ObjectiveTo explore the clinical features, primary lesions and prognosis of optic nerve metastases.MethodsSeven 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.ResultsAmong 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, 4 patients 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.ConclusionsWith 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.
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
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 analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON). MethodsAn 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. ResultsAmong 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. ConclusionsVision 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.
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 observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON).MethodsA 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.ResultsThirty 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).ConclusionsEON 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.
ObjectiveTo observe the clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON).MethodsA 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.ResultsAmong 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.ConclusionsAQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica.
ObjectiveTo investigate the application of critical flicker fusion frequency (CFF) in non-arteritic anterior ischemic optic neuropathy (NAION). MethodsA 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. ResultsThe 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). ConclusionThe 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.
ObjectiveTo evaluate the occurrence of nocturnal hypotension (NHP) in nonarteritic anterior ischemic optic neuropathy (NAION). MethodsA 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. ResultsAccording 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). ConclusionsThe 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.