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Stephanie J Chiu,1,2 Simon J Hickman,2,3 Irene M Pepper,1,2 Jennifer HY Tan,1,2 John Yianni,2,4 Joanna M Jefferis1,2,5 1Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield, UK; 2Department of Medical Education, University of Sheffield, Sheffield, UK; 3Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK; 4Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield, UK; 5Department of Neuro-Ophthalmology, Manchester Royal Eye Hospital, Manchester, UKCorrespondence: Joanna M JefferisManchester Royal Eye Hospital, Oxford Road, Manchester, M13 9WL, UKTel +44 0161 276 1234Email jojefferis@doctors.org.ukAbstract: Vestibular schwannomas (VSs), also called acoustic neuromas, are benign intracranial neoplasms of the vestibulocochlear (VIII) cranial nerve. Management options include “wait-and-scan,” stereotactic radiosurgery and surgical resection. Due to the proximity of the VIII nerve to the facial (VII) nerve in the cerebello-pontine angle, the VII nerve is particularly vulnerable to the effects of surgical resection. This can result in poor eye closure, lagophthalmos and resultant corneal exposure post VS resection. Additionally, compression from the tumor or resection can cause trigeminal (V) nerve damage and a desensate cornea. The combination of an exposed and desensate cornea puts the eye at risk of serious ocular complications including persistent epithelial defects, corneal ulceration, corneal vascularization, corneal melting and potential perforation. The abducens (VI) nerve can be affected by a large intracranial VS causing raised intracranial pressure (a false localizing sign) or as a result of damage to the VI nerve at the time of resection. Other types of neurogenic strabismus are rare and typically transient. Contralaterally beating nystagmus as a consequence of vestibular dysfunction is common post-operatively. This generally settles to pre-operative levels as central compensation occurs. Ipsilaterally beating nystagmus post-operatively should prompt investigation for post-operative cerebrovascular complications. Papilledema (and subsequent optic atrophy) can occur as a result of a large VS causing raised intracranial pressure. Where papilledema follows surgical resection of a VS, it can indicate that cerebral venous sinus thrombosis has occurred. Poor visual function following VS resection can result as a combination of all these potential complications and is more likely with larger tumors.Keywords: vestibular schwannoma, post-operative complications, papilledema, facial nerve paralysis, neurotrophic keratopathy, nystagmus

Acute promyelocytic leukemia (APML) can lead to pseudotumour cerebri (PTC), either due to direct effects of the disease or as a complication of its treatment with the vitamin A derivative all-trans-retinoic acid or arsenic. We report the case of a patient with sight-threatening papilledema secondary to APML-induced PTC who was treated with bilateral optic nerve sheath fenestration. [ABSTRACT FROM AUTHOR]

Corticosteroids shorten the period of functional impairment following relapses in optic neuritis and multiple sclerosis (MS); however they have not, thus far, been shown to affect the final level of [...]

There is a large historical database of dual-echo conventional spin-echo (CSE) magnetic resonance images in multiple sclerosis (MS). If new analysis techniques can be developed then this database could provide valuable information. We have investigated a technique in which the late echo of a dual-echo data set is subtracted from the corresponding early echoyielding images, which appear qualitatively similar to T1-weighted images. This study investigated whether the hypointense lesions on the 'pseudo-T1' images (created as described above) were related to hypointense lesions on conventional T1-weighted images. The hypointense lesion areas were measured by a blinded observer using a computer-assisted contouring technique applied to pseudo-T1 and T1-weighted CSE images obtained from 17 patients with secondary progressive MS (SPMS). The mean hypointense lesion area from T1-weighted images was 2218- 2072 mm[sup 2], compared to 1426-1353 mm[sup 2] from pseudo-T1 images (p = 0.008). There was, however, a strong correlation between the values obtained from the two sets of images (r = 0.93, p < 0.001). The strong correlation between the values obtained from the two sets of images suggests that pseudo-T1 images may be useful to investigate a subgroup of more destructive lesions in MS from historical databases and in future prospective studies when imaging time is limited. [ABSTRACT FROM AUTHOR]

The cytoplasmic membrane compartmentalises the bacterial cell into cytoplasm and periplasm. Proteins located in this membrane have a defined topology that is established during their biogenesis. However, the accuracy of this fundamental biosynthetic process is unknown. We developed compartment-specific fluorescence labelling methods with up to single-molecule sensitivity. Application of these methods to the single and multi-spanning membrane proteins of the Tat protein transport system revealed rare topogenesis errors. This methodology also detected low level soluble protein mislocalization from the cytoplasm to the periplasm. This study shows that it is possible to uncover rare errors in protein localization by leveraging the high sensitivity of fluorescence methods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Author Achillefs Kapanidis has a financial interest in Oxford NanoImager which manufactures the fluorescence microscope used in this work. Author Achillefs Kapanidis is a member of the Editorial Board of the Journal of Molecular Biology.’, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recognising optic chiasmal disease early is important in order to avoid irreversible visual loss and the potential risk of mortality for patients. Yet, there is frequently a delay in the initial diagnosis. Whilst the signs of optic chiasmal disease, particularly the perimetric findings, are well documented in the recent literature, the symptoms have been less well reported. Whilst some patients with optic chiasmal disease will be asymptomatic, many will complain of visual symptoms including symptomatic field defects, problems with central vision, difficulty with near tasks, binocular visual disturbances, colour vision disturbances, photophobia, phosphenes, glare, and rarely, oscillopsia and visual hallucinations. Others may have headache or the severe and sudden visual symptoms associated with pituitary apoplexy. The visual symptoms may be vague or non-specific, even when there are significant bitemporal visual field defects. We aim in this review to describe the presenting visual symptoms of optic chiasmal disease, and to illustrate these with selected qualitative descriptions from the literature. Our hope is that this will aid clinicians in eliciting a careful history of the sometimes subtle symptoms that may be present.

Paraneoplastic neurological syndromes (PNS) occur in about 1 in 300 cases of cancer. The usual mechanism is that an antigen on the cancer sets off an immune response that then cross-reacts with a nervous system antigen. The presentation is usually with a subacute progressive neurological disorder. The management of these conditions is usually of both the underlying tumor and immunomodulation to suppress the autoimmune response. There are a number of these conditions that can present to the Neuro-Ophthalmology clinic, either as a discrete condition affecting vision or eye movements or as part of a more widespread neurological disorder. This article will discuss these conditions, their management and prognosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background and Objectives: The idiopathic intracranial hypertension randomized controlled weight trial (IIH:WT) established that weight loss through bariatric surgery significantly reduced intracranial pressure when compared with a community weight management intervention. This substudy aimed to evaluate the amount of weight loss required to reduce intracranial pressure and to explore the effect of different bariatric surgical approaches., Methods: IIH:WT was a multicenter randomized controlled trial. Adult women with active idiopathic intracranial hypertension and a body mass index ≥35 kg/m 2 were randomized to bariatric surgery or a community weight management intervention (1:1). This per-protocol analysis evaluated the relationship between intracranial pressure, weight loss, and the weight loss methods. A linear hierarchical regression model was used to fit the trial outcomes, adjusted for time, treatment arm, and weight., Results: Sixty-six women were included, of whom 23 had received bariatric surgery by 12 months; the mean age was 31 (SD 8.7) years in the bariatric surgery group and 33.2 (SD 7.4) years in the dietary group. Baseline weight and intracranial pressure were similar in both groups with a mean weight of 119.5 (SD 24.1) and 117.9 (SD 19.5) kg and mean lumbar puncture opening pressure of 34.4 (SD 6.3) and 34.9 (SD 5.3) cmCSF in the bariatric surgery and dietary groups, respectively. Weight loss was significantly associated with reduction in intracranial pressure (R 2 = 0.4734, p ≤ 0.0001). Twenty-four percentage of weight loss (weight loss of 13.3 kg [SD 1.76]) was associated with disease remission (intracranial pressure [ICP] ≤ 25 cmCSF). Roux-en-Y gastric bypass achieved greater, more rapid, and sustained ICP reduction compared with other methods., Discussion: The greater the weight loss, the greater the reduction in ICP was documented. Twenty four percentage of weight loss was associated with disease remission. Such magnitude of weight loss was unlikely to be achieved without bariatric surgery, and hence, consideration of referral to a bariatric surgery program early for those with active idiopathic intracranial hypertension may be appropriate., Trial Registration: ClinicalTrials.gov Identifier: NCT02124486; ISRCTN registry number ISRCTN40152829; doi.org/10.1186/ISRCTN40152829., Classification of Evidence: This study provides Class II evidence that weight loss after bariatric surgery results in reduction in intracranial pressure in adult women with idiopathic intracranial hypertension. This study is Class II because of the use of a per-protocol analysis., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

We came together in March 2021 for a joyous celebration of Dr Gordon Plant's incredible career. This is a report of the meeting tidings., Competing Interests: No potential conflict of interest was reported by the authors., (© 2021 Taylor & Francis Group, LLC.)

Background: There are increasing numbers of referrals to ophthalmology departments due to blurred optic disc margins. In light of this and the COVID-19 pandemic we aimed to assess whether these patients could be safely assessed without direct contact between the clinician and patient., Methods: We retrospectively reviewed the records of consecutive patients seen in our 'blurred disc clinic' between August 2018 and October 2019. We then presented anonymous information from their referral letter, their visual fields and optic nerve images to two consultant neuro-ophthalmologists blinded to the outcome of the face-to-face consultation. In the simulated virtual clinic, the two consultants were asked to choose an outcome for each patient from discharge, investigate or bring in for a face-to-face assessment., Results: Out of 133 patients seen in the blurred disc clinic, six (4.5%) were found to have papilloedema. All six were identified by both neuro-ophthalmologists as needing a face-to-face clinic consultation from the simulated virtual clinic. One hundred and twenty (90%) patients were discharged from the face-to-face clinic at the first consultation. The two neuro-ophthalmologists chose to discharge 114 (95%) and 99 (83%) of these respectively from the simulated virtual clinic. The virtual clinic would have potentially missed serious pathology in only one patient who had normal optic discs but reported diplopia at the previous face-to-face consultation., Conclusions: A virtual clinic model is an effective way of screening for papilloedema in patients referred to the eye clinic with suspicious optic discs. Unrelated or incidental pathology may be missed in a virtual clinic.

Previously, optic neuritis was thought to be typical, i.e. idiopathic or multiple sclerosis (MS) related, associated with a good visual prognosis, or atypical, i.e. not associated with MS and requiring corticosteroids or plasma exchange for vision to recover. More recently, the importance of optic neuritis in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein (MOG) antibody disease has become more appreciated. The results of the Optic Neuritis Treatment Trial (ONTT) has influenced how optic neuritis is treated around the world. For this review we surveyed the international literature on optic neuritis in adults. Our aims were first to find the reported incidence of optic neuritis in different countries and to ascertain what percentage of cases were seropositive for anti-aquaporin 4 and anti-MOG antibodies, and second, to document the presenting features, treatment, and outcomes from a first episode of the different types of optic neuritis from these countries, and to compare the results with the outcomes of the ONTT cohort. From these data we have sought to highlight where ambiguities currently lie in how to manage optic neuritis and have made recommendations as to how future treatment trials in optic neuritis should be carried out in the current antibody testing era., (© 2021 Taylor & Francis Group, LLC.)

Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse., Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH., Design, Setting, and Participants: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020., Interventions: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33)., Main Outcomes and Measures: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0., Results: Of the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -6.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, -9.5 to -2.4 cm CSF; P = .001) and at 24 months (adjusted mean [SE] difference, -8.2 [2.0] cm CSF; 95% CI, -12.2 to -4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -7.2 [1.8] cm CSF; 95% CI, -10.6 to -3.7 cm CSF; P < .001) and at 24 months (adjusted mean [SE] difference, -8.7 [2.0] cm CSF; 95% CI, -12.7 to -4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -21.4 [5.4] kg; 95% CI, -32.1 to -10.7 kg; P < .001) and at 24 months (adjusted mean [SE] difference, -26.6 [5.6] kg; 95% CI, -37.5 to -15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm., Conclusions and Relevance: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission., Trial Registration: ClinicalTrials.gov Identifier: NCT02124486.

Background/aims: Optic nerve sheath fenestration (ONSF) is a surgical intervention in the management of idiopathic intracranial hypertension (IIH) infrequently performed in the United Kingdom. Numerous surgical approaches have been described, including medial transconjunctival, lateral and endoscopic. We describe our outcomes and complications from ONSF via a supero-medial eyelid skin crease incision in patients with IIH., Methods: We performed a retrospective review of consecutive patients undergoing ONSF for IIH between January 2011 and December 2017 by a single surgeon., Results: Thirty patients were included in the analysis with a median follow-up of 14.5 months. Bilateral ONSFs were undertaken in 27 (90%). The data from one eye per patient were analysed. The mean kinetic perimetry score in mean radial degrees of the I4e isopter improved from 27.3° to 35.7°, p = 0.04. After removing cases with optic atrophy, the median modified Frisén grade of papilloedema improved from 2.5 to 1.0, p = 0.007. A total of 5/30 (17%) patients had complications: two (7%) had recurrence/late failure (one managed medically and one with cerebrospinal fluid [CSF] diversion surgery), one had transient cotton wool spots post-operatively, one had transient retinal haemorrhages and one patient had a transiently oval pupil. No patients had repeat ONSF, but CSF diversion surgery was subsequently carried out in 4/30 (13%) patients., Conclusions: ONSF via a supero-medial eyelid skin crease approach is effective at improving visual function in patients with IIH. The complication rates are low when compared with CSF diversion surgery and other surgical approaches for ONSF.

Background: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses., Methods: Eighty-six acute ON cases were randomized to receive phenytoin (4-6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL)., Results: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo - phenytoin was -44 pg/ml at 3 months (P = 0.019) and -27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and -1.6 pg/ml at 6 months (P = 0.766)., Conclusions: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized., (© 2020 European Academy of Neurology.)

While its use is still widespread within the medical retina field, fundus fluorescein angiography (FFA) is increasingly falling out of favour in the investigation of neuro-ophthalmological disease, with the introduction of new technologies, particularly optical coherence tomography. FFA does, however, provide useful diagnostic and prognostic information in many neuro-ophthalmological diseases including papilloedema, pseudo-papilloedema, optic neuropathies and central retinal artery occlusion to name a few. We aim to summarise the main FFA findings in each of these conditions and highlight where FFA is of most use in providing complementary information to other modes of investigation.

Purpose of Review: Nutritional optic neuropathy is a potential cause of severe visual loss; however, appropriate and timely management can result in excellent visual outcomes. The purpose of this review is to outline our current understanding of the treatment and outcomes for nutritional optic neuropathy., Recent Findings: Current understanding of nutritional optic neuropathy has been greatly aided by some well-reported and investigated epidemics of the condition, most notably the Cuban epidemic optic neuropathy of the early 1990s. More recently, there is an emerging literature surrounding nutritional deficiencies that can occur in patients who have undergone bariatric surgery. There also continues to be a stream of case reports in the literature that add to our understanding. Nutritional optic neuropathy has a great deal of overlap with toxic optic neuropathies and hereditary optic neuropathies and should not be thought of in isolation from these conditions. The mainstay of treatment for nutritional optic neuropathy involves identifying and replacing deficient nutrients as well as identifying and eliminating contributory toxins. It is also important to identify contributory genetic factors and to consider the broader social, economic and societal factors which may contribute.

We describe here a case series of six patients referred to the Neuro-ophthalmology service in Sheffield, UK with possible acute unilateral optic neuritis. Each patient had a triad of unilateral photophobia, ipsilateral retro-ocular pain, and ipsilateral loss of vision. All patients had normal ocular examinations and investigation findings with no objective structural or functional abnormalities identified. Patients were treated by weaning-off regular analgesia and, where appropriate, commencing migraine prophylaxis. In the three patients with complete recovery of pain, there was also complete recovery of vision. We propose that this is a migraine syndrome and that the decreased visual acuity is a functional consequence of the pain and photophobia.

A recent study found that increased optic canal area on magnetic resonance imaging was associated with worse papilloedema in idiopathic intracranial hypertension (IIH). We repeated this study using more accurate computerized tomography derived measurements. Optic canal dimensions were measured from 42 IIH patients and 24 controls.  These were compared with papilloedema grade.  There was no correlation between any of the optic canal measurements and papilloedema grade and no significant difference in optic canal measurements between patients and controls. Our results cast doubt on the existing literature regarding the association between optic canal size and the degree of papilloedema in IIH. CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH.

Membrane proteins play vital roles in inside-out and outside-in signal transduction by responding to inputs that include mechanical stimuli. Mechanical gating may be mediated by the membrane or by protein(s) but evidence for the latter is scarce. Here we use force spectroscopy, protein engineering and bacterial growth assays to investigate the effects of force on complexes formed between TonB and TonB-dependent transporters (TBDT) from Gram-negative bacteria. We confirm the feasibility of protein-only mediated mechanical gating by demonstrating that the interaction between TonB and BtuB (a TBDT) is sufficiently strong under force to create a channel through the TBDT. In addition, by comparing the dimensions of the force-induced channel in BtuB and a second TBDT (FhuA), we show that the mechanical properties of the interaction are perfectly tuned to their function by inducing formation of a channel whose dimensions are tailored to the ligand.

Our aim is to report 13 unusual cases of acquired, temporal sectoral scotomas. Such stationary "wedge" field defects have been reported previously in cases of presumed congenital nasal hypoplasia of the optic disc and as a complication of vitreoretinal surgery. To our knowledge, the literature provides no reports of similar defects occurring spontaneously. This is a descriptive clinical case series of 13 patients presenting with sub-acute monocular temporal visual field loss. All were clinically assessed and investigated with Goldmann perimetry, automated Humphrey visual fields, retinal optical coherence tomography, orbital ultrasound, and standard and multi-focal electroretinography. Cases were followed with serial perimetry for a mean of 3.9 years (range: 6 months to 10 years). Goldmann and Humphrey perimetry both demonstrated "wedge"-shaped defects extending temporally from an apex contiguous with, or lateral to, the blind spot. There was no evidence of optic disc drusen, glaucoma, disc hypoplasia, or focal retinitis. Sectoral optic disc swelling was not present in any patient at presentation. In all cases, the visual field defect remained stable. One patient developed a similar defect in the fellow eye after an interval of 5 years. Here we describe 13 cases of acquired, stationary temporal wedge scotomas, novel in the literature. Although the aetiology is uncertain, we propose damage to the nasal rim of the optic disc as a likely mechanism.

Background: Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis., Methods: We did a randomised, placebo-controlled, double-blind phase 2 trial at two UK academic hospitals in London and Sheffield. Patients with acute optic neuritis aged 18-60 years, presenting within 2 weeks of onset, with visual acuity of 6/9 or worse, were randomly assigned (1:1) by minimisation via a web-based service to oral phenytoin (maintenance dose 4 mg/kg per day if randomised before or on July 16, 2013, and 6 mg/kg per day if randomised on or after July 17, 2013) or placebo for 3 months, stratified by time from onset, centre, previous multiple sclerosis diagnosis, use of disease-modifying treatment, and use of corticosteroids for acute optic neuritis. Participants and treating and assessing physicians were masked to group assignment. The primary outcome was retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline, analysed in a modified intention-to-treat population of all randomised participants who were followed up at 6 months. Safety was analysed in the entire population, including those who were lost to follow-up. The trial is registered with ClinicalTrials.gov, number NCT 01451593., Findings: We recruited 86 participants between Feb 3, 2012, and May 22, 2014 (42 assigned to phenytoin and 44 to placebo). 29 were assigned to phenytoin 4 mg/kg and 13 to phenytoin 6 mg/kg. Five participants were lost to follow-up, so the primary analysis included 81 participants (39 assigned to phenytoin and 42 to placebo). Mean 6-month RNFL thickness in the affected eye at 6 months was 81.46 μm (SD 16.27) in the phenytoin group (a mean decrease of 16.69 μm [SD 13.73] from baseline) versus 74.29 μm (15.14) in the placebo group (a mean decrease of 23.79 μm [13.97] since baseline; adjusted 6-month difference of 7.15 μm [95% CI 1.08-13.22]; p=0.021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo. Treatment was well tolerated, with five (12%) of 42 patients having a serious adverse event in the phenytoin group (only one, severe rash, was attributable to phenytoin) compared with two (5%) of 44 in the placebo group., Interpretation: These findings support the concept of neuroprotection with phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated sodium channels selectively. Further investigation in larger clinical trials in optic neuritis and in relapsing multiple sclerosis is warranted., Funding: US National Multiple Sclerosis Society, Multiple Sclerosis Society of Great Britain and Northern Ireland, Novartis, UK National Institute for Health Research (NIHR), and NIHR UCLH/UCL Biomedical Research Centre., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Internet video sharing sites allow the free dissemination of educational material. This study investigated the quality and educational content of videos of eye movement disorders posted on such sites., Methods: Educational neurological eye movement videos were identified by entering the titles of the eye movement abnormality into the search boxes of the video sharing sites. Also, suggested links were followed from each video. The number of views, likes, and dislikes for each video were recorded. The videos were then rated for their picture and sound quality. Their educational value was assessed according to whether the video included a description of the eye movement abnormality, the anatomical location of the lesion (if appropriate), and the underlying diagnosis., Results: Three hundred fifty-four of these videos were found on YouTube and Vimeo. There was a mean of 6,443 views per video (range, 1-195,957). One hundred nineteen (33.6%) had no form of commentary about the eye movement disorder shown apart from the title. Forty-seven (13.3%) contained errors in the title or in the text. Eighty (22.6%) had excellent educational value by describing the eye movement abnormality, the anatomical location of the lesion, and the underlying diagnosis. Of these, 30 also had good picture and sound quality. The videos with excellent educational value had a mean of 9.84 "likes" per video compared with 2.37 for those videos without a commentary (P < 0.001). The videos that combined excellent educational value with good picture and sound quality had a mean of 10.23 "likes" per video (P = 0.004 vs videos with no commentary). There was no significant difference in the mean number of "dislikes" between those videos that had no commentary or which contained errors and those with excellent educational value., Conclusions: There are a large number of eye movement videos freely available on these sites; however, due to the lack of peer review, a significant number have poor educational value due to having no commentary or containing errors. The number of "likes" can help to identify videos with excellent educational value but the number of "dislikes" does not help in discerning which videos have poor educational value.

Sarcoidosis can affect the optic nerves by means of optic disc oedema secondary to posterior uveitis, optic disc oedema secondary to raised intracranial pressure, optic neuritis, optic atrophy secondary to compression or infiltration from a primary central nervous system lesion, and primary granuloma of the optic nerve head. The authors report the use of optical coherence tomography in assessing the response to immunosuppression in a 57-year-old woman with an optic nerve head granuloma.

Optic perineuritis (OPN) is now defined as "a form of idiopathic orbital inflammatory disease, in which the specific target tissue is the optic nerve sheath". It may be idiopathic or may occur as part of an underlying systemic inflammatory disease. It is a rare disorder and information regarding its presentation and management is only available in case reports and small case series. This review will discuss the contribution of these recent articles to what is known about idiopathic and secondary OPN. Suggestions will also be made as to how to investigate and treat a patient presenting with OPN.

Identifying the contributions to thermodynamic stability of capsids is of fundamental and practical importance. Here we use simulation to assess how mutations affect the stability of lumazine synthase from the hyperthermophile Aquifex aeolicus, a T = 1 icosahedral capsid; in the simulations the icosahedral symmetry of the capsid is preserved by simulating a single pentamer and imposing crystal symmetry, in effect simulating an infinite cubic lattice of icosahedral capsids. The stability is assessed by estimating the free energy of association using an empirical method previously proposed to identify biological units in crystal structures. We investigate the effect on capsid formation of seven mutations, for which it has been experimentally assessed whether they disrupt capsid formation or not. With one exception, our approach predicts the effect of the mutations on the capsid stability. The method allows the identification of interaction networks, which drive capsid assembly, and highlights the plasticity of the interfaces between subunits in the capsid., (© 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.)

Aim: To describe the presentation of an internuclear ophthalmoplegia (INO) associated with the use of anti-tumor necrosis factor α (anti-TNFα) medication., Methods: A case report of a woman, aged 27 years, who developed facial numbness, blurred vision, and diplopia on right gaze. She had a history of Crohn's disease, which was being treated by the anti-TNFα drug, adalimumab. On examination, a left INO was found., Treatment: The patient was prescribed a short course of corticosteroids and adalimumab treatment was discontinued., Results: Magnetic resonance imaging demonstrated typical demyelinating lesions including one responsible for the INO. Following a short course of corticosteroids and the discontinuation of the adalimumab treatment, the INO resolved, resulting in a swift improvement of ocular motility over a 2-week period., Conclusion: Anti-TNFα therapies have been associated with the development of demyelinating diseases. The presentation of a brainstem syndrome in a patient on anti-TNFα therapy should lead to investigation for central nervous system demyelination and cessation of the medication.

A retrospective notes review was conducted for 50 consecutive patients who underwent shunt surgery for idiopathic intracranial hypertension (IIH). The decimal visual acuity and the mean radial degrees (MRD) of the I4e isopter of the Goldmann visual field were measured pre-operatively and after a mean follow-up period of 1123 days (range: 13-3551 days). A ventriculo-peritoneal shunt was the first procedure in 38 patients and a lumbo-peritoneal shunt in 12. The mean decimal visual acuity of the worse affected eye improved from 0.75 to 0.84, p  = 0.011. The MRD score of the worse affected eye improved on average from 25.6° to 35.5°, p  < 0.0001. In those with significant pre-operative visual impairment in their worse affected eye (defined as an MRD score ≤30°), the MRD score improved on average from 10.3° to 26.5°, p  = 0.0008. The mean number of surgical procedures for each patient was 2.8 (range: 1-15). Taking all surgical procedures into account, post-operative complications were experienced by 30 patients. At last follow-up, 28 patients still complained of headache, 8 of whom had the intervention performed primarily for headache. Shunting can improve visual function in patients with IIH. There is significant post-operative morbidity and often the need for repeated procedures. Headache also commonly remains in these patients. There is a need for a randomised controlled trial of operative interventions in IIH. Sample size calculations for such a trial to treat significant vision loss are presented.

Case reports of patients with mal-functioning metal-on-metal hip replacement (MoMHR) prostheses suggest an association of elevated circulating metal levels with visual and auditory dysfunction. However, it is unknown if this is a cumulative exposure effect and the impact of prolonged low level exposure, relevant to the majority of patients with a well-functioning prosthesis, has not been studied. Twenty four male patients with a well-functioning MoMHR and an age and time since surgery matched group of 24 male patients with conventional total hip arthroplasty (THA) underwent clinical and electrophysiological assessment of their visual and auditory health at a mean of ten years after surgery. Median circulating cobalt and chromium concentrations were higher in patients after MoMHR versus those with THA (P<0.0001), but were within the Medicines and Healthcare Products Regulatory Agency (UK) investigation threshold. Subjective auditory tests including pure tone audiometric and speech discrimination findings were similar between groups (P>0.05). Objective assessments, including amplitude and signal-to-noise ratio of transient evoked and distortion product oto-acoustic emissions (TEOAE and DPOAE, respectively), were similar for all the frequencies tested (P>0.05). Auditory brainstem responses (ABR) and cortical evoked response audiometry (ACR) were also similar between groups (P>0.05). Ophthalmological evaluations, including self-reported visual function by visual functioning questionnaire, as well as binocular low contrast visual acuity and colour vision were similar between groups (P>0.05). Retinal nerve fibre layer thickness and macular volume measured by optical coherence tomography were also similar between groups (P>0.05). In the presence of moderately elevated metal levels associated with well-functioning implants, MoMHR exposure does not associate with clinically demonstrable visual or auditory dysfunction.

Multiple sclerosis can affect vision in many ways, including optic neuritis, chronic optic neuropathy, retrochiasmal visual field defects, higher order cortical processing, double vision, nystagmus and also by related ocular conditions such as uveitis. There are also side effects from recently introduced multiple sclerosis treatments that can affect vision. This review will discuss all these aspects and how they come together to cause visual symptoms. It will then focus on practical aspects of how to recognise when there is a vision problem in a multiple sclerosis patient and on what treatments are available to improve vision., (© 2013 Elsevier B.V. All rights reserved.)