Which factors are associated with quality of life in patients with Graves' orbitopathy presenting for orbital decompression surgery?

Purpose: Graves’ orbitopathy (GO) is associated with changes in the appearance of the eyes and visual dysfunction. Patients report feeling socially isolated and unable to continue with day-to-day activities. This study aimed at investigating the demographic, clinical, and psychosocial factors associated with quality of life in patients presenting for orbital decompression surgery. Methods: One-hundred and twenty-three adults with GO due for orbital decompression at Moorfields Eye Hospital London were recruited prospectively. Clinical measures including treatment history, exophthalmos, optic neuropathy, and diplopia were taken by an ophthalmologist. Participants completed psychosocial questionnaires, including the Graves’ Ophthalmopathy Quality of Life Scale (GO-QOL), the Hospital Anxiety and Depression Scale, and the Derriford Appearance Scale. Hierarchical multiple regression analyses were used to identify predictors of quality of life. Results: Higher levels of potential cases of clinical anxiety (37%) and depression (26%) were found in this study sample than in patients with other chronic diseases or facial disfigurements. A total of 55% of the variance in GO-QOL visual function scores was explained by the regression model; age, asymmetrical GO and depressed mood were significant unique contributors. In all, 75% of the variance in GO-QOL appearance scores was explained by the regression model; gender, appearance-related cognitions and depressed mood were significant unique contributors. Conclusion: Appearance-related quality of life and mood were particularly affected in this sample. Predominantly psychosocial characteristics were associated with quality of life. It is important when planning surgery for patients that clinicians be aware of factors that could potentially influence outcomes

New insights into the pathogenesis and nonsurgical management of Graves orbitopathy

Graves orbitopathy, also known as thyroid eye disease or thyroid-associated orbitopathy, is visually disabling, cosmetically disfiguring and has a substantial negative impact on a patient’s quality of life. There is increasing awareness of the need for early diagnosis and rapid specialist input from endocrinologists and ophthalmologists. Glucocorticoids are the mainstay of treatment; however, recurrence occurs frequently once these are withdrawn. Furthermore, in >60% of cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required. Clinical trials have shown that considerable benefit can be derived from the addition of antiproliferative agents (such as mycophenolate or azathioprine) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab, which reduces proptosis, rituximab (anti-CD20), which reduces inflammation, and tocilizumab, which potentially benefits both of these parameters. Other strategies such as orbital radiotherapy have had their widespread role in combination therapy called into question. The pathophysiology of Graves orbitopathy has also been revised with identification of new potential therapeutic targets. In this Review we provide an up-to-date overview of the field, outline the optimal management of Graves orbitopathy and summarize the research developments in this area to highlight future research questions and direct future clinical trials

A patient-initiated treatment model for blepharospasm and hemifacial spasm: a randomized controlled trial

Background: To test, in a two-arm, single center, superiority, randomized controlled trial, the efectiveness of and costs associated with a patient-initiated treatment model for people with hemifacial spasm (HFS) and blepharospasm (BEB) in comparison to usual care. Methods: One hundred and thirty patients with HFS or BEB, aged 18 years or over, were recruited from a nurse-led botulinum toxin type A clinic at an eye hospital in the United Kingdom (UK), completed baseline measures and were randomized (1:1). The intervention group determined their own botulinum toxin type A (BoNT/A) treatment schedule during the trial period (9months) and received an information leafet with a “hotline” number to book an appoint‑ ment. Usual care appointments were scheduled by treating clinicians. Data analysts were blind to study group. The primary outcomes were disease severity and functional disability, as measured by the Jankovic Rating Scale and Blepharospasm Disability Index, respectively. Secondary outcomes included quality of life, anxiety and depression, satisfaction with care, confdence in the service, economic costs and employment days lost. Results: Sixty-fve patients were randomized to each group. The intervention demonstrated no statistically signif‑ cant diference to usual care for any of primary outcomes. On secondary outcomes the levels of anxiety difered signifcantly (F2, 142.39 =1.65, p =0.02), with the intervention arm exhibiting a decrease and the control arm an increase (Hedges’ g=−0.26 [99% CI -0.83, 0.32]). No other statistically signifcant diferences were found for sec‑ ondary outcomes. Overall healthcare costs and costs to the patient were on average £198.95 less (95% CI -£256.76, £654.67; p =0.10) per participant for those in the intervention compared to usual care, although this fnding was not signifcant. Conclusions: We did not observe diferences between the patient-initiated treatment model and usual care for peo‑ ple with BEB or HFS, on any primary outcome measure, quality of life, or depression. The patient-initiated treatment model may, however, have the potential to save healthcare costs and reduce anxiety. Patients using this new model were also equally as satisfed in the service and confdent in their care as those receiving treatment as usual

Flight Performance Handbook for Orbital Operations: Orbital Mechanics and Astrodynamics Formulae, Theorems, Techniques, and Applications

This handbook provides parametric data useful both to the space vehicle designer and mission analyst. It provides numerical and analytical relationships between missions and gross vehicle characteristics as a function of performance parameters. The effects of missile constraints and gross guidance limitations plus operational constraints such as launch site location, tracking net location, orbit visibility and mission on trajectory and orbit design parameters are exhibited. The influence of state-of- the-art applications of solar power as compared to future applications of nuclear power on orbit design parameters, such as eclipse time, are among the parameters included in the study. The principal aim, however, is in providing the analyst with useful parametric design information to cover the general area of earth satellite missions in the region of near-earth to cislunar space and beyond and from injection to atmospheric entry and controlled descent. The chapters are organized around the central idea of orbital operations in the 1961-1969 era with emphasis on parametric flight mechanics studies for ascent phase and parking orbits, transfer maneuvers, rendezvous maneuver, operational orbit considerations, and operational orbit control. The results are based almost entirely on the principles of flight and celestial mechanics. Numerous practical examples have been worked out in detail. This is especially important where it has been difficult or impossible to represent all possible variations of the parameters. The handbook contains analytical formulae and sufficient textual material to permit their proper use. The analytic methods consist of both exact and rapid, approximate methods. Scores of tables, working graphs and illustrations amplify the mathematical models which, together with important facts and data, cover the engineering and scientific applications of orbital mechanics. Each of the five major chapters are arranged to provide a rapid review of an entire astrodynamic subject. By the use of compact graphical and tabular presentation the full scope of the material is made available in an easy-to-use style. Throughout the volume the analyst is shown, by means of suitable introductions, notes, authoritative examples, and cross-references the vital interrelation of the various orbital mechanics topics in the general field of earth satellites and satellite rendezvous. The handbook is designed to give the analyst rapid, reliable access to the mathematics of orbital mechanics needed for virtually any working requirements

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

ObjectiveThis study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls.MethodThis prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq.ResultsRNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED.ConclusionThis study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents