Neuro-Ophthalmic Literature Review

Neuro-Ophthalmic Literature Review David Bellows, Noel Chan, John Chen, Hui-Chen Cheng, Peter MacIntosh, Jenny Nij Bijvank, Michael Vaphiades, and Konrad Weber A potential biomarker for NMOSD You Y, Zhu L, Zhang T, Shen T, Fontes A, Yiannikas C, Parratt J, Barton J, Schulz A, Gupta V, Barnett MH. Evidence of Müller Glial Dysfunction in Patients with Aquaporin-4 Immunoglobulin G– Positive Neuromyelitis Optica Spectrum Disorder. Ophthalmology. 2019 Jun 1;126(6):801–10. Having a biomarker to identify patients with neuromyelitis spectrum disorder (NMOSD) before the results of laboratory testing can be obtained would be of great value in choosing the best management for patients who present with optic neuritis. In this study, the authors analysed and compared a combination of full-field electroretinography (ERG), retinal tissue volume (using spectraldomain optical coherence tomography) and Western blot immunohistochemistry in four groups of patients. These consisted of patients who were seropositive for AQP4-IgG, those who were seronegative for AQP4-IgG, those with multiple sclerosis and normal subjects. Patients who were positive for MOG-IgG were included in the NMOSD seronegative group. Altogether, 44 eyes with NMOSD, 262 eyes with multiple sclerosis and 56 normals were included in the study. The authors found no difference in scotopic ERG between three of the groups; normal subjects, those with multiple sclerosis and those with seronegative NMOSD. However, a significantly reduced b-wave amplitude was observed in patients who were seropositive for AQP4. The decrease in amplitude was not associatedwith either visual acuity or a previous history of optic neuritis. The reduction in b-wave amplitude only occurred in scotopic (as opposed to photopic) ERG which is consistent with Müller cell dysfunction. Interesting observations were made regarding the OCT of the macula. The authors noted that the thicknesses of the Henle fibre outer nuclear (HFONL) and inner segment (IS) layers were thinned in seropositive NMOSD with or without a previous history of optic neuritis. However, no thinning was noted in patients with multiple sclerosis. Quite the contrary, a small degree of thickening in HFONL was observed in patients with multiple sclerosis who had a previous history of optic neuritis. Because of the small sample size, seronegative NMOSD subjects were excluded from this portion of the study. The results of the immunohistochemical arm of the study were consistent with earlier reports that have shown AQP4 to be predominantly expressed in Müller cells. The authors were able to demonstrate that AQP4 is strongly expressed in the Henle fibre layer of the retina. This study has produced convincing evidence of Müller cell dysfunction in patients with seropositive NMOSD and, importantly, raises the possibility that a combination of OCT and ERG can be used as an early biomarker in identifying patients with seropositive NMOSD. David Bellows Aetiologies of paediatric ocular motor nerve palsies in Asia Kyung-Ah Park, Sei Yeul Oh, Ju-HongMin, Byoung Joon Kim & Yikyung Kim. Acquired onset of third, fourth, and sixth cranial nerve palsies in children and adolescents. Eye. 2019;965-973. Literature has previously reported trauma as the most common acquired cause for third and fourth nerve palsies in the paediatric population while neoplasm is accountable for sixth nerve palsy in most. Many of these studies were however published before the advent of high-resolution CONTACT John J. Chen Chen.john@mayo.edu Department of Ophthalmology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA NEURO-OPHTHALMOLOGY 2019, VOL. 43, NO. 5, 346–353 https://doi.org/10.1080/01658107.2019.1653059 © 2019 Taylor & Francis Group, LLC magnetic resonance imaging (MRI), such as modified fully refocused steady-state sequences (e.g. CISS/FIESTA-C/B-FFE). This is a retrospective case series describing the aetiologies of third, fourth and sixth cranial nerve palsies in children and adolescents from a single tertiary neuroophthalmic service in Asia with the help of highresolution MRI. Sixty-six patients aged 0–19 years old were included in this study. Neoplasia involving the central nervous system was the most common cause of third, fourth and sixth cranial nerve palsies both in children (20%) and adolescents (31%). Overall, apart from neoplasm (23%), the most common causes included idiopathic (14%), inflammation (11%) and non-aneurysmal vascular contact (11%). The most common cause of fourth cranial nerve palsy was late decompensation of congenital fourth nerve palsy (46%) with the evidence of absence or atrophy of fourth nerve and/ or superior oblique muscle in the paretic eye. Only four patients presented with combined ocular motor nerve palsies of which 75% were attributable to Miller Fisher syndrome (MFS), while one patient was secondary to cavernous sinus thrombophlebitis. Of note, three patients with intracranial haemorrhage presented with isolated cranial nerve palsy without other additional neurological signs. Among six patients with MFS, two of them presented with bilateral sixth cranial nerve palsies and one presented with unilateral sixth cranial nerve palsy. The authors suggested to consider the possibility of MFS in cases of isolated third, fourth or sixth cranial nerve palsy as well. This retrospective case series confirmed that acquired ocular motor nerve palsy can be an ominous sign for serious pathology in paediatrics. Two patients with negative conventional MRI results were later found to have neoplasia. This highlights the importance of repeated neuroimaging with high-resolution MRI and correct sequences, especially in juvenile patients. Noel Chan Does time equal vision in the acute treatment of NMO? Hadas Stiebel-Kalish, Mark Andrew Hellmann, Michael Mimouni, Friedemann Paul, Omer Bialer, Michael Bach, and Itay Lotan. Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis? Neurol Neuroimmunol Neuroinflamm. 2019;6:e572. For years, the North American Optic Neuritis Treatment Trial (ONTT) has shaped the acute treatment of optic neuritis. Intravenous methylprednisolone (IVMP) has been shown to accelerate recovery but does not affect the final visual outcome in Multiple Sclerosis (MS) related optic neuritis. However, the clinical course of optic neuritis (ON) in neuromyelitis optic spectrum disease (NMOSD) and patients with serum IgG autoantibodies to myelin oligodendrocyte glycoprotein (MOG) are different, and the recommended treatment includes high dose IVMP, plasma exchange and immunoabsorption. Historically, NMOSDON has been associated with a poor visual outcome and one may wonder if it is related to the delay in treatment. This retrospective study included 18 seropositive NMO-ON and 9 MOG-IgG related ON from a consecutive cohort and the best-corrected visual acuity (BCVA) at 3 months was correlated with the respective time to IVMP from symptom onset. The median BCVA at 3 months of patients treated >7 days was 20/100 with an OR 5.50 of failure to regain 20/20 vision and an OR 10.0 of failure to regain 20/30 vision as compared with patients treated within 7 days. The authors constructed ROC curves to identify the cut point within the time window for administration of IVMP that translates into an improvement of BCVA at 3 months. They identified the cut point to be Day 4 or earlier with sensitivity and specificity of 71.4% and 76.9%, respectively. Their results echoed with other previous studies in demonstrating the beneficial effect of hyperacute IVMP in the acute management of NMO or MOG-IgG related optic neuritis. The authors quoted “Time is tissue” as a principle that is evolving in the treatment of neuro-immunological diseases in lieu of the irreversible inflammatory axonal damage and Wallerian degeneration. Limitations of the study include its retrospective nature, short follow-up duration and lack of evaluation of other visual parameters such as visual field or colour vision. Subgroup analysis NEURO-OPHTHALMOLOGY 347