Retinal nerve fibre layer thinning is associated with worse visual outcome after optic neuritis in children with a relapsing demyelinating syndrome

Eyre, Michael; Hameed, A. Shahul; Wright, Sukhvir; Brownlee, Wallace; Ciccarelli, Olga; Bowman, Richard; Lim, Ming; Wassmer, Evangeline; Thompson, Dorothy; Hemingway, Cheryl; Hacohen, Yael

doi:10.1111/dmcn.13757

Cited by 33 publications

(34 citation statements)

References 33 publications

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“…Of these, 202 articles were selected and assessed for eligibility at the full-text level. After careful evaluation, 35 studies were included that met the inclusion criteria ( 8 , 29 , 30 , 33 , 36 , 39 , 41 , 45 , 47 , 48 , 51 – 54 , 57 , 59 , 63 , 65 , 66 , 68 , 69 , 71 , 72 , 74 – 85 ). The detailed flow chart is presented in Supplementary Figure 9 .…”

Section: Resultsmentioning

confidence: 99%

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

et al. 2020

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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.

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Section: Resultsmentioning

confidence: 99%

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

et al. 2020

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“…Furthermore, the percentage reductions in EDSS score in groups receiving PLEX on days ≤ 15 and days 16 to 30 were significantly greater than those in the groups treated on days 31 to 60 and days 61 to 90 (all, P < 0.05) [ 40 ]. Although two large retrospective studies in adults [ 22 •, 41 ] and one small retrospective study in children with MOG-Ab and ON [ 42 ] demonstrated favorable visual outcome, patients with MOG-Ab can manifest with severe visual loss and permanent paresis or ataxia [ 43 ]. A more aggressive, treatment-resistant, disease course may be seen in younger children in view of the increase susceptibility of the myelinating brain to MOG-Ab disease, as the autoantibody-mediated damage to the not fully matured (uncompact myelin) may result in secondary damage and irreversible axonal loss [ 44 ].…”

Section: Part 4: How To Treat?mentioning

confidence: 99%

Treatment Approaches for MOG-Ab-Associated Demyelination in Children

Hacohen

Banwell

2019

Curr Treat Options Neurol

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Purpose of reviewThe purpose of this review is to summarize current understanding regarding the treatment of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination in children. Emphasis is placed on the unique obstacles we face when predicting the risk of relapse and the important implications of such challenges when planning treatment protocols.Recent findingsMOG-Abs are consistently identified in a range of acquired demyelinating syndromes (ADS) in adults and children with a clinical phenotype distinct of MS and AQP4-Ab neuromyelitis optica spectrum disorder. Although initially thought to be associated with a benign disease, recent reports of children who are treatment-resistant and developed progressive disability over time raise important questions about how children with relapsing MOG-Ab disease should be managed.SummaryMOG-Abs are common in children with ADS with both monophasic and relapsing disease courses. Treatment of patients with MOG-Ab-associated demyelination includes management of acute relapses and chronic immunotherapy for those with relapsing disease. Emerging consensus supports distinction of treatment strategies from those typically used for relapsing remitting MS, and several groups debate whether to follow treatment protocols akin to those for AQP4-Ab NMOSD. A key challenge remains predicting the severity of the disease at onset. Collaborative international consensus to derive shared clinical evaluative platforms standardized biological and neuroimaging protocols which can be used clinically, and partnered research programs are required to advance personalized treatment for children with MOG-Ab-associated demyelination.

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“…Atrophy of the brain (in particular the thalami) and spinal cord, measured longitudinally, correlates with disability accumulation and cognition, and could be used as a quantitive outcome measure both clinically and as part of clinical trials . Similarly, optical coherence tomography can be used alongside clinical parameters as an objective measure of neuroaxonal loss in children with optic neuritis …”

Section: Future Perspectives and Areas Of Researchmentioning

confidence: 99%

“…79 Similarly, optical coherence tomography can be used alongside clinical parameters as an objective measure of neuroaxonal loss in children with optic neuritis. 80 Another important area of development is that of induction versus escalation therapy. 81 The current approach to treatment of paediatric-onset multiple sclerosis involves initiation of treatment with safer but probably less-efficacious first-line therapies, then subsequently proceeding to more-efficacious second-line therapies as required ('escalation').…”

Section: Future Perspectives and Areas Of Researchmentioning

confidence: 99%

Paediatric multiple sclerosis: a new era in diagnosis and treatment

Duignan

Brownlee

Wassmer

et al. 2019

Develop Med Child Neuro

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Multiple sclerosis is a chronic immune‐mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) and aquaporin‐A antibodies (AQP4‐Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long‐term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow‐up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long‐term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short‐ and long‐term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon‐β1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. What this paper adds Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody‐mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

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Retinal nerve fibre layer thinning is associated with worse visual outcome after optic neuritis in children with a relapsing demyelinating syndrome

Cited by 33 publications

References 33 publications

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

AQP4-IgG and MOG-IgG Related Optic Neuritis—Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis

Treatment Approaches for MOG-Ab-Associated Demyelination in Children

Paediatric multiple sclerosis: a new era in diagnosis and treatment

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