ObjectiveMyelin oligodendrocyte glycoprotein–immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments.MethodsWe determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy.ResultsSeventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3–61 years; 33% <18 years), and 59% were female. The median annualized relapse rate (ARR) before treatment was 1.6. On maintenance immunotherapy, the proportion of patients with relapse was as follows: mycophenolate mofetil 74% (14 of 19; ARR 0.67), rituximab 61% (22 of 36; ARR 0.59), azathioprine 59% (13 of 22; ARR 0.2), and IV immunoglobulin (IVIG) 20% (2 of 10; ARR 0). The overall median ARR on these 4 treatments was 0.3. All 9 patients treated with multiple sclerosis (MS) disease-modifying agents had a breakthrough relapse on treatment (ARR 1.5).ConclusionThis large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

A pathological hallmark of neurodegenerative tauopathies, including Alzheimer's disease and a group of clinically heterogeneous frontotemporal dementias, is the presence of intracellular neurofibrillary protein lesions (reviewed in Spillantini and Goedert, TINS 10 (1998) 428). The principal component of these structures is the microtubule-associated protein tau. Although tau is normally a highly soluble protein enriched in axons, in these deposits, it is abnormally hyperphosphorylated, insoluble, and redistributed to the somatodendritic compartments of neurons. Through ultrastructual analyses, it has been determined that the tau protein in these lesions is filamentous and organized into paired-helical filaments, straight filaments, or ribbon-like filaments (Goedert et al., The Molecular and Genetic Basis of Neurological Disease (1997) 613). By the dynamic binding of microtubules, tau is thought to promote the structural stability of axons, but whether tau aggregates contribute to neurodegeneration through a direct toxicity on normal cellular functions such as organelle transport or an indirect effect on microtubule stability, is currently unknown. The identification of mutations in the tau locus in patients with familial frontotemporal dementia and Parkinsonism linked to chromosome 17 has demonstrated that mutations in tau are sufficient to cause neurodegenerative disease (Poorkaj et al., Ann. Neurol. 43 (1998) 815; Hutton et al., Nature 393 (1998) 702). To elucidate the mechanisms by which tau dysfunction contributes to neuronal loss, we have sought to model human tauopathies in a genetically tractable organism. Here we describe the isolation of a Drosophila tau cDNA (GenBank accession number AY032977), the production of antibodies that recognize the encoded protein, and their use in determining the expression and subcellular localization of the fly tau protein.

Congenital fibrosis of the extraocular muscles (CFEOM) is a strabismus syndrome characterized by non-progressive, restrictive ophthalmoplegia of the extraocular muscles and congenital blepharoptosis. Three clinical phenotypes for familial CFEOM (CFEOM1, 2, and 3) have been delineated, for which two genes have been identified to date: KIF21A for CFEOM1 and 3 and PHOX2A/ARIX for CFEOM2. Insights gained from molecular genetics have strengthened the hypothesis that CFEOM results from the dysinnervation of the extraocular muscles supplied by the oculomotor and/or trochlear nerves. Continued study of this syndrome should help to further elucidate the pathogenesis of eye movement disorders.

Retinopathy of prematurity is marked by the proliferative vascularization of the retina in preterm babies. An understanding of the molecular pathogenesis of ROP provides the basis for identifying novel therapeutic targets for treatment. Using the mouse model of oxygen-induced retinopathy, the roles of the hypoxia induced factors vascular endothelial growth factor and erythropoietin as well as the maternally derived factors insulin-like growth factor-1 and omega-3 polyunsaturated fatty acids have begun to be elucidated. Understanding the phase specific effects of these factors will serve to guide the development of non destructive treatments for ROP and for other ischemic retinopathies including diabetic retinopathy and neovascular age-related macular degeneration.

Children and adults with Neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas involving the eyelid, orbit, periorbital and facial structures (termed OPPN) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. Despite NF1 being a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. While medical and surgical interventions have been reported, there are no agreed upon criteria for when OPPN require therapy and which treatment produces the best outcome. Since a multi-disciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual and or aesthetic sequelae complicates the design of evidence based studies and feasible clinical trials. In September 2013, a multi-disciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. This consensus statement provides recommendations for ophthalmologic monitoring and outlines treatment indications, forthcoming biologic therapy, while also discussing challenges to performing clinical trials in this complicated condition.

Sporadic optic pathway gliomas (OPGs) have been reported to cause more vision loss than OPGs associated with neurofibromatosis type-1, but long-term visual outcome data are limited. The purpose of this study was to report the visual outcomes of a cohort of pediatric patients with sporadic OPGs. This was a retrospective, cohort study at a tertiary care pediatric hospital and cancer institute. The study included all patients with sporadic OPGs evaluated from 1990 to 2014. The primary outcome was visual acuity at final follow-up. Secondary outcomes were risk factors for a poor visual outcome and the rate of progression. There were 59 pediatric patients included in the study. Median age at presentation was 2.5 years old and median follow-up was 5.2 years. In the worse eye at final follow-up, 16 patients (27 %) were 20/30 or better, 9 patients (15 %) were between 20/40 and 20/80, and 34 patients (58 %) were 20/100 or worse. In the better eye at final follow-up, 33 patients (56 %) were 20/30 or better, 11 patients (19 %) were between 20/40 and 20/80, and 15 patients (25 %) were 20/100 or worse. Risk factors for a poor visual outcome included younger age at presentation, optic nerve pallor, and tumor extent. Of the 54 patients (92 %) who received treatment, 40 (74 %) experienced disease progression during or after treatment. A majority of pediatric patients with sporadic OPGs had significant long-term visual impairment. In spite of treatment, tumor progression is common. Serial ophthalmic examinations with quantitative vision measurements are essential in the management of sporadic OPGs.

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In severely myopic patients, there is a high prevalence of astigmatism that is predominantly with-the-rule. The degree of myopic spherical refractive error is correlated with astigmatism severity but is not a risk factor for the presence of astigmatism.