NIHRDataInsights/HRCSData huggingface dataset:
Title: A Functional Optical Coherence Tomography Ophthalmoscope
Funder: Innovate UK

Abstract: An ageing population and the growing burden of chronic disease are factors which are now common to almost all advanced industrial societies. With these broad demographic and epidemiological shifts comes an increasing burden of eye related conditions. Conditions such as Diabetic Retinopathy where the number of people with the condition globally will grow from 126 million in 2010 to 191 million by 2030, Age-related Macular degeneration where the number of affected individuals in the UK will increase by 25% by 2020 to 800,000 and Glaucoma where the number of cases of primary open angle glaucoma in England and Wales is estimated to increase by a third over the next 20 years to around 650,000. Objective assessment of retinal function is the most accurate and robust measure of pathology in eye related diseases. Several diseases may result in a similar retinal appearance as observed using structural imaging techniques. Functional imaging will allow more accurate stratification of patients into causes of disorders and could enable this earlier in the disease. A more accurate diagnosis will save costs by avoiding ineffective treatment. Catching diseases sooner enables earlier treatment and enhances prospects for maintaining and restoring vision, thereby prolonging independent living. This project aims to develop and assess clinically novel technology that is required to perform non-invasive functional imaging of the retina. It will be led by a globally leading manufacturer in retinal imaging who aims to bring this technology to the eye screening market.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Harnessing the tissue-protective potential of erythropoietin (EPO) to prevent diabetic retinopathy
Funder: Diabetes UK

Abstract: Diabetic retinopathy remains a leading cause of blindness and is characterised by progressive dysfunction of the retinal microvasculature leading to impaired perfusion and retinal hypoxia. This proposal aims to investigate whether a unique version of a protein called erythropoietin (EPO) could help to alleviate diabetesrelated eye damage without the potentially harmful side effects normally experienced with EPO treatment.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Over-expression of VEGF165b as a novel therapeutic agent in diabetic retinopathy
Funder: Diabetes UK

Abstract: The proposed project is to perform proof of principal pre-clinical studies required to develop a new treatment for people with diabetes that has the potential to prevent blindness safely and effectively. This grant will investigate if a naturally occurring variant of a drug currently used to improve vision in patients with diabetic retinopathy will protect eyes from diabetes-related damage without the associated blood and nerve vessel damage and with a less invasive administrative regime than the currently used drug.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Inflammation in diabetic retinopathy: how is it influenced by cataract surgery?
Funder: Diabetes UK

Abstract: Diabetic retinopathy (DR) and diabetic cataract (DC) are the two major vision-related complications in diabetic patients. Current therapies for DR are not satisfactory and DR remains the major cause of visual impairment in people of working age. Cataract surgery is highly successful in restoring vision. However, this procedure may possess a big risk when it is conducted in diabetic patients. Compelling evidence suggests that cataract surgery increases the risk of developing DR and accelerates the progression of pre-existing DR. The reason for this connection between cataract surgery and DR is unknown. In this proposal, we will investigate how cataract surgery promotes pro-inflammatory pathology, in the vascular, neural and glial components of the retina using an established model of murine DR. We will then investigate whether blocking specific inflammatory pathways can prevent or reduce cataract surgery-mediated DR progression. The data obtained in this pre-clinical evaluation will be extremely important to guide clinicians on the management of diabetic patients who require cataract surgery.


Research activity codes: 6.4 SURGERY
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Investigation of adverse side-effects of anti-VEGF therapy in the diabetic retina
Funder: Diabetes UK

Abstract: Diabetic macular oedema (DMO) is a major cause of vision loss during diabetic retinopathy. The disease is caused by the leakage of fluid from damaged retinal blood vessels, especially in the macula. Vascular endothelial growth factor (VEGF) is known to play an important role in DMO pathology and, following success in age-related macular degeneration, anti-VEGF reagents have become a standard therapy for DMO. Ranibizumab is the licensed VEGF inhibitor to treat DMO in the UK and the drug is delivered into the vitreous of the eye once every 4~6 weeks. The therapy has shown significant efficacy, however, since VEGF is a known retinal survival factor, long-term safety remains unknown. In a preliminary study, we have observed substantial neural retinal degeneration following prolonged VEGF depletion in the eyes of diabetic mice compared to non-diabetic controls. Therefore, we have concerns that long-term anti-VEGF therapy in DMO patients may cause severe adverse effects to the visual system. This proposal will use established pre-clinical models and parallel cell cultures to address important questions: i) Does prolonged VEGF neutralisation cause adverse effects to diabetic eyes? ii) What is the precise nature and time-frame of pathology? iii) Are adverse effects arising from anti-VEGF therapy reversible after discontinuation?


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: The role of VEGF-A in retinal neuron survival in diabetic retinopathy: functional assessment and potential neuroprotection solutions.
Funder: Diabetes UK

Abstract: Vascular endothelial growth factor A (VEGF-A) is a therapeutic target for angiogenic- and vascular permeability-related pathologies, including blinding diseases such as diabetic retinopathy (DR) and age-related macular degeneration. We and others have shown VEGF-A also plays an important role in neuronal development and neuroprotection, including in the retina. Therefore, antagonism of VEGF-A in DR may pose a possible risk to neuron survival. We recently demonstrated that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival; results that were confirmed in animals. Importantly, we observed that VEGF-A blockade significantly exacerbates neuronal cell death, including pilot findings in a rodent model of DR. These results highlight the need to better define risks associated with ocular VEGF-A antagonists. This project aims to firstly, investigate the role of VEGF-A in retinal neuron survival and function in a model of DR, to help identify potential clinical risks; and, secondly, to therapeutically manage the risk, by validating a novel neuroprotectant/anti-VEGF-A combination therapy strategy for patients being treated for DR. This strategy could potentially offer protection to neurons under stress due to VEGF-A deprivation. Together, these findings will have important clinical implications as ocular VEGF-A antagonist use becomes more prevalent in diabetes.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Can automated analysis of sequential retinal images of people attending diabetic
Funder: Chief Scientist Office (Scotland)

Abstract: The prevalence of diabetes is steadily increasing and screening for eye disease complications is struggling to meet the demand. Automated image analysis combined with the extensive photographic data collected through a decade of systematic diabetic retinopathy screening gives us an opportunity to understand the progression of this disease better than ever before. We will use automated image analysis of sequential photographs from retinal screening to quantify disease changes in retinal images. The analysis results will be treated as potential risk factors for referral from retinal screening to ophthalmology within five years. Using screening programme grades from patient screens one to five years after the analysed photographs we will determine which potential risk factors predict referral from retinal screening to ophthalmology. This will provide useful information for optimising eye screening resources for best possible care of people with diabetes.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Modelling the cost-effectiveness of adopting risk stratified screening intervals within the national diabetic retinopathy screening programme in Scotland
Funder: Chief Scientist Office (Scotland)

Abstract: With the prevalence of diabetes increasing by ~4% annually in Scotland, costs of screening for diabetic retinopathy are set to rise indefinitely unless efficiency gains can be realised. While the early identification of people at risk of sight loss from diabetic retinopathy is beneficial, many patients currently screened annually in Scotland face a low risk of progression prior to their subsequent screening visit. This project will use longitudinal screening data held by the Scottish Care Information-Diabetes Collaboration to model the risk of developing referable retinopathy by individual level clinical and demographic characteristics. By utilising derived probabilities of progression within a state transition micro-simulation model, we will be able to assess the cost and health impact of adopting longer/shorter screening intervals for different groups of patients. This will help identify ways in which the national screening programme can be safely reconfigured to meet the growing demand for screening within budget constraints.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: A multicentre phase III randomised controlled single masked clinical trial to test the clinical efficacy of LightMasks at preventing dark adaptation in the treatment of early diabetic macular oedema (CLEOPATRA)
Funder: Department of Health (England)

Abstract: Research Design: A multicentre Phase III Randomised Controlled Single-Masked Clinical trial to test the clinical efficacy of light-masks at preventing dark adaptation in the treatment of early (non-centre involving diabetic macular oedema (DMO). A subset of patients (n=30)will have additional mechanistic evaluations. Study population: Participants will include people with type I and type II diabetes referred to eye clinics from the Diabetes Screening Service with OCT evidence of non-centre involving DMO in whom laser can be deferred for at least 6 months. Planned interventions:The active intervention group will wear light-masks with an output of 100 cd.m2 at night during sleep. The control arm will wear a ‘dummy mask’ in which the light output is zero. Compliance will be monitored randomly using data-loggers that monitor mask charging current. The primary outcome measure will be the change from baseline in absolute thickness of the zone of maximum retinal thickness as determined by OCT at 12 months. Secondary outcomes measures at 12 and 24 months include proportion requiring macular laser or antiVEGF treatment; change in retinal thickness in all ETDRS zones; change in visual acuity; safety and tolerability; change in measures on the validated sleep questionnaires. Assessment and follow up: Patients will be seen at 4 monthly intervals for 2 years. Proposed sample size: With 300 patients we anticipate 240 to be followed up (20% dropout). This is sufficient to provide 90% power to detect a 15 micrometre in mean change of retinal thickness at the zone of maximal thickness between arms using a two sided analysis of covariance test adjusting for baseline at the 5% level of significance assuming a standard deviation of 35.7 micrometres. Statistical analysis: The primary outcome will be analysed using two-sided analysis of covariance between groups receiving lightmasks (active) and dummy masks (control) with adjustment for baseline. The primary timepoint will be 12 months. Sample size will be reassessed when 50 patients complete six-month follow-up. Analysis of covariance logistic regression and Cox regression will also be undertaken to analyse secondary and mechanistic outcomes of continuous binary and time to occurrence type respectively. Project timetables including recruitment rate: This is a 42 months study. We have previously recruited 42 patient in 6 months at one centre. So we expect recruitment to be completed in 12 months. The follow-up is for 24 months. The primary outcome analyses will be done at 12 months and all secondary outcome measures will be done at 12 and 24 months. Analyses on mechanstic evaluation will be done when the 30 participants complete the 12 months follow-up.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: The UK-Philippines Remote Retinal Evaluation Collaboration in Health: Diabetic Retinopathy (REACH-DR)
Funder: Medical Research Council

Abstract: Systematic population based screening for diabetic retinopathy (DR) through remote retinal imaging has been shown to reduce the rate of diabetes-related visual loss. This approach has been successfully employed in the UK national DR screening programs (DRSP). However, UK-DRSP utilize costly retinal imaging devices and operates on a budget of an average £26 per screening episode. Establishing DRSP in Lower and Middle Income countries (LMICs) has to date been difficult due to limited resources coupled with cultural and geographic barriers that prevent access to care. However, there have been significant advances in mobile retinal imaging devices which are suitable for implementation in LMICs at a significantly lower cost. Information technology platforms have also substantially developed allowing rapid integration of new technology. In this project we intend to prospectively perform a head to head multiple device validation study to evaluate the agreement on image analysis outcomes and treatment requirements and subsequently cost effectiveness of current retinal imaging devices in the context of a resource limited setting. Retinal imaging platforms will be compared to accepted standard Early Treatment Diabetic Retinopathy Study (ETDRS) 7 field photography, ultrawide imaging and macular optical coherence tomography. Results of this validation study will allow modelling of various screening strategies and selection of the most cost effective device in the Philippines and similar regions globally. The ultimate goal of our study is to establish a DRSP within the target population and provide the framework for development and implementation of DRSP in the Philippines. We intend to rapidly translate the validation and cost-effectiveness analysis into clinical use by performing an initial screening of the target communities for DR. This will allow the benefit to be immediately realized and deployed in a real-world setting.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy
Funder: Department of Health and Social Care

Abstract: In the UK, there are an estimated 4.8 million people affected by diabetes; most of whom will develop diabetic retinopathy (DR) and require lifelong follow-up to prevent visual loss.(1) There is considerable uncertainty as to which people with DR will progress to severe sight-threatening retinopathy (proliferative DR, PDR). Identifying prognostic factors for PDR would enable the NHS to prioritise services for those at highest risk, thereby reducing healthcare costs and increasing efficiency. There is an urgent issue of capacity for eye care within the NHS.(2) People with diabetes attending for eye care consistently express the wish to know their risk of eye complications – if high risk, they can receive priority for eye health care and support to control modifiable risk factors. People at low risk would value reducing the burden and discomfort of frequent hospital visits. This review will receive consumer peer review. A Cochrane Review is highly likely to change policy/practice. There is substantial literature on this topic that has not been assessed rigorously using the latest methods for prognostic reviews. We estimate there will be between 40-50 included studies. This review includes complex methods of study assessment, risk of bias and analysis; the experienced review team includes clinical, methodological and statistical expertise. References/Other: (1) https://www.diabetes.org.uk/about_us/news/diabetes-prevalence-2019, accessed 13th September 2021. (2) https://www.rcophth.ac.uk/wp-content/uploads/2019/01/RCOphth-A4-Census-Infographic.pdf, accessed 13th September 2021.

Lay abstract: See Plain English Summary

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Genetics and Epidemiology of Diabetic Retinopathy
Funder: Wellcome Trust

Abstract: Background Diabetic eye disease, or diabetic retinopathy (DR), is a common complication of diabetes. 1.5 million people in the UK have DR of whom 140,000 have sight-threatening diabetic retinopathy (STDR). STDR is a leading cause of blindness in working age people, associated with lifetime costs of up to ~£237,000 per patient. It remains unclear why some patients with DR progress to STDR while others do not. Individuals with a family member who has STDR are more likely to develop STDR themselves, implying that genetics play an important role. My approach My study aims to determine what factors influence the development of STDR. Genetic, dietary and other lifestyle information gathered from >26,000 participants with diabetes in the UK Biobank and EPIC norfolk projects will be linked with their eye records from the National Diabetic Eye Screening Programme. My analysis will then compare patients who have STDR with those who do not. Expected impact of my work Understanding the underlying genetics of STDR may reveal biological targets for new treatments. My findings could also help improve healthcare resource allocation by better predicting which patients with diabetes are at highest risk of developing STDR, based on their individual genetic and non-genetic risk factors.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Development of a cost-effectiveness model for optimization of the screening interval in diabetic retinopathy screening.
Funder: Department of Health (England)

Abstract: Our aims and objectives are to:• Use demographic and routinely collected clinical information from 15000 patients in 85 Gloucestershire GP practices to develop a risk score for each patient and to identify patient groups whose risk of retinopathy progression is low and whose screening interval can be safely extended;• Model what the influence of the grading classification error is on over referrals and under referrals and how that influence changes over time taking into account sequential grading results and hospital outcome results comparing screening intervals that vary according to risk score against current standard practice (annual screening intervals for all patients) and other fixed-interval approaches.• Extend our results to multi-ethnic populations • Determine if assigning diabetic patients to differing diabetic retinopathy screening intervals using a risk estimation model is cost-effective when compared to current practice which is annual screening of all eligible patients with diabetes;• Estimate the economic benefits if personalised screening intervals were to be applied to the National Screening Programme in England. Research Design and Methods:There are 4 project phases:Phase 1: GDRSS risk factor approach Phase 2: Monitoring interval approach Phase 3: Extension to an ethnically diverse populationPhase 4 - Cost-effectiveness & cost-utility analysis.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: EYE;METABOLIC AND ENDOCRINE
Title: Hydrogen sulfide as a novel guardian of the retinal vascular endothelial glycocalyx; new therapeutic opportunities.
Funder: Medical Research Council

Abstract: We will examine whether our novel slow release hydrogen sulfide (H2S) donors can be used to treat diabetic retinopathy. The early stages of diabetic retinopathy are characterised by enhanced leukostasis in the retinal microvessels, resulting in vessel blockage. Reduction in thickness of the endothelial surface layer i.e. glycocalyx, in diabetes may exacerbate this by exposing endothelial adhesion molecules. Thus, interventions to prevent/reverse glycocalyx damage caused by diabetic insult could offer a novel treatment option for diabetic retinopathy. Our previous data suggest that therapeutic administration of the gaseous transmitter H2S may fulfil this role; we showed a significant loss of plasma H2S in diabetes which was associated with microvascular dysfunction and importantly have shown that the H2S donor GYY1437 prevents hyperglycaemia-associated glycocalyx loss. Thus, we will examine, using cellular, animal and human studies, the mechanisms by which our H2S donors protect the glycocalyx from diabetes-associated degradation and their in vivo therapeutic potential. Using cultured retinal endothelial cells we will examine the effects of H2S on the secretion/activity of glycocalyx degrading enzymes using activity assays, zymography and immunoblotting. These studies will be complemented by studies into the effects of H2S on the synthesis of glycocalyx components using immunoblotting, chromatography and also TaqMan low density qPCR arrays to identify endothelial gene expression changes in response to H2S. The functional role of H2S-mediated glycocalyx protection will be assessed by examining the effects of the H2S donors on diabetes-associated pro-inflammatory vascular responses i.e. increased adhesion molecule exposure (in vitro) and increased leukostasis and vascular permeability in vivo using an established rat model. Finally, we will examine whether circulating H2S levels correlate with the degree of severity of diabetic retinopathy in man.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: EYE;METABOLIC AND ENDOCRINE