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.
Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. NMO pathogenesis is thought to involve binding of anti-aquaporin-4 (AQP4) auto-antibodies to astrocytes, which causes complement-dependent cytotoxicity (CDC) and downstream inflammation leading to oligodendrocyte and neuronal injury. Vasculocentric deposition of activated complement is a prominent feature of NMO pathology. In recent years, a number of groups have found complements play an important role in the pathogenesis of NMO, and basic researches in NMO therapy due to its specificity and uniformity. Its inhibition would protect against proteins in the classical complement pathway so that cure the disease. This review will expound the the role of complement signaling pathway in the pathogenesis of NMO, and provide reference for a more in-depth understanding and clinical treatments of NMO.
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.
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.
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.
Plasma exchange (PE) is a therapeutic blood component replacement method. The blood of patients is first separated into plasma and blood cell components using a blood cell separator in vitro, the plasma containing harmful pathogenic substances is then discarded and replaced with the same volume of exchange solution. Finally the separated blood cells together with the exchange solution are returned back to the blood circulation of patients. By reducing the circulating antibodies, abnormal plasma proteins or cytokines and other pathogenic molecules, PE can block the disease process. PE has a good therapeutic effect on neuromyelitis optica-related optic neuritis (NMO-ON), which shows resistant to glucocorticoid therapy for the first onset. The American Society for Apheresis guideline evaluates PE for acute optic neuritis as a recommended grade 1B, type II indication. In the implementation of PE treatment for NMO-ON and other diseases, indications and contraindications should be strictly adhered to the guideline, treatment procedures and protocols should be optimized, common adverse events and its prevention and management should be known and alerted. It is important to conduct multi-center clinical cooperation and a high standard clinical randomized controlled study, to find out the optimal time window, the best protocol, and the associated factors for the efficacy and prognosis of PE in NMO-ON.
ObjectiveTo observe the blood perfusion of optic nerve and macular areas and investigate its relationship with visual field defect in nonarteritic anterior ischemic optic neuropathy (NAION).MethodsTwelve consecutive unilateral NAION patients (course of disease ＜3 months) and 12 healthy Chinese adults were enrolled in the study. The affected eyes and fellow eyes from 12 NAION patients were defined as group A and group B; 12 eyes from 12 healthy adults were defined as group C. Best corrected visual acuity (BCVA), intraocular pressure (IOP), indirect ophthalmoscope and computer optometry were performed on all of the three groups of patients. Visual field (VF) and optical coherence tomography (OCT) were performed on NAION patients. Logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Compared to group B, logMAR BCVA, mean deviation (MD) and pattern standard deviation (PSD) in group A were significant decreased (t=3.278, −4.909, 4.130, P＜0.05). There was no significant difference in spherical equivalent, IOP, peripapillary retinal nerve fibre layer (pRNFL) between group A and group B (t=0.000, 0.890, 1.215; P＞0.05). OCT angiography (OCTA) was used to measure the flow area (FA) at optic disc, flow area at radial peripapillary capillaries (RCFA) and FA, non-perfusion area (NFA), parafoveal vessel density (PVD) and parafoveal vascular index (PVI) in macular area. Pearson correlations between the deficiency of optic blood flow and visual field were analyzed.ResultsThe differences of FA at optic disc and peripapillary RCFA among 3 groups were significant (F=4.162, 3.357; P＜0.050). Compared to group B (t=−5.822, −7.467; P＜0.001) and C (t=9.435, 4.615, P＜0.05), FA at optic disc and peripapillary RCFA in group A was significantly reduced. There is several NAION showed quadrantal FA decreased in optic nerve. However, there was no significant difference in optic disc FA and peripapillar RCFA between group B and C (F=0.004, 0.030; P＞0.050). There was no differences of FA, NFA, PVD and PVI among 3 groups (F=0.488, 1.107, 0.493, 1.086, 1.098, 0.093, 1.093, 1.221; P＞0.05). Positive correlation between optic disc FA, peripapillary RCFA and MD (r=0.542, 0.585; P＜0.05) were observed. However, there was no significant correlation between optic disc FA, peripapillary RCFA and PSD (r=−0.404, −0.430; P＞0.05), and negatively correlated to BCVA (r=−0.617, −0.596; P＜0.05). PRNFL was negatively correlated to optic disc FA (r=−0.643, P＜0.05), but not correlated to peripapillary RCFA (r=−0.377, P＞0.05).ConclusionsThe optic disc blood flow reduced in affected eyes of unilateral NAION whose disease course was less than 3 months, while the macular perfusion was normal. There was a positive correlation between optic disc flow and visual field.
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.
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.