Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder (NMOSD). Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was (26.2±12.0) years. Duration of disease was 2.3 - 25.8 years, the mean duration was (9.2±5.9) years. Best corrected vision activity (BCVA), expanded disability status scale (EDSS), annualized relapsing rate (ARR) were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was (28.4±4.9) months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye (t=4.256), ARR (t=2.900), EDSS (t=4.620) with the significant differences (P＜0.05).Thirteen relapses in 9 patients were observed. B lymph cells were more than 0.01% in all relapses. There was no significant difference on the BCVA in better eye (t=1.840, P＞0.05). There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age (t=0.67, P=0.51), whether underwent plasma exchange treatment (χ2=1.61, P＞0.05), with/without auto-immune antibody ratio (χ2=1.61, P＞0.05). Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated.
Objective To observe the effect of intravenous methylprednisolone (IVMP) pulse therapy on the best corrected visual acuity (BCVA) and the number of relapses in patients with neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) after total IVMP dose. MethodsA retrospective clinical study. From March 2020 to February 2023, 23 patients of 27 eyes with NMOSD-ON in Shanxi Eye Hospital were included in the study. BCVA examinations were performed on all affected eyes using the international standard visual acuity chart, which was statistically converted into logMAR visual acuity. Serum aquaporin-4 antibody (AQP4-IgG) was detected by indirect immunofluorescence assay based on cell detection technology in all patients. According to Guideline for the diagnosis and treatment of NMOSD spectrum disorders in China (2021 edition), patients were given IVMP impact therapy. Among them, 18 and 5 patients received 1 000 and 500 mg/d IVMP pulse therapy respectively for 3-5 consecutive days, followed by a reduction to 500 or 250 mg/d for 2-3 consecutive days. The average total IVMP dose during the treatment was 4 500 mg (1 500-5 250 mg). The changes in BCVA at 1 week, 1 month, 3 months, and 6 months after treatment were observed for the initial and post-treatment BCVA of ≤0.1, ＞0.1-<0.5, and ≥0.5. The changes of BCVA at 1 week and 1, 3 and 6 months after treatment were observed. The comparison of BCVA between different age, disease duration, and IVMP total dose conditions was performed using the Mann-Whitney U test. The comparison of BCVA between different relapse times was performed using the Kruskal-Wallis test. The influence of IVMP total dose on the number of relapses during the 6-month follow-up was analyzed using χ2 test. The factors affecting BCVA ≥0.5 after 6 months of IVMP treatment were analyzed by logistic regression, and the correlation between ΔlogMAR BCVA and IVMP pulse total dose was analyzed by Spearman correlation. ResultsIn 23 cases with 27 eyes, there were 3 males and 20 females. The median age was 35 years. The median duration of illness was 5 days. There were 21 (91.30%, 21/23) positive and 2 (8.70%, 2/23) negative cases of AQP4-IgG, respectively. There were 3 cases (13.04%, 3/23) with the first course of disease and 4 eyes (14.81%, 4/27). There were 20 cases (86.96%, 20/23) with recurrence course and 23 eyes (85.19%, 23/27). The median time from initial onset to the initiation of corticosteroid treatment was 7 days. During the 6-month follow-up after treatment, 5 patients (21.74%, 5/23) relapsed in 6 eyes (22.22%, 6/27), all of which were patients with initial relapse course. Among them, recurred 1 or ≥2 times in 4 (66.67%, 4/6) and 2 (33.33%, 2/6) eyes respectively. BCVA≤0.1, ＞0.1-＜0.5, ≥0.5 in 20, 4, 3 eyes and 3, 13, 11 eyes at the beginning and 6 months after treatment, respectively. There was significant difference in the number of eyes with BCVA≤0.1, ＞0.1-＜0.5 and ≥0.5 at different time after treatment (χ2=40.772, P＜0.001). The treatment effect of female patients was better than that of male patients. The patients with initial BCVA≥0.1 had more increased eye number of BCVA than those with BCVA＜0.1, the patients with first course of disease had more increased eye number of BCVA than those with recurrent course of disease, and the patients with total dose of IVMP ＞4 500 mg had less increased eye number of BCVA than those with total dose ≤4 500 mg. The differences were statistically significant (Z=?2.449, ?2.904, ?2.485, ?2.286; P=0.014, 0.004, 0.013, 0.022). Logistic regression analysis showed that the higher the initial BCVA≤0.1 and the total impact dose of IVMP, the lower the possibility of obtaining BCVA≥0.5 after treatment (odds ratio=0.069, 0.899; 95% confidence interval 0.010-0.463, 0.798-0.998; P=0.006, 0.020). Spearman correlation analysis showed that ΔlogMAR BCVA was negatively correlated with total impact dose of IVMP (rs=?0.472, P=0.013). There was no significant difference in the number of recurrence after different total doses of IVMP (P＞0.05). ConclusionsIVMP total dose ≤4 500 mg can achieve better BCVA prognosis compared with IVMP total dose ＞4 500 mg. IVMP total dose has no effect on the number of recurrences after treatment.
Neuromyelitis optica-related optic neuritis (NMO-ON) is a kind of severe optic nerve disease, which always leads to replase, poor prognosis, and even blindness. Aquaporin 4 antibody (AQP4-IgG) is the main diagnostic biomarker for neuromyelitis optica with high specificity. Serum myelin oligodendrocyte glycoprotein antibody (MOG-IgG) is helpful for the diagnosis of AQP4-IgG negative patients. The study of biomarkers is helpful to deeply understand the pathogenesis of NMO-ON, help the diagnosis of the disease, and finally make precise treatment. Orbital MRI can help to differentiate MOG-IgG positive from AQP4-IgG positive neuromyelitis optica and optic neuritis, which is very important for the diagnosis of NMO-ON. At present, the standardized treatment of NMO-ON can be divided into two clinical stages: acute stage and remission stage. Corticosteroids and plasma exchange are the main treatments in acute stage, aiming at alleviating acute inflammatory reaction and improving prognosis. Immunosuppressive agents and biological agents are the main treatments in remission stage, aiming at preventing or reducing recurrence. With the development of the diagnosis and treatment of NMO-ON, we find that it is more and more important to strengthen the construction of neuro-ophthalmology team in China, establish clinical epidemiological database of NMO-ON, and carry out multi-centre, large-sample, prospective clinical control studies in China to provide evidence-based medicine for Chinese people. In addition, we need to strengthen efforts to establish and improve the diagnostic criteria for NMO-ON and the promotion of diagnostic and therapeutic criteria, and strive to improve the clinical diagnosis and treatment level of NMO-ON in China.
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.
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.
Objective To observe the ocular manifestations and therapeutic effect of multiple sclerosis (MS) and neuromyelitis optica (NMO) with ocular symptoms.Methods The clinical data of 107 patients who was diagnosed with MS and NMO with ocular symptoms in our hospital were retrospectively analyzed, including 81 MS patients and 26 NMO patients.The counting of erythocytes and leukocyte，protein content and oligoclonal bands were detected by MRI and cerebrospinal fluid (CSF) in order to ensure the clinical diagnosis with MS and NMO. All the patients had undergone regular ophthalmologic examination of visual acuity，slit lamp microscope and fundus examination.In addition，visual field and visual evoked potential (VEP) examination were performed to analyze the clinical characteristics of ocular manifestations.The patients were received therapy with large dose methylprednisolone or activating blood and dissolving stasis and trophic nerve by chinese medicine. The effects of three methods on ocular manifestations were analyzed. All the patients were followed up for one month to five years. Results Among 81 MS patients，retrobulbar neuritis occurred in 24 patients (29.6%), the other common symptoms included paralytic strabismus and diplopia（30.3%）. Among 26 NMO patients，acute papillitis occurred in 12（46.2%），while retrobulbar neuritis occurred in 14 (53.8%). The most common symptom of both MS and NMO was impaired vision and high abnormal rate. The results of MRI showed that demyelinating lesions beside ventricle was the most performance in MS patients，while abnormalities in spinal cord were found in NMO patients.The results of CSF showed that the positive oligoclonal bands was 75.3% and 19.2% in MS and NMO patients respectively. The potential time delay and (or) amplitude declination were observed by VEP. Large dose methylprednisolone can improve vision and diplopia in a short period.Conclusion The abnormal ocular manifestations of MS and NMO patients are common and complicated. Ocular symptoms has important reference value in the early diagnosis of MS and NMO.
Neuromyelitis optica (NMO) is an autoimmune inflammatory diseases of the central nervous systems (CNS) mainly affecting the optic nerves and spinal cord. It has the characteristics of high recurrence rate and poor prognosis. NMO related optic neuritis is a common neuro-ophthalmic disease which often results in permanent visual loss or even blindness. Aquaporin 4 (AQP4) antibody is a specific and pathogenic autoantibody in NMO patients. Although AQP4 is expressed in multiple tissues, NMO pathology is remarkably limited to the CNS. Corticosteroids and other immunosuppressive drugs are the standard managements for NMO patients, in order to reduce the relapses and the severity of the acute attack. Multiple avenues of investigation in the laboratory have significantly advanced our understanding of NMO pathophysiology, which is helpful for our understanding of immunologic and nonimmunologic mechanisms. Many offer significant means for NMO therapy by selectively targeting pathways. In the future, moving these agents from the bench to the bedside offers the opportunity to identify safe and effective therapies that limit CNS injury and preserve visual function.
Neuromyelitis optica spectrum disorder (NMOSD) is a immune-mediated demyelinating disease of the central nervous system, characterized by high recurrence and disability rates. Preventing relapses is crucial in the treatment of this condition. Monoclonal antibodies have emerged as a novel and rapidly evolving clinical therapeutic strategy targeting NMOSD in recent years. An increasing number of studies and clinical trials have also confirmed the effectiveness and safety of monoclonal antibodies. Rituximab, a monoclonal antibody targeting the B-cell surface antigen CD20, has been widely used in the treatment of NMOSD. Currently, in China, the only approved monoclonal antibody for treating NMOSD is Inebilizumab, which targets the B-cell surface antigen CD19. Additionally, various monoclonal antibodies, such as interleukin-6 receptor inhibitors and complement C5 inhibitors, have been used in the treatment of NMOSD. With the deepening of the research on the pathogenesis of NMOSD, the molecular mechanism of disease-related immune network is further clarified, and multi-center clinical trials are widely carried out. More accurate monoclonal antibody treatment strategies for NMOSD will be applied to clinical practice, benefiting more patients.
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.