'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Regulation of inflammation in choroidal neovascularization in age related macular degeneration

La dégénérescence maculaire liée à l'âge (DMLA) est la cause la plus fréquente de déficience visuelle centrale irréversible chez les personnes de plus de 50 ans dans les pays industrialisés, avec des impacts sociétaux et financiers majeurs. La DMLA est une maladie à multiples facettes provoquée par des interactions entre les facteurs de risque et les antécédents génétiques et l'inflammation joue un rôle important. Les effets pro-inflammatoires provoquent une perturbation de l'environnement sousrétinien physiologiquement immunosuppresseur. L'accumulation de phagocytes mononucléaires (PM) dans l'espace sous-rétinien qui s'ensuit est au coeur de l'étiologie des formes atrophiques et humides de la DMLA. Après l’usage de tabac, l'obésité est l'un des facteurs de risque modifiables les plus importants. Nous avons démontré que les régimes riches en graisses exacerbent la néovascularisation choroïdienne (NVC) en modifiant le microbiote intestinal. La dysbiose intestinale entraîne une perméabilité intestinale accrue, une inflammation chronique de bas grade, une augmentation des PM sur le site de l'angiogenèse pathologique dans l'oeil et exacerbe finalement la NVC. La modification du microbiote peut réduire l'inflammation et atténuer la NVC et peut ainsi fournir des traitements peu intrusifs et rentables pour prévenir ou retarder la DMLA exsudative. Une autre option thérapeutique qui pourrait réduire la NVC par modulation inflammatoire consiste à piéger localement les ligands de NRP1 avec un piège dérivé de NRP1. Les ligands de NRP1 sont élevés dans le vitré des patients atteints de DMLA. Nous avons constaté que les PM exprimant NRP1 favorisaient la NVC en atténuant la production de facteurs inflammatoires et en favorisant l'activation alternative, donnant aux PM un caractère pro-angiogénique. Les PM moins inflammatoires et plus de type M2 qui sont enrichis avec l'âge et exacerbent la NVC peuvent être modulés et devenir moins nuisibles en empêchant l'activation de NRP1. Cette thèse explore deux angles dans lesquels la régulation de l'inflammation peut influencer la formation de NVC et jette les bases du développement futur de nouveaux traitements préventifs primaires et secondaires efficaces dans le contexte de la DMLA.Age related macular degeneration (AMD) is the most common cause of irreversible central vision impairment in people over 50 in industrialized countries, with major societal and financial impacts. AMD is a multifaceted disease provoked by interactions among environmental risk factors and genetic backgrounds in which inflammation plays an important role. Proinflammatory effects cause a disruption of the physiologically immunosuppressive subretinal environment. The ensuing accumulation of mononuclear phagocytes in the subretinal space is central to the etiology of both atrophic and wet forms of AMD. After smoking, obesity is one of the most important modifiable risk factors. We demonstrate that high-fat diets exacerbate choroidal neovascularisation (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low-grade inflammation, increases recruitment of microglia and macrophages to the site of pathological angiogenesis in the eye and ultimately exacerbates CNV. Modifying microbiota can reduce systemic and local choroidal inflammation and attenuate pathological neovascularization and may thus provide minimally intrusive and cost-effective paradigms to prevent or delay exudative AMD. Another therapeutic option that could reduce CNV through inflammatory modulation is locally trapping ligands of NRP1 with a NRP1-derived trap. Ligands for NRP1 are elevated in the vitreous of patients with AMD at times of active CNV. We found that NRP1-expressing MPs promote CNV by mitigating production of inflammatory factors and promoting alternative activation, giving the MPs a pro-angiogenic character. The less inflammatory and more M2-like MPs that are enriched with age and exacerbate CNV can be rendered less detrimental by hindering NRP1 activation. This thesis explores two angles wherein regulation of inflammation can influence the formation of CNV and lays the groundwork for future development of novel effective primary and secondary preventive treatments for AMD

Automating the eye examination using optical coherence tomography

Optical coherence tomography (OCT) devices are becoming ubiquitous in eye clinics worldwide to aid the diagnosis and monitoring of eye disease. Much of this uptake relates to the ability to non-invasively capture micron-resolution images, enabling objective and quantitative data to be obtained from ocular structures. Although safe and reasonably quick to perform, the costs involved with operating OCT devices are not trivial, and the requirement for OCT and other imaging in addition to other clinical measures is placing increasing demand on ophthalmology clinics, contributing to fragmented patient pathways and often extended waiting times. In this thesis, a novel “binocular optical coherence tomography” system that seeks to overcome some of the limitations of current commercial OCT systems, is clinically evaluated. This device incorporates many aspects of the eye examination into a single patient-operated instrument, and aims to improve the efficiency and quality of eye care while reducing the overall labour and equipment costs. A progressive framework of testing is followed that includes human factors and usability testing, followed by early stage diagnostic studies to assess the agreement, repeatability, and reproducibility of individual diagnostic features. Health economics analysis of the retinal therapy clinic is used to model cost effectiveness of current practice and with binocular OCT implementation. The binocular OCT and development of other low-cost OCT systems may improve accessibility, however there remains a relative shortage of experts to interpret the images. Artificial intelligence (AI) is likely to play a role in rapid and automated image classification. This thesis explores the application of AI within retinal therapy clinics to predict the onset of exudative age-related macular degeneration in fellow eyes of patients undergoing treatment in their first eye. Together with automated and simultaneous imaging of both eyes with binocular OCT and the potential for low-cost patient-facing systems, AI is likely to have a role in personalising management plans, especially in a future where preventive treatments are available

The MATE study : a 24 month, multicentre, pilot, randomised controlled trial comparing standard care with individualised treat and extend regimen for treatment of neovascular age-related macular degeneration with aflibercept

Purpose: Various treatment regimens have been described for anti-vascular endothelial growth factors (VEGF) in neovascular age-related macular degeneration (nvAMD). Recently, these include treating nvAMD with aflibercept using a ‘Treat & Extend’ (T&E) regimen. However, important questions regarding efficacy and treatment burden remain unanswered. The MATE study was a 24-month, prospective, multicentre, pilot, randomised controlled trial (RCT) comparing standard care with T&E in treating patients with aflibercept, in order to inform a future large-scale RCT.Methods: The study adopted a mixed methodology, with the primary outcome to assess feasibility by recruitment rates and in-depth interviews of trial staff at the end of recruitment and year one. All interviews were transcribed and analysed using thematic analysis. Forty patients were randomised to receive aflibercept for nvAMD as per either standard care or a T&E regimen across the UK in six NHS Ophthalmology units. Baseline demographics, mean change in visual acuity and central retinal thickness from baseline to 12 and 24 months, and number of treatments and visits over 24 months were collected as secondary outcomes.Results: The recruitment rate was 3.07 participant/month. Key themes in recruitment phase interviews were human factors, protocol-related issues, recruitment processes and challenges; key themes in year one interviews were variation in practice and challenges. Both arms showed a trend towards gain in visual acuity in the first year which was not maintained in the standard care arm at the end of 24 months. These were achieved with one less treatment in the T&E arm.Conclusion: Minimising set up delays, optimising recruitment strategy, accounting for variation in practice at sites are key factors in the recruitment and running of a multicentre, randomised controlled trial in this context