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.
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.
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.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system. Three monoclonal antibodies were recently approved as maintenance therapies for aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive NMOSD (eculizumab, inebilizumab, and satralizumab). Neurol Neuroimmunol Neuroinflamm published international Delphi consensus on the management of AQP4-IgG+ NMOSD in May 31, 2023. Twenty-five statements reached consensus after two voting rounds by 24 Delphi panel experts. Inebilizumab and satralizumab have been listed in China, and off-label immunosuppressants and biologics are also used in clinical practice. However, there are no standard treatment recommendations in use of these biologics and maintenance therapy of NMOSD. Therefore, the interpretation of this consensus, focusing on the initial use of monoclonal drugs, the conversion between monoclonal drugs and immunosuppressants, as well as the application and safety of special populations, is conducive to improving the normative and effective use of of monoclonal drugs in NMOSD y ophthalmologists and neurologists
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system that primarily affects the optic nerves and spinal cord. Most patients have positive serum antibody of aquaporin-4 (AQP4), which targets the AQP4 protein expressed on the end-feet of astrocytes. Although the prevalence of NMOSD is limited, the recurrence rate is high. Repeated and severe immune-mediated attacks can quickly lead to blindness and paralysis if undiagnosed and untreated. While high-dose methylprednisolone and plasma exchange are used in the acute phase, the treatment for recurrent prevention is limited. In recent years, researchers developed several kinds of monoclonal antibodies targeting different nodes of immune pathogenic process, including satralizumab (an interleukin-6 receptor inhibitor), inebilizumab (an antibody against CD19+ B cells), and eculizumab (an antibody blocking the C5 component of complement). In several randomized controlled clinical trials, these monoclonal antibodies decreased the relapse rate significantly in NMOSD. These emerging treatments have greatly changed the treatment of NMOSD.
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.
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.
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.
ObjectiveTo investigate the alteration of retinal perfusion in aquaporin-4 antibody (AQP4-ab) positive neuromyelitis optica spectrum disorders (NMOSD) patients by optical coherence tomography angiography (OCTA).MethodsA case-control study. Forty-eight AQP4-ab positive NMOSD patients (96 eyes) and 20 age and gender matched healthy controls (40 eyes) were recruited from September 2015 to August 2017 at the Eye & ENT Hospital of Fudan University. Patients of both eyes were included in the groups. The patients were further divided into 4 subgroups (0 ON, 1 ON, 2 ON, 3+ ON group) according to the number of episodes of ON (0, 1, 2, or 3+) with respect to 30、22、31、13 eyes. 0 ON group had no history of ON episodes; 1 ON group, 2 ON group, and 3+ ON group had ON episodes 1, 2, ≥3 times, respectively. All patients underwent complete ophthalmological examinations including BCVA, visual field and OCTA examination. The BCVA was recorded for each eye using metric notation from the Snellen chart, and then converted to the logarithm of the minimum angle of resolution. The central visual field was assessed using a Humphrey Field Analyzer 750 and the mean deviation (MD) was determined. OCTA scans of the optic disc (4.5 mm × 4.5 mm) and macula (6 mm × 6 mm) were acquired. Radial peripapillary capillary (RPC) vessel density, superficial capillary plexus vessel density (SVD), the thickness of ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were determined. The generalized estimating equations was performed to compare the difference of BCVA, MD, pRNFL thickness, GCIPL thickness, RPC vessel density and SVD among the groups and the correlations between retinal perfusion and retinal structure, visual function were analyzed. ResultsThe RPC vessel density and SVD were significant lower in the 0 ON group compared with healthy group (Wald χ2=7.190, 10.134; P＜0.01), however, the BCVA, pRNFL and GCIPL thickness were not significant difference between the two groups (Wald χ2=2.308, 1.020, 2.558; P＞0.05). The BCVA, visual field MD, RPC vessel density, SVD, pRNFL and GCIPL were significant lower in 1 ON, 2 ON and 3+ ON groups compared with healthy group and 0 ON group (Wald χ2=12.390, 11.346, 38.860, 18.040, 45.418, 26.608; P＜0.001 ), but the parameters had no significant difference among the three groups (P＞0.05). The RPC vessel density was significantly correlated with pRNFL thickness (β=0.372, standard error=0.018, P＜0.001), and the SVD was significantly correlated with GCIPL thickness (β=0.115, standard error=0.204, P＜0.001). The MD and BCVA was significantly correlated with peripapillary vessel density after adjustment for other variables (BCVA: β=0.025, standard error=0.005, P=0.000; visual field MD: β=0.737, standard error=0.185, P=0.000).ConclusionsSubclinical primary retinal vasculopathy may occur in NMOSD prior to ON attack, the ON attack may further impair visual function, retinal structure and perfusion, however, the extent of injure is not relevant with the increase of ON attack. The peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients.