NIHRDataInsights/HRCSData huggingface dataset:
Title: Faricimab for treating wet age-related macular degeneration [ID3898 ]
Funder: Department of Health and Social Care

Abstract: The macula is the central part of the retina responsible for colour vision and perception of fine detail. Age-related macular degeneration (AMD) refers to the deterioration in the cells of the retinal pigment layer at the macula area, which can lead to severe visual impairment in the affected eye._x000D_ _x000D_ AMD is a common cause of vision loss in people aged over 50 years and is associated with the loss of central vision and visual distortion. There are 2 main types of AMD, wet (neovascular) and dry (non-neovascular). Wet AMD usually develops much more quickly than dry AMD and is characterised by choroidal neovascularisation, which describes the formation of immature blood vessels that grow between the retinal pigment epithelial cells and the photoreceptor cells in the centre of the retina. These new blood vessels are fragile and more likely to haemorrhage, which causes scarring of the macula leading to vision impairment. Wet AMD accounts for around 10% of all cases of AMD and about 60% of advanced (late-stage) cases[1]. In the UK, prevalence of wet AMD is estimated to be 1.2% (2.5% in those aged 65 or above and 6.3% in those aged 80 or above) with an estimated 40,000 new cases of wet AMD in the UK each year[2]._x000D_ _x000D_ The NICE guideline on AMD (NG82) recommends offering intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Anti-VEGF medications that are licensed options for the treatment of wet AMD are ranibizumab, aflibercept solution for injection and brolucizumab. NICE TA155, TA294 and TA672 recommend treatment with these options when the best-corrected visual acuity is between 6/12 and 6/96, there is no permanent structural damage to the central fovea, the lesion size is less than or equal to 12 disc areas in greatest linear dimension and there is evidence of recent presumed disease progression. NG82 also recommends considering antiVEGF treatment for wet AMD with best-corrected visual acuity of 6/96 or worse if it will benefit the person’s overall visual function (for example, if the affected eye is the person’s better-seeing eye)._x000D_ _x000D_ References_x000D_ _x000D_ 1. Patient Info (2021). Age-related Macular Degeneration. Accessed September 2021._x000D_ 2. Owen, C.G., Jarrar, Z., Wormald, R., Cook, D.G., Fletcher, A.E. and Rudnicka, A.R. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. British Journal of Ophthalmology, 2012, 96: 752-756

Lay abstract: To appraise the clinical and cost effectiveness of faricimab within its marketing authorisation for treating wet age-related macular degeneration.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: EYE
Title: Interventions for myopia control in children: a living systematic review and network meta-analysis
Funder: Department of Health and Social Care

Abstract: There is a global pandemic of myopia. Currently, 30-50% of adults in the UK are myopic (short-sighted) rising to approximately 90% in young adults in parts of East Asia. (1) Myopia places a considerable cost burden on those affected and, importantly, is also a significant risk factor for blinding eye disease (e.g. glaucoma, myopic maculopathy and retinal detachment). There is urgent need to develop safe and effective treatments to slow down its progression in children and reduce the risk of future ocular morbidity and visual impairment. (2) This is an extremely active research field with important implications for children, parents and practitioners, who require an up-to-date assessment of the relative benefits/harms of treatment. A living review and network meta-analysis is the best way to provide relevant and timely evidence. It will be a substantial contribution to this field where practice is changing rapidly, not always supported by evidence. The College of Optometrists have identified this as a key question requiring evidence (3). This is a high-priority topic for consumers given the high and increasing prevalence of myopia, the serious life-long impact of the condition, and the fact that treatment is given to children, requiring high levels of certainty of benefits/harms. References/Other: (1) Dolgin E. The myopia boom. Nature. 2015 Mar 19;519(7543):276-8. doi: 10.1038/519276a. (2) Bullimore MA, Brennan NA Myopia Control: Why Each Diopter Matters.Optom Vis Sci. 2019 Jun; 96(6):463-465. doi: 10.1097/OPX.0000000000001367. (3) College of Optometrists. Myopia management. 2021. URL: https://www.college-optometrists.org/thecollege/policy/myopia-management.html

Lay abstract: See Plain English Summary

Research activity codes: 6.1 PHARMACEUTICALS;6.3 MEDICAL DEVICES;6.7 PHYSICAL
Health categories: EYE
Title: Preventing avoidable blindness through smart home-monitoring of vision
Funder: Economic and Social Research Council

Abstract: We have already developed the core technology, and published preliminary data regarding its diagnostic accuracy. (A large scale multicentre clinical trial will also be ultimately required, but this is outside the scope of this present funding.) The focus of this particular project will instead be on making Eyecatcher an attractive commercial proposition. Specifically, we shall: > Evidence the desirability of Eyecatcher among potential users (patients & clinicians). > Evidence the enhanced usability of Eyecatcher (in comparison to other potential eye care home-monitoring solutions). > Establish the commercial use case. In particular, by defining which clinical settings and patient subgroups to target in future. > Refine and polish the device based on user feedback.

Lay abstract: Glaucoma is the second leading cause of irreversible blindness. It affects 1 in 50 people over 40 years old, all of whom must currently travel to hospital once or twice a year for vision checks. Over 1M such "monitoring" assessments are carried out by the NHS every year. These hospital visits are not only inconvenient: they are unsustainable. Even before COVID, NHS backlogs meant that twenty patients a month were going blind due to delayed glaucoma appointments, and patient numbers are expected to double by 2030. Hospital-only monitoring is also insufficient for the 1 in 23 people with the most aggressive form of glaucoma. Such individuals are liable to experience sudden, irreversible sight loss between hospital appointments. The solution is home-monitoring. If people could check their own vision at home, then sight loss could be detected more quickly, conveniently, and cheaply. People could choose to test their vision more frequently, or when they started to notice a change: allowing sight loss to be flagged and treated sooner. Lower risk patients could attend fewer hospital appointments: reducing unnecessary travel, and freeing up resources to focus on those most in need. And by testing vision at home, more time in the clinic could be spent talking to the doctor face-to-face. That is why over the last eight years we have developed Eyecatcher: the world's first validated vision test for glaucoma home-monitoring. The challenge now is to scale up Eyecatcher, and get it into the hands of patients, in a sustainable, cost-effective way.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: EYE
Title: Unravelling the molecular complexity behind ocular maldevelopment
Funder: Wellcome Trust

Abstract: Aim: Investigating the relationship between genotype, gene expression and phenotype of microphthalmia, anophthalmia and ocular coloboma (MAC), which collectively causes one-third of life-long blindness and severe visual impairment in children worldwide. Research questions: What are the pathogenic variants underlying MAC? How do molecular subtypes correlate with phenotype and stratify clinical risk? What molecular pathways are involved in human eye development? What is the relationship between genotype and gene expression in microphthalmia? Key goals and methodology: 1. Whole genome sequencing of 30 parent-offspring trios with isolated MAC and longitudinal phenotyping. Establish an international reference network to stratify a well-defined cohort to improve care pathways and future research. 2. Temporal comparative analysis of DNA methylome (bisulfite conversion and Illumina Infinium EPIC BeadChips) and transcriptome (65 million reads per sample using Illumina HiSeq-2500) in the developing human eye between 4-9 weeks gestation. 3. Model 3D human microphthalmic optic cups using iPSC technology with isogenic controls using CRISPR/Cas9 gene-editing. DNA methylome and transcriptome analysis to assess disruption of molecular pathways. Outcomes: Establish a molecular framework for ocular maldevelopment. Identify drug targets and develop therapeutics. Improve genetic diagnosis, counselling and management. Elucidate shared molecular mechanisms between embryonic tissue fusion defects and late-onset visual sensory disorders.

Lay abstract: Eye birth defects (termed ocular maldevelopment), including abnormally small eyes, clefts of the eye, and complete absence of any eyes, occur within the first 4-9 weeks of pregnancy. They cause over a third of blindness in children worldwide, resulting in profound life-long impact on both patient and family. Only a few genes have been found to cause ocular maldevelopment, the majority remain undiscovered and currently there is no treatment available. Key goals: 1. To determine the genetic causes of ocular maldevelopment, whilst carefully detailing the disease characteristics over time to see if any specialist care is needed to minimise associated health problems 2. To identify chemical changes (called methylation) in our DNA that influence genes being switched on or off at crucial points during normal eye development, to form a reference guide for comparison with patients 3. To make a human 3D model of the developing eye from stem cells derived from patient's skin to investigate changes in genes that cause ocular maldevelopment and allow us to develop new therapies Applications and benefits: Accurate diagnosis and genetic counselling. Improved care pathways for patients and families. Once we understand the genetic causes, a real focus on treatments can be made.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative age-Related macular degeneration (TIGER): a European randomised controlled surgical trial
Funder: Fight for Sight

Abstract: We aim to test the hypothesis that vitrectomy, subretinal TPA, intravitreal gas tamponade and aflibercept are superior to aflibercept monotherapy, with respect to BCVA.


Research activity codes: 6.4 SURGERY
Health categories: EYE
Title: Ocular Repair and Regeneration Programme grant
Funder: Fight for Sight

Abstract: Glaucoma is the commonest cause of irreversible blindness worldwide. It is characterized by progressive retinal ganglion cell (RGC) loss and axonal damage to the optic nerve. Although present treatments may control progression, many patients continue to develop visual impairment and become blind. There are 7 million people blinded by Glaucoma globally1. Currently there are no therapies to restore RGC or axonal function. Clinically, it is now clear that only a small number of RGC and their axons are needed to maintain functional vision (albeit with reduced vision), and that the loss of a small number of remaining RGC/axons can have profound effects on function and quality of life. Stem cell transplantation, not to replace the RGC and their axons, but to provide physical and metabolic support to these cells, has the potential to reverse RGC/axonal damage, restore useful visual function and improve quality of life in patients affected by the disease. Our work, previously supported by the MRC, provides the basis for this proposal which aims to validate the use of Müller glia (MG) with stem cell characteristics derived from retinal organoids formed by induced pluripotent stem cells (iPSC), to create a cell therapy to treat severe glaucoma. Since all the methodology and expertise are in place at our Institution, we envisage that the research will generate tangible outputs within the 2-year period for which support is requested. The work involves co-operation of non-clinical interdisciplinary scientists and specialist clinician scientists with a well-established track record in the field.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE
Title: Building a photoreceptor: Defining RPGR’s role in disc morphogenesis
Funder: Wellcome Trust

Abstract: My research aims to further define the pathological biochemistry of RPGR-mediated X-linked Retinitis Pigmentosa (RPGR/XLRP), an inherited retinal dystrophy that causes blindness and has no treatment. I hope better understanding of disease mechanism will help identify potential therapeutic options. Photoreceptor outer segments have evolved from primary cilia to compartmentalise the visual pigment rhodopsin into an elaborate structure of folded membranes, known as discs, enabling normal vision. Failure of disc morphogenesis results in photoreceptor degeneration; the hallmark of Retinitis Pigmentosa (RP). Recent work suggests that photoreceptor disc formation is an actin-mediated process, but the exact mechanism by which they form is unknown. RPGR mutations account for 20% of RP and my previous work suggests RPGR regulates actin turnover in the photoreceptor connecting cilium. I hypothesise that RPGR acts as an assembly platform that recruits actin binding proteins to promote morphogenic membrane curvature at the distal connecting cilium, resulting in disc formation. My work in this application will examine my hypothesis. I will use animal models of RPGR/XLRP and endogenously tagged proteins to determine the biochemcial processes that underpin the disease using a combination of molecular biology, novel interactomic experiments and super-resolution imaging.

Lay abstract: Retinitis Pigmentosa (RP) is an inherited eye condition that causes death of the light-sensing photoreceptor cells at the back of the eye, causing blindness. Mutations in several genes cause RP, which has no treatment. Mutations in one particular gene, RPGR, causes 20% of all cases and results in a particularly severe form of disease. The reason no treatment exists for RPGR-related disease is that we don’t know the function of RPGR in the light-sensing photoreceptor cells. Previous work by myself (and others) suggests it helps to regulate the inner skeleton of the photoreceptor cells. If we knew exactly what role it played, we might be able to design treatments for the disease. My work focuses on attempting to fully uncover RPGR’s function in the photoreceptor. I hope one day this will lead to us correcting the errors that lead to photoreceptor death, thus preventing visual loss in this devastating disease.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: Action in Vision
Funder: Wellcome Trust

Abstract: How do vision and motor actions interact? A textbook will answer that vision guides movements but this view has been challenged over the last decade. The most striking realisation was the extent to which locomotion modulates neural activity in primary visual cortex, thalamus dLGN, superior colliculus and even the retina (collectively Early Visual System or EVS). Therefore movements can guide visual processing but the nature of this effect is unknown. The most pressing question regards the specificity of these interactions. In EVS different visual features (size, luminance, colour, direction …) are processed along parallel channels, at least 30 in the mouse retina. Since different motor actions (e.g. picking a fine thread, kicking a ball) require different visual features, I expect the interactions between vision and movements to be quite specific to the nature of the actions performed. Due to technological limitations the only available data are obtained in head-fixed animals where only one type of action – locomotion – can be observed. To overcome these limitations I developed a system to quantify movements in unconstrained animals. I will use this system to understand how different movements affect distinct visual channels in EVS, modify the neural code(s) and ultimately influence behaviour.

Lay abstract: Vision is an active process intrinsically tied to body movements. How do vision and motor actions interact? The traditional view maintained that vision guides motor actions. Recent evidence challenged this view showing that neural activity in the early visual system (including thalamus dLGN and retina) is modulated by movements. Therefore motor actions can guide vision but the nature of this phenomenon is poorly understood. A major question regards the specificity of this effect. I expect the impact of movements on vision to be specific to the nature of the actions being performed. However, due to technological limitations, experimental data are limited to head-fixed preparations that only allow for one type of motor action – locomotion. To overcome these limitations I developed a system for quantifying motor actions in unrestrained animals. Combining experiments and computation I will unveil the neural encoding of visuomotor integration in the early visual system.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: EYE
Title: A Suite of Studies Exploring the Impact of Vision Care on Achieving the Sustainable Development Goals in Low and Middle-Income Countries
Funder: Wellcome Trust

Abstract: The following will extend our previous successful trials on impact of vision care on children's education and adult productivity: • CLEVER (Cognitive Level Enhancement through Vision Exams and Refraction): The first randomized trial to assess impact of eye care delivery (near and distance spectacles) on reducing rates of cognitive decline with aging, enrolling 874 participants >= 60 years in Hyderabad, India. • Piloting and delivery of STABLE (Slashing Two-wheeled Accidents By Leveraging Eyecare): The first randomized trial on the impact of vision care (distance spectacles) on traffic safety in a lower-middle income country (Vietnam), involving 875 young myopic motorcycle users. • Piloting and delivery of THRIFT (Transforming Households with Refraction and Innovative Financial Technology): A randomized trial on the impact of free reading glasses to support use of smartphone banking apps in Bangladesh among 400 elderly recipients of government Old Age Allowance payments. • ZEAL (Zimbabwe Eyecare And Learning) formative research on hyperopia and educational outcomes in Zimbabwe: . This work involving 2000 school-aged children in order to prepare for an eventual randomized trial will assess a novel, low cost vision test we have designed to screen for hyperopia, while examining the impact of uncorrected hyperopia on children’s current reading levels.

Lay abstract: Background: Our past studies have shown that free glasses improve children's studies and adult's work productivity, helping launch large government and industry programs to provide glasses in China and India. We will expand studies to new areas where vision transforms lives. Approach: We will study the impact of giving glasses on: • Slowing cognitive decline in Indian nursing home residents. Three-quarters of them need glasses, and there is evidence vision loss may be linked to cognitive decline, but definite proof is needed. • Improving safety of young motorcycle drivers in Vietnam, who have high rates of both poor vision and accidents. • Enhancing use of smartphone banking apps among the elderly in Bangladesh receiving digital government benefits, who cannot see to use smartphones • Improving learning among far-sighted children in Zimbabwe. Impact: Vision programs launched by successful studies can deliver better mental health in aging, safer streets, enhanced financial resilience and improved children's learning.

Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;5.3 MEDICAL DEVICES;6.3 MEDICAL DEVICES
Health categories: EYE
Title: Deciphering AMD by deep phenotyping and machine learning
Funder: Wellcome Trust

Abstract: We will identify the structural changes leading to and associated with cell degeneration in the retina in patients with early age-related-macular-degeneration (AMD). This will pinpoint what makes AMD progress towards visual loss (late AMD). This will be achieved via machine learning, genotyping and high resolution phenotyping of early AMD patients using retrospective and prospective data. Patients will undergo state-of-the-art imaging of the major tissues; neurosensory retina, retinal pigment epithelium and choriocapillaris to identify the sequence of cell degeneration. We will control for genetic risk by genotyping to infer ancestry and to identify individuals with extreme polygenic risk scores. Thus accounting for confounder effects of cryptic genetic diversity. Machine learning will be utilized to generate a generalized model of AMD progression on a population basis, enabling us to assess individual deviation from normal ageing. Structural imaging biomarkers will be developed in already collected extensive imaging databases, and validated in a prospective cohort study. Biomarkers will: 1) detect conversion to late AMD earlier; 2) discriminate slow/fast progressors and 3) identify therapeutic targets. Results should improve clinical trial design by better characterizing study populations and result in novel therapies by identifying the underlying mechanisms of one of the largest unmet medical needs.

Lay abstract: Age-related-macular-degeneration (AMD) is a very common cause of blindness. Unfortunately, doctors don’t know who will progress to the sight threatening stage of the disease. Some patients progress slowly or not at all and others quickly. We can teach computers to analyse high resolution images of the inside of the eye. We have access to hundreds of thousands of such images from patients with AMD and patients who don’t have AMD. These images allow us to train computers to identify what eye changes appear in patients with AMD. Once the computers have learnt this, we expect they will identify new changes we haven’t thought of. Using this approach we think we will be able to better predict which patients will progress. This should help us develop better treatments and enter the most appropriate patients into clinical trials. It should allow us to better understand why AMD develops too.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: EYE
Title: An innovative online platform to enable online virtual vision checks utilising AR and AI.
Funder: Innovate UK

Abstract: Eyebou is a UK-based tele-optometry SME with a core project team of Amy Fehilly (Project Lead), Farris Massoudi (Regulatory/Technical Lead), Jaleh Caprez (Commercial/Product Lead) and Mai Monavar (Optometrist). Eyebou is solving a significant unmet need by designing a state-of-the-art virtual vision checker and an online app/platform that offers users a one-of-a-kind experience, where they can interact with optometrists to discuss eye health issues and treatment plans. The added advantage is that appointments can be sought online by users from the comfort of their homes. This will save time and reduce the amount of effort in seeking in-person appointments.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: EYE