Pharmacotherapy for uveitis: current management and emerging therapy.

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects

Outcomes important to patients with non-infectious posterior segment-involving uveitis:a qualitative study

Objective: Uveitis, a group of disorders characterised by intraocular inflammation, causes 10–15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior-segment involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU but these may not represent patients’ and carers’ concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients’ and carers’ lives, and to explore what outcomes of treatment are important to them.Methods: Four focus group discussions were undertaken to understand the perspectives of adult patients (n=18) and carers (n=10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema (UMO). Discussions were audio recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains. Results: Eleven core domains were identified as important to patients and carers undergoing treatment for PSIU comprising: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control.Conclusion: The domains identified represent patients and carers experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.Ethical approval: Ethical approval was obtained from the United Kingdom National Research Ethics Service (Reference 17-WM-0111).<br/

Hydrodynamics of the stream-disk impact in interacting binaries

We use hydrodynamic simulations to provide quantitative estimates of the effects of the impact of the accretion stream on disks in interacting binaries. For low accretion rates, efficient radiative cooling of the hotspot region can occur, and the primary consequence of the stream impact is stream overflow toward smaller disk radii. The stream is well described by a ballistic trajectory, but larger masses of gas are swept up and overflow at smaller, but still highly supersonic, velocities. If cooling is inefficient, overflow still occurs, but there is no coherent stream inward of the disk rim. Qualitatively, the resulting structure appears as a bulge extending downstream along the disk rim. We calculate the mass fraction and velocity of the overflowing component as a function of the important system parameters, and discuss the implications of the results for X-ray observations and doppler tomography of cataclysmic variables, low-mass X-ray binaries and supersoft X-ray sources.Comment: 16 pages, including 8 figures. 1 color figure as a jpeg. ApJ, in pres

Stability analysis of non-autonomous reaction-diffusion systems: the effects of growing domains

By using asymptotic theory, we generalise the Turing diffusively-driven instability conditions for reaction-diffusion systems with slow, isotropic domain growth. There are two fundamental biological differences between the Turing conditions on fixed and growing domains, namely: (i) we need not enforce cross nor pure kinetic conditions and (ii) the restriction to activator-inhibitor kinetics to induce pattern formation on a growing biological system is no longer a requirement. Our theoretical findings are confirmed and reinforced by numerical simulations for the special cases of isotropic linear, exponential and logistic growth profiles. In particular we illustrate an example of a reaction-diffusion system which cannot exhibit a diffusively-driven instability on a fixed domain but is unstable in the presence of slow growth

COSUMO: study protocol for the development of a core outcome set for efficacy and effectiveness trials in posterior segment-involving uveitis

Abstract Background Uveitis, a group of disorders characterised by intraocular inflammation, causes 10–15% of total blindness in the developed world. The most sight-threatening uveitis affects the posterior segment of the eye (posterior-segment involving uveitis (PSIU)). Numerous different outcomes have been used in clinical trials evaluating alternative treatments for uveitis, limiting inter-trial comparison and aggregation of data. We aim to develop a core outcome set (COS) that would provide a standardised set of outcomes to be measured and reported in all effectiveness trials for PSIU. Methods A three-phase design will be used informed by recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Phase 1: a comprehensive list of outcomes will be identified through both a systematic review of effectiveness trials of PSIU and qualitative research with stakeholders. The qualitative study will comprise focus groups with patients and their carers in parallel with one-to-one telephone interviews with health professionals and policy-makers. In the focus groups, patients will be grouped according to whether or not their uveitis is complicated by the sight-threatening condition uveitic macular oedema (UMO) since it is hypothesised that the presence of UMO may significantly impact on patient experience of PSIU. Phase 2: Delphi methodology will be used to reduce the range of potential outcomes for the core set. Up to three Delphi rounds will be used through an online survey. Participants will be asked to rate the importance of each outcome on a 9-point Likert scale where 9 is most important. Phase 3: a consensus meeting will be held with key stakeholders to discuss the Delphi results and ratify the final outcomes to be included in the COS. Discussion The development of an agreed COS for PSIU would help ensure that outcomes which matter to key stakeholders are captured and reported in a consistent way. A COS for PSIU would allow greater comparison and aggregation of data across trials for the better evaluation of established and emerging therapies through evidence synthesis and meta-analysis to inform clinical guidelines and health policy. Trial registration COMET. http://comet-initiative.org/studies/details/640 . August 2015