP4-lgG negative group were 0.72 pg/ml and 0.73 pg/ml, respectively. TNF-α concentrations were 4.17 pg/ml and 3.88 pg/ml, respectively. IFN-γ concentrations were 2.15 pg/ml and 2.55 pg/ml, respectively. Compared with before treatment, serum levels of IL-6, TNF-α and IFN-γ in AQP4-lgG positive patients were significantly decreased, with statistical significance (Z=－2.668, －2.547, －2.201; P=0.008, 0.011, 0.028). Serum levels of IL-6 and TNF-α were significantly decreased in AQP4-lgG negative patients, and the difference was statistically significant (Z=－2.501, －1.978; P=0.012, 0.048). ConclusionGlucocorticoid may play a therapeutic role by affecting the levels of serum IL-6, TNF-α, IFN-γ in patients with NMOSD-ON.
ObjectiveTo observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients, and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.MethodsA retrospective case study. From September 2009 to March 2014, 132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study. Among the patients, 74 patients (56.06%) were involved in optic nerve for the first time, among which 63 patients (47.72%) were involved in optic nerve alone, and 11 patients (8.33%) were involved in optic nerve and spinal cord at the same time. The recurrence rate was 62.88% (twice or more). All patients underwent BCVA, slit lamp microscope, fundus examination, thyroid function, sex hormones, and serum AQP-4Ab detection. BCVA was recorded at admission and before discharge from hospital, and worse BCVA was recorded in binocular patients. The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.ResultsAmong the 74 patients with optic nerve involved in the first onset, 50 patients with BCVA＜0.1 at the initial diagnosis (67.57%); AQP-4Ab positive was found in 56 patients, which including 13, 9 and 34 patients of AQP-4Ab titer 5 - 60, 61 - 100 and ＞100 RSRU/ml. After 2 weeks of treatment, BCVA improved in 40 patients (71.42%), including 11 (84.62%), 6 (66.67%) and 23 (67.64%) of AQP-4Ab titer 5 - 60, 61 - 100 and ＞ 100 RSRU/ml. Among 132 patients, 98 patients (74.24%) were AQP-4Ab positive. There were 73 patients (55.30%) with abnormal immune rheumatoid index.ConclusionsThe optic nerve is involved in 56.06% patients with NMO for the first time, and 67.57% of the patients had poor vision with BCVA＜0.1. BCVA prognosis is better in patients with serum AQP-4Ab titer of 5 - 60 RSRU/ml.
Plasma exchange (PE) is a therapeutic blood component replacement method. The blood of patients is first separated into plasma and blood cell components using a blood cell separator in vitro, the plasma containing harmful pathogenic substances is then discarded and replaced with the same volume of exchange solution. Finally the separated blood cells together with the exchange solution are returned back to the blood circulation of patients. By reducing the circulating antibodies, abnormal plasma proteins or cytokines and other pathogenic molecules, PE can block the disease process. PE has a good therapeutic effect on neuromyelitis optica-related optic neuritis (NMO-ON), which shows resistant to glucocorticoid therapy for the first onset. The American Society for Apheresis guideline evaluates PE for acute optic neuritis as a recommended grade 1B, type II indication. In the implementation of PE treatment for NMO-ON and other diseases, indications and contraindications should be strictly adhered to the guideline, treatment procedures and protocols should be optimized, common adverse events and its prevention and management should be known and alerted. It is important to conduct multi-center clinical cooperation and a high standard clinical randomized controlled study, to find out the optimal time window, the best protocol, and the associated factors for the efficacy and prognosis of PE in NMO-ON.
The first edition of “The Chinese expert consensus on the diagnosis and treatment of optic neuritis” have been published in Chinese Journal of Ophthalmology in 2014. Seven years later, more evidence-based medicine has been accumulated in the treatment of optic neuritis. It is necessary to update or formulate guidelines to guide clinical practice. Based on the methods and procedures for developing evidence -based guidelines, Neuro-Ophthalmology Group of Ophthalmology Branch of Chinese Medical Association and Evidence-based Medicine Centre of Lanzhou University/World Health Organization Collaborating Centre for Guideline Implementation and Knowledge Translation created the first “An evidence-based guideline for the diagnosis and treatment of demyelinating optic neuritis in China (2021)”, which aimed to improve the level of clinical diagnosis and treatments of demyelinating optic neuritis. This guideline proposes a new subtype classification of demyelinating optic neuritis to guide precision treatment. It also gives new suggestions about clinical treatment hotspots in the acute and chronic phases, including the application of immunosuppressants and rituximab and other biological agents.
ObjectiveTo observe and analyze the subtype-specific prognostic factors for visual recovery in patients with demyelinating optic neuritis (DON) after glucocorticoid pulse therapy. MethodsA retrospective cohort study. A total of 195 patients (249 eyes) with DON diagnosed by ophthalmology examination at Department of Ophthalmology, Xi'an People's Hospital (Xi'an Fourth Hospital) from January 2021 to December 2024 were included in the study. According to the results of serum antibody detection and clinical diagnostic criteria, the patients were divided into the neuromyelitis optica spectrum disorder (NMOSD)-associated optic neuritis (ON) (NMOSD-ON) group, the myelin oligodendrocyte glycoprotein antitide-associated ON (MOG-ON) group, and the double antibody negative ON group. They were 51 cases (58 eyes), 72 cases (103 eyes), and 72 cases (88 eyes) respectively. Baseline clinical data, imaging characteristics, and treatment protocols were collected. The primary endpoints were complete visual recovery [best-corrected visual acuity (BCVA) ≥1.0] and moderate recovery (BCVA ≥0.5) at 3 months post-onset. Multivariate logistic regression was used to identify independent prognostic factors for visual outcomes within each subtype. ResultsAt 3 months post-onset, complete recovery rates were 9 (15.5%, 9/58) in the NMOSD-ON group, 64 (62.1%, 64/103) in the MOG-ON group, and 31 (35.2%, 31/88) in the double-seronegative ON group. The results of multivariate regression analysis showed that age [odds ratio (OR) =0.901, 95% confidence interval (CI) 0.854-0.950, P＜0.001] and peak visual acuity (OR=0.311, 95%CI 0.147-0.660, P=0.002) and the involvement of optic nerve length ≥1/2 (OR=3.849, 95%CI 1.083-13.682, P=0.037) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the double antibody negative ON group. Age (OR=0.958, 95%CI 0.933-0.983, P=0.001) was the only influencing factor for the complete recovery of visual acuity in the affected eyes of the MOG-ON group. Peak visual acuity (OR=0.288, 95%CI 0.090-0.927, P=0.037) and optic nerve involvement length ≥1/2 (OR=19.974, 95%CI 1.905-209.559, P=0.013) were the influencing factors for the complete recovery of visual acuity in the affected eyes of the NMOSD-ON group. Age (OR=0.936, 95%CI 0.890-0.983, P=0.009), time from onset to intravenous infusion of methylprednisolone sodium succinate intervention (OR=0.854, 95%CI 0.759-0.961, P=0.009), optic disc edema (OR=4.405, 95%CI 1.108-17.512, P=0.035) and peak visual acuity (OR=0.13, 95%CI 0.046-0.365, P＜0.001) were the influencing factors for the moderate recovery of visual acuity in the affected eyes of the double antibody negative ON group. Peak visual acuity was the only influencing factor for the moderate recovery of visual acuity in the MOG-ON group (OR=0.060, 95%CI 0.010-0.352, P=0.002) and the NMOSD-ON group (OR=0.163, 95%CI 0.053-0.500, P=0.001). ConclusionsThe prognostic factors for visual recovery in patients with DON after glucocorticoid pulse therapy are subtype-specific. Peak visual acuity is a common predictor for all subtypes. For NMOSD-ON and double antibody-negative ON, attention should be paid to the length of optic nerve lesions. MOG-ON is age-related. Early intravenous infusion of methylprednisolone sodium succinate for double antiantibody negative ON is more likely to achieve moderate vision recovery.
Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord. Neuromyelitis optica related optic neuritis (NMO-ON) is a common neuro-ophthalmic disease which often results in permanent blindness. The discovery of aquaporin 4 antibodies confirms that neuromyelitis optica is a distinct disease entity different from multiple sclerosis. In patients with NMO-ON, the correct therapeutic approach has to recognize two distinct clinical situations: treatment of the acute attacks and prevention of the relapses. With the in-depth study of the pathogenesis of NMOSD, new treatments are emerging in different targets of the disease. This review gives an update of latest treatment of NMO-ON, emphasizing both current situation and future immunotherapy strategies.
Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
Objective To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD). Methods Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed. Results Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P＞0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048). Conclusions The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis.
Objective To observe the clinical features and visual function of recurrent neuromyelitis optica (NMO). Methods Thirty-four patients with NMO were enrolled in this retrospective case series study. The patients included two males and 32 females. The average first onset age was (35.03plusmn;14.56) years old and the average recurrent rate were (4.24plusmn;2.45) times. The recurrent rate of optic neuritis (ON) ranged from two to 12 times. The recurrent rate of ON was two times in 15 eyes of 10 patients, ge;three times in 37 eyes of 24 patients. Vision acuity, direct ophthalmoscope, fundus pre-set lens examination, visual field and visual evoked potential (VEP) were evaluated. Clinical features were observed. The abnormal rate of optic nerve including optic edema and atrophy; abnormal rate of visual field including decreasing retinal sensitivity, central and paracentral scotoma, ring scotoma, half field defects, tunnel visual field, visual field centrality constriction; abnormal rate of VEP including Prolonged latent phase and/or decreasing amplitude of P100 wave from patients of first episode or recurrence was analyzed. Serum NMO-IgG was detected from 28 patients by indirect immunofluorescence technique to observe its positive rate. Results All patients were characterized by repeated episodes of ON and myelitis. The main clinical feature of ON was visual loss, and the main clinical features of myelitis included sensory disability, dyskinesia and vesicorectal disorder. Blindness rate was 41.67% after the first attack of ON, 33.33% after two relapses, and 64.86% after ge; three relapses. The difference of blindness rate between first attack and two episodes was not significant (chi;2=0.270,P=0.603). However, the blindness rate in patients having ge; three episodes was significantly higher than those having two episodes (chi;2=4.300,P=0.038). With recurrence rate increasing, the abnormal rate of the optic nerve (chi;2=6.750,P=0.034）and VEP（chi;2=6.990,P=0.030）increased. But the abnormal rate of visual field did not increase along with recurrent rate (chi;2=0.660,P=0.718). Seropositive rate of NMO-IgG did not differ significantly between patients with first attack ON and that with recurrent ON (chi;2=1.510,P=0.470). But the seropositive patients had significantly higher bilateral blindness rate than seronegative patients (chi;2=5.063,P=0.027). Conclusions NMO are characterized by recurrent ON and myelitis. Visual loss, sensory disability, dyskinesia and vesicorectal disorder are the main clinical features. With recurrence rate increasing, the blindness rate, abnormalities the optic nerve and the abnormity rate of VEP increase. Seropositive recurrent NMO patients have higher bilateral blindness rate than seronegative patients.