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-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.
Neuro-ophthalmology is an interdisciplinary discipline that spans multiple disciplines such as ophthalmology, neurology, and neurosurgery, and plays an important role in ophthalmology. Since the establishment of the Neuro-Ophthalmology Group in 2011, it has shown a good momentum of accelerated development of neuroophthalmology team building, promoting the process of neuroophthalmology standardization and strengthening interdisciplinary cooperation. However, there is still a gap between the level of neuro-ophthalmology in China and that in developed countries, which still cannot get rid of the stage of introduction and imitation. It is still a long way to form neuro-ophthalmology with unique characteristics in China. In the future, we should carry out clinical research while advancing basic research work, and establish a standard training system to strengthen the training of neuroophthalmologists. It is expected that in the next 10 years, China's neuro-ophthalmic diagnosis and research level will be significantly improved, and a number of landmark academic achievements will be achieved, and a number of internationally and domestically renowned neuro-ophthalmologist will be trained to further enhance the international academic status of neuro-ophthalmic research in China.
On September 27, 2022, the first international standard of Diagnosis and Classification of Optic Neuritis was published online in Lancet Neurology, the top journal of neurology. The publication of this standard fills the gap in the international diagnosis and classification of optic neuritis (ON), promotes the consistency of the global diagnosis classification of ON, and helps ophthalmologists and neurologists to diagnose ON more accurately in the future. In recent decades, although Chinese ophthalmologists have made great progress in their understanding of ON and diagnosis and treatment level, it is still necessary to continue to strengthen the standardized training of Chinese neuro-ophthalmologist specialists, cooperate to establish a national ON clinical epidemiology database, carry out Chinese multi-center clinical studies, and further verify and optimize the international ON diagnostic system in future clinical practice. The ON diagnostic standards and treatment standards are gradually improved for China.
The first edition of “The Chinese expert consensus on the diagnosis and treatment of optic neuritis” have been published in Chinese Journal of Ophthalmology in 2014. Seven years later, more evidence-based medicine has been accumulated in the treatment of optic neuritis. It is necessary to update or formulate guidelines to guide clinical practice. Based on the methods and procedures for developing evidence -based guidelines, Neuro-Ophthalmology Group of Ophthalmology Branch of Chinese Medical Association and Evidence-based Medicine Centre of Lanzhou University/World Health Organization Collaborating Centre for Guideline Implementation and Knowledge Translation created the first “An evidence-based guideline for the diagnosis and treatment of demyelinating optic neuritis in China (2021)”, which aimed to improve the level of clinical diagnosis and treatments of demyelinating optic neuritis. This guideline proposes a new subtype classification of demyelinating optic neuritis to guide precision treatment. It also gives new suggestions about clinical treatment hotspots in the acute and chronic phases, including the application of immunosuppressants and rituximab and other biological agents.
ObjectiveTo observe 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 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.
ObjectiveTo observe the clinical and imaging characteristics of radiation optic neuropathy (RION). MethodsA 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. ResultsOf 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). ConclusionsThe 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.
ObjectiveTo 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).MethodsThis 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 χ2 test was used for comparison among multiple groups.ResultsAmong 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 (χ2=4.732), male (χ2=4.263) and female (χ2=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 of RNFL, 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.ConclusionsThe 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.
ObjectiveTo 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).MethodsA 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 by t test.ResultsCompared 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).ConclusionsThe 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.