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Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.
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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
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Objective:To observe the clinical and imaging characteristics of radiation optic neuropathy (RION).Methods:A retrospective clinical study. A total of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021 were included in this study. There were 23 males (36 eyes) and 20 females (33 eyes). The age of patients at the time of radiation therapy was 49.54±13.14 years. The main dose of radiotherapy for lesions was 59.83±14.12 Gy. Sixteen patients were treated with combined chemotherapeutic agents. The clinical details of best corrected visual acuity (BCVA) and color photography of the fundus were collected. Forty-six eyes underwent optical coherence tomography (OCT), visual field were examined in 30 eyes, magnetic resonance imaging (MRI) were performed in 40 eyes. The BCVA examination was performed using Snellen visual acuity chart, which was converted to minimum resolution angle logarithm (logMAR) visual acuity during recording. Hyperbaric oxygen therapy (HBOT) was performed in 10 patients (13 eyes), 9 patients (12 eyes) were treated with intravenous methylprednisolone (IVMP), 12 patients (23 eyes) were treated with HBOT combined with IVMP and control group of 12 patients (21 eyes) were only treated with basal treatment. And grouped accordingly. To observe the changes in onset, recovery, and final BCVA of the affected eye as well as thickness changes of the retinal nerve fiber layer (RNFL) of the optic disc and inner limiting membrane-retinal pigment epithelium (ILM-RPE) layer of the macular area, and final outcome of BCVA with different treatment modalities in affected eyes. The RNFL and ILM-RPE layer thicknesses were compared between patients with different disease duration as well as between treatment regimens using independent samples t-test. Results:Of the 43 cases, vision loss was monocular in 17 patients (39.53%, 17/43) and binocular in 26 patients (60.47%, 26/43). The latency from radiotherapy to onset of visual loss was 36.33±30.48 months. The duration of RION ranged from 1 week to 10 years, in which the disease duration of 37 eyes ≤2 months. Subacute visual acuity loss was present in 41 eyes. logMAR BCVA<1.0, 1.0-0.3, >0.3 were 45, 15, and 9 eyes, respectively. Optic disc pallor and optic disc edema were found in 10 (27.03%, 10/37), 3 (8.11%, 3/37) eyes, respectively, within 2 months. The superior RNFL [95% confidence interval ( CI) 2.08-66.56, P=0.038] and the outer circle of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) (95% CI 4.37-45.39, P=0.021) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened (95% CI-32.95--4.20, P=0.015) significantly during the first two months. The inner circle temporal quadrant of the ILM-RPE layer thickened (95% CI -42.22--3.83, P=0.022) significantly from the third to sixth month, and the RNFL except for the temporal quadrants and the average RNFL, inner circle superior quadrant and outer circle of the ILM-RPE layer thinned significantly after 6 months ( P<0.05). Among the 40 eyes that underwent MRI examination, 33 eyes (82.50%, 33/40) were affected by T1 enhancement of optic nerve, including 23 eyes (69.70%, 23/33) in intracranial segment; 12 eyes with thickening and long T2 signal (36.36%, 12/33). After treatment, BCVA was restored in 17 eyes (24.6%, 17/69) and final BCVA improved in 9 eyes (13.0%, 9/69). There was no significant difference between HBOT, IVMP and HBOT combined with IVMP therapy in improving BCVA recovery or final BCVA compared with the control group, respectively ( t=-1.04, 0.61, 1.31,-1.47, -0.42, 0.46; P>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-thickening-thinning. MRI shows T1 enhancement of the optic chiasma and segments of the optic nerve, and the enhanced segments are usually accompanied by thickening and long T2. HBOT and IVMP have no obvious effect on RION.
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Objective:To analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON).Methods:An ambidirectional cohort study. From June 1, 2015 to June 1, 2019, 103 patients with AQP4 antibody-positive NMOSD-ON in Department of Neuro-ophthalmology, The First Medical Center of PLA General Hospital were included. All patients of followed-up period were ≥24 months. According to the best corrected visual acuity (BCVA) at the last follow-up, the affected eyes were divided into the low vision group [log of minimum resolution angle (logMAR) BCVA≥1.0] and the non-low vision group (logMAR BCVA<1.0), 66 and 37 cases, respectively. The two groups of patients were compared the genernal clinical characteristics, and the logistic regression model and COX proportional hazard model were used to analyze the relevant factors affecting the patient's visual prognosis and recurrence.Results:Among the 103 cases, 96 cases (93.2%, 96/103) were female; 94 cases (91.3%, 94/103) had unilateral disease; 48 cases (46.6%, 48/103) were the first onset; 85 cases (82.5%, 85/103) were effected by eye pain or orbital pain; 21 cases (20.4%, 21/103) had optic disc edema; 51 cases (49.5%, 51/103) serologically autoimmune antibody test were positive. Orbital magnetic resonance imaging (MRI) was performed in 101 cases. There was no obvious abnormal signal in visual pathways except for 5 cases (5.0%, 5/101); 96 cases (95.0%, 96/101) had abnormal signal in the visual path, and the optic nerve was found in the orbit; 52 cases had abnormal optic nerve in orbital segment (51.5%, 52/101); 37 cases (35.9%, 37/103) recurred within 24 months. The recovery of logMAR BCVA after the first onset and the logMAR BCVA at the first onset, at 6 months of follow-up in two groups were 1.4±1.0, 0.3±0.4, 1.9±0.7 and 0.4±0.5, 2.1±0.6, 0.3±0.4, respectively; and there were statistically significant differences between the two groups of patients at different times ( Z=-4.967,-7.603,-8.027; P<0.001). Logistic regression multivariate analysis showed that recovery of BCVA≥1.0 logMAR after the first onset [odds ratio ( OR)=226.276, P<0.001 ] and the number of attacks ( OR=8.554, P=0.003) were independent risk factors for low vision. Multivariate analysis of the Cox proportional hazards model showed the higher the MRI score [hazard ratio ( HR)=0.588, P=0.007] and plasma exchange ( HR=0.124, P=0.049) in the acute phase were protective factors for recurrence. Conclusions:Vision loss accompanied by eye pain or orbital pain is the main symptom of onset AQP4 antibody-positive NMOSD-ON, a small number of patients have disc edema, 49.5% patients serologically autoimmune antibody test are positive. Abnormal optic nerve signals can be seen in 95.0% of patients in orbital MRI, and 51.5% patients have abnormalities in the orbital optic nerve. The worse the recovery of BCVA after the first onset and the greater the number of attacks are unfavorable factors affecting the prognosis of vision. High MRI scores and plasma exchange in the acute phase are favorable factors to prevent the recurrence of the disease.
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Objective:To evaluate the occurrence of nocturnal hypotension (NHP) in nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A evidence-based medicine study. Chinese and English as search terms for NAION and NHP was used to search literature in PubMed of National Library of Medicine, Embase, Web of science, Cochrane Library, Clinical Trials, Wanfang, and China National Knowledge Infrastructure and China Biology Medicine disc. Incomplete or irrelevant literature and review literature were excluded. The literature was meta-analyzed using Review Manager 5.4 and STATA 15.0. The 95% confidence interval ( CI) were selected as the estimated value of effect size, the occurrence of NHP in NAION was calculated, and sensitivity analysis and publication bias analysis were also performed to assess the robustness of pooled outcomes. Results:According to the search strategy, 159 articles were initially retrieved, and 8 articles were finally included for meta-analysis, three prospective studies and five retrospective studies. The occurrence of NHP in NAION was 43% (95% CI, 0.36-0.50). Sensitivity analyses confirmed that the evidence was robust. Subgroup analyses showed that the occurrence of NHP in NAION nearly the same in White patients (47%, 95% CI 0.39-0.55) and Chinese patients (41%, 95% CI 0.32-0.51). The occurrence of NHP in NAION was higher in using night mean artery pressure (45%, 95% CI 0.31-0.60) as the diagnostic criteria than using night systolic blood pressure & night diastolic blood pressure (40%, 95% CI 0.32-0.50). Conclusions:The occurrence of NHP in NAION was 43%; the occurrence was similar in patients of different ethnicities. The diagnosis rate could be improved by using nMAP < 70 mm Hg (1 mm Hg=0.133 kPa) as a diagnostic criterion for NHP. Careful intervention should be taken for the blood pressure of patients with NAION and NHP.
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Objective:To investigate the application of critical flicker fusion frequency (CFF) in non-arteritic anterior ischemic optic neuropathy (NAION).Methods:A cross-sectional study. From January 2021 to September 2021, a total of 58 NAION patients (105 eyes) (NAION group) and 33 cases (63 eyes) in the healthy control (HC) group were included from Department of Ophthalmology of First Medical Center, PLA General Hospital. Patients underwent best-corrected visual acuity (BCVA), optical coherence tomography (OCT), visual field, CFF and flash visual evoked potential (F-VEP) examinations. BCVA examination was performed using a Snellen decimal visual acuity chart and was converted to logarithm of the minimum angle of resolution visual acuity. In the affected eyes group, there were 56 cases (72 eyes), 31 cases (43 eyes) male and 25 cases (29 eyes) female, with an average age of 49.28±11.42 years old. And the affected eyes were divided into 4 groups: <1, 1-<3, 3-<6 and >6 months according to the time interval from onset to CFF examination, which were 20(27.8%), 26 (36.1%), 17 (23.6%) and 9 (12.5%) eyes, respectively. According to the BCVA ≥0.5, 0.1-0.5, <0.1 in CFF examination, the affected eyes were divided into a mild, moderate, and severe degree, 33 (45.8%), 32(44.4%) and 7 (9.8%) eyes, respectively. Sixty-three eyes of 33 cases were in the HC group. There were 17 cases(31 eyes) males and 16 cases (32 eyes) females, with an average age of 35.18±10.96 years. Hand-held CFF detector type 2 (Japan, NEITZ company) was used for the CFF examination. The thickness of peripheral retinal nerve fiber layer (pRNFL), macular inner limiting membrane retinal pigment epithelium (mILM-RPE), F-VEP peak time and peak value and mean visual field defect (MD) values were recorded within 1 week of CFF examination. The CFF value of the above subgroups was analyzed in order using one-way ANOVA. Pearson correlation analysis was used for the correlation between CFF and F-VEP peak time, peak value, BCVA and MD. The correlations between BCVA, visual field, F-VEP, and CFF were analyzed.Results:The trichromatic values of red, green and yellow in NAION affected eyes were 22.56±10.30, 24.10±11.51, 24.81±11.41 Hz, respectively, which was significantly reduced compared with the HC group ( t=-10.53,-11.11,-11.36; P<0.05). There was no significant difference in CFF-red, green, and yellow values at different time points after the onset of the disease ( F=2.075, 1.893, 2.073; P>0.05). Compared CFF-red, green, and yellow values in NAION-affected eyes with different degrees, the difference was statistically significant ( F=31.579, 27.332, 32.055; P<0.05). The results of correlation analysis showed that the peak time of F-VEP ( r=-0.362, -0.379,-0.357; P<0.05), BCVA ( r=-0.705,-0.695,-0.714; P<0.05), and which was negatively correlated with CFF three color. MD and CFF were positively correlated ( r=0.486, 0.435, 0.450; P<0.05). Conclusion:The CFF value of the affected eye is decreased significantly in NAION-affected eyes, and CFF is more sensitive than F-VEP in reflecting visual impairment, and has a good correlation with visual function and latency of F-VEP.
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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.
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Objective:To observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).Methods:A cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid(mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow- up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression. Results:Thirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow- up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation( P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027). Conclusions:EON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery.
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Objective:To investigate the clinical, laboratory and imaging evaluation, treatment and prognosis of patients with idiopathic hypertrophic pachymeningitis (IHP) with ophthalmic manifestations as the first symptom.Methods:A retrospective case analysis. Eight patients displaying symptoms of IHP were recruited from the Neuro-ophthalmology Department in the First Medical Center of Chinese PLA General Hospital from January 2016 to April 2019 were inculed in this study. There were 6 males and 2 females, aged from 11 to 65 years, with an average age of 48.00±19.08 years. The course of disease ranged from 30 days to 7.5 years, with an average course of 17.00±30.08 months. The age, symptoms and signs of all patients were recorded. All patients underwent ophthalmic examination, orbit or brain MRI or CT examinations, blood routine examination, biochemistry, tumor markers, immunity, hepatitis B, syphilis, HIV, thyroid function and other laboratory tests, and lumbar puncture was performed to measure the cerebrospinal fluid (CSF) pressure and indicators. The clinical manifestations, orbital or brain MRI imaging and laboratory examination characteristics were summarized. Treatment and prognosis were also observed.Results:In total of 8 patients, visual loss was presented in 6 patients, visual loss and diplopia were presented in 1 patient, and diplopia was presented in 1patient. Binocular involvement in 7 patients and monocular involvement in 1 patient. Other symptoms including headache and hear loss and so on. Optic disc edema in 1 eye and optic disc pallor in 6 eyes were reviewed by fundus examination. The laboratory examination showed that the angiotensin converting enzyme abnormal in 4 patients, the anti-thyroid peroxidase antibody abnormal in 3 patients and immunoantibodies positive in 3 patients. CSF measurements showed that the protein level elevated in all patients. Orbit and/or brain MRI and CT examination showed that optic nerve involvement in 6 patients, oculomotor nerve involvement in 1 patient, and cavernous sinus region involvement in 2 patients. Glucocorticoid was effective in all patients, and the visual acuity significantly improved in 4 patients, the diplopia was completely resolved in 2 patients, and the disease modifying therapy (DMT) was combined to prevent recurrence in 7 patients. No recurrence was observed in an average follow-up time of 26.63±16.55 months.Conclusions:IHP patients may be first visit an ophthalmologist due to vision loss in bilateral eyes simultaneous or sequentially. IHP patients are often associated with headache and other cranial nerve paralysis symptoms. Definitive diagnosis of IHP depends on imaging examination. Glucocorticoid treatment is effective in early phase, but it is tendency to progress and relapse, suggesting combined with DMT as early as possible.
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Objective:To observe the clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON).Methods:A retrospective case series. Twenty-three eyes of 14 children with AQP4-PON who were clinically confirmed in the Department of Ophthalmology of the First Medical Center of the Chinese PLA General Hospital from January 2015 to December 2018 were included in the study. All patients underwent BCVA, fundus color photography, and magnetic resonance imaging (MRI). OCT was performed on 15 eyes of 10 patients, and the peripapillary retinal nerve fiber layers (pRNFL), macular ganglion cell-inner plexiform layers (mGCIPL) thickness of the affected eyes were measured. Cell-based indirect fluorescent immunoassay was used to detect serum AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. The follow-up time ranged from 28 to 59 months. The clinical, neuroimaging characteristics and prognosis of the children were analyzed.Results:Among 14 children, 2 were male (14.3%) and 12 were female(85.7%). The mean age of onset was 13.3±3.0 years. On the first visit, there were 10 unilateral patients and 4 bilateral patients. The first manifestations were 11 patients of optic neuritis (78.6%), 2 patients of posterior pole syndrome (14.3%), and 1 patient of myelitis (7.1%). There were 10 patients (71.4%) with eye pain, and 5 patients(35.7%) combined with autoantibodies positive. When the first onset time was less than 2 weeks, fundus examination revealed disc edema in 7 eyes (38.9%). After 3 months, the average pRNFL and mGCIPL thickness of 15 eyes underwent OCT examination were 62.33±11.07 and 54.17±5.42 μm, respectively. Orbital MRI showed that the optic nerve showed a long T2 signal in 14 patients (100.0%) and 11 patients (78.6%) with T1 intensive lesions. When the first onset was less than 2 weeks, 16 eyes (88.9%) had BCVA≤0.1, and 7 eyes(38.9%) had BCVA≤0.1 and 9 eyes (50.0%) with BCVA≥0.5 after glucocorticoid treatment. Recurrence occurred in 11 patients during follow-up and was treated with immunosuppressive agents. At the last visit, in 14 patients, 9 eyes (64.3%) were involved in both eyes, and 5 patients (35.7%) progressed to neuromyelitis optica; in 23 eyes, 8 eyes (34.8%) had BCVA≥0.5.Conclusions:AQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica.
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Objective@#To compare the changes of spontaneous brain activity in myelin oligodendrocyte glycoprotein antibody (MOG-Ab) positive and Aquaporin 4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorder (NMOSD) by using resting-state functional magnetic resonance imaging (fMRI).@*Methods@#A case control study was designed.A total of 11 NMOSD patients with positive MOG-Ab and 21 NMOSD patients with positive AQP4-Ab were enrolled from October 2006 to May 2017 in PLA General Hospital.Thirty-four healthy controls closely matched in age, sex and education were recruited and underwent resting-state fMRI scans.The amplitude of low-frequency fluctuation (ALFF) was extracted to investigate the spontaneous brain activity.This study was approved by Ethics Committee of PLA General Hospital (S2019-111-01). All subjects enrolled signed informed consent.@*Results@#Two patients in the MOG-Ab positive group had seizure history, and no seizure history was observed in AQP4-Ab positive group and healthy control group.Compared with healthy control group, all patients in MOG-Ab positive group and AQP4-Ab positive group had significantly increased ALFF values of prefrontal gyrus.The ALFF values of bilateral anterior central gyrus and bilateral posterior central gyrus in AQP4-Ab positive group were 1.89±0.56 and 2.10±0.69, respectively, which were lower than 3.32±1.15 and 3.61±1.23 in MOG-Ab positive group, the differences were statistically significant (both at P<0.001, AlphaSim correction).@*Conclusions@#Resting-state fMRI could provide new evidence of possibly multi-focal disease mechanisms.Hyperactivity in prefrontal cortex, motor cortex and somatosensory cortex might reflect differences in pathological processes between MOG-Ab positive and AQP4-Ab positive NMOSD patients.
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Objective To analyze the clinical features and prognosis of adult optic neuritis patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-ON) or aquaporin 4 antibody (AQP4-ON).Methods A retrospective study. From December 2015 to February 2018, in the Beijing Chaoyang Hospital of Capital Medical University and Chinese PLA General Hospital, 162 eyes of 132 patients with positive serum MOG antibody and AQP4 were included in the study. There were 42 MOG-ON patients (49 eyes, 31.8％), 90 AQP4-ON patients (113 eyes, 68.2％). The clinical features of optic neuritis (annual recurrence frequency, incidence of optic disc edema), brain and optic nerve enhanced MRI, serum autoimmune antibodies and cerebrospinal fluid test results were compared between MOG-ON and AQP4-ON patients. All patients were treated with intravenous methylprednisolone sodium succinate in the acute phase and then switched to oral prednisone acetate tablets. The average follow-up time was 15 months. The glucocorticoid dependence, visual prognosis, spinal cord symptoms, and myelitis at the last follow-up were comparatively analyzed between MOG-ON and AQP4-ON patients. The comparison of the count data was performed by χ2 test, and the measurement data were compared byt test.Results Compared with AQP4-ON patients, MOG-ON patients had higher annual recurrence frequency (t=3.760,P=0.005), higher incidence of optic disc edema (χ2=14.777,P<0.001), higher incidence of hormone dependence (χ2=25.496,P<0.001), and better visual prognosis (χ2=28.759, P<0.001). MOG-ON patients were more likely to involve the optic nerve, AQP4-ON patients were more likely to involve the optic chiasm and the optic tract. There was a significant difference in the location of lesions between MOG-ON and AQP4-ON patients (χ2= 5.447,P= 0.015). The proportion of AQP4-ON patients with autoimmune antibodies was significantly higher than that of MOG-ON patients (χ2 = 20.453,P<0.001). The results of cerebrospinal fluid test showed that the white blood cell count of patients with MOG-ON and AQP4-ON were within the normal range, but the IgG level of AQP4-ON patients was significantly higher than that of MOG-ON patients (t=8.669,P<0.001). At the last follow-up, there were 7 and 29 patients of myelitis in MOG-ON and AQP4-ON patients respectively (χ2=3.494,P=0.046).Conclusions The clinical characteristics of MOG-ON were different from AQP4-ON. The incidence of optic disc edema and recurrence rate were higher, but the proportion of autoimmune antibodies was lower. MOG-ON was more likely to show hormone dependence, but the visual prognosis was better. AQP4-ON was easily involved in optic chiasm and optic tract, and the incidence of myelitis was higher.
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Objective To explore the clinical features,primary lesions and prognosis of optic nerve metastases.Methods Seven patients (11 eyes) with optic nerve metastatic tumor diagnosed by the examinations of ophthalmology,laboratory and pathology in Chinese PLA General Hospital from April 2015 to September 2017 were included in this study.All patients underwent BCVA,flash VEP,OCT,orbital MRI,serum tumor marker,cerebral spinal fluid detection and PET-CT.Histopathological examination of primary or near superficial metastases was performed.The follow-up period was ranged from 16 to 44 months,with the mean of 23.0 ± 10.9 months.The clinical characteristics,primary tumor,imaging features,treatment and clinical prognosis in the patients were analyzed.Results Among 7 patients,there were 5 males and 2 females,with the mean age of 53.90± 14.99 years;3 patients with unilateral optic nerve involvement,4 patients with bilateral optic nerve involvement;5 patients (71.4％) first diagnosed in ophthalmology.Five patients (45.5％) were misdiagnosed as optic neuritis,optic disc edema in 6 eyes (54.5％).All of them appear loss of visual acuity,including 8 eyes (72.7％) with BCVA＜ 0.1,2 eyes (18.2％) with BCVA 0.1-0.5,1 eye (9.1％) with BCVA ＞ 0.5.MRI results show that 1 patient with intraorbital segment,1 patient with internal segment of optic canal,4patients with intracranial segment,1 patient with intracranial segment and optic chiasma involved simultaneously,4 patients involving surrounding tissue.There were 4 patients (57.1％) with lung cancer,2 patients (28.6％) with kidney cancer,1 patient (14.3％) with gastric cance;6 patients (85.7％) with metastasis from other sites,2 patients with brain metastasis (1 patient with meningitis carcinomatosa).There were 2 patients (28.6％) with previous primary cancer surgery.After diagnosis,1 patient received chemotherapy,1 patient received radiotherapy,5 patients gave up treatment.At the end of follow-up,1 patient (1 eye) of chemotherapy with BCVA increased by 2 line;1 patient (2 eyes) of radiotherapy with no change in BCVA;of the 5 patients who gave up treatment,1 patient died of disease,1 patient lost follow-up,and 3 patients (4 eyes) had no change in BCVA.Conclusions With atypically clinical manifestations,the optic nerve metastases easily misdiagnosed as optic neuritis,and with poor therapeutic effect.Primary lesions are mostly found in lung cancer.
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Objective To observe the effects of penetrance,different time of onset and mutation sites on retinal nerve fiber layer (RNFL) and macular thickness in patients with Leber's hereditary optic neuropathy (LHON).Methods This was a cross-sectional observational study.A total of 88 patients with LHON and 1492 relatives of the maternal relatives (gene carriers) who received treatment in People's Liberation Army General Hospital from 2015 to 2017 were included in the study.Among the 1492 family members,there were 694 males and 798 females.Peripheral venous blood was extracted from all subjects for mitochondrial DNA testing,and penetrance was calculated.A total of 117 patients underwent BCVA and SD-OCT examinations,including 82 patients and 35 gene carriers.The BCVA examination was performed using the Snellen visual acuity chart,which was converted into logMAR visual acuity.The thickness of RNFL,ganglion cell complex (GCC) and inner limiting membrane (ILM)-RPE were measured with OCT instrument.The mean follow-up was 50.02± 86.27 months.The disease course was divided into 6 stages including ≤3 months,4-6 months,7-12 months and ＞ 12 months.The thickness of RNFL,GCC and ILM-RPE in patients with different time of onset and mutation sites were comparatively analyzed by covariance analysis.Categorical variables were expressed as a percentage,and the x2 test was used for comparison among multiple groups.Results Among the 1492 family members,285 were diagnosed with LHON and highly suspected clinical manifestations (19.10％),including 190 males (21.98％) and 95 females (11.90％).The total penetrance rates of 11778,14484 and rare mutation sites were 19.84％ (228/1149),20.50％ (33/161),and 13.19％ (24/182) respectively;male penetrance rates were 28.87％ (153/530),27.28％ (20/72),and 18.48％ (17/92) and female penetrance rates were 12.12％ (75/619),14.61％ (13/89) and 7.78％ (7/90).There was no significant difference in total (x2=4.732),male (x2=4.263) and female (x2=4.263) penetrance between different mutation sites (P=0.094,0.110,0.349).Compared with non-pathogenic carriers,the thickness of the RNFL,GCC and ILM-RPE were all different in the four stages (≤3months,4-6 months,7-12 months and ＞12 months).The thickness ofRNFL,GCC and ILM-RPE decreased with the time of onset (P=0.000).There were significant differences in the thickness of each of the GCC and ILM-RPE layers in the macular area of LHON patients with different mutation sites (P＜ 0.05).Among them,the site 11778 and 3460 had the most severe damage in all quadrants of macular GCC and ILM-RPE layer,followed by 14484 site,and the rare site had the least damage in all quadrants.Conclusions The penetrance of LHON patients is 19.10％.With the extension of the onset time (within 1 year),the RNFL layer of the optic disc and all quadrants of the macular GCC and ILM-RPE layer gradually thinned.Compared with 11778 and rare site,14484 site,and the rare site had the lighter damage on the thickness of RNFL,GCC and ILM-RPE.
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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 (x2=1.61,P＞ 0.05),with/without auto-immune antibody ratio (x2=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.