Healthcare professionals' views on the most important outcomes for non-infectious uveitis of the posterior segment: A qualitative study.

BACKGROUND: Uveitis comprises a range of conditions that result in intraocular inflammation. Most sight-threatening uveitis falls into the broad category known as Non-infectious Posterior Segment-Involving Uveitis (PSIU). To evaluate treatments, trialists and clinicians must select outcome measures. The aim of this study was to understand healthcare professionals' perspectives on what outcomes are important to adult patients with PSIU and their carers. METHODS: Twelve semi-structured telephone interviews were undertaken to understand the perspectives of healthcare professionals. Interviews were audio recorded, transcribed and thematically analysed. Findings were compared with the views of patients and carers and outcomes abstracted from a previously published systematic review. RESULTS: Eleven core domains were identified as important to healthcare professionals: (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. Healthcare professionals recognised a similar range of domains to patients and carers but placed more emphasis on certain outcomes, particularly in the disease control domain. In contrast the range of outcomes identified via the systematic review was limited. CONCLUSION: Healthcare professionals recognise all of the published outcome domains as patients/carers in the previous publication but with subtly differing emphasis within some domains and with a priority for certain types of measures. Healthcare professionals discussed the disease control and side effects/complications to a greater degree than patients and carers in the focus groups.

OCT Assisted Quantification of Vitreous Inflammation in Uveitis.

Purpose: Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH. Methods: In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed. Results: One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03). Conclusions: OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities. Translational Relevance: OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.

Development of a Core Outcome Set for Clinical Trials in Non-infectious Uveitis of the Posterior Segment.

PURPOSE: To develop an agreed upon set of outcomes known as a "core outcome set" (COS) for noninfectious uveitis of the posterior segment (NIU-PS) clinical trials. DESIGN: Mixed-methods study design comprising a systematic review and qualitative study followed by a 2-round Delphi exercise and face-to-face consensus meeting. PARTICIPANTS: Key stakeholders including patients diagnosed with NIU-PS, their caregivers, and healthcare professionals involved in decision-making for patients with NIU-PS, including ophthalmologists, nurse practitioners, and policymakers/commissioners. METHODS: A long list of outcomes was developed based on the results of (1) a systematic review of clinical trials of NIU-PS and (2) a qualitative study of key stakeholders including focus groups and interviews. The long list was used to generate a 2-round Delphi exercise of stakeholders rating the importance of outcomes on a 9-point Likert scale. The proportion of respondents rating each item was calculated, leading to recommendations of "include," "exclude," or "for discussion" that were taken to a face-to-face consensus meeting of key stakeholders at which they agreed on the final COS. MAIN OUTCOME MEASURE: Items recommended for inclusion in the COS for NIU-PS. RESULTS: A total of 57 outcomes grouped in 11 outcome domains were presented for evaluation in the Delphi exercise, resulting in 9 outcomes directly qualifying for inclusion and 15 outcomes being carried forward to the consensus meeting, of which 7 of 15 were agreed on for inclusion. The final COS contained 16 outcomes organized into 4 outcome domains comprising visual function, health-related quality of life, treatment side effects, and disease control. CONCLUSIONS: This study builds on international work across the clinical trials community and our qualitative research to construct the world's first COS for NIU-PS. The COS provides a list of outcomes that represent the priorities of key stakeholders and provides a minimum set of outcomes for use in all future NIU-PS clinical trials. Adoption of this COS can improve the value of future uveitis clinical trials and reduce noninformative research. Some of the outcomes identified do not yet have internationally agreed upon methods for measurement and should be the subject of future international consensus development.

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 AND ANALYSIS: Four focus group discussions were undertaken to understand the perspectives of adult patients (=18) and carers (10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema. 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 healthcare, (9) treatment burden, (10) treatment side effects, and (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.

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

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.

The effectiveness of pharmacological agents for the treatment of uveitic macular oedema (UMO): a systematic review protocol.

BACKGROUND: Macular oedema (MO) describes the accumulation of fluid in the central part of the retina, known as the 'macula' which provides central vision. MO is the leading cause of sight loss in patients with intraocular inflammation (uveitis). There is a lack of consensus over the treatment of uveitic macular oedema (UMO). The proposed systematic review will evaluate the evidence on the effectiveness of pharmacological agents used to treat UMO. All systemic, local, or topical pharmacological agents will be included. METHOD/DESIGN: Standard systematic review methodology will be employed to identify, select and extract data from comparative studies (randomised/non-randomised trials and observational studies) of the pharmacological interventions in patients with UMO. Searches will be conducted through bibliographic databases (Cochrane Library, MEDLINE, EMBASE and CINAHL) and clinical trials registers. No restriction will be placed on either language or year of publication. Translation of non-English language articles will be undertaken to minimise selection bias. The primary outcome of interest will be best corrected visual acuity and secondary outcomes will be adverse events, health-related quality of life, assessment of UMO using central macular thickness (e.g. by optical coherence topography (OCT)), clinical and angiographic assessment of UMO, clinical estimation of vitreous haze. Risk of bias assessment appropriate to each study design will be undertaken. Data will be grouped by comparison, tabulated and narratively synthesised. Meta-analysis will be undertaken where clinical and methodological homogeneity exists. Subgroup and sensitivity analyses, also network analyses and intra/inter-pharmacological class analyses will be undertaken where deemed appropriate. DISCUSSION: A number of published studies have investigated the effectiveness of the pharmacological agents used to treat UMO. However, there is no recent systematic review that synthesises this evidence. This systematic review will analyse the effectiveness of systemic, local and topical therapies to treat UMO. The findings will provide important evidence to inform clinical and health policy decision-making for the treatment of UMO. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42015019170.