Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

Common Design and Data Elements Reported on Idiopathic Intracranial Hypertension Trials: A Systematic Review.

BACKGROUND: There are an increasing number of controlled clinical trials and prospective studies, ongoing and recently completed, regarding management options for idiopathic intracranial hypertension (IIH). We present a Common Design and Data Element (CDDE) analysis of controlled and prospective IIH studies with the aim of aligning essential design and recommending data elements in future trials and enhancing data synthesis potential in IIH trials. METHODS: We used PubMed and ClinicalTrials.gov to screen for ongoing and published trials assessing treatment modalities in people with IIH. After our search, we used the Nested Knowledge AutoLit platform to extract pertinent information regarding each study. We examined outputs from each study and synthesized the data elements to determine the degree of homogeneity between studies. RESULTS: The most CDDE for inclusion criteria was the modified Dandy criteria for diagnosis of IIH, used in 9/14 studies (64%). The most CDDE for outcomes was change in visual function, reported in 12/14 studies (86%). Evaluation of surgical procedures (venous sinus stenting, cerebrospinal fluid shunt placement, and others) was more common, seen in 9/14 studies (64%) as compared with interventions with medical therapy 6/14 (43%). CONCLUSIONS: Although all studies have similar focus to improve patient care, there was a high degree of inconsistency among studies regarding inclusion criteria, exclusion criteria, and outcomes measures. Furthermore, studies used different time frames to assess outcome data elements. This heterogeneity will make it difficult to achieve a consistent standard, and thus, making secondary analyses and meta-analyses less effective in the future. Consensus on design of trials is an unmet research need for IIH.

The Pressure of Headache at the United Kingdom CSF Disorders Day 2023.

Headache in intracranial disorders drives significant disability in our patients. Management principles for secondary headaches require a multidisciplinary approach with expertise from the neurological, neuro-ophthalmological, neuroradiological, and neurosurgical specialities. The Pressure of Headache was the theme of the annual United Kingdom CSF Disorders Day and saw speakers and panellists from Australia, Europe, and the United States. Among the topics presented were the newest concepts underpinning idiopathic intracranial hypertension management and spontaneous intracranial hypotension. Advances in our knowledge of cerebrospinal fluid secretion and the visual snow syndrome debate were particular highlights. This review provides a summary of the research on headache disorders that overlap the neuro-ophthalmological axis of care for patients.

Vision Threatening Raised Intracranial Pressure Associated with Recreational Nitrous Oxide Use.

Nitrous oxide is used as an anaesthetic and analgesic agent in the medical setting and is known to cause raised intracranial pressure. The use of nitrous oxide recreationally for the drug's euphoric and relaxant properties has been linked to multiple neurological and psychiatric sequelae including neuropathy, myelopathy, and psychosis. We describe a case of a young person who declared heavy nitrous oxide use resulting in vision-threatening papilloedema secondary to raised intracranial pressure. He underwent emergency lumbar drainage alongside high-dose acetazolamide and parenteral vitamin B12 injections. To our knowledge, there have yet to be other reports of cases where heavy nitrous oxide use has caused secondary pseudotumor cerebri syndrome.

EUNOS 2023 Practical Neuro-Ophthalmology Course: Groningen, The Netherlands, June 1st-2nd, 2023.

The European Neuro-Ophthalmology Society (EUNOS) practical neuro-ophthalmology course, henceforth referred to as the EUNOS course, took place in 2023 in Groningen, the Netherlands. This two-day international event featured a blend of plenary lecture sessions, workshops, and case reports, providing a practical update on fundamental neuro-ophthalmology topics for residents and young specialists in both neurology and ophthalmology.

Assessment of the Quality, Accountability, and Readability of Online Patient Education Materials for Optic Neuritis.

Most cases of optic neuritis (ON) occur in women and in patients between the ages of 15 and 45 years, which represents a key demographic of individuals who seek health information using the internet. As clinical providers strive to ensure patients have accessible information to understand their condition, assessing the standard of online resources is essential. To assess the quality, content, accountability, and readability of online information for optic neuritis. This cross-sectional study analyzed 11 freely available medical sites with information on optic neuritis and used PubMed as a gold standard for comparison. Twelve questions were composed to include the information most relevant to patients, and each website was independently examined by four neuro-ophthalmologists. Readability was analyzed using an online readability tool. Journal of the American Medical Association (JAMA) benchmarks, four criteria designed to assess the quality of health information further were used to evaluate the accountability of each website. Freely available online information. On average, websites scored 27.98 (SD ± 9.93, 95% CI 24.96-31.00) of 48 potential points (58.3%) for the twelve questions. There were significant differences in the comprehensiveness and accuracy of content across websites (p < .001). The mean reading grade level of websites was 11.90 (SD ± 2.52, 95% CI 8.83-15.25). Zero websites achieved all four JAMA benchmarks. Interobserver reliability was robust between three of four neuro-ophthalmologist (NO) reviewers (ρ = 0.77 between NO3 and NO2, ρ = 0.91 between NO3 and NO1, ρ = 0.74 between NO2 and NO1; all p < .05). The quality of freely available online information detailing optic neuritis varies by source, with significant room for improvement. The material presented is difficult to interpret and exceeds the recommended reading level for health information. Most websites reviewed did not provide comprehensive information regarding non-therapeutic aspects of the disease. Ophthalmology organizations should be encouraged to create content that is more accessible to the general public.

The Impact of Valsalva Manoeuvres and Exercise on Intracranial Pressure and Cerebrovascular Dynamics in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics in IIH. People with IIH were prospectively enrolled and had an intraparenchymal telemetric ICP sensor inserted. Three participants (age [mean ± standard deviation]: 40.3 ± 13.9 years) underwent continuous real-time ICP monitoring coupled with cerebrovascular haemodynamic assessments during VMs and moderate exercise. Participants had IIH with supine ICP measuring 15.3 ± 8.7 mmHg (20.8 ± 11.8 cm cerebrospinal fluid (CSF)) and sitting ICP measuring -4.2 ± 7.9 mmHg (-5.7 ± 10.7 cmCSF). During phase I of a VM ICP increased by 29.4 ± 13.5 mmHg (40.0 ± 18.4 cmCSF) but returned to baseline within 16 seconds from VM onset. The pattern of ICP changes during the VM phases was associated to that of changes in blood pressure, the middle cerebral artery blood velocity and prefrontal cortex haemodynamics. Exercise led to minimal effects on ICP. In conclusion, VM-induced changes in ICP were coupled to cerebrovascular haemodynamics and showed no sustained impact on ICP. Exercise did not lead to prolonged elevation of ICP. Those with IIH experiencing VMs (for example, during exercise and labour) may be reassured at the brief nature of the changes. Future research must look to corroborate the findings in a larger IIH cohort.

Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study.

Background: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure occurring predominantly in women with obesity. The pathogenesis is not understood. We have applied untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry to characterize the cerebrospinal fluid (CSF) and serum in IIH compared to control subjects. Methods and findings: Samples were collected from IIH patients (n = 66) with active disease at baseline and again at 12 months following therapeutic weight loss. Control samples were collected from gender- and weight-matched healthy controls (n = 20). We identified annotated metabolites in CSF, formylpyruvate and maleylpyruvate/fumarylpyruvate, which were present at lower concentrations in IIH compared to control subjects and returned to values observed in controls following weight loss. These metabolites showed the opposite trend in serum at baseline. Multiple amino acid metabolic pathways and lipid classes were perturbed in serum and CSF in IIH alone. Serum lipid metabolite pathways were significantly increased in IIH. Conclusions: We observed a number of differential metabolic pathways related to amino acid, lipid, and acylpyruvate metabolism, in IIH compared to controls. These pathways were associated with clinical measures and normalized with disease remission. Perturbation of these metabolic pathways provides initial understanding of disease dysregulation in IIH.

Quality standards for the care of people with giant cell arteritis in secondary care.

OBJECTIVE: GCA is the commonest primary systemic vasculitis in adults, with significant health economic costs and societal burden. There is wide variation in access to secondary care GCA services, with 34% of hospitals in England not having any formal clinical pathway. Quality standards provide levers for change to improve services. METHODS: The multidisciplinary steering committee were asked to anonymously put forward up to five aspects of service essential for best practice. Responses were qualitatively analysed to identify common themes, subsequently condensed into domain headings, and ranked in order of importance. Quality standards and metrics for each domain were drafted, requiring a minimum 75% agreement. RESULTS: 13 themes were identified from the initial suggestions. Nine quality standards with auditable metrics were developed from the top 10 themes. Patient Access, glucocorticoid use, pathways, ultrasonography, temporal artery biopsy, PET scan access, rheumatology/ophthalmology expertise, education, multidisciplinary working have all been covered in these quality standards. Access to care is a strand that has run through each of the developed standards. An audit tool was developed as part of this exercise. CONCLUSION: These are the first consensus auditable quality standards developed by clinicians from rheumatology and ophthalmology, nursing representatives and involvement of a patient charity. We hope that these standards will be adopted by commissioning bodies to provide levers for change from the improvement of patient care of individuals with GCA.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study.

OBJECTIVE: To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls. BACKGROUND: Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study. METHODS: We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls). RESULTS: A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20-1.58; and aHR 1.40, 95% CI 1.19-1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86-1.13; and aHR 0.98, 95% CI 0.83-1.14, respectively). CONCLUSION: Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.

Asymptomatic idiopathic intracranial hypertension: Prevalence and prognosis.

BACKGROUND: Little is known about the presentation and prognosis of asymptomatic idiopathic intracranial hypertension (IIH). Papilloedema can be found incidentally on routine fundus examination, with many of these patients actually having symptoms on direct questioning. The aim was to evaluate visual and headache outcomes in people with IIH who present with or without symptoms. METHODS: Prospective observational cohort study, between 2012 and 2021, 343 people with confirmed IIH diagnosis were enrolled in the IIH:Life database. Outcomes such as vision (LogMAR); Humphrey visual field perimetric mean deviation (PMD) and optical coherence tomography (OCT) and headache were evaluated using LOESS (locally weighted scatterplot smoothing) graphs and regression analysis. RESULTS: One hundred and twenty-one people had incidentally found papilloedema, with 36 people with completely asymptomatic presentations. Those with asymptomatic IIH at diagnosis had similar visual prognosis compared to those with symptomatic disease. Sixty-six percent of the asymptomatic cohort became symptomatic during follow-up, and of these the predominant symptom was headache (96%). Headache frequency during follow-up was lower in the asymptomatic cohort. CONCLUSIONS: The prognosis of those with IIH who present with or without symptoms is similar.

Interpretation of telemetric intracranial pressure recordings in people with idiopathic intracranial hypertension after shunt implantation.

BACKGROUND: The M.scio telesensor (Aesculap-Miethke, Germany) is a device integrated within a ventriculoperitoneal (VP) shunt for non-invasive measurement of the intracranial pressure (ICP). The purpose of this study was to analyze the telemetric recordings with the M.scio system in shunted patients with idiopathic intracranial hypertension (IIH), in order to determine reference values and assist the interpretation of telemetric data. METHODS: This was a cohort study of consecutive patients with fulminant IIH who underwent primary VP shunt insertion between July 2019 and June 2022. The first telemetric measurements after surgery in the sitting and supine positions were analyzed. Telemetric ICP values, wave morphology, and pulse amplitude were determined for functioning and malfunctioning shunts. RESULTS: Fifty-seven out of 64 patients had available telemetric recordings. The mean ICP was - 3.8 mmHg (standard deviation (SD) = 5.9) in the sitting and 16.4 mmHg (SD = 6.3) in the supine position. The ICP curve demonstrated pulsatility in 49 (86%) patients. A pulsatile curve with mean ICP in the above ranges indicated a functioning shunt, whereas the lack of pulsatility was challenging to interpret. There was a significant positive correlation between ICP versus amplitude, ICP versus body mass index (BMI), and amplitude versus BMI. CONCLUSIONS: This clinical study defined ICP values and curves in IIH patients with a shunt. The results will assist the interpretation of telemetric ICP recordings in clinical decision making. More research is required to model longitudinal recordings and explore the link between telemetric measurements with clinical outcomes.

Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial Hypertension.

The link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.

The UK CSF Disorders Day 2022.

The annual United Kingdom cerebrospinal fluid disorders meeting made its return to the University of Birmingham, United Kingdom, following the break in proceedings due to the coronavirus pandemic. Cerebrospinal fluid disorders require a multi-disciplinary approach with inputs from the neurological, neuro-ophthalmological, neuroradiological, and neurosurgical specialities. The annual meeting presented the newest concepts underpinning idiopathic intracranial hypertension pathophysiology and the advances in intracranial pressure monitoring and treatment.

Different Characteristics of Pre-Pubertal and Post-Pubertal Idiopathic Intracranial Hypertension: A Narrative Review.

Idiopathic intracranial hypertension (IIH) affects both children and adults. There are currently no clinical trials in IIH for those who are adolescents or children. The aims of this narrative review were to characterise the differences between pre- and post-pubertal IIH and to highlight the need to be more inclusive in clinical trial planning and recruitment. A detailed search of the scientific literature was performed using the PubMed database, from inception until 30 May 2022 using keywords. This included English language papers only. The abstracts and full texts were reviewed by two independent assessors. The literature revealed that the pre-pubertal group had a more variable presentation. The presenting features in the post-pubertal paediatric group were more akin to adults with headache as the dominant feature. They were also more likely to be female and have an increased body mass index. A clear limitation of the literature was that a number of paediatric studies had variable inclusion criteria, including secondary causes of raised intracranial pressure. Pre-pubertal children do not display the same predilection towards the female sex and obesity as post-pubertal children, who have a similar phenotype to the adult cohort. Inclusion of adolescents in clinical trials should be considered given the similar phenotype to adults. There is a lack of consistency in the definition of puberty, making the IIH literature difficult to compare. Inclusion of secondary causes of raised intracranial pressure has the potential to confound the accuracy of analysis and interpretation of the results.

Idiopathic intracranial hypertension: Evaluation of births and fertility through the Hospital Episode Statistics dataset.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) predominantly affects women of reproductive age with obesity, and these women have a distinct profile of hyperandrogenism and insulin resistance. Polycystic ovary syndrome (PCOS) has an established adverse fertility phenotype that typically affects obese women. As IIH may impact reproductive health, we sought to evaluate fertility, gestational complications and pregnancy outcome in IIH. DESIGN: Prospective cohort study from English Hospital Episode Statistics dataset. SETTING: English hospitals, UK. POPULATION: Women aged 18-45 years seen in English hospitals between 1 April 2002 and 31 March 2019. Patients were required to have an IIH diagnosis and were compared with those with PCOS and general population female controls. MAIN OUTCOME MEASURES: Pregnancies resulting in live births, complications of gestational diabetes and pre-eclampsia, and method of delivery. RESULTS: Data was collected from 17 587 IIH, 199633 PCOS and 10 947 012 women in the general population. The live birth rate, adjusted for age, was significantly lower among women with IIH (54.1%) than PCOS (67.9%), p < 0.0001 and the general population (57.7%), p < 0.0001. Pre-eclampsia and gestational diabetes risks were higher following a diagnosis of IIH (5.3-fold and 2.7-fold, respectively, p < 0.0001) compared with the general population controls. Following a diagnosis of IIH, elective caesarean section rates were more than twice that of general population (odds ratio [OR] 2.4) and prior to a diagnosis of IIH (OR 2.2). CONCLUSIONS: These data indicate there are lower age-adjusted total pregnancy rates, increased risk of pre-eclampsia and gestational diabetes, and a doubling of elective caesarean section rates in those with a diagnosis of IIH.

Building trust in real-world data: lessons from INSIGHT, the UK's health data research hub for eye health and oculomics.

PURPOSE OF REVIEW: In this review, we consider the challenges of creating a trusted resource for real-world data in ophthalmology, based on our experience of establishing INSIGHT, the UK's Health Data Research Hub for Eye Health and Oculomics. RECENT FINDINGS: The INSIGHT Health Data Research Hub maximizes the benefits and impact of historical, patient-level UK National Health Service (NHS) electronic health record data, including images, through making it research-ready including curation and anonymisation. It is built around a shared 'north star' of enabling research for patient benefit. INSIGHT has worked to establish patient and public trust in the concept and delivery of INSIGHT, with efficient and robust governance processes that support safe and secure access to data for researchers. By linking to systemic data, there is an opportunity for discovery of novel ophthalmic biomarkers of systemic diseases ('oculomics'). Datasets that provide a representation of the whole population are an important tool to address the increasingly recognized threat of health data poverty. SUMMARY: Enabling efficient, safe access to routinely collected clinical data is a substantial undertaking, especially when this includes imaging modalities, but provides an exceptional resource for research. Research and innovation built on inclusive real-world data is an important tool in ensuring that discoveries and technologies of the future may not only favour selected groups, but also work for all patients.

Total Anterior Staphyloma Secondary to Acanthamoeba Keratitis.

ABSTRACT: There are very few published cases of total anterior staphyloma, all of which have been reported as secondary to fungal keratitis. This study reports the clinical and histopathological findings and subsequent management of a 27-year-old healthy female patient who developed total anterior staphyloma after poor compliance with treatment for clinically diagnosed acanthamoeba keratitis. She underwent a successful evisceration with good long-term results. This case highlights that total anterior staphyloma may also result from untreated keratitis which is not fungal in origin. In cases of fungal and acanthamoeba keratitis, patient compliance with both treatment and follow-up is paramount to avoid vision-threatening sequelae that present significant challenges in their management.