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An abstract of the article "NMR Based Metabolomic Analysis of CSF in Neurological Diseases: A Diagnostic Tool?," by A. J. Sinclair, A. K. Ball, M. R. Viant, and colleagues is presented.

An abstract of the article "Cytokine Profiles in Idiopathic Intracranial Hypertension," by A. K. Ball, A. J. Sinclair, S. Rauz, and colleagues is presented.

Abstract: Our understanding of demyelinating optic neuritis has substantially evolved over the past 2 decades. With advancements in serological testing, antibodies against myelin oligodendrocyte glycoprotein (MOG) have been recently discovered in a distinct subset of demyelinating neuroinflammatory disease. Although MOG-immunoglobulin G (IgG)-associated disorder (MOGAD) has previously been seen as a component of neuromyelitis optica spectrum disorder (NMOSD), evidence increasingly suggests that it should be distinguished as a separate condition. The distinction of MOGAD from aquaporin-4 IgG NMOSD is imperative as treatment plans need to be tailored to its unique disease course and prognosis. The purpose of this review is to explore the nature and outcomes of MOGAD optic neuritis to help guide acute and long-term immunosuppressive treatment decisions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Objective: Vision loss has a significant impact on physical, mental and social well-being. Eye clinic liaison officers (ECLOs) have a crucial role in providing holistic care for patients with visual impairment. The aim of this study was to review the work of an ECLO over a period of 1 year at an NHS Trust to determine the volume of work and the areas of support provided by the ECLO., Methods and Analysis: A secondary data analysis of the ECLO case notes for all patients reviewed by the ECLO at University Hospitals Birmingham (UHB) NHS Trust during the year 2019, was performed. Demographic data and certification of visual impairment (CVI) status were noted. The main outcome variable recorded was the categories of support provided by the ECLO. Case vignettes were chosen to illustrate the variety of support offered to individual patients., Results: A total of 1127 consecutive participants were reviewed by the ECLO at University Hospitals Birmingham (UHB) NHS Trust during the year 2019. Areas of support most commonly provided by the ECLO included aiding the process of registration for CVI, and assistance in accessing benefits, social support and low vision support. Severely sight impaired patients required significantly more areas of support than sight impaired patients (Χ 2 =52.7, p=2.16×10 -6 ). Three case vignettes, chosen by the ECLO, highlighted the positive impact of the ECLO with respect to emotional support, practical advice and as a point of contact ensuring continuity of care, also during the COVID-19 pandemic., Conclusions: The ECLO at UHB NHS Trust provides a core patient service within the ophthalmology department by being a key source of practical and emotional support and the crucial link between healthcare, social care and voluntary services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic autoimmune manifestation of cutaneous malignant melanoma. Patients classically present with acute onset night blindness, positive visual phenomena and visual field defects, and typically have significantly reduced quality of life as a result. Early recognition of MAR is of prognostic significance as it can precede the diagnosis of primary or metastatic malignant melanoma, and early treatment can lower the risk of irreversible immunological damage to the retinal cells with improved visual outcomes. The focus of our review article is therefore to raise awareness of MAR and present the latest evidence relating to the investigation and management of this condition., (© 2019 British Association of Dermatologists.)

Background: Overdiagnosis of papilloedema is common and carries significant potential for morbidity from over-investigation and over-treatment. We aimed to determine the community prevalence of false positive diagnosis of papilloedema (FPE) on fundus imaging., Methods: We evaluated fundus images from a community cross-section of 198 12-14-year-olds from the Avon Longitudinal Study of Parents and Children (ALSPAC) longitudinal cohort study database and patient images from our hospital departmental database with and without papilloedema. We asked clinicians, in isolation, to rate the subjects as a forced choice task to "papilloedema" or "not papilloedema" based on the fundus images alone. Raters comprised (i) four neuro-ophthalmologists, (ii) four ophthalmologists, (iii) four neurologists and (iv) four emergency medicine physicians., Results: The prevalence of FPE in the ALSPAC population, defined as images mistaken as papilloedema by χ% of raters (P χ ) varied from P 100  = 0% to P 50  = 21.3 ± 3.9%. In the hospital population, there was a lower rate of FPE, P 50  = 7.1 ± 10.8%. Sensitivity for papilloedema detection approached 100%, though three raters incorrectly labelled the same patient with unilateral disc swelling as normal, all other cases were detected by all raters., Conclusions: Fundus photography assessment in isolation is highly sensitive but poorly specific for papilloedema detection. Using this method to screen the general population has significant potential for harm as overdiagnosis occurs, even in the hands of experienced clinicians.

The aim was to capture interdisciplinary expertise from a large group of clinicians, reflecting practice from across the UK and further, to inform subsequent development of a national consensus guidance for optimal management of idiopathic intracranial hypertension (IIH)., Methods: Between September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regularly. A comprehensive systematic literature review was performed to assemble the foundations of the statements. An international panel along with four national professional bodies, namely the Association of British Neurologists, British Association for the Study of Headache, the Society of British Neurological Surgeons and the Royal College of Ophthalmologists critically reviewed the statements., Results: Over 20 questions were constructed: one based on the diagnostic principles for optimal investigation of papilloedema and 21 for the management of IIH. Three main principles were identified: (1) to treat the underlying disease; (2) to protect the vision; and (3) to minimise the headache morbidity. Statements presented provide insight to uncertainties in IIH where research opportunities exist., Conclusions: In collaboration with many different specialists, professions and patient representatives, we have developed guidance statements for the investigation and management of adult IIH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Congenital colour vision deficiency (CVD), commonly called 'colour blindness', affects around 8% of men and 0.4% of women. Although many aspects of health (e.g. change in colour of urine) and healthcare (e.g. coloured medication, colour-coded diagnostic tests), and modern life depend upon colour coding (e.g. graphs, maps, signals), the impact of colour blindness on everyday life is not generally considered a topic of importance. This study is the first to create and validate a questionnaire measuring the quality of life (QoL) impact of being colour blind., Methods: This study consisted of two phases. Firstly, the questionnaire design and development phase was led by an expert panel and piloted on a focus group. Secondly, an online sample of 128 men and 291 women filled in the questionnaire, and the psychometric properties of the questionnaire were analysed using principal components analysis (PCA). The scores of colour blind (CB) participants and normal-sighted controls, controlling for age and sex, were compared using matched t-tests., Results: The PCA resulted in a questionnaire with three domains (or subscales): QoL for Health & Lifestyle, QoL for Work, and QoL for Emotions. Controlling for age, there was a significantly greater negative impact on QoL for CB people than normal-sighted controls in regards to confusion over colour in various aspects of their health (p = 5 × 10 -7 ), work (p = 1.3 × 10 -7 ), and emotional life (p = 6 × 10 -5 )., Conclusion: Colour blindness can significantly impact quality of life for health, emotions, and especially careers. The tool developed here could be useful in future clinical studies to measure changes in CBQoL in response to therapy in conditions where colour vision is affected. We also discuss ways in which everyday problems related to colour vision might be reduced, for example, workplaces could avoid colour coding where a non-colour alternative is possible.

Adult patients who present with papilloedema and symptoms of raised intracranial pressure need urgent multidisciplinary assessment including neuroimaging, to exclude life-threatening causes. Where there is no apparent underlying cause for the raised intracranial pressure, patients are considered to have idiopathic intracranial hypertension (IIH). The incidence of IIH is increasing in line with the global epidemic of obesity. There are controversial issues in its diagnosis and management. This paper gives a practical approach to assessing patients with papilloedema, its investigation and the subsequent management of patients with IIH., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Giant cell arteritis (GCA) is a common inflammatory condition that affects medium and large-sized arteries and can cause sudden, permanent blindness. At present there is no alternative to early treatment with high-dose corticosteroids as the recommended standard management. Corticosteroid-induced side effects can develop and further disease-related ischaemic complications can still occur. Alternative and adjunctive therapies are sought. Aspirin has been shown to have effects on the immune-mediated inflammation in GCA, hence it may reduce damage caused in the arterial wall., Objectives: To assess the safety and effectiveness of low-dose aspirin, as an adjunctive, in the treatment of giant cell arteritis (GCA)., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2014), EMBASE (January 1980 to January 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) web site (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 24 January 2014., Selection Criteria: We planned to include only randomised controlled trials (RCTs) comparing outcomes of GCA with and without concurrent adjunctive use of low-dose aspirin., Data Collection and Analysis: Two authors independently assessed the search results for trials identified by the electronic searches. No trials met our inclusion criteria, therefore we undertook no assessment of risk of bias or meta-analysis., Main Results: We found no RCTs that met the inclusion criteria., Authors' Conclusions: There is currently no evidence from RCTs to determine the safety and efficacy of low-dose aspirin as an adjunctive treatment in GCA. Clinicians who are considering the use of low-dose aspirin as an adjunctive treatment in GCA must also recognise the established haemorraghic risks associated with aspirin, especially in the context of concurrent treatment with corticosteroids. There is a clear need for effectiveness trials to guide the management of this life-threatening condition.

Background: We report an interesting case of asymptomatic retinal involvement in an encephalopathic patient enabling early identification of Susac's syndrome., Case Presentation: A 39-year-old Caucasian lady with hearing loss and encephalopathy was referred for ophthalmic assessment, including screening for branch retinal artery occlusions characteristic of Susac's syndrome. Clinical features included severe headaches, right-sided hypoacusis, dysphasia and poor memory. Routine blood tests were normal. MRI brain showed numerous hyperintense lesions mainly in corpus callosum. Although she was visually asymptomatic, dilated funduscopy detected bilateral multiple peripheral branch retinal artery occlusions which were confirmed on fluorescein angiography. She was subsequently started on intravenous steroids and pulsed cyclophosphamide which improved her symptoms within 48 hours. Full recovery was made with no new arterial occlusions on four months follow-up., Conclusion: The case further establishes the crucial role of a detailed ophthalmic examination supported by fluorescein angiography in the assessment of these patients, who are at risk of being misdiagnosed and undertreated.

The appearance of the optic disc is a key measure of disease status in idiopathic intracranial hypertension (IIH). The Frisén classification describes stages of optic disc swelling (grades 0-5). It is the only classification of papilloedema, and is used internationally in clinical and research practice. Despite this, there has been very limited evaluation of the scale. We assessed the inter-rater reproducibility and ability to discriminate optic disc changes over time using the Frisén classification compared with a system of ranking papilloedema severity in patients with IIH. Paired disc photographs (before and after treatment) were obtained from 47 patients with IIH (25 acute and 22 chronic). Six neuro-ophthalmologists blinded to patient identity, clinical information and chronology of the photographs reviewed the discs and allocated a Frisén grade and ranked the paired discs in order of papilloedema severity (disc ranking). A total of 188 optic disc photographs were reviewed. All six reviewers agreed in only three comparisons (1.6%) when using the Frisén classification, compared with 42 comparisons (45.2%) when using disc ranking. The probability of agreement between any two reviewers was 36.1% for Frisén grade and 70.0% for disc ranking. Disc ranking had significantly greater sensitivity for finding differences in degree of disc oedema, identifying a difference in 75.3% of paired photographs compared to 53.2% detected using the Frisén classification (p < 0.001). This study demonstrated the limited reproducibility and discriminative ability of the Frisén classification in identifying changes in serial optic disc photographs in IIH. Simple optic disc ranking appears to be a more sensitive and reliable tool to monitor changes in optic disc appearance. The use of disc ranking in clinical practice and research studies is recommended to monitor alterations in optic disc appearance until alternative schemes, specific to IIH, have been developed.

Background: The role of cerebrospinal fluid (CSF) diversion in treating idiopathic intracranial hypertension (IIH) is disputed., Method: We conducted a 10-year, retrospective case note review to evaluate the effects of CSF diversion in IIH. Symptoms, signs and details of shunt type, complications and revisions were documented at baseline, 6, 12 and 24 months post-operatively., Results: Fifty-three IIH patients were shunted [predominantly lumboperitoneal (92%)]. The most common symptom pre-surgery was headache (96%). Post-operatively, significantly fewer patients experienced declining vision and visual acuity improved at 6 (p = 0.001) and 12 months (p = 0.016). Headache continued in 68% at 6 months, 77% at 12 months and 79% at 2 years post-operatively. Additionally, post-operative low-pressure headache occurred in 28%. Shunt revision occurred in 51% of patients, with 30% requiring multiple revisions., Conclusion: We conclude that CSF diversion reduces visual decline and improves visual acuity. Unfortunately, headache remained in the majority of patients and low-pressure headache frequently complicated surgery. Over half of the patients required shunt revision with the majority of these requiring multiple revisions. We suggest that CSF shunting should be conducted as a last resort in those with otherwise untreatable, rapidly declining vision. Alternative treatments, such as weight reduction, may be more effective with less associated morbidity.

The cause of idiopathic intracranial hypertension (IIH) remains unknown, and no consensus exists on how patients should be monitored and treated. Acetazolamide is a common treatment but has never been examined in a randomised controlled trial. The objectives of this pilot trial are to prospectively evaluate the use of acetazolamide, to explore various outcome measures and to inform the design of a definitive trial in IIH. Fifty patients were recruited from six centres over 23 months and randomised to receive acetazolamide (n = 25) or no acetazolamide (n = 25). Symptoms, body weight, visual function and health-related quality-of-life measures were recorded over a 12-month period. Recruited patients had typical features of mild IIH and most showed improvement, with 44% judged to have IIH in remission at the end of the trial. Difficulties with recruitment were highlighted as well as poor compliance with acetazolamide therapy (12 patients). A composite measure of IIH status was tested, and the strongest concordance with final disease status was seen with perimetry (Somers' D = 0.66) and optic disc appearance (D = 0.59). Based on the study data, a sample size of 320 would be required to demonstrate a 20% treatment effect in a substantive trial. Clinical trials in IIH require pragmatic design to involve sufficiently large numbers of patients. Future studies should incorporate weighted composite scores to reflect the relative importance of common outcome measures in IIH.

Context: The etiology of idiopathic intracranial hypertension (IIH) is unknown. We hypothesized that obesity and elevated intracranial pressure may be linked through increased 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity., Objective: The aim was to characterize 11β-HSD1 in human cerebrospinal fluid (CSF) secretory [choroid plexus (CP)] and drainage [arachnoid granulation tissue (AGT)] structures, and to evaluate 11β-HSD1 activity after therapeutic weight loss in IIH., Design and Setting: We conducted in vitro analysis of CP and AGT and a prospective in vivo cohort study set in two tertiary care centers., Patients or Other Participants: Twenty-five obese adult female patients with active IIH were studied, and 22 completed the study., Intervention: Fasted serum, CSF, and 24-h urine samples were collected at baseline, after 3-month observation, and after a 3-month diet., Main Outcome Measures: Changes in urine, serum, and CSF glucocorticoids (measured by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry) after weight loss were measured., Results: 11β-HSD1 and key elements of the glucocorticoid signaling pathway were expressed in CP and AGT. After weight loss (14.2±7.8 kg; P<0.001), global 11β-HSD1 activity decreased (P=0.001) and correlated with reduction in intracranial pressure (r=0.504; P=0.028). CSF and serum glucocorticoids remained stable, although the change in CSF cortisone levels correlated with weight loss (r=-0.512; P=0.018)., Conclusions: Therapeutic weight loss in IIH is associated with a reduction in global 11β-HSD1 activity. Elevated 11β-HSD1 may represent a pathogenic mechanism in IIH, potentially via manipulation of CSF dynamics at the CP and AGT. Although further clarification of the functional role of 11β-HSD1 in IIH is needed, our results suggest that 11β-HSD1 inhibition may have therapeutic potential in IIH.

A 69-year-old hypertensive woman with a hyperdynamic, left brachio-basilic dialysis fistula presented with a long history of throbbing in her head, swelling of the left side of the face and two months of right visual loss with gross swelling of the right optic disc. Tight stenosis of left brachiocephalic vein was found to be causing retrograde flow into the left jugular vein which normalised after dilatation and stenting with resolution of the papillodema.

Objective: To observe intracranial pressure in women with idiopathic intracranial hypertension who follow a low energy diet., Design: Prospective cohort study., Setting: Outpatient department and the clinical research facility based at two separate hospitals within the United Kingdom., Participants: 25 women with body mass index (BMI) >25, with active (papilloedema and intracranial pressure >25 cm H(2)O), chronic (over three months) idiopathic intracranial hypertension. Women who had undergone surgery to treat idiopathic intracranial hypertension were excluded., Intervention: Stage 1: no new intervention; stage 2: nutritionally complete low energy (calorie) diet (1777 kJ/day (425 kcal/day)); stage 3: follow-up period after the diet. Each stage lasted three months., Main Outcome Measure: The primary outcome was reduction in intracranial pressure after the diet. Secondary measures included score on headache impact test-6, papilloedema (as measured by ultrasonography of the elevation of the optic disc and diameter of the nerve sheath, together with thickness of the peripapillary retina measured by optical coherence tomography), mean deviation of Humphrey visual field, LogMAR visual acuity, and symptoms. Outcome measures were assessed at baseline and three, six, and nine months. Lumbar puncture, to quantify intracranial pressure, was measured at baseline and three and six months., Results: All variables remained stable over stage 1. During stage 2, there were significant reductions in weight (mean 15.7 (SD 8.0) kg, P<0.001), intracranial pressure (mean 8.0 (SD 4.2) cm H(2)O, P<0.001), score on headache impact test (7.6 (SD 10.1), P=0.004), and papilloedema (optic disc elevation (mean 0.15 (SD 0.23) mm, P=0.002), diameter of the nerve sheath (mean 0.7 (SD 0.8) mm, P=0.004), and thickness of the peripapillary retina (mean 25.7 (SD 36.1) micro, P=0.001)). Mean deviation of the Humphrey visual field remained stable, and in only five patients, the LogMAR visual acuity improved by one line. Fewer women reported symptoms including tinnitus, diplopia, and obscurations (10 v 4, P=0.004; 7 v 0, P=0.008; and 4 v 0, P=0.025, respectively). Re-evaluation at three months after the diet showed no significant change in weight (0.21 (SD 6.8) kg), and all outcome measures were maintained., Conclusion: Women with idiopathic intracranial hypertension who followed a low energy diet for three months had significantly reduced intracranial pressure compared with pressure measured in the three months before the diet, as well as improved symptoms and reduced papilloedema. These reductions persisted for three months after they stopped the diet.

We sought to evaluate the diagnostic accuracy of metabolomic biomarker profiles in neurological conditions (idiopathic intracranial hypertension (IIH), multiple sclerosis (MS) and cerebrovascular disease (CVD) compared to controls with either no neurological disease or mixed neurological diseases). Spectra of CSF (n = 87) and serum (n = 72) were acquired using (1)H NMR spectroscopy. Multivariate pattern recognition analysis was used to identify disease-specific metabolite biomarker profiles. The metabolite profiles were then used to predict the diagnosis of a second cohort of patients (n = 25). CSF metabolite profiles were able to predict diagnosis with a sensitivity and specificity of 80% for both IIH and MS. The CVD serum metabolite profile was 75% sensitive and specific. On analysing the second patient cohort, the established metabolite biomarker profiles generated from the first cohort showed moderate ability to segregate patients with IIH and MS (sensitivity:specificity of 63:75% and 67:75%, respectively). These findings suggest that NMR spectroscopic metabolic profiling of CSF and serum can identify differences between IIH, MS, CVD and mixed neurological diseases. Metabolomics may, therefore, have the potential to be developed into a clinically useful diagnostic tool. The identification of disease-unique metabolites may also impart information on disease pathology., ((c) 2009 John Wiley & Sons, Ltd.)

Objective: The aetiology of idiopathic intracranial hypertension (IIH) is not known, but its association with obesity is well-recognized. Recent studies have linked obesity with abnormalities in circulating inflammatory and adiposity related cytokines. The aim of this study was to characterize adipokine and inflammatory cytokine profiles in IIH., Design: Paired serum and cerebrospinal fluid (CSF) specimens were collected from 26 patients with IIH and compared to 62 control subjects. Samples were analysed for leptin, resistin, adiponectin, insulin, IL-1beta, IL-6, IL-8 (CXCL8), TNFalpha, MCP-1 (CCL2), hepatocyte growth factor, nerve growth factor and PAI-1 using multiplex bead immunoassays., Results: CSF leptin was significantly higher in patients with IIH (P = 0.001) compared to controls after correction for age, gender and body mass index (BMI). In the control population, BMI correlated with serum leptin (r = 0.34; P = 0.007) and CSF leptin (r = 0.51; P < 0.0001), but this was not the case for the IIH population. Profiles of other inflammatory cytokines and adipokines did not differ between IIH patients and controls once anthropometric factors had been accounted for., Conclusions: IIH was characterized by significantly elevated CSF leptin levels which did not correlate with BMI. We suggest that CSF leptin may be important in the pathophysiology of IIH and that obesity in IIH may occur as a result of hypothalamic leptin resistance.

Purpose: To establish the contemporary aetiology of adult superior oblique palsy (SOP)., Materials and Methods: A retrospective consecutive case series of 150 persons diagnosed with SOP between 1 January 1999 and 31 May 2005 at a neuro-ophthalmology centre in the West Midlands, the United Kingdom. Interrogating two different hospital databases identified all cases. A case note review was performed on all participants to determine demographics and aetiology based on diagnostic criteria, neuroimaging used, and outcome., Results: We identified 133 unilateral isolated, 7 unilateral associated with other cranial nerve involvement, and 10 bilateral cases of SOP. Eighty-six were acquired, 51 congenital, and 13 undetermined. Of the unilateral isolated cases, 38.3% were considered to be congenital, 29.3% followed trauma, 23.3% were presumed to be vasculopathic in origin, and no cause could be established in 7.5%. All presumed microvascular-associated palsies resolved within 6 months of presentation. Unilateral SOPs associated with other cranial nerve palsies were commonly caused by trauma (71.4%), followed by tumour and undetermined causes (both 14.3%). Trauma was the most frequent cause of bilateral SOP (50%), followed by tumours and undetermined causes (both 20%), with congenital causes being uncommon (10%)., Conclusion: We present a contemporary aetiological spectrum for adult SOP, with the lowest incidence of undetermined cases published in the medical literature. Neuroimaging did not change the management for the vast majority of cases and should be prompted by atypical presentations.

Aim: To document the causal association of iron deficiency anaemia (IDA) and intracranial hypertension (IH)., Methods: A consecutive case note review of patients with a clinical diagnosis of idiopathic intracranial hypertension (IIH) and anaemia presenting to a tertiary referral unit over a 2.5-year period. Demographics, aetiology and clinical details were recorded and analysed., Results: Eight cases were identified from 77 new cases presenting with IIH. All 8 had documented microcytic anaemia with clinical evidence of raised intracranial pressure. There was no evidence of venous sinus thrombosis on MRI and MR venography in 7 subjects and on repeated CT venography in 1. On correction of anaemia alone, 7 cases resolved. One patient with severe progressive visual loss underwent ventriculoperitoneal shunt in addition to treatment of anaemia, with good outcome. The incidence of this association is 10.3%., Conclusion: These cases present an association between IDA and IH, in the absence of cerebral sinus thrombosis. As a clinically significant proportion of cases presenting with signs of IIH have IDA, we recommend all patients presenting with IIH have full blood counts and if they are found to be anaemic, they should be treated appropriately., (Copyright 2009 S. Karger AG, Basel.)

Idiopathic intracranial hypertension (IIH) is a common blinding condition amongst the young obese female population (20 per 100,000) characterised by elevated intracranial pressure (ICP). The aetiology of IIH is not known. In this review we explore the literature investigating the pathogenesis of IIH and suggest additional hypotheses. Chronic inflammation is emerging as an aetiological factor in the pathogenesis of obesity and we propose that this may be a feature of IIH. Obesity is also related to dysregulation of cortisol production by the pre-receptor enzyme, 11beta-hydroxysteroid dehydrogenase, and we speculate that this may have a role in the pathogenesis of obesity and raised ICP seen in IIH.

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain. The balance between CSF production and drainage, in part, facilitates a normal intracranial pressure. The secretion of Na(+) and anions by the CP creates an osmotic gradient driving water into the ventricles. This is opposite to classical Na(+) transporting tissues, such as the kidney, where Na(+) and water reabsorption is mediated by 11beta-hydroxysteroid dehydrogenase type 2 that protects the mineralocorticoid receptor by abrogating active cortisol to inactive cortisone. In the human ocular ciliary epithelium, Na(+) and water secretion is dependent on a novel mediator of ciliary epithelial Na(+) transport, 11beta-HSD type 1 (11beta-HSD1), that generates intraocular cortisol. In a mechanism analogous to that of the embryologically related ocular ciliary epithelium, we propose that autocrine regulation of intracranial cortisol is dependent on 11beta-HSD1 expression in the CP epithelial cells. By conducting immunolocalisation studies on brains from New Zealand White Albino rabbits, we defined the expression of 11beta-HSD1 in the secretory CP epithelial cells. Enzyme assays performed on intact rabbit CP whole tissue explants confirmed predominant 11beta-HSD1 activity, generating cortisol that was inhibited by glycyrrhetinic acid (an 11beta-HSD inhibitor). Using the real time-polymerase chain reaction, rabbit CP tissue was found to express levels of 11beta-HSD1, glucocorticoid receptor alpha and serum and glucocorticoid-regulated kinase 1 mRNA comparable to that expressed in rabbit ocular ciliary body, thereby highlighting the similarity between these two tissues. Furthermore, an enzyme-linked immunosorbent assay of rabbit CSF revealed a median cortisol concentration of 1.7 nmol/l (range 1.4-4.3 nmol/l, n = 9). Our data have identified a functional 11beta-HSD1 within the CP, mediating intracranial cortisol bioavailability. Expression of 11beta-HSD1 may be fundamental in the regulation of CSF secretion and the local generation of cortisol may represent a pathophysiological mechanism underlying cortisol-dependent neuroendocrine diseases.

Objective: To describe the clinical findings and refine the clinical diagnostic criteria for dominant optic atrophy based on eight British families in which the diagnosis was confirmed by linkage analysis., Design and Participants: Case series; 92 subjects in 8 pedigrees had both eyes examined., Intervention: Family members received a domiciliary examination based on best-corrected visual acuity, color vision using Ishihara and Hardy Richter Rand (HRR) plates, confrontation field testing using a red target, and optic disc evaluation using a direct ophthalmoscope. Genomic DNA was extracted from leukocytes or buccal mucosal cells and genotyped using 12 fluorescently labeled microsatellite markers from the region 3q27-q29., Main Outcome Measures: Subjects were classified clinically as definitely or possibly affected on the basis of the domiciliary examination before genetic analysis, and these results were compared with the haplotype analysis., Results: Clinically, 43 subjects were identified as definitely affected, 4 as possibly affected, and 45 as unaffected. Visual acuity in affected subjects ranged from 6/6 to count fingers and declined with age. On genetic analysis, a haplotype was identified in each family, which was found in all definitely affected members but not in those regarded as unaffected. The four possibly affected individuals also bore the haplotype that segregated with the disease., Conclusions: Simple clinical tests are highly efficacious in diagnosing dominant optic atrophy. Contrary to accepted criteria, symptoms begin before the age of 10 years in only 58% of affected individuals. Visual acuity in affected subjects is highly variable. A mild degree of temporal or diffuse pallor of the optic disc and minimal color vision defects, in the context of a family with dominant optic atrophy, are highly suggestive of an individual being affected, even if the visual acuity is normal. This widens the generally accepted diagnostic criteria for this disease.

Dominant optic atrophy, Kjer type, is an autosomal dominant disorder causing progressive loss of visual acuity and colour vision from early childhood. The gene (OPA1) has variable expressivity, a penetrance of 0.98, and the locus has been localised to 3q28-29. We have genotyped nine British families with the disease using 12 polymorphic microsatellite markers from this region. Linkage and haplotype analysis shows the OPA1 gene to be located in a 2.3 cM interval between markers D3S1601 and D3S2748. One family showed no evidence of linkage with the chromosome 3 markers, suggesting for the first time that locus heterogeneity for this disease may exist, although exclusion for linkage is based on unaffected subjects. In addition, analysis of recombinants has enabled us to order the 12 markers along chromosome 3.

Objectives: To perform DNA linkage studies in an extensive 5-generation British pedigree with dominant optic atrophy and to validate the efficacy of domiciliary screening for affected members., Methods: Family members received a domiciliary examination based on corrected visual acuity, color vision, visual field defects, and optic disc appearance; DNA linkage analysis was performed using 7 microsatellite markers on 3q27-qter., Results: Based on the results of the ophthalmic examination, 15 members could be classified as definitely affected, 1 probably affected, and 25 unaffected. Two-point linkage analysis gave significant maximum lod scores at theta [corrected] = 0.00, with the markers D3S3669, D3S3590, and D3S3642. A haplotype segregating with the disease was identified in affected individuals, including the probably affected subject. Informative meioses defined the disease interval between markers D3S1601 and D3S1265., Conclusions: Domiciliary screening was effective in identifying all 16 affected members of a British family with dominant optic atrophy. The typical clinical features were present. The location of the OPA1 gene in this new British family seems to be in the 3q27-28 region and is the same as that reported in Danish, Cuban, and French families, suggesting no genetic heterogeneity in this disorder.

Prominent amongst last year's diverse papers on the retina were a study of the clinical manifestations of dominant cerebellar ataxia with pigmentary macular dystrophy, a review of the pathogenesis of carcinoma associated retinopathy, the Ischaemic Optic Neuropathy Decompression Trial, and a review of congenital optic disc anomalies. Ocular complications of several neurosurgical procedures were also reported during this period.

A questionnaire designed to survey current corneal graft practice was sent to 498 consultant ophthalmologists in the United Kingdom. Three hundred and twenty-nine completed questionnaires (66%) were returned. Seventy per cent of these were from consultants who perform corneal grafts, of whom 36% had a specialist interest in corneal surgery. The survey found that most consultants preferred to perform corneal grafts on an inpatient basis with the patient under general anaesthesia. Agreement (> 80%) was also found in the following areas: use of a hand-held trephine, concurrent cataract surgery (if indicated), post-operative immunosuppression, and refraction to assess post-operative astigmatism. There was less agreement on the choice of donor material, use of tissue matching, donor-trephine size disparity, suture technique, relative timing of trabeculectomy surgery (if required), the management of intraocular lenses during surgery for pseudophakic bullous keratopathy, timing of discharge after surgery, use of prophylactic acyclovir, management of astigmatism, routine removal of all corneal sutures, and discharge of uncomplicated cases from routine follow-up.

Flash and pattern visual evoked potentials were recorded in 8 patients (13 eyes) with dysthyroid optic neuropathy (DON), diagnosed using the American Thyroid Association classification. All were treated with systemic steroids, but 4 patients (6 eyes) also required orbital decompression. Flash VEP (P2) and pattern VEP (P100) were recorded prior to and 2 weeks after commencing steroid treatment or decompression. Fifteen patients with Graves orbitopathy but without DON, and 20 healthy subjects, acted as controls. Before treatment visual acuity was reduced in 10 eyes and visual fields were abnormal in 5, but the VEP was abnormal in all 13, with the group mean amplitude of P2 and P100 significantly less than controls, and the group mean P100 latency significantly greater than controls. After treatment with high-dose steroids or surgical decompression there were significant improvements in the group mean amplitude of P2 and P100, and significant reductions in P2 and P100 latency; however, individually, improvements in amplitude were more significant than improvements in latency. We conclude that the VEP to flash and pattern stimuli provides a useful diagnostic and monitoring tool in patients with DON, combining objectivity with quantitative analysis.

A characteristic pattern of dissociated eye movements was observed in a large proportion of our patients with a variety of craniosynostosis syndromes. These anomalies simulate overaction of the inferior oblique and underaction of the superior oblique muscles which, however, cannot fully explain the abnormalities. In a number of cases, excyclorotation of the muscle cone was observed, with the upper pole of the eye tilted away from the midline. It is postulated that such excyclorotation of the eyes will lead to dissociated eye movements which can be explained on physiological grounds according to Hering's law. This paper presents a review of our patients and evidence to support this hypothesis.