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Structural and Functional Alterations in Visual Pathway After Optic Neuritis in MOG Antibody Disease: A Comparative Study With AQP4 Seropositive NMOSD.

ABSTRACT: Background: Optic neuritis (ON) is an important clinical manifestation of neuromyelitis optic spectrum disease (NMOSD). Myelin oligodendrocyte glycoprotein (MOG) antibody-related and aquaporin 4 (AQP4) antibody-related ON show different disease patterns. The aim of this study was to explore the differences in structure and function of the visual pathway in patients with ON associated with MOG and AQP4 antibodies. Methods: In this prospective study, we recruited 52 subjects at Beijing Tiantan Hospital, including 11 with MOG Ig+ ON (MOG-ON), 13 with AQP4 Ig+ ON (AQP4-ON), and 28 healthy controls (HCs). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of optic radiation (OR), primary visual cortex volume (V1), brain volume, and visual acuity (VA) were compared among groups. A multiple linear regression was used to explore associations between VA and predicted factors. In addition, we used optical coherence tomography (OCT) to examine thickness of the peripapillary retinal nerve fiber layer (pRNFL) and retinal ganglion cell complex (GCC) in a separate cohort consisting of 15 patients with ON (8 MOG-ON and 7 AQP4-ON) and 28 HCs. Results: Diffusion tensor imaging showed that the FA of OR was lower than controls in patients with AQP4-ON (p = 0.001) but not those with MOG-ON (p = 0.329) and was significantly different between the latter two groups (p = 0.005), while V1 was similar in patients with MOG-ON and AQP4-ON (p = 0.122), but was lower than controls in AQP4-ON (p = 0.002) but not those with MOG-ON (p = 0.210). The VA outcomes were better in MOG-ON than AQP4-ON, and linear regression analysis revealed that VA in MOG-ON and AQP4-ON was both predicted by the FA of OR (standard β = -0.467 and -0.521, p = 0.036 and 0.034). Both patients of MOG-ON and AQP4-ON showed neuroaxonal damage in the form of pRNFL and GCC thinning but showed no statistically significant difference (p = 0.556, 0.817). Conclusion: The structural integrity of OR in patients with MOG-ON, which is different from the imaging manifestations of AQP4-ON, may be a reason for the better visual outcomes of patients with MOG-ON.

SUBMITTER: Gao C

PROVIDER: S-EPMC8220215 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: To describe a Japanese girl with unilateral optic neuritis who was seropositive for the anti-myelin-oligodendrocyte glycoprotein (MOG). Serial recordings of the pattern visual evoked potentials (pVEPs) were made to follow the dynamic changes of the disease activity. Observations: A 5-year-old girl developed a sudden reduction of vision and deep ocular pain in her right eye. On examination at our university hospital, the best-corrected visual acuity (BCVA) was light perception, and a swelling of the optic disc and tortuous vessels at the posterior pole of the right eye were observed. MRI demonstrated that her right optic nerve was hyperintense on short TI inversion recovery (STIR) sequence. A diagnosis of right papillitis was made, and she was treated with steroid pulse therapy followed by a gradual tapering of oral prednisolone. The visual acuity decreased to no light perception and plasmapheresis combined with high-dose intravenous immunoglobulin therapy was performed. The decimal visual acuity rapidly improved and recovered to 1.2, and no recurrence was observed for at least 1 year. On day 19, she was found to be anti-MOG antibody positive and anti-Aquaporin 4 antibody negative. pVEPs were recorded during the course of the disease process which showed the dynamic changes of the physiology of the visual pathways. The implicit times of the N75 and P100 components were prolonged in the right eye in the acute phase. The right visual acuity remained at 1.2 for at least 1 year, but the implicit times of the N75 and P100 components of the pVEPs of the right eye were still prolonged compared to left eye. Conclusion: Our findings indicate a positive relationship between the anti-MOG antibodies-positivity and the prolonged pVEPs. Further analyses of the pVEPs and other clinical findings of the optic neuritis are needed to establish the clinical significance of the anti-MOG antibodies positivity and optic neuritis for the diagnosis, treatment, and prognosis for this disease.

Project description:Background: Optic neuritis (ON) is a cardinal manifestation of multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-, and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease. However, the prevalence of AQP4-IgG seropositivity and MOG-IgG seropositivity in isolated ON is unclear, and studies comparing visual outcomes and optical coherence tomography (OCT)-derived structural retinal measures between MS-ON, AQP4-ON, and MOG-ON eyes are limited by small sample sizes. Objectives: (1) To assess the prevalence of AQP4-IgG and MOG-IgG seropositivity among patients presenting with isolated ON; (2) to compare visual outcomes and OCT measures between AQP4-ON, MOG-ON, and MS-ON eyes. Methods: In this systematic review and meta-analysis, a total of 65 eligible studies were identified by PubMed search. Statistical analyses were performed with random effects models. Results: In adults with isolated ON, AQP4-IgG seroprevalence was 4% in non-Asian and 27% in Asian populations, whereas MOG-IgG seroprevalence was 8 and 20%, respectively. In children, AQP4-IgG seroprevalence was 0.4% in non-Asian and 15% in Asian populations, whereas MOG-IgG seroprevalence was 47 and 31%, respectively. AQP4-ON eyes had lower peri-papillary retinal nerve fiber layer (pRNFL; -11.7 μm, 95% CI: -15.2 to -8.3 μm) and macular ganglion cell + inner plexiform layer (GCIPL; -9.0 μm, 95% CI: -12.5 to -5.4 μm) thicknesses compared with MS-ON eyes. Similarly, pRNFL (-11.2 μm, 95% CI: -21.5 to -0.9 μm) and GCIPL (-6.1 μm, 95% CI: -10.8 to -1.3 μm) thicknesses were lower in MOG-ON compared to MS-ON eyes, but did not differ between AQP4-ON and MOG-ON eyes (pRNFL: -1.9 μm, 95% CI: -9.1 to 5.4 μm; GCIPL: -2.6 μm, 95% CI: -8.9 to 3.8 μm). Visual outcomes were worse in AQP4-ON compared to both MOG-ON (mean logMAR difference: 0.60, 95% CI: 0.39 to 0.81) and MS-ON eyes (mean logMAR difference: 0.68, 95% CI: 0.40 to 0.96) but were similar in MOG-ON and MS-ON eyes (mean logMAR difference: 0.04, 95% CI: -0.05 to 0.14). Conclusions: AQP4-IgG- and MOG-IgG-associated disease are important diagnostic considerations in adults presenting with isolated ON, especially in Asian populations. Furthermore, MOG-IgG seroprevalence is especially high in pediatric isolated ON, in both non-Asian and Asian populations. Despite a similar severity of GCIPL and pRNFL thinning in AQP4-ON and MOG-ON, AQP4-ON is associated with markedly worse visual outcomes.

Project description:ObjectiveTo investigate whether visual disability which is known to accumulate by poor recovery from optic neuritis (ON) attacks can be lessened by early treatment, we investigated whether the time from symptom onset to high-dose IV methylprednisolone (IVMP) affected visual recovery.MethodsA retrospective study was performed in a consecutive cohort of patients following their first aquaporin-4 (AQP4)-IgG or myelin oligodendrocyte glycoprotein (MOG)-IgG-ON. Best-corrected visual acuity (BCVA) in ON eyes at 3 months (BCVA3mo) was correlated with time to IVMP (days). In cases of bilateral ON, 1 eye was randomly selected.ResultsA total of 29 of 37 patients had ON (27 AQP4-seropositive neuromyelitis optica spectrum disorder [NMOSD] and 9 MOG-IgG-ON), 2 of whom refused treatment. Of the 27 patients included, 10 presented later than 7 days from onset. The median BCVA3mo of patients treated >7 days was 20/100 (interquartile range 20/100-20/200). Patients treated >7 days had an OR of 5.50 (95% CI 0.88-34.46, p = 0.051) of failure to regain 0.0 logMAR vision (20/20) and an OR of 10.0 (95% CI 1.39-71.9) of failure to regain 0.2 logMAR vision (20/30) (p = 0.01) compared with patients treated within 7 days. ROC analysis revealed that the optimal criterion of delay in IVMP initiation was ≤4 days, with a sensitivity and specificity of 71.4% and 76.9%, respectively.ConclusionsIn this retrospective study of ON with AQP4 and MOG-IgG, even a 7-day delay in IVMP initiation was detrimental to vision. These results highlight the importance of early treatment for the long-term visual recovery in this group of patients. A prospective, multicenter study of the effects of timing of IVMP is currently underway.Classification of evidenceThis study provides Class IV evidence that hyperacute treatment of AQP4 and MOG-ON with IVMP increases the chance for good visual recovery (20/20 vision) and that even a greater than 7-day delay in treatment is associated with a higher risk for poor visual recovery.

Project description:Optic neuritis (ON) in patients with anti-myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies has been associated with a better clinical outcome than anti-aquaporin 4 (AQP4)- IgG ON. Average retinal nerve fiber layer thickness (RNFL) correlates with visual outcome after ON.The aim of this study was to examine whether anti-MOG-IgG ON is associated with better average RNFL compared to anti-AQP4-IgG ON, and whether this corresponds with a better visual outcome.A retrospective study was done in a consecutive cohort of patients following anti-AQP4-IgG and anti-MOG-IgG ON. A generalized estimating equation (GEE) models analysis was used to compare average RNFL outcomes in ON eyes of patients with MOG-IgG to AQP4-IgG-positive patients, after adjusting for the number of ON events. The final mean visual field defect and visual acuity were compared between ON eyes of MOG-IgG and AQP4-IgG-positive patients. A correlation between average RNFL and visual function was performed in all study eyes.Sixteen patients were analyzed; ten AQP4-IgG-positive and six MOG-IgG-positive. The six patients with MOG-IgG had ten ON events with disc edema, five of which were bilateral. In the AQP4-IgG-positive ON events, 1/10 patients had disc edema. Final average RNFL was significantly better in eyes following MOG-IgG-ON (75.33μm), compared to 63.63μm in AQP4-IgG-ON, after adjusting for the number of ON attacks (GEE, p = 0.023). Mean visual field defects were significantly smaller (GEE, p = 0.046) among MOG-IgG positive ON eyes compared to AQP-IgG positive ON eyes, but last visual acuity did not differ between the groups (GEE, p = 0.153). Among all eyes, average RNFL positively correlated with mean visual field defect (GEE, p = 0.00015) and negatively correlated with final visual acuity (GEE, p = 0.00005).Following ON, RNFL is better preserved in eyes of patients with MOG-IgG antibodies compared to those with AQP4-IgG antibodies, correlating with better visual outcomes.

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Structural and Functional Alterations in Visual Pathway After Optic Neuritis in MOG Antibody Disease: A Comparative Study With AQP4 Seropositive NMOSD.

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