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Papagiannuli E.,Academic Unit of Ophthalmology | Edmunds M.R.,Academic Unit of Ophthalmology | Scollo P.,Academic Unit of Ophthalmology | Southworth S.,Academic Unit of Ophthalmology | And 2 more authors.
Ocular Immunology and Inflammation | Year: 2016

Purpose: To establish how much uveitis patients know about their own condition and to investigate the contribution of demographic factors to that knowledge. Methods: A self-designed questionnaire, comprising 20 questions about uveitis, was distributed to 200 consecutive patients attending a uveitis clinic. The questionnaire requested demographic details and required responses to uveitis-specific knowledge questions. Postcode was used to determine level of social deprivation using Index of Multiple Deprivation 2007. Univariate analyses with the Mann–Whitney test and Kruskal–Wallis test were utilized. Multivariable logistic regression was performed to simultaneously measure the independent influence of demographic variables on the level of patients’ understanding of their condition. Results: Of the respondents, 62% were female, 71% aged >40 years and 67% of white ethnic origin, with 41% having been under the care of a uveitis specialist for >10 years and 72% attending ≥3 clinic appointments in the preceding 12 months. Median questionnaire score (out of 60) was 27 (interquartile range, IQR 15). Females scored significantly higher than males (30 vs 24; p = 0.001), but there was no difference according to age, ethnicity, or social deprivation quintile, nor the duration patients had been under ophthalmic review or number of clinic attendances in the preceding 12 months. Multivariable analyses determined no independent influence of any of the factors on the uveitis questionnaire score. Conclusions: Uveitis patients’ understanding of their condition is poor. This has relevance for adherence to treatment, follow-up clinic attendance, and eventual outcomes in these patients. © 2016, Taylor & Francis. All rights reserved.

Edmunds M.R.,Academic Unit of Ophthalmology | Huntbach J.A.,West Birmingham Hospitals NHS Trust | Durrani O.M.,West Birmingham Hospitals NHS Trust
Ophthalmic Plastic and Reconstructive Surgery | Year: 2014

PURPOSE: Previous studies have extensively investigated the pathophysiology, genetics, and lifestyle risk factors of thyroid-associated ophthalmopathy (TAO). The aim of this study was to investigate the independent contribution of ethnic origin, social grade, and level of social deprivation to TAO severity in a large, multiethnic, and urban population. METHODS: Retrospective case note review of all TAO patients seen at Birmingham and Midland Eye Centre, United Kingdom over a 14-year period. Ethnicity (White, Asian, or Black) was recorded, and residence postcode was used to determine social grade (National Readership Survey classification) and level of social deprivation (Index of Multiple Deprivation 2007). TAO severity was defined by European Group on Graves' Orbitopathy criteria. Moderate-to-severe: necessity for TAO treatment with oral or intravenous steroid, long-term immunosuppressants, or orbital radiotherapy. Sight-threatening: presence of dysthyroid optic neuropathy (DON) or need for urgent orbital decompression surgery. Multivariable logistic regression was performed to measure the independent influence of ethnicity, social grade, and social deprivation on indicators of severe TAO. RESULTS: Lower social grade was significantly associated with increased odds ratio (OR) of TAO patients having severe TAO, including treatment with oral (OR: 2.3 (95% CI 1.1-5.1) p = 0.03) and intravenous steroid (OR: 2.6 (95% CI 1.0-7.0) p = 0.04) and DON (OR: 4.0 (95% CI 1.2-12.7) p = 0.02), compared with those of highest social grade. Similar results were observed for social deprivation. Ethnicity had no independent association with any measure of TAO severity. CONCLUSIONS: In this cohort, lower social grade and higher social deprivation, but not ethnicity, had independent, statistically significant association with more severe TAO. © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.

PubMed | Academic Unit of Ophthalmology
Type: Journal Article | Journal: Clinical and experimental immunology | Year: 2010

Activation of complement occurs during autoimmune retinal and intraocular inflammatory disease as well as neuroretinal degenerative disorders. The cleavage of C5 into fragments C5a and C5b is a critical event during the complement cascade. C5a is a potent proinflammatory anaphylatoxin capable of inducing cell migration, adhesion and cytokine release, while membrane attack complex C5b-9 causes cell lysis. Therapeutic approaches to prevent complement-induced inflammation include the use of blocking monoclonal antibodies (mAb) to prevent C5 cleavage. In these current experiments, the rat anti-mouse C5 mAb (BB5.1) was utilized to investigate the effects of inhibition of C5 cleavage on disease progression and severity in experimental autoimmune uveoretinitis (EAU), a model of organ-specific autoimmunity in the eye characterized by structural retinal damage mediated by infiltrating macrophages. Systemic treatment with BB5.1 results in significantly reduced disease scores compared with control groups, while local administration results in an earlier resolution of disease. In vitro, contemporaneous C5a and interferon-gamma signalling enhanced nitric oxide production, accompanied by down-regulation of the inhibitory myeloid CD200 receptor, contributing to cell activation. These experiments demonstrate that C5 cleavage contributes to the full expression of EAU, and that selective C5 blockade via systemic and local routes of administration can suppress disease. This presents great therapeutic potential to protect against tissue damage during autoimmune responses in the retina or inflammation-induced degenerative disease.

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