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AimsThe optimal immunosuppressive therapy (IST) in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) remains uncertain. This study aimed to observe the disease course of MOG-ON and evaluate the therapeutic efficacy and tolerability of conventional immunosuppressants through Chinese cohort analysis.MethodsThis bidirectional cohort study included 121 patients with MOG-ON between January 2015 and December 2018. The clinical features and annualised relapse rate (ARR) of patients with and without IST were analysed.ResultsThe median age at onset was 17.5 years, and the sex ratio (F:M) was 1.24. Of 121 patients, 77 patients relapsed and 61 patients were younger than 18 years at disease onset. The overall median ARR of 63 patients in the non-IST group was 0.5, with 46.0% patients showing relapse at a median follow-up of 33.5 months. In the IST group, the ARR decreased from 1.75 pre-IST to 0.00 post-IST in 53 patients who received IST exceeding 6 months, with 20.8% patients showing relapse at a median follow-up of 23.8 months. The relapse rates of patients treated with rituximab (RTX) and mycophenolate mofetil (MMF) were not statistically different, but the rate of discontinuation was significantly lower in the RTX-treated group (18.2% vs 57.7%, p=0.0017).ConclusionThis study provides Class III evidence that both MMF and RTX may lower disease activity in patients with MOG-ON, and RTX showed better tolerability than MMF. However, observation after a single attack remains a good option because less than half of patients not on treatment suffered a relapse.

Background Several neuroimaging studies demonstrated that optic neuritis (ON) leads to functional and anatomical architecture changes in the brain. The alterations of interhemispheric functional connectivity (IFC) in patients with AQP4-ON and myelin oligodendrocyte glycoprotein (MOG)-ON are not well understood. Purpose To investigate the differential patterns of VMHC in patients with AQP4-ON and MOG-ON. Material and Methods Twenty-one patients with AQP4-ON, 11 patients with MOG-ON, and 34 healthy controls underwent resting-state MRI scans. One-way ANOVA was used to identify regions in which the zVMHC differed among the three groups. Post hoc two-sample t-tests were then conducted to compare zVMHC values between pairs of groups. Pearson correlation analysis was conducted to reveal relationships between mean zVMHC values and clinical variables in the AQP4-ON and MOG-ON groups. Results The results revealed significant differences in zVMHC values in the PreCG among the three groups. Compared to the control group: the AQP4-ON group showed significantly lower VMHC values in the superior temporal gyrus, inferior frontal gyrus, and PreCG; and the MOG-ON group showed significantly higher zVMHC values in the PostCG. Compared to the AQP4-ON group, the MOG-ON group showed significantly lower zVMHC values in the PreCG/PostCG (voxel-level PConclusion Patients with AQP4-ON and those with MOG-ON showed abnormal VMHC in the motor cortices, sensorimotor cortices, and frontal lobe, possibly indicating impaired sensorimotor function in patients with ON. Moreover, differential patterns of VMHC in patients with AQP4-ON, compared to patients with MOG-ON, might serve as a clinical indicator for classification of ON.

To investigate the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein antibody-seropositive optic neuritis (MOG-ON) in patients with varying ages of onset in China.Patients displaying symptoms of MOG-ON were recruited from the Neuro-ophthalmology Department in the Chinese People's Liberation Army General Hospital from January 2016 to May 2018. They were assigned to one of three subgroups based on age of onset: pediatric (18 years), young (18-46 years), and middle-aged (46 years) MOG-ON.110 patients (188 eyes) were assessed, including 58 pediatric (52.7%), 34 young (30.9%), and 18 middle-aged (16.4%) patients. Of the pediatric patients, 93.9% had good recovery of visual acuity (≥0.5) compared with 79.7% of young patients and 66.7% of middle-aged patients (p .001). The annual relapse rate was lower in the pediatric group than young and middle-aged groups (0.32 ± 0.50 vs 0.73 ± 0.87 vs 0.49 ± 1.08, p = .036). Six children (10.3%) were diagnosed with acute disseminated encephalomyelitis, while seven young patients (20.6%) were diagnosed with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder upon follow-up. The average peripapillary RNFL and macular GCIPL thicknesses were not statistically different between subgroups (p = .996, p = .608). Overall, MRIs of the optic nerve showed perineural enhancement in 52.0% of patients and longitudinal extensive involvement in 87.7%. MRIs also revealed a greater proportion of pediatric patients with intracranial optic nerve involvement than in the other two subgroups (45.4% vs. 21.2% vs. 36.7%, p = .014).Pediatric ON was the most common MOG-ON subgroup. Pediatric patients had different clinical features, including better recovery of visual acuity, lower annual relapse rate, and more intracranial optic nerve involvement than young and middle-aged patients. Additionally, age of onset may be a potential predictor for determining visual prognosis with MOG-ON.

Purpose: To prospectively investigate the efficacy and tolerance of low-dose rituximab (RTX) for the treatment of neuromyelitis optica-associated optic neuritis (NMO-ON).Methods: Optic Neuritis patients with seropositive aquaporin 4-antibody (AQP4-Ab) were diagnosed with NMO-ON and recruited for treatment with low-dose RTX (100 mg * 4 infusions) and were then followed monthly for a minimum of 3 months. Reinfusion of 100 mg RTX was given when the CD19+ B lymphocyte frequency was elevated to above 1%. The serum AQP4-Ab level was tested by an enzyme-linked immunosorbent assay (ELISA).Results: A total of 43 NMO-ON patients (1 male/42 female, 75 involved eyes) were included in this study. CD19+ B cell clearance in the peripheral blood was induced in 97.7% of patients after induction treatment. A significant decrease in serum AQP4-Ab concentration was observed after induction treatment (P = 0.0123). The maintenance time of B cell clearance was 5.2 ± 2.25 months. The relapse-free rate was 92.3% in patients followed-up for over 12 months, and patients with non-organ-specific autoimmune antibodies tended to relapse within 6 months. A total of 96.2% of patients had stable or improved vision, and a decrease in the average expanded disability status scale (EDSS) score was found. Structural alterations revealed by optic coherence tomography were observed in both ON and unaffected eyes. The rates of infusion-related reactions and long-term adverse events (AEs) were 18.6 and 23.1%, respectively. No severe AEs was observed.Conclusions: Low-dose rituximab is efficient and well-tolerated in treating NMO-ON.

Purpose: The purpose of this study was to examine the differences in immunopathogenesis based on the cytokine/chemokine profiles in myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-positive and -negative groups. Methods: We measured the levels of T-helper cell 17 (Th17) cell-related cytokines/chemokines in 74 serum samples, which were divided into four groups: healthy control (HC) group (n = 15), idiopathic demyelinating optic neuritis (IDON) group (n = 20), aquaporin 4 (AQP4)-IgG-positive optic neuritis (ON) group (n = 18), and MOG-IgG positive-ON group (n = 21). Serum IL17, IL21, IL28, IL31, CXCL1, CXCL2, CCL2, CCL11, CCL20, and LT-α were detected. Results: The serum of the MOG-IgG-positive ON patients showed an obvious elevation of Th17 cell-related cytokines/chemokines compared with that of all the MOG-IgG-negative ON patients. Serum IL17 and IL21 were significantly higher in the ON patients with MOG-IgG positive than in all the other three groups. The serum levels of IL28, IL31, CXCL1, and CCL11 were higher in the ON patients with MOG-IgG positive than in the HC group and the IDON group. The serum concentration of CCL2, CXCL2, and CCL20 in the MOG-IgG-positive and AQP4-IgG-positive group is higher than that of the HC group. No difference in serum LT-α level was found among the four groups. Adjusted multiple regression analyses showed a positive association of IL17 and IL21 levels with the serum concentration of MOG-IgG in the ON patients. Conclusion: The elevated serum level of Th17 cell-related cytokine/chemokines may play an important role in the pathogenesis of MOG-IgG-positive demyelinating ON.

Background: Optic nerve lymphoma can present a diagnostic challenge because of its confusing clinical features and the difficulty of obtaining lesion tissue for biopsy. The objective of this study was to find some flags of lymphomatous infiltration of optic nerves. Methods: We report two cases of optic nerve lymphoma and conduct a literature review to determine whether a common diagnostic characteristic can be identified. Results: We examined 22 optic nerve lymphoma cases. Thirteen cases were systemic lymphoma infiltration of the optic nerve, five were primary central nervous system lymphoma (PCNSL), and four were primary isolated optic nerve lymphoma. Twenty patients manifested significant enlargement of the lesions in orbital/brain MRI. Seventeen contrast-enhanced MRIs showed abnormal enhancement of the optic nerve. All PCNSL and isolated optic nerve lymphoma patients in the series showed marked enhancement. Moderate and subtle enhancement was found in systemic lymphoma patients only. At the enhancement site, six isolated optic nerve lymphoma and PCNSL patients presented intrinsic enhancement, ten systemic patients showed both optic nerve and sheath enhancement, and one demonstrated sheath enhancement. Cerebrospinal fluid (CSF) tests showed elevated protein levels in six patients, and a neoplasm in one patient. We found abnormality of CSF immunity in both of our patients. Conclusion: Combined characteristics of orbital MRI and CSF tests may facilitate expeditious suspicion establishment of optic nerve lymphoma.

Background/aimsTo evaluate the status of myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) in chronic relapsing inflammatory optic neuropathy (CRION) and investigate its different clinical characteristics and prognosis.MethodsPatients diagnosed with CRION were recruited by the Neuro-ophthalmology Department of the Chinese People's Liberation Army General Hospital from December 2015 to April 2017. Based on antibody status, they were assigned to either the MOG-CRION or seronegative-CRION groups.ResultsA total of 33 patients (38 eyes) were assessed and divided into the following groups: 22 (66.7%) MOG-CRION and 11 (33.3%) seronegative-CRION. The ratio of female to male was 1:1, and 81.8% of total CRION patients were adults (≥18 years). A total of 29 eyes (76.3%) showed severe visual loss (20/40) during the final follow-up. The mean onset age of MOG-CRION patients was 28 ± 16 years (range 6–62), which was significantly younger than that of seronegative-CRION (45 ± 12 years, range 22–59) (p=0.029). The intraorbital and canalicular segments were highly involved in the orbital MRI of CRION patients. During the final follow-up, MOG-CRION patients had more bilateral involvement (p=0.008) and higher annualised relapse rates compared with the seronegative-CRION patients (p=0.019).ConclusionCRION was predominantly found in adults with unilateral ON and exhibited a higher rate of seropositive MOG-IgG. MOG-CRION, which may be a disparate subtype of MOG-IgG-induced demyelinating disease that needs further investigation, was found in younger patients at onset, with more bilateral involvement and more relapse tendency.

Background Neuromyelitis optica-optic neuritis (NMO-ON) patients are routinely treated with intravenous methylprednisolone (IVMP). For the patients nonresponsive to IVMP, more effective but aggressive therapy of plasma exchange (PE) should be employed instead of IVMP in the first line. Purpose To assess the visual outcomes of NMO-ON patients after IVMP by radiomics analysis of whole brain diffusion tensor imaging (DTI) data. Study type Retrospective. Population In all, 57 NMO-ON patients receiving IVMP therapy for 3 days. Field strength/sequence 3.0T; DTI images acquired by a single-shot echo planar image sequence; T1 images acquired by 3D fast spoiled gradient echo (3D-FSPGR) MRI. Assessment In all, 200 DTI measures were extracted from the DTI data and employed as features to construct a radiomics assessment model for visual outcomes of NMO-ON patients after IVMP. The assessment performance was evaluated by area under the receiver operating characteristic curve (AUC), classification accuracy (ACC), sensitivity, specificity, and positive and negative predicted values (PPV and NPV). The selected DTI measures would reveal the white matter impairments related to visual recovery of NMO-ON patients. Statistical tests The relationship between the selected DTI measures and the clinical visual characteristics were investigated by Pearson correlation, Spearman's rank correlation, and one-way analysis of variance analysis. Results The radiomics model obtained an ACC of 73.68% (P = 0.002), AUC of 0.7931, sensitivity of 0.6207, specificity of 0.8571, PPV of 0.8182, and NPV of 0.6857 in assessing visual outcomes of the NMO-ON patients after IVMP treatment. The selected DTI measures revealed white matter impairments related to the visual outcomes in the white matter tracts of vision-relevant regions, motor-related regions, and corpus callosum. The white matter impairments were found significantly correlated with the disease duration and the length of lesions in the optic nerve. Data conclusion Radiomics analysis of DTI data has great potential in assessing visual outcomes of NMO-ON patients after IVMP therapy. Level of evidence 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1365-1373.

Background/AimsTo investigate clinical characteristics and prognosis of paediatric optic neuritis (PON) in patients seropositive for myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in China.MethodsChildren displaying initial onset of optic neuritis (ON) were recruited from the Neuro-ophthalmology Department in the Chinese People’s Liberation Army General Hospital from January 2016 to August 2017. They were assigned into three groups based on antibody status: MOG-Ab-seropositive ON (MOG-ON), aquaporin-4 antibody-seropositive ON (AQP4-ON) and double seronegative ON (seronegative-ON).ResultsTotally 48 patients were assessed, including 25 MOG-ON (52.1%), 7 AQP4-ON (14.6%) and 16 seronegative-ON (33.3%). The MOG-ON and seronegative-ON cohorts had equal ratios of female/male, but the AQP4-ON cohort was predominantly females (100%). The patients with MOG-ON were significantly younger at onset compared with the AQP4-ON group. Of the MOG-ON eyes, 97.6% had good recovery of visual acuity (VA) (≥0.5) compared with33.3% of AQP4-ON eyes (p=0.052). Two children in the MOG-ON group ended up being diagnosed with acute disseminated encephalomyelitis, while only one patient in the AQP4-ON group developed neuromyelitis optica during follow-up. Patients with MOG-ON had thicker peripapillary retinal nerve fibre layers overall and in the superior and inferior quadrants than in patients with AQP4-ON (p=0.005, p=0.002 and p=0.024, respectively). In addition, the macular ganglion cell-inner plexiform in MOG-ON eyes became significantly thicker than in AQP4-ON eyes (p=0.029). Orbital MRI revealed a larger proportion of patients with MOG-ON had intracranial optic nerve involvement than patients with seronegative-ON (51.2% vs 17.4%, p=0.009).ConclusionMOG-ON was the most common PON subtype in China. MOG-ON had different clinical features including earlier age of onset, equal female/male ratio, better recovery of VA and thicker peripapillary retinal nerve fibre and macular ganglion cell-inner plexiform layers. MOG-Abs may be a potential biomarker for determining visual prognosis with PON.

Single-shot echo-planar imaging is the conventional diffusion-weighted imaging (C-DWI) sequence for evaluating orbital disease. However, its utility is restricted in small organs like the chiasma and optic nerve. This study was conducted to investigate the utility of field-of-view optimized and constrained undistorted single-shot diffusion-weighted imaging (FOCUS-DWI) for evaluating the chiasma and optic nerve in acute optic neuritis, making comparisons with C-DWI. FOCUS-DWI and C-DWI were performed on 36 acute optic neuritis patients and 16 normal controls. Two readers assessed image quality using 5-point Likert scales. Differences in the visual assessments and apparent diffusion coefficient (ADC) values between C-DWI and FOCUS-DWI were evaluated. Inter-observer agreement in the qualitative data was assessed using Cohen’s kappa coefficients. Inter- and intra-observer agreements in the ADC values were evaluated using intraclass correlation coefficients. FOCUS-DWI was superior to C-DWI in all aspects of the image evaluations. The Cohen’s kappa coefficients for FOCUS-DWI were almost perfect (0.81–1) or substantial (0.61–0.80) for all the image quality categories. In the FOCUS-DWI images, the structural conspicuity of the chiasma and canalicular and cisternal segments was significantly superior on coronal views than on axial views (P

ObjectiveParaneoplastic optic neuropathy (PON) is relatively uncommon, and the visual outcomes and prognosis of this disease have not been well documented. The aim of this study was to investigate the clinical features and prognosis of antibody-mediated PON.MethodsClinical data were retrospectively collected from hospitalised patients diagnosed with PON at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital from January 2015 to June 2017.ResultsA total of seven patients (four females and three males, 13 involved eyes) were included with a mean age of 56.28±11.32 years (36–70 years). Simultaneous or early sequential bilateral eye involvement (5/7, 71.4%) was common in the patients with PON. Severe vision loss (≤0.1) was seen in 76.9% (10/13) of the eyes. There were 13 eyes in the acute phase of the disease, and six eyes presented with optic disc oedema. All patients had definite evidence of paraneoplastic-associated antibodies (three with serum positive for antiamphilphysin, one for anti-PNMA2 (Ma2/Ta), one for anti-Yo, one for anti-Ma2 and one for anti-CV2). All of the serum samples were negative for myelin oligodendrocyte glycoprotein antibody and two patients companied with seropositive for the aquaporin-4 antibody. Five patients had history of primary malignancy, including thyroid cancer, type B thymoma, testicular seminoma, cervical cancer and lung carcinoma. Two patients had positive paraneoplastic syndrome antibodies (anti-Yo and antiamphiphysin), but the solid tumour had not been found through a PET scan. Visual acuity in 9/13 (69.2%) eyes was below 0.1, and all of the patients survived to the follow-up with no metastatic lesions.ConclusionsPON is relative rare, with a predominance of bilateral involvement and more with a poor visual prognosis. Paraneoplastic antibody testing can contribute to the diagnosis of PON, distinct from other types of optic neuropathies, which can help doctors to find the primary cancer earlier to guide further treatment.

Background To investigate the application of critical flicker fusion frequency (CFF) in demyelinating optic neuritis (DON). Methods A total of 127 eyes in 69 DON patients and 63 eyes in 33 healthy control (HC) groups were included between January 2021 and September 2021. Patients underwent best-corrected visual acuity (BCVA), visual field, optical coherence tomography (OCT), flash visual evoked potential (F-VEP), and CFF examinations. The patients were divided into different subgroups according to antibody subtypes, different degrees of visual acuity impairment, the different time intervals from onset to CFF examination, and performed subgroup analysis. The correlations between CFF and other ophthalmological examination: BCVA, visual field, flash visual evoked potential (F-VEP), in DON patients were analyzed in order. Results The trichromatic values of red, green, and yellow in DON affected eyes were 21.83 ± 9.03, 23.66 ± 10.21, 24.09 ± 10.77 Hz, respectively, which was significantly reduced compared with the HC group (t = −14.82, −14.22, −14.00; P 0.05), whereas, a significant decrease of CFF trichromatic value was found in severe visual acuity impairment (P Conclusions A significant decrease of CFF value was found in DON-affected patients, and it has a good correlation with visual function and latency of F-VEP, and it can provide more valuable information about the impairment of visual function.

Background To evaluate the feature of different retinal layer segmentation in neuromyelitis optica spectrum disorders (NMOSD) with spectral-domain optical coherence tomography (SD-OCT) and to compare it with that in multiple sclerosis (MS), healthy controls (HC), and idiopathic optic neuritis (ION). Methods We retrieved four electronic databases, including Pubmed, Embase, Cochrane Library, and Web of Science from inception to September 1st, 2021. A meta-analysis was performed to compare different retinal layer segmentation thicknesses between patients with or without a history of optic neuritis (ON) in NMOSD and the control group, including patients with MS, HC, and ION. Results Forty-two studies were included and the interval between the last ON onset and examination was greater than 3 months. Compared with that in HC eyes, the loss of retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GC-IPL) was serious in NMOSD eye especially after ON. Moreover, compared with that in ION eyes or MS-related-ON eyes, the injury to the peripapillary retinal nerve fiber layer (pRNFL) was severe in NMOSD-related-ON eyes. In addition, the correlation coefficient between pRNFL and prognostic visual acuity was 0.43. However, the one-arm study revealed the inner nuclear layer (INL) was thickened in NMOSD-related-ON eyes compared with HC eyes. Conclusion Inclusion of the RNFL and macular GC-IPL is recommended for monitoring disease progression and attention should be paid to changes in the INL.

Neuromyelitis optica (NMO) is a severe inflammatory autoimmune CNS disorder triggered by binding of an IgG autoantibody to the aquaporin 4 (AQP4) water channel on astrocytes. Activation of cytolytic complement has been implicated as the major effector of tissue destruction that secondarily involves myelin. We investigated early precytolytic events in the evolving pathophysiology of NMO in mice by continuously infusing IgG (NMO patient serum-derived or AQP4-specific mouse monoclonal), without exogenous complement, into the spinal subarachnoid space. Motor impairment and sublytic NMO-compatible immunopathology were IgG dose dependent, AQP4 dependent, and, unexpectedly, microglia dependent. In vivo spinal cord imaging revealed a striking physical interaction between microglia and astrocytes that required signaling from astrocytes by the C3a fragment of their upregulated complement C3 protein. Astrocytes remained viable but lost AQP4. Previously unappreciated crosstalk between astrocytes and microglia involving early-activated CNS-intrinsic complement components and microglial C3a receptor signaling appears to be a critical driver of the precytolytic phase in the evolving NMO lesion, including initial motor impairment. Our results indicate that microglia merit consideration as a potential target for NMO therapeutic intervention.

Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging (T2WI) with fat saturation and enhanced T1 weighted imaging (T1WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2WI images. The normal optic nerve (NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic (ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement (ONwEN), affected optic nerve without enhancement (ONwoEN), contralateral normal appearing optic nerve (NAON) and NON.Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN (both P=0.000), ONwEN vs. NON (both P=0.000) and NAON vs. NON (both P

Background Several cases of neuromyelitis optica spectrum disorder (NMOSD) caused by interferon alpha (IFN-α) treatment in hepatitis C were reported in past literatures, but NMOSD resulted from IFN-α treatment in tumor has not yet been reported previously. Methods A unique case of NMOSD caused by IFN-α therapy in malignant melanoma is presented. Related cases about NMOSD caused by IFN-α therapy on Pubmed were reviewed further. Results A 40-year-old Chinese woman was diagnosed as right breast skin malignant melanoma and received melanoma resection in April 2012, then underwent IFN-α-2b therapy (5 million IU every time, 3 times/week) from May 2012 to Sep 2016. In December 2016, the patient developed bilateral optic neuritis, with no light perception at her worst. After a month-long glucocorticoid treatment, she could see finger movement from 40 cm. Serum positive anti-AQP-4 antibody was found by enzyme-linked immunosorbent assay (ELISA, 75.9 u/ml) in Feb 2017 and indirect immunofluorescence testing (IIFT, 1:320) in Sep 2017. Methylprednisolone (8 mg/day) and rituximab (0.1 g/every 6 months) were used for prevention. On the follow up visit in Jan 2019, she could see finger movement from 1 m, and no melanoma and NMOSD relapse were complained. Literature review only found 3 cases of NMOSD caused by IFN-α treatment in hepatitis. Conclusions A unique case of NMOSD with positive anti-AQP-4 antibody after IFN-α treatment in malignant melanoma was reported. Type I IFNs may be pro-inflammatory in NMOSD and this possible consequence of IFNs use should be cautioned in future practice.

Purpose. To describe different clinical characteristics and prognosis of optic neuritis (ON) in male patients with seropositive aquaporin-4 antibody (AQP4-Ab) or myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in China. Method. Males with ON were recruited from the Neuro-ophthalmology Department of the Chinese People’s Liberation Army, General Hospital from January 2016 to February 2018. They were assigned to two groups based on antibodies status: MOG-Ab-seropositive ON (MOG-ON) and aquaporin-4 Ab-seropositive ON (AQP4-ON). Results. Seventy-six male patients were assessed, including 44 MOG-ON (57.9%) and 32 AQP4-ON (42.1%). The MOG-ON patients were significantly younger at onset compared to the AQP4-ON group (p<0.001). Frequencies of optic disc swelling, presence of abnormal autoimmune antibodies, and elevated levels of CSF IgG were significantly higher in the AQP4-ON group than the MOG-ON group (p=0.040, p=0.016, and p=0.10, respectively). At the final visit, 85.3% of MOG-ON eyes had increased visual acuity (≥0.5) compared to 35.1% of AQP4-ON eyes (p<0.001). The ratio of this steroid-dependent condition is higher in MOG-ON patients than the AQP4-ON group (p<0.001). The ratio of conversion to NMO is higher in the AQP4-ON group than the MOG-ON group, with more AQP4-ON patients developing NMO by the follow-up (p=0.012). MOG-ON patients had thicker average peripapillary retinal nerve fiber layers and macular ganglion cell-inner plexiform than AQP4-ON patients (p=0.008 and p=0.012, respectively). Orbital MRI revealed more AQP4-ON patients had chiasmal involvement than MOG-ON patients (p<0.001). Conclusion. Male MOG-ON patients had different clinical features including earlier age of onset, higher optic disc swelling ratio, better visual acuity recovery, thicker peripapillary retinal nerve fiber and macular ganglion cell-inner plexiform layers, and less chiasmal involvement than male AQP4-ON patients. Serum antibody may be a potential biomarker for determining visual prognosis in male ON.

The aim of this study was to evaluate the differences between macular inner retinal layers and peripapillary retinal nerve fibre layer (pRNFL) thickness in Chinese patients with neuromyelitis spectrum optic neuritis (NMOSD-ON) and isolated optic neuritis (ION) with only one episode.This cross-sectional study included 35 patients (35 eyes) with NMOSD-ON (NMO-IgG seropositive) and 46 patients (46 eyes) with ION after one episode. Spectral domain optical coherence tomography (SD-OCT) was used to quantify pRNFL, macular RNFL (mRNFL), ganglion cell and inner plexiform layers (GCIPL) and inner nuclear layer (INL) thickness using an automated algorithm. Differences in OCT parameters between NMOSD-ON and ION were compared after adjusting for age, sex and disease duration.The pRNFL and mRNFL in some locations (average pRNFL, nasal pRNFL, nasal inferior (NI) pRNFL, nasal/temporal (N/T) ratio pRNFL, average mRNFL, inner temporal mRNFL, outer nasal mRNFL and outer temporal mRNFL) in NMOSD-ON differed significantly from those in ION (all p 0.05). These parameters had moderate diagnostic accuracy, with area under curves (AUCs) ranging from 0.684 to 0.762 for pRNFL and from 0.660 to 0.700 for mRNF. The thickness of GC-IPL and INL in all sectors was similar in NMOSD-ON and ION (p 0.05). This study and our meta-analysis of four previous studies obtained consistent results, with pooled mean difference (MD) -10.4 μm (95% CI: -12.4 to -8.4, p 0.001) for pRNFL, -1.5 μm (95% CI: -3.5 to 0.6, p = 0.158) for mRNFL and 0.2 μm (95% CI: -0.4 to 0.9, p = 0.490) for GC-IPL, respectively.Neuromyelitis spectrum optic neuritis (NMOSD-ON) patients had more pRNFL and mRNFL loss compared to ION patients after one episode. Spectral domain optical coherence tomography (SD-OCT) may help to distinguish NMOSD-ON from ION with only moderate diagnostic accuracy.

Little work has been performed on the long-term outcome of optic neuritis (ON) according to the status of aquaporin-4 antibody (AQP4-Ab) and long-term prognosis in older patients in China. This study retrospectively analyzed medical records in a cohort of Chinese patients with 5-year follow-up according to AQP4-Ab status and ages from January 2009 to December 2010. The clinical features, laboratory findings and risk factors for prognosis were analyzed. A total of 128 ON patients were included, 66.4 % of whom were female. The median age at onset was 36.8 years (range 18-73). Serum AQP4-Ab was positive in 45 (35.2 %) patients, with greater frequency in the female, bilateral, and recurrent ON groups (48.2, 42.5 and 53.6 %, respectively). Seropositive AQP4-Ab ON patients had worse visual recovery compared to seronegative patients (p = 0.033). The average and four quadrants of retinal nerve fiber layer (RNFL) thickness were significantly thinner in the seropositive group than in the seronegative group (p

Radiation-induced optic neuropathy (RION) is a severe ocular complication in patients with nasopharyngeal carcinoma (NPC) following external beam radiation therapy. However, the systemic risk factors for this condition remain unclear. Therefore, patients with NPC who received radiotherapy between 2004 and 2007 at the Sun Yat-Sen University Cancer Center were retrospectively reviewed in this case-control study. The study included 40 RION patients and 40 patients in the control group, who were strictly matched to the RION patients by tumor histopathology, location, Union for International Cancer Control-Tumor Node Metastasis classification and radiotherapy protocol. Univariate and multivariate statistical regression analyses were performed to identify factors predictive of RION. The univariate analysis demonstrated that age (>60 years), gender (female) and chemotherapy significantly affected the risk of RION, whereas diabetes, hypertension and hepatitis B virus infection did not exert a significant effect. The results of the multivariate analysis suggested that only gender and chemotherapy were significantly associated with an increased incidence of RION. Therefore, the results of the present study suggested that female gender and chemotherapy constitute risk factors for the development of RION following radiotherapy for NPC. The ocular symptoms of high-risk patients should be carefully investigated and reported by ophthalmologists.

Ethambutol is a common cause of drug-related optic neuropathy. Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss. Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function. Therefore, we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy. The thickness of peripapillary retinal nerve fiber layer, macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients (22 eyes) using optical coherence tomography. Twenty-four healthy age- and sex-matched participants (48 eyes) were used as controls. Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls. The average macular thickness was strongly positively correlated with central visual sensitivity loss (r (2) =0.878, P=0.000). These findings suggest that optical coherence tomography can be used to efficiently screen patients. Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy.

Background: Plasma exchange (PE) is often considered as an effective treatment for neuromyelitis optica spectrum disorder (NMOSD) and several inflammatory demyelinating disorders of the central nervous system. This study aimed to evaluate the visual outcomes of Chinese patients with severe acute isolated optic neuritis (ON) who received PE therapy after high-dose intravenous methylprednisolone (IVMP) treatment. Methods: Thirty-seven acute isolated ON patients experiencing their first attack of severe visual impairment without neurological disability were recruited. All subjects received five cycles of double-filtration plasmapheresis. Visual acuity (VA) was documented at onset, 1 day before PE treatment, at each cycle of PE therapy and at the 1-month follow-up visit. Results: This study included 26 female (70.3%) and 11 male (29.7%) subjects, and 18 subjects (48.6%) had bilateral involvement. The time window between onset and PE treatment was 27.3 ± 12.7 days (range: 6–53 days). Mean VA (logMAR) of the studied eyes at onset, 1-day before PE treatment/after IVMP and after the fifth PE treatment were 3.41 ± 1.50, 2.61 ± 1.64 and 1.66 ± 1.52, respectively ( p 20/800 after IVMP and PE treatments, among which five eyes (13.5%) recovered to Snellen VA 20/20 ( p Conclusion: This study revealed that PE treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. Better visual outcomes can be achieved with early PE treatment.

Purpose The ocular choroid is a sensitive biomarker of vascular perfusion in optic neuritis (ON) patients due to its vascular structures. The purpose of this study was to evaluate alterations in sub-macular choroidal thicknesses (sub-MCT) in aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) sero-positive neuromyelitis optica spectrum disease (AQP4-IgG+/NMOSD) and isolated ON (ION) patients using optical coherence tomography (OCT). Methods A total of 208 ON patients (275 eyes) and healthy controls (HCs) who underwent sub-MCT and retinal microstructure detection with OCT were enrolled in this study. Results Among all the ON patients, 102 (49.0%) cases were identified as serum AQP4-IgG-positive, with 106 (51.0%) cases being negative, excluding multiple sclerosis as the ION cohort. The sub-MCT in the AQP4-IgG+/NMOSD patients decreased in 0-6 months after ON attacks. However, for the ION cohort, the sub-MCT decreased in 0-2 months and then stayed normal or slightly increased in 2-4 months after the first ON attack, finally sharply decreasing after 6 months. For unilateral AQP4-IgG+/NMOSD patients, eyes without ON also presented retinal layer thinning and sub-MCT slight reduction independent of ON attacks. Conclusions The sub-MCT in AQP4-IgG+/NMOSD patients were reduced at all stages of ON, which distinguished the ION patients as decreasing only at chronic stage of ON. It implied that ocular vascular hypoperfusion plays a potential role in ON pathogenesis and the different patterns could be caused by the distinct pathogenesis of AQP4-IgG+/NMOSD and ION.

Background: Migraine is a chronic neurological disorder. However, its pathogenesis is still unclear. This study aimed to measure the posterior ocular structure in patients with migraine using enhanced depth imaging (EDI)-optical coherence tomography (OCT) and explore the probable pathogenesis of migraine. Methods: A total of 115 patients diagnosed with migraine and 50 healthy volunteers were recruited. These participants underwent an ocular examination to exclude the ocular diseases. Retinal nerve fiber layer thickness, macular thickness, and choroid thickness were assessed using EDI-OCT. Results: The nasal peripapillary retinal nerve fiber layer (pRNFL) was significantly thinner in the migraine with aura group (p = 0.001) than that in the control group. The inferior inner macular layer was thinner in the migraine with aura group (p = 0.005). The 3 subfields of choroid were significantly thinner in the migraine with aura group (p = 0.044, 0.008, and 0.029). However, there was no difference between the migraine without aura group and the control group. The nasal pRNFL in migraine with aura was negatively correlated with the product of duration (months) and number of attacks/month (p = 0.039). Conclusion: The changes in the ocular posterior structure may serve as evidence of the trigeminovascular system mechanism underlying migraine and transneuronal retrograde degeneration of the primary visual cortex, which reflects the cortical spreading depression.

Adult demyelinating optic neuritis (ON) with positive myelin-oligodendrocyte glycoprotein antibody (MOG-Ab) has distinct clinical features. This study aimed to investigate the point prevalence, relationship with steroid dependency and prognosis value of MOG-Ab in adult ON.Clinical data analysis was undertaken in adults with ON admitted between December 2014 and January 2016. Patients were classified into three groups based on aquaporin-4 antibody (AQP4-Ab) and MOG-Ab status: AQP4-ON, MOG-ON and seronegative-ON.A total of 158 adults with ON (190 eyes) were assessed, including 31 MOG-ON (19.6%), 67 AQP4-ON (42.4%) and 60 seronegative-ON (38.0%) cases. The female-to-male ratio was significantly lower in MOG-ON (1.8:1) than that in AQP4-ON (8.6:1) groups (p = .005). The median age, percentage of bilateral ON and visual loss at the nadir at onset was similar among the three groups. Thirty-eight eyes (76%) in the MOG-ON group showed good visual recovery (20/40) in the final visit, which is statistically better than that in the AQP4-ON and seronegative-ON groups (p .001 and p = .006, resoectively). Fifteen adults with ON (9.5%) showed dependency on steroid, which was particularly prominent in the MOG-ON group (11/31, 35.5%) and rarely presented in the AQP4-ON (2, 3.0%) and seronegative-ON (2, 3.3%) groups. Results suggested less loss of pRNFL in MOG-ON than that in AQP4-ON group (p .001), and a larger proportion of canalicular segment involved in MOG-ON adults (p = .007 and p .001).MOG-ON had the smallest proportion of acute demyelinating ON in Chinese adults. One third of adults with MOG-ON predominantly showed a substantial dependency on steroids and relapse on steroid reduction or cessation, which rarely presented in AQP4-ON and seronegative-ON adults.

PURPOSE To analyse the clinical characteristics of simultaneous bilateral ON patients in China. METHODS This retrospective study was done on 51 primary bilateral ON patients between April 2008 and July 2016 at the Chinese People's Liberation Army General Hospital. Fifty eight primary unilateral ON patients formed the control group. Demographic data, clinical course, serum autoantibody status, connective tissue disorders, magnetic resonance imaging and visual functions were compared. RESULTS The mean age at disease onset in the bilateral group was younger than that of the unilateral group (p = 0.001). Cerebrospinal fluid (CSF) total cell count and CSF total protein were significantly higher in the bilateral group (p = 0.001, p = 0.025). Aquaporin-4 (AQP4) antibodies were detected in 39% and 21% of the bilateral and unilateral patients, respectively (p = 0.03). Twenty two percent of the bilateral patients fulfilled the diagnosis of neuromyelitis optica (NMO); 7% in the unilateral group did so (p = 0.03). Serum autoantibodies (ANA, SSA, SSB, etc.) were found in 49% of the bilateral patients and 29% of the unilateral patients (p = 0.035). After treatment, the bilateral patients were significantly more prone to severe visual disability eventually than their unilateral counterparts (p = 0.002). Patients with MOG-IgG (myelin oligodendrocyte glycoprotein-IgG) represented 26% of the patients negative for AQP4-IgG. Myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) sero-positive patients were more likely to recover than the other patients (p

To review the clinical features of optic neuritis (ON) combined with chronic hepatitis B (CHB) retrospectively.Clinical data were reviewed for hospitalized patients diagnosed with isolated ON combined with chronic hepatitis B (CHB-ON) in the Chinese People's Liberation Army General Hospital. The ON diagnosis was confirmed following the criteria of the Optic Neuritis Treatment Trial (ONTT) group. The diagnostic criteria for CHB was serological positivity for hepatitis B surface antigen (HBsAg) for more than 6 months. Other infectious conditions that might lead to bias were excluded.A total of 13 patients (6 female and 7 male, 23 involved eyes) diagnosed with CHB-ON were selected. A total of 12/13 patients presented as atypical ON: 10/13 of the patients exhibited simultaneous or early sequential bilateral eye involvement; 11/13 involved eyes in the acute phase presented with pronounced optic disc edema; and 11/13 patients exhibited corticosteroid resistant. A total of 12/23 affected eyes suffered severe vision loss (20/200) at the end of the follow-up period, which averaged 13.7 (4-31) months. None of the patients progressed to multiple sclerosis (MS) or neuromyelitis optica (NMO). All blood samples were negative for serological aquaporin 4-antibody using the cell-based assay.CHB-ON usually presented as the atypical form. Chronic hepatitis B virus infection may lead to the tendency for ON exacerbation.

Objective. This study aims to describe the clinical manifestations and outcomes in a cohort of older Chinese patients.Method. A retrospective study of patients aged ≥ 45 years who had a first episode of optic neuritis (ON) between May 2008 and November 2012. Clinical features at onset and last follow-up were analyzed within subgroups (age 45–65 years and age ≥ 65 years).Results. 76 patients (99 eyes) were included, of which 58% were females. The mean age at presentation was 55.53 ± 8.29 years (range: 45–83 years). Vision loss was severe at presentation, with initial best corrected vision activity (BCVA) Conclusion. Chinese patients in the age group ≥ 65 years with ON are less likely to develop NMOSD or MS. Notwithstanding, they had more severe visual loss at onset and poor recovery.

Junqing Wang,1,* Yuan Tian,2,* Yi Shao,3,* Hui Feng,1 Limin Qin,1 Weiwei Xu,1 Hongjuan Liu,1 Quangang Xu,1 Shihui Wei,1 Lin Ma2 1Department of Ophthalmology, 2Department of Radiology, Chinese PLA General Hospital, Beijing, 3Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Objective: Many previous studies have demonstrated that neuromyelitis optica (NMO) patients have abnormalities of brain anatomy and function. However, differences in spontaneous brain activity between myelin oligodendrocyte glycoprotein (MOG)-IgG ON and aquaporin 4(AQP4)-neuromyelitis optica-optic neuritis (ON) remain unknown. In the current study, we investigated the brain neural homogeneity in MOG-IgG ON versus AQP4-IgG NMO-ON subjects by regional homogeneity (ReHo) method using magnetic resonance imaging (MRI). Patients and methods: A total of 32 NMO-ON and ON subjects (21 with AQP4-IgG+NMO-ON and 11 with MOG-IgG+ON) and 34 healthy controls (HCs) closely matched for age were recruited, and scans were performed for all subjects. A one-way analysis of variance (ANOVA) was performed to determine the regions in which the ReHo was different across the three groups. NMO-ON and ON subjects were distinguished from HCs by a receiver operating characteristic (ROC) curve. The relationship between the mean ReHo in many brain regions and clinical features in NMO subjects was calculated by Pearson correlation analysis. Results: Compared with HCs, MOG-IgG+ON subjects had significantly decreased ReHo values in the posterior lobe of the left cerebellum and increased ReHo values in the left inferior frontal gyrus, right prefrontal gyrus, and left precentral/postcentral gyrus. AQP4-IgG+NMO-ON subjects showed higher ReHo values in the left inferior frontal gyrus and right middle temporal/occipital gyrus. Compared with MOG-IgG+ON subjects, AQP4-IgG+NMO-ON subjects had lower ReHo values in the posterior lobe of the right cerebellum.AQP4-Ig+NMO-ON subjects showed higher ReHo values in the left precentral/postcentral gyrus and right superior temporal gyrus. Conclusion: AQP4-IgG+NMO-ON and MOG-IgG+ON subjects showed abnormal synchronized neuronal activity in many brain regions, which is consistent with deficits in visual, motor, and cognitive function. Furthermore, different patterns of synchronized neuronal activity occurred in the AQP4-IgG+NMO-ON and MOG-IgG+ON. Keywords: neuromyelitis optica-optic neuritis, MOG-IgG, AQP4-IgG, regional homogeneity, resting state, functional magnetic resonance imaging

Background/aimsTo investigate the clinical features of Chinese patients with seropositive myelin oligodendrocyte glycoprotein antibody (MOG-Ab) optic neuritis (ON) and patients with seropositive aquaporin-4 antibody (AQP4-Ab) ON.MethodsIn this retrospective observational study, sera from patients with demyelinating ON were tested for MOG-Ab and AQP4-Ab with a cell-based assay. Clinical characteristics were compared between MOG-Ab-related ON (MOG-ON) and AQP4-Ab-related ON (AQP4-ON), including visual performances, serum autoantibodies and features on MRI.ResultsA total of 109 affected eyes from 65 patients with demyelinating ON (20 MOG-ON and 45 AQP4-ON) were included. The onset age of MOG-ON was younger than AQP4-ON (MOG-ON: 20.2±17.4 years old, AQP4-ON: 35.6±15.7 years old, P=0.001). Onset severity was not different between these two groups (P=0.112), but patients with MOG-ON showed better visual outcomes (P=0.004). Half of the MOG-ON had a relapsing disease course. Nineteen per cent of patients with AQP4-ON presented coexisting autoimmune disorders, but there were no coexisting autoimmune disorders among patients with MOG-ON. Optic nerve head swelling was more prevalent in patients with MOG-ON (PConclusionsMOG-ON is not rare in Chinese demyelinating patients. It underwent a severe vision loss at onset but had relatively better visual recovery than patients with AQP4-ON. MOG-ON might have an unique pathogenesis different from AQP4-ON.

To evaluate the clinical features and prognosis of atypical optic neuritis (ON) with seronegative aquaporin-4 (AQP4) antibody in Chinese patients.All patients with first or relapsing ON were recruited from the Neuro-ophthalmology Department of the Chinese People's Liberation Army General Hospital from January 2013 to December 2014 and assigned to one of three groups based on diagnosis: atypical ON, typical ON and neuromyelitis optica spectrum disorder (NMOSD)-ON.A total of 173 patients were included in the cohort. Fifty patients (28.9%) were AQP4-Ab-positive and diagnosed with NMOSD-ON. Of 123 patients with seronegative AQP4-Ab, 37 (30.1%) patients had atypical ON, with male predominance (25, 67.6%). The atypical ON group (compared with the typical ON and NMOSD-ON groups) had a significantly lower female:male ratio (1:2.1 vs 1.8:1 and 9:1, respectively, p=0.001 and p0.001), an older mean age of onset (44.8, 13-71 years vs 36.9, 13-73 years and 36.2, 13-66 years, p=0.003 and p=0.004), a lower rate of good (≥0.5) visual recovery (6.7% vs 79.8% and 30.9%, p0.001 and p0.001) and (compared with the NMOSD-ON group) a lower recurrence rate during a 2-year follow-up (29.3% vs 60%, p=0.009). However, none developed to multiple sclerosis or neuromyelitis optica in the atypical ON group.Atypical ON with seronegative AQP4-Ab had unique clinical features in this Chinese cohort, including male predominance, an older age of onset, worse visual acuity recovery and resistance to corticosteroid therapy. This condition may be a distinct nosological entity with an unusual clinical and therapeutic profile.

Microglial activation has been recognized as a neuropathological feature in diabetic retinopathy. But the early spatiotemporal characterization of microglial activation in the retina and the optic nerve of diabetic animals has not been fully investigated. The purpose of this study was to investigate early sequential changes of microglia in the retinas of rats with streptozotocin-induced diabetes. Microglia in the optic nerves of rats with streptozotocin-induced diabetes were also studied. In 4-week, 8-week, and 12-week diabetic and normal control rats, microglial activation in the retinas and optic nerves was evaluated by immunolabeling with OX-42 antibody. Density, proportion of activation, and laminar distribution of retinal microglia were quantified. The retinal mRNA level of Iba-1, a microglial-specific marker, was measured by real-time PCR. The density of retinal microglia was not different between diabetic and control rats, but the proportion of activated microglia increased significantly in diabetic rats at each time point. The proportion of microglia increased obviously in the nerve fiber layer and the ganglion cell layer while decreasing in the inner plexiform layer in 12-week diabetic rats. Moreover, retinal Iba-1 mRNA expression increased in 8-week and 12-week diabetic rats. Processes of microglia in the optic nerves of control rats were aligned with the long axis of nerve fibers, while the alignment was disturbed in diabetic rats. Morphology, proportion of activation, distribution, and mRNA expression of retinal microglia changed characteristically with the progression of the disease in early-stage diabetic rats.

Pathological optic disc cupping (ODC) is predominantly referred to as glaucoma; however, it is not only glaucoma that leads to pathological optic disc excavation. A number of other nonglaucomatous diseases also result in optic atrophy and excavation of the optic disc. Therefore, in the present study, the etiology of nonglaucomatous optic disc cupping (NGODC) was analyzed and differentiated from glaucomatous optic disc cupping (GODC). The morphology and clinical data of 19 eyes, from 12 patients exhibiting NGODC, were analyzed. Of the 12 cases, none were diagnosed with glaucoma, four presented with optic neuritis, one with Devic’s disease, one with Leber’s hereditary optic neuropathy, two with pituitary adenoma, one with basal ganglia cerebral hemorrhage, one with cilioretinal artery occlusion associated with central retinal vein occlusion, one with central retinal artery occlusion and the remaining patient exhibited optic nerve injuries. The key features that differentiated NGODC from GODC were the color of the optic disc rim and the correlation between visual field defects and the disc appearance. The focally notched disc also aided in distinguishing between the two disorders. The results of the present study indicated that it is critical to acknowledge that nonglaucomatous diseases also lead to ODC and that distinguishing between them is necessary.

Introduction: There are few studies focusing on Binocular hepatitis B related optic neuritis (HB-ON) and associated therapies are still limited. We present a case of HB-ON which has been cured with therapeutic plasma exchange (TPE). Patient concerns: The patient was diagnosed as acute hepatitis B in hepatology and got a rapid loss of binocular visual acuity (2/100 in the right eye and no light perception in the left eye) after the onset. Diagnosis: Hepatitis B related optic neuritis. Interventions: Methylprednisolone and therapeutic plasma exchange. Outcomes: The treatment of high dose methylprednisolone was not curative. After 5 TPE sessions, the patient's best corrected visual acuity (BCVA) returned to 20/20 in the right eye and finger counting (FC)/40 cm in the left eye. One month later, the visual acuity increased to 5/100 in the left eye. Conclusion: This is the first case in which we used TPE to cure HB-ON. Also, it can demonstrate the relationship between HB-ON and immunopathogenesis. The case may provide an effective method for the treatment of hormone invalid and disabled ON in clinical practice.

In the present study, the changes in the retinal nerve fiber layer (RNFL) thickness associated with Leber’s hereditary optic neuropathy (LHON) were examined by Cirrus high definition-optical coherence tomography (OCT), and the correlation between the RNFL thickness and the best corrected visual acuity (BCVA) was evaluated. A cross-sectional study was performed. Sixty-eight eyes from patients with LHON and 30 eyes from healthy individuals were scanned. Affected eyes were divided into 5 groups according to disease duration: Group 1, ≤3 months; group 2, 4–6 months; group 3, 7–9 months; group 4, 10–12 months; and group 5, >12 months. The RNFL thickness of the temporal, superior, nasal and inferior quadrants and the 360° average were compared between the LHON groups and the control group. The eyes in groups 1 and 2 were observed to have a thicker RNFL in the superior, nasal and inferior quadrants and a higher 360°-average RNFL thickness compared with those of the control group (P

This study retrospectively analyzed the frequency of anti-thyroid antibodies (ATAs) and thyroid disease in patients with optic neuritis (ON).Tests of serum thyroglobulin (TG) and thyroid peroxidase (TPO) antibodies and thyroid function were performed in 97 ON patients. Blood also was drawn to test for AQP4-Ab using cell-based and enzyme-linked immunosorbent assays. Comparisons of the frequencies of ATAs, thyroid diseases and thyroid function were performed based on AQP4-Ab status.Seropositive AQP4-Ab was found in 47/97 (48.5%) patients. ATA was considered positive in 34/97 (35.1%) patients. The prevalence of ATA was two times higher (P = 0.019) in the AQP4-Ab+ group compared to the AQP4-Ab- group. AQP4-Ab+ ON patients exhibited lower FT3 (P = 0.006) and FT4 (P = 0.025) levels and a higher prevalence of definite Hashimoto thyroiditis (HT) (P = 0.005). Among AQP4-Ab+ patients, those with HT had a worse visual outcome than non-HT patients.A high prevalence of ATAs and HT was found in AQP4-Ab+ ON patients, and AQP4-Ab+ patients with HT exhibited worse visual outcomes than non-HT patients.

Objectives This study aimed to analyse the structural injury of the peripapillary retinal nerve fibre layer (pRNFL) and segmented macular layers in optic neuritis (ON) in aquaporin4-antibody (AQP4-Ab) seropositivity(AQP4-Ab-positiveON) patients and in AQP4-Ab seronegativity (AQP4-Ab-negative ON) patients in order to evaluate their correlations with the best-corrected visual acuity (BCVA) and the value of the early diagnosis of neuromyelitis optica (NMO). Design This is a retrospective, cross-sectional and control observational study. Methods In total, 213 ON patients (291 eyes) and 50 healthy controls (HC) (100 eyes) were recruited in this study. According to a serum AQP4-Ab assay, 98 ON patients (132 eyes) were grouped as AQP4-Ab-positive ON and 115 ON patients (159 eyes) were grouped as AQP4-Ab-negative ON cohorts. All subjects underwent scanning with spectralis optical coherence tomography (OCT) and BCVA tests. pRNFL and segmented macular layer measurements were analysed. Results The pRNFL thickness in AQP4-Ab-positive ON eyes showed a more serious loss during 0–2 months (-27.61μm versus -14.47 μm) and ≥6 months (-57.91μm versus -47.19μm) when compared with AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON preferentially damaged the nasal lateral pRNFL. The alterations in the macular ganglion cell layer plus the inner plexiform layer (GCIP) in AQP4-Ab-positive ON eyes were similar to those in AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON eyes had entirely different injury patterns in the inner nuclear layer (INL) compared with AQP4-Ab-negative ON eyes during the first 6 months after the initial ON attack. These differences were as follows: the INL volume of AQP4-Ab-positive ON eyes had a gradual growing trend compared with AQP4-Ab-negative ON eyes, and it increased rapidly during 0–2 months, reached its peak during 2–4 months, and then decreased gradually. The pRNFL and GCIP in AQP4-Ab-positive ON eyes had positive correlations with BCVA. When the pRNFL thickness decreased to 95%CI (50.77μmto 60.85μm) or when the GCIP volume decreased to 95%CI (1.288 mm3to 1.399 mm3), BCVA began to be irreversibly damaged. Conclusion The structural alterations of pRNFL and GCIP could indicate the resulting visual damage. In addition, the injury pattern of INL could be a potential structural marker to predict the conversion of ON to NMO.

Purpose. Although optic neuritis (ON) in children is relatively common, visual outcomes and factors associated with the condition have not been well documented. The aim of this study was to evaluate the clinical features and visual outcomes of ON in Chinese children.Methods. Patients with a first episode of ON at a tertiary neuroophthalmic centre in China were assessed and followed up for at least three months. Visual outcomes and clinical, laboratory, and neuroimaging findings were reviewed. In patients with bilateral ON, only the eyes with worse visual acuity (VA) at presentation were used for statistical analysis.Results. Seventy-six children (76 eyes) with a first episode of ON were included. The mean age was 11.8 years, 60.5% were females, and 48.7% had bilateral involvement. The children were followed up for an average of 18.5 months (age range, 3–48 months). Vision loss at presentation was severe, with VA < 20/200 in 37 eyes (48.7%). At the final visit, 3 (3.9%) eyes had VA of at least 20/20, and 41 (53.9%) eyes had VA of at least 20/40. The final VA in 35 eyes (46.1%) was worse than 20/40. Children aged ≤ 10 years had better predicted visual outcomes when compared to children over 10 years (odds ratio = 2.73, 95% confidential interval: 1.05–7.07, andP=0.039). The other features of this cohort, such as sex, experienced bilateral attack, VA at presentation, presence of optic disc edema, systemic diseases, magnetic resonance imaging (MRI) findings, and aquaporin-4 (AQP-4) antibody status, were not significantly correlated with the final visual outcome.Conclusion. The data revealed the clinical characteristics and visual outcomes of ON in Chinese children. ON in children was associated with severe vision loss and relatively good visual recovery. The age at onset could predict the final visual function.

Neuromyelitis optica spectrum disorders (NMOSDs) are blindness-causing neuritis. In NMOSD patients, NMO-IgG evokes astrocytopathy that in turn causes demyelination. While measurement of NMO-IgG titer will help neurologists make the diagnosis of NMOSDs, it is not sufficient to evaluate the severity of astrocytopathy. In this study, we compared the different levels of an astrocyte biomarker in cerebrospinal fluid of NMOSD patients with good or poor recovery, and then linked their differences to the changes in remyelinating promoter (CXCL12) levels. Our results indicate that NMO-IgG down-regulated CXCL12 and impaired the remyelinating process, this may be a mechanism contributing to the poor recovery of NMOSDs.

The detection of anti-aquaporin-4 autoantibody (AQP-4 Ab) is crucial to detect patients who will develop neuromyelitis optica (NMO); however, there are few studies on the AQP-4 Ab serostatus of patients with neuromyelitis optica spectrum ON. We analyzed the clinical and paraclinical features of neuromyelitis optica spectrum ON patients in China according to the patients' AQP4-Ab serostatus. 125 patients with recurrent and bilateral ON with simultaneous attacks were divided into AQP-4 Ab-seropositive and -seronegative groups. Demographic, clinical, serum autoantibody data, connective tissue disorders (CTDs), visual performance were compared. A Visual Acuity (VA) of less than 0.1 during acute ON attacks occurred more frequently in the seropositive group (p = 0.023); however, there was not a significant difference between groups on VA recovery after the first attack. The seropositive group experienced the worst outcome during the last attack (p = 0.017). Other co-existing autoimmunity antibodies (p < 0.001) and CTDs (p < 0.001) were more prevalent in seropositive patients. There were no significant differences on VA recovery and RNFLT combined with other autoantibodies or CTDs. The two groups did not differ significantly with regard to time to relapse, annualized relapse rates, time of diagnosis NMO, or RNFL. There were no significant differences on VA recovery and RNFLT combined with other autoantibodies or CTDs. RNFLT was thinner in NMO seropositive patients. Although AQP-4 Ab expression predicted poor visual outcome, positive patients were usually associated with mild symptoms at first onset. Anti-SSA/SSB antibody or Sjogren syndrome may be associated with AQP-4 Ab in neuromyelitis optica spectrum ON.

Background Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy. Methods We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-α, IL-1β and ICAM-1 levels were also measured. Results We observed the retinal pericytes, endothelial injury/death and breakdown of blood–retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1β were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-α. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF. Conclusions Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.

Background Optic neuritis (ON) is often associated with other clinical or serological markers of connective tissue diseases (CTDs). To date, the effects of autoantibodies on ON are not clear. Purpose To assess the prevalence, clinical patterns, and short outcomes of autoantibodies and Sjogren’s syndrome (SS) involvement in Chinese ON patients and evaluate the relationship between ON, including their subtypes, and autoantibodies. Methods A total of 190 ON patients were divided into recurrent ON (RON), bilateral ON (BON), and isolated monocular ON (ION). Demographic, clinical, and serum autoantibodies data were compared between them with and without SS involvement. Serum was drawn for antinuclear antibody (ANA), extractable nuclear antigen antibodies (SSA/SSB), rheumatoid factor (RF), anticardiolipin antibodies (ACA), and anti-double-stranded DNA antibody (A-ds DNA), anticardiolipin antibody (ACLs), anti-β2-glycoprotein I (β2-GPI) and Aquaporin-4 antibodies (AQP4-Ab). Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate the atrophy of the optic nerve. Results 68 patients (35.79%) had abnormal autoantibodies, 26(13.68%) patients met diagnostic criteria for CTDs, including 15(7.89%) patients meeting the criteria for SS. Antibodies including SSA/SSB 23 (30.26%) (p1 and p 2

Ankylosing spondylitis (AS), which primarily affects the sacroiliac joints, spine, and enthuses, is a chronic inflammatory rheumatic disorder. Acute anterior uveitis is the most common ophthalmologic involvement, whereas optic neuritis (ON) rarely coexists with AS.[1] ON is an immune-mediated inflammation of the optic nerve, which could be the initiated symptom of multiple sclerosis (MS) or neuromyelitis optica (NMO). Bilateral simultaneous ON with long enhanced optic nerve lesions in magnetic resonance imaging (MRI) was considered as features of NMO spectrum disorders (NMOSDs). However, comprehensive review of the current literature showed little evidence of AS as an accompanied autoimmune condition in NMO,[2] and the specific biomarker aquaporin-4 antibody (AQP4-Ab) was negative in our patient. In the current report, we present the first case of ON with active AS in a Chinese male patient. The association between the two diseases remains to be evaluated. A male patient aged 31 years suffered sudden decreased vision in two eyes without ocular pain. The vision loss began with central scotoma and darkened in the whole visual field, equivalent in the two eyes, and quickly progressed to no-light-perception (NLP) in several hours. The immediate fundus examination revealed slight swelling optic disc with normal retina. Symmetrical thickening of temporal peripapillary retinal nerve fiber layer was revealed by optical coherence tomography. Fundus fluorescence angiography showed mild fluorescence of the optic disc in a later phase. The initial diagnosis of bilateral ON was made. However, no efficient treatment was given by the local hospital. Twenty days later, the patient came to us with bilateral pale optic discs. Visual acuity (VA) in the right eye was light-perception while in the left eye was still NLP. Bilateral mydriasis was found, and the relative afferent papillary defect was positive in the left pupil. Flash-visual evoked potential of the two eyes showed severely decreased amplitude of P100 while bilateral electroretinogram was normal. Brain, cervical thoracic and orbital MRI were performed and showed bilateral optic nerves enlargement, T2 hyperintensity, and gadolinium enhancement [Figure 1]. Figure 1 The image evidences of optic neuritis in our clinic (20 days after onset). The appearance of optic discs were pale with blurred border in both right (a) and left (b) eyes; (c) Orbital magnetic resonance imaging showed gadolinium enhancement in bilateral ... Blood tests showed greatly increased C-reaction protein (CRP) of 107 mg/L (normal range: 0–8 mg/L), erythrocyte sedimentation rate (ESR) of 88 mm/h (normal range: 0–15 mm/h), and strong positive HLA-B27 (98%, normal range: 0–7.14%). The examination of serum used the best available method (cell-based assay) revealed negative AQP4-Ab. The results of other serologic testing of antinuclear antibody spectrum, anti-neutrophil cytoplasmic antibody, rheumatoid factor, anticardiolipin antibody, angiotensin converting enzyme, syphilitic serologic test, and paraneoplastic tests were all negative. Lumbar puncture was performed and showed normal cerebral-spinal fluid (CSF) in the routine tests, including the cell count and protein concentration, as well as negative oligoclonal bands. The patient's father had a history of AS for 20 years. The diagnosis of AS was confirmed for the patient himself 10 months ago according to the New York criteria.[1] He received nonsteroidal anti-inflammatory drugs and sulfasalazine irregularly, together with intraarticular injection of corticosteroid to control the symptoms. When the visual symptoms occurred, bilateral gonarthritis was found. The severe back pain lasted and the morning stiffness prolonged from several minutes to more than 0.5 h. Exudation of bilateral knee joints cavity and bilateral sacroiliitis of grade 2 were revealed by ultrasonography and computed tomography, respectively. The significantly elevated ESR and CRP, combined with a Bath Ankylosing Spondylitis Disease Activity Index of 5.5 indicated the co-existed active AS. The patient was treated with intravenous methylprednisolone, which began with 1 g for 3 days, then followed by oral 1 mg/kg for 10 days and tapered. VA in the right eye improved to hand move when discharged and to 0.02 after our follow-up period of 2 years, but VA in the left eye was continuously NLP. Eye inflammation in AS is largely restricted to the uvea. To date, the co-existed AS and ON were only reported in three cases, but no reaction of AS was observed during ON onset. ON could be the initiated symptoms of MS. The typical ON with the unilateral visual loss, eye pain in movement, and spontaneously recovery will develop to MS in 50% after 15 years according to the results of the ON treatment trial. Nevertheless, the atypical clinical appearance of bilateral eyes involved, optic disc edema, and severe visual loss without eye pain were considered as having lower risks for developing MS. Co-existence of MS and AS was reported in several cases,[3] but the mechanics were still uncertain. A peptide of myelin basic protein was reported to be a ligand of HLA-B27 and both AS and MS may share the similar pathologic pathway of activation of T lymphocytes with the environmental factors. Besides, a causal association between anti-tumor necrosis factor (TNF)-α blockers (infliximab, etanercept, and adalimumab, etc.), which target the overexpressed TNF-α in sacroiliac joints and widely employed against AS, and onset of MS or ON may exists.[4] Yet, our patient had no history of using anti-TNF-α medicine. Moreover, atypical ON was showed in this case, and CSF was negative for intrathecal production of oligoclonal bands, which may indicate non-MS mediated etiology. Atypical ON may indicate a high prevalence of serum AQP4-Ab, and ON with seropositive AQP4-Ab was covered in the term of NMOSDs. The diagnostic criteria of NMOSDs including classical NMO and some limited forms, which may have the same pathogenesis mechanisms of astrocyte damage with complement and antibody mediated cytotoxicity. Serum AQP4-Ab, known as NMO-IgG, the presence of which was over 70% sensitive and 100% specific by cell-based assay for clinically defined NMO,[5] is critical in distinguishing NMO related ON from MS. Moreover, 10–25% of patients clinically diagnosed with NMO are seronegative for AQP4-IgG. Hence, extended follow-up in our patient was necessary. In conclusion, this is the first case of severe bilateral ON with active AS. Further investigations should be made in the ON population of China and may provide more clinical evidences for this phenomenon. Financial support and sponsorship This work is supported by the National “863” Plan Biological and Medical Technology Project “Development of equipments in diagnosis and visual function evaluation for optic neuritis” (No. 2015AA020511). Conflicts of interest There are no conflicts of interest.

A 12‑year‑old Chinese girl presented with gradual vision loss and insulin‑dependent diabetes mellitus and was suspected to suffer from Wolfram syndrome (WFS). A series of clinical examinations were performed, as well as direct DNA sequencing to screen the entire coding region of the WFS1 gene in the patient's family, including her parents and a brother. Ophthalmological examination revealed counting fingers/10 cm in the right eye and hand motions/10 cm in the left eye. Ophthalmoscopical examination identified bilateral optic atrophy without any signs of diabetic retinopathy. A hearing test was performed and revealed that the hearing ability for high frequency sounds was decreased. Urinary output in 24 h was >5,000 ml. In addition, a base substitution at c.2411T>C (Leu804Pro) in exon 8 was identified which was homozygous with the patient and heterozygous with the healthy parents and the brother. In the present case, a neuroophthalmology consult performed in the early stages of the disease was crucial for early diagnosis. In addition, this case study highlights the importance of performing a hearing test as well as collecting and analyzing 24‑h urine output in patients presenting with juvenile diabetes mellitus patients and optic atrophy without any signs of diabetic retinopathy.

Neovascular glaucoma (NVG) is a rare but severe complication of hypoperfusion retinopathy. Our objective was to analyse the clinical features of NVG secondary to carotid artery atherosclerosis, moyamoya disease and Takayasu arteritis.Thirty-six cases (36 eyes) with hypoperfusion retinopathy associated with NVG were retrospectively analysed. Each patient had their visual acuity assessed and fundus examined by fundus fluorescein angiography, colour Doppler flow imaging, magnetic resonance angiography, digital subtraction angiography and other techniques.Eyes belonging to 30 males and six females were analysed. There were 24 right eyes and 12 left eyes. The ages of these patients ranged 18 to 78 years and the mean age was 40 years. The visual acuities ranged from light perception to 0.8 (decimal notation). Posterior segment manifestations included mid-peripheral intraretinal haemorrhages and narrowed retinal arteries. All eyes were associated with either an ipsilateral common carotid artery obstruction or a severe bilateral obstruction of the internal carotid arteries.The characteristic clinical features are presented during the process of the disease. Degeneration of the ocular fundus was predominantly on one side. The retinal manifestations included mid-peripheral haemorrhages and dilated retinal veins. High intraocular pressure and excavation and atrophy of the optic disc were common. In the eyes that were examined, neovascularisation was observed in the iris and anterior chamber and various visual field defects were present.

Background Diabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent. Objective To assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy. Methods A literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software. Results Thirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88μm, 95%CI: -4.44 to -1.32, P = 0.0003) and in studies applying Scanning Laser Polarimeter (-4.21μm, 95%CI: -6.45 to -1.97, P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant (-3.79μm, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99μm, 95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88μm, 95%CI: -4.93 to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22μm, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients. Conclusion Peripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention.

BackgroundDiffusion tensor imaging (DTI) has been used for the evaluation of the white matter integrity. In this study, we evaluated optic nerve impairment in patients with neuromyelitis optica (NMO) using DTI.Methodology/principal findingsOptic nerve DTI were performed on 28 NMO patients and 38 normal controls. Fractional anisotropy (FA) values were measured in the anterior, middle, and posterior parts of the intraorbital optic nerve segment. For the posterior intraorbital optic nerve, FA values of BI (0.20±0.07), MI (0.24±0.16), and NA (0.25±0.14) decreased significantly compared with that of NC (0.43±0.07) (PConclusions/significanceDecreased FA value in the intraorbital optic nerve, especially in the posterior part of the nerve, was demonstrated as a characteristic MR feature for NMO-related optic nerve impairment.

Background To characterize macular thickness (MT) changes in Leber’s hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). Methods Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ≤3 months; 2nd group: 3–6 months; 3rd group: 6–9 months; 4th group: 9–12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. Results Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P