Retinal vascular calibre - a potential biomarker for early renal and retinal diseases?
Lead Research Organisation:
Queen's University Belfast
Department Name: Centre for Public Health
Abstract
Chronic kidney disease (CKD) is common in older people sharing overlapping risk factors with some diseases of the eye, including a complication of diabetes mellitus which affects the back of the eye (the retina) called diabetic retinopathy. CKD is more common in people with diabetes. Unfortunately some individuals with diabetic kidney disease develop progressive kidney failure and may eventually need dialysis. Previous research has suggested measurement of the blood vessels within the retina using a non-invasive procedure may provide early indications of some of the vascular complications associated with diabetes, such as those affecting the kidney and the eye. With recent advances in imaging and analysis technology, this non-invasive examination is now carried out routinely within the National Health Service as part of a regular screening programme for diabetic retinopathy. This application evaluates participant information collected from several large independent population-based CKD and diabetes cohort studies to determine whether measuring retinal blood vessels would help identify older or diabetic individuals with increased risk of developing kidney or eye complications. This may provide opportunities for earlier treatment to prevent or slow the onset of these complications.
The prevalence of diabetes is rising significantly in the United Kingdom and globally resulting in increased numbers of people being treated for diabetic complications. In the UK and elsewhere, kidney failure associated with diabetes is the commonest cause of end-stage renal disease (requiring dialysis or kidney transplant). Up to 40% of individuals with diabetes will develop diabetic kidney disease. Diabetic retinopathy is the primary cause of blindness in the UK working population and annually more than 2,000 people suffer permanent sight loss secondary to this complication. If our research demonstrated that retinal vascular measurements were predictive of CKD, diabetic kidney disease or diabetic retinopathy, then it could become a further component of the UK diabetic retinopathy screening programme, refining this process in terms of target age, disease duration and interval screening to maximise efficiency. Persons predicted to have highest risk of complications could be targeted for additional treatments to reduce their individual risk of diabetic kidney disease or diabetic retinopathy.
Although previous population-based studies suggest that retinal vessel measurements may provide an early prognostic indication of subsequent renal and visual dysfunction, the findings have not always been consistent. The reasons for these inconsistencies are primarily due to small sample sizes and loss of study participants during long-term follow-up. As such, this project will address these difficulties through collaborations with the principal investigators for all the major studies within this research field (to provide data relevant to the proposed outcomes) and limit the deficiencies affecting independent studies. This project will examine the relationships between measures of kidney function and retinal vessel diameter. Measurements will be assessed in a large number of individuals from population-based studies at baseline entry and again after 5 years follow-up. Variation in renal and visual function will be determined and assessed against retinal blood vessel measurements. Follow-up analysis of the findings will be undertaken in several large cohorts of participants with CKD or diabetes to establish if retinal blood vessel measurements are predictive of subsequent decline in visual or renal function. We anticipate our findings could be independently replicated and validated shortly after completion of the proposed study. If confirmed, this novel data could lead to additional clinical benefit being derived from routine retinal screening programmes i.e. identification of persons at increased risk of diabetic retinopathy, diabetic kidney disease or CKD.
The prevalence of diabetes is rising significantly in the United Kingdom and globally resulting in increased numbers of people being treated for diabetic complications. In the UK and elsewhere, kidney failure associated with diabetes is the commonest cause of end-stage renal disease (requiring dialysis or kidney transplant). Up to 40% of individuals with diabetes will develop diabetic kidney disease. Diabetic retinopathy is the primary cause of blindness in the UK working population and annually more than 2,000 people suffer permanent sight loss secondary to this complication. If our research demonstrated that retinal vascular measurements were predictive of CKD, diabetic kidney disease or diabetic retinopathy, then it could become a further component of the UK diabetic retinopathy screening programme, refining this process in terms of target age, disease duration and interval screening to maximise efficiency. Persons predicted to have highest risk of complications could be targeted for additional treatments to reduce their individual risk of diabetic kidney disease or diabetic retinopathy.
Although previous population-based studies suggest that retinal vessel measurements may provide an early prognostic indication of subsequent renal and visual dysfunction, the findings have not always been consistent. The reasons for these inconsistencies are primarily due to small sample sizes and loss of study participants during long-term follow-up. As such, this project will address these difficulties through collaborations with the principal investigators for all the major studies within this research field (to provide data relevant to the proposed outcomes) and limit the deficiencies affecting independent studies. This project will examine the relationships between measures of kidney function and retinal vessel diameter. Measurements will be assessed in a large number of individuals from population-based studies at baseline entry and again after 5 years follow-up. Variation in renal and visual function will be determined and assessed against retinal blood vessel measurements. Follow-up analysis of the findings will be undertaken in several large cohorts of participants with CKD or diabetes to establish if retinal blood vessel measurements are predictive of subsequent decline in visual or renal function. We anticipate our findings could be independently replicated and validated shortly after completion of the proposed study. If confirmed, this novel data could lead to additional clinical benefit being derived from routine retinal screening programmes i.e. identification of persons at increased risk of diabetic retinopathy, diabetic kidney disease or CKD.
Technical Summary
This project will establish if retinal image analysis can provide novel biomarkers for chronic kidney disease (CKD), diabetic kidney disease or diabetic retinopathy using data from well-characterised prospective population-based and diabetes cohort studies using a two-stage meta-analysis approach on individual participant data.
Individuals will be stratified into two groups using measures of renal function (estimated glomerular filtration [eGFR]). The stable kidney function group are individuals in whom eGFR measurements remained >60mL/min/1.73m2 from baseline to 5 year follow-up. Retinal vascular calibre measurements in this "stable" kidney function group will be compared to retinal vascular calibre in individuals with progressive decline in kidney function. This "declining kidney function" group will contain individuals in whom eGFR decreased over 5 years to <60mL/min/1.73m2. Retinal vascular calibre will be correlated with risk of developing progressive CKD or retinal complications (including non-proliferative or proliferative diabetic retinopathy). Estimates of association will be undertaken using logistic regression and meta-analysis approaches independently in each study initially and then combined. This strategy will facilitate potential study-specific design bias and covariates not uniformly defined across studies, which can make evaluation of a combined model difficult. Adjustment for appropriate confounders will be made.
This approach will also be evaluated in diabetes cohorts with multiple measurements of kidney function (eGFR; urinary albumin/creatinine ratio) to determine if retinal vascular calibre can identify individuals at increased risk of renal and retinal complications. This research will help determine whether measuring retinal vascular calibre, as part of the NHS diabetic retinopathy screening programme, would offer additional clinical value in identifying patients at highest risk of developing renal failure or sight threatening retinopathy.
Individuals will be stratified into two groups using measures of renal function (estimated glomerular filtration [eGFR]). The stable kidney function group are individuals in whom eGFR measurements remained >60mL/min/1.73m2 from baseline to 5 year follow-up. Retinal vascular calibre measurements in this "stable" kidney function group will be compared to retinal vascular calibre in individuals with progressive decline in kidney function. This "declining kidney function" group will contain individuals in whom eGFR decreased over 5 years to <60mL/min/1.73m2. Retinal vascular calibre will be correlated with risk of developing progressive CKD or retinal complications (including non-proliferative or proliferative diabetic retinopathy). Estimates of association will be undertaken using logistic regression and meta-analysis approaches independently in each study initially and then combined. This strategy will facilitate potential study-specific design bias and covariates not uniformly defined across studies, which can make evaluation of a combined model difficult. Adjustment for appropriate confounders will be made.
This approach will also be evaluated in diabetes cohorts with multiple measurements of kidney function (eGFR; urinary albumin/creatinine ratio) to determine if retinal vascular calibre can identify individuals at increased risk of renal and retinal complications. This research will help determine whether measuring retinal vascular calibre, as part of the NHS diabetic retinopathy screening programme, would offer additional clinical value in identifying patients at highest risk of developing renal failure or sight threatening retinopathy.
Planned Impact
Who will benefit from this research?
Chronic kidney disease (CKD) is common, harmful and treatable and an important public health issue. As prevalence increases with age, the disease burden will increase with our ageing population. CKD is an independent risk factor for other diseases, particularly cardiovascular disease, commonly coexisting with other cardiovascular conditions necessitating co-management alongside other diseases and risk factors such as diabetes and hypertension, as well as the social needs that come with frailty and multiple conditions. In a minority of cases, CKD progresses to end stage renal disease (ESRD), which may require renal replacement therapy. This progression and the risks of other vascular events, such as stroke and heart failure can be reduced if CKD is identified and managed. Early diagnosis is therefore essential. Therefore ageing members of our society and individuals with chronic vascular disease will benefit from the outputs of this study.
The societal and economic costs attributed to CKD are immense. Treatment of ESRD, the most severe form of CKD, is resource intensive for the NHS. The current cost of treatment has been estimated at ~2% of the total NHS budget, yet individuals with ESRD comprise only 0.05% of the total population. As such society will benefit from reduced financial requirements for treatment of ESRD attributed to early intervention.
Social deprivation has been associated with a higher incidence and prevalence of CKD in developed countries. Furthermore, CKD progresses more rapidly in socially deprived patients. The effects on both incidence and progression are mediated through many intermediate factors at an individual-level including low birth weight, smoking, obesity, diabetes and hypertension and poor compliance with treatment, or regional variation, for example; variation in quality of primary care services and poorer access to secondary care. While measures of socioeconomic status (SES) are difficult to compare between studies, the effect of SES will be assessed within the context of the proposed primary outcome measures.
How will they benefit from this research?
CKD has historically been a significantly under-diagnosed condition. Historically many patients with CKD were diagnosed late with many requiring emergency dialysis. Early detection and evidence based management is cost effective, in both financial and human terms. The expected benefits of early diagnosis include:
1. Prevention of cardiovascular disease may be improved because people found to have early CKD are also at increased risk of premature cardiovascular disease and so can be identified earlier.
2. Reduction in hospitalisation through earlier diagnosis.
3. Progression to ESRD is delayed or prevented.
4. A reduction in lost working lives for people with ESRD who are too ill to work, and the social care cost of supporting people with ESRD.
Although it is currently not possible to repair kidney damage, it does not mean decline will definitely ensue. Assuming a healthier lifestyle with treatment for blood pressure and other conditions, it is possible to live without symptoms and prevent further decline of kidney function. In addition, reductions in preventable deaths due to kidney disease may be attributed to healthier lifestyles and diets through life-style modification. This will be of immense benefit to the patient, the NHS, public health policy makers and society as a whole. Earlier diagnosis of CKD is central to leveraging these benefits.
Practitioners and policy makers will benefit from new evidence that we will generate on the value (if proven) of a new prognostic marker.
Those commissioning research will be able to identify the future priorities for research in the area.
Chronic kidney disease (CKD) is common, harmful and treatable and an important public health issue. As prevalence increases with age, the disease burden will increase with our ageing population. CKD is an independent risk factor for other diseases, particularly cardiovascular disease, commonly coexisting with other cardiovascular conditions necessitating co-management alongside other diseases and risk factors such as diabetes and hypertension, as well as the social needs that come with frailty and multiple conditions. In a minority of cases, CKD progresses to end stage renal disease (ESRD), which may require renal replacement therapy. This progression and the risks of other vascular events, such as stroke and heart failure can be reduced if CKD is identified and managed. Early diagnosis is therefore essential. Therefore ageing members of our society and individuals with chronic vascular disease will benefit from the outputs of this study.
The societal and economic costs attributed to CKD are immense. Treatment of ESRD, the most severe form of CKD, is resource intensive for the NHS. The current cost of treatment has been estimated at ~2% of the total NHS budget, yet individuals with ESRD comprise only 0.05% of the total population. As such society will benefit from reduced financial requirements for treatment of ESRD attributed to early intervention.
Social deprivation has been associated with a higher incidence and prevalence of CKD in developed countries. Furthermore, CKD progresses more rapidly in socially deprived patients. The effects on both incidence and progression are mediated through many intermediate factors at an individual-level including low birth weight, smoking, obesity, diabetes and hypertension and poor compliance with treatment, or regional variation, for example; variation in quality of primary care services and poorer access to secondary care. While measures of socioeconomic status (SES) are difficult to compare between studies, the effect of SES will be assessed within the context of the proposed primary outcome measures.
How will they benefit from this research?
CKD has historically been a significantly under-diagnosed condition. Historically many patients with CKD were diagnosed late with many requiring emergency dialysis. Early detection and evidence based management is cost effective, in both financial and human terms. The expected benefits of early diagnosis include:
1. Prevention of cardiovascular disease may be improved because people found to have early CKD are also at increased risk of premature cardiovascular disease and so can be identified earlier.
2. Reduction in hospitalisation through earlier diagnosis.
3. Progression to ESRD is delayed or prevented.
4. A reduction in lost working lives for people with ESRD who are too ill to work, and the social care cost of supporting people with ESRD.
Although it is currently not possible to repair kidney damage, it does not mean decline will definitely ensue. Assuming a healthier lifestyle with treatment for blood pressure and other conditions, it is possible to live without symptoms and prevent further decline of kidney function. In addition, reductions in preventable deaths due to kidney disease may be attributed to healthier lifestyles and diets through life-style modification. This will be of immense benefit to the patient, the NHS, public health policy makers and society as a whole. Earlier diagnosis of CKD is central to leveraging these benefits.
Practitioners and policy makers will benefit from new evidence that we will generate on the value (if proven) of a new prognostic marker.
Those commissioning research will be able to identify the future priorities for research in the area.
Organisations
- Queen's University Belfast (Lead Research Organisation)
- UK Biobank (Collaboration)
- National University of Singapore (Collaboration)
- QUEEN'S UNIVERSITY BELFAST (Collaboration)
- University of Dundee (Collaboration)
- Trinity College Dublin (Collaboration)
- Eyenuk (United States) (Collaboration)
- University of Bristol (Collaboration)
People |
ORCID iD |
Gareth McKay (Principal Investigator) |
Publications
Zang J
(2019)
Differential Expression of Urinary Exosomal MicroRNAs miR-21-5p and miR-30b-5p in Individuals with Diabetic Kidney Disease.
in Scientific reports
Paterson EN
(2018)
Dietary patterns and chronic kidney disease: a cross-sectional association in the Irish Nun Eye Study.
in Scientific reports
McKay GJ
(2018)
Retinal microvascular parameters are not associated with reduced renal function in a study of individuals with type 2 diabetes.
in Scientific reports
Fetit AE
(2019)
A multimodal approach to cardiovascular risk stratification in patients with type 2 diabetes incorporating retinal, genomic and clinical features.
in Scientific reports
Williams MA
(2015)
Age-Related Macular Degeneration-Associated Genes in Alzheimer Disease.
in The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
Neville CE
(2018)
Dietary Patterns and Retinal Vessel Caliber in the Irish Nun Eye Study.
in The journal of nutrition, health & aging
Cheung CY
(2022)
A deep learning model for detection of Alzheimer's disease based on retinal photographs: a retrospective, multicentre case-control study.
in The Lancet. Digital health
Yuen V
(2021)
Deep-Learning-Based Pre-Diagnosis Assessment Module for Retinal Photographs: A Multicenter Study.
in Translational vision science & technology
Description | EU Panel Member: Horizon 2020 'Health, Demographic Change & Wellbeing' panel member (SC1-DTH-12-2020) Use of Real-World Data to advance research on the management of complex chronic conditions. |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | EU Panel member: HORIZON-HLTH-2022-STAYHLTH-01-04-two-stage. Trustworthy artificial intelligence (AI) tools to predict the risk of chronic non communicable diseases and/or their progression |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | EU funding panel member: Horizon Europe Marie Sktodowska-Curie Doctoral Networks LIF panel Vice Chair (HORIZON-MSCA-2021-DN-01) |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Horizon 2020 Innovative Medicines Initiative 2 (H2020-JTI-IMI2-2015-01, Topic 2) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | Horizon 2020 Marie Sktodowska-Curie Individual Fellowships (H2020-MSCA-IF-2016) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | Horizon 2020 Marie Sktodowska-Curie Individual Fellowships (H2020-MSCA-IF-2018) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | Horizon 2020 Marie Sktodowska-Curie Innovative Training Networks (H2020-MSCA-ITN-2016) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | Horizon 2020 Marie Sktodowska-Curie Innovative Training Networks (H2020-MSCA-ITN-2017) |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | Participation in advisory Committee as appointed scientific advisor - Northern Ireland Kidney Research Fund |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | CARDI Fellowship Programme |
Amount | £282,745 (GBP) |
Funding ID | LP2:4 |
Organisation | Centre for Ageing Research and Development in Ireland (CARDI) |
Sector | Academic/University |
Country | Ireland |
Start | 09/2014 |
End | 08/2018 |
Description | DEL Studentship |
Amount | £60,000 (GBP) |
Organisation | Government of Northern Ireland |
Department | Department for Employment and Learning Northern Ireland (DELNI) |
Sector | Public |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Description | Department of Education and Learning PhD Studentship |
Amount | £65,000 (GBP) |
Organisation | Government of Northern Ireland |
Department | Department for Employment and Learning Northern Ireland (DELNI) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 09/2020 |
Description | Enabling Award |
Amount | £32,624 (GBP) |
Funding ID | STL/5088/14 |
Organisation | Government of Northern Ireland |
Department | Department of Health, Social Services and Public Safety Northern Ireland (DHSSPSNI) |
Sector | Public |
Country | United Kingdom |
Start | 05/2016 |
End | 05/2017 |
Description | Enabling Research Award |
Amount | £7,587 (GBP) |
Funding ID | STL/4936/14 |
Organisation | HPSS R and D Office |
Sector | Academic/University |
Country | United Kingdom |
Start | 02/2015 |
End | 08/2016 |
Description | Grant Funding Scheme |
Amount | £199,431 (GBP) |
Organisation | Diabetes UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2016 |
End | 07/2019 |
Description | Heart Trust Fund Royal Victoria Hospital |
Amount | £29,960 (GBP) |
Organisation | Heart Trust Fund Royal Victoria Hospital |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2015 |
End | 01/2017 |
Description | Queen's University Belfast School of Medicine, Dentistry and Biomedical Sciences Travel Scholarship |
Amount | £6,700 (GBP) |
Organisation | Queen's University Belfast |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2014 |
End | 02/2014 |
Description | EPSRC |
Organisation | University of Dundee |
Department | School of Science and Engineering |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am the independent chair for the EPSRC funded project entitled 'Multi-modal retinal biomarkers for vascular dementia: developing enabling image analysis tools (EP/M005976/1; £922,996)' |
Collaborator Contribution | The partners are ascertaining and evaluating the utility of retinal imaging markers as a biomarker for vascular dementia risk. |
Impact | This project just started in Autumn 2015 and is yet to generate any outcomes. The approach is multidisciplinary with input from clinicians, imaging specialists, computer programmes and public health. |
Start Year | 2015 |
Description | Measuring Mediterranean Diet adherence and its association with healthy ageing: the NICOLA and TILDA studies |
Organisation | Queen's University Belfast |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration is based on a funding application for 2.014 million euros to the Investigator Programme for Science Foundation Ireland 2014 to look at the potential of a Mediterranean diet (MD) on healthy ageing. The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) and The Irish Longitudinal Study of Ageing (TILDA) are comprehensive and complementary longitudinal studies of ageing in Ireland, which represent an ideal resource to determine how the MD pattern is associated with healthy ageing. I had responsibility for Work package 5: assessment of retinal vascular health in TILDA and NICOLA study using SIVA software to identify and measure retinal microvasculature parameters from digital photographs. This application is currently under review. |
Collaborator Contribution | This proposal is directly relevant to human nutrition under the Diagnostics and Biomarkers in the area of Food for Health theme, as it aims to develop a multiple biomarker approach to the assessment of adherence to the Mediterranean Diet and explore links with healthy ageing.This theme includes biomarkers for dietary exposure/dietary pattern, and the work described is validating dietary assessment methods and developing novel biomarker approaches to the assessment of the Mediterranean diet pattern in both observational and intervention studies. A second topic is described as research underpinning the relationship between diet and disease. The proposal is focused on assessing the link between adherence to a Mediterranean diet and healthy ageing in older people, as defined by maintenance of cognitive function (avoidance of cognitive decline), maintenance of muscle mass, function and physical strength (avoidance of sarcopenia and frailty), retinal vessel health (avoidance of eye disease), and cardiometabolic health (avoidance of cardiovascular disease), and is therefore relevant to this topic. A further topic focuses on biomarkers indicative of the health promoting properties of food. Again the proposal is directly relevant, focusing on the use of retinal vessel health as an early indicator of cerebrovascular disease risk, cognitive decline and dementia risk. |
Impact | This collaboration brings together investigators from clinical and research backgrounds across several disciplines including public health, dementia, nutrition, food science vision and medical statistics. |
Start Year | 2014 |
Description | Measuring Mediterranean Diet adherence and its association with healthy ageing: the NICOLA and TILDA studies |
Organisation | Queen's University Belfast |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration is based on a funding application for 2.014 million euros to the Investigator Programme for Science Foundation Ireland 2014 to look at the potential of a Mediterranean diet (MD) on healthy ageing. The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) and The Irish Longitudinal Study of Ageing (TILDA) are comprehensive and complementary longitudinal studies of ageing in Ireland, which represent an ideal resource to determine how the MD pattern is associated with healthy ageing. I had responsibility for Work package 5: assessment of retinal vascular health in TILDA and NICOLA study using SIVA software to identify and measure retinal microvasculature parameters from digital photographs. This application is currently under review. |
Collaborator Contribution | This proposal is directly relevant to human nutrition under the Diagnostics and Biomarkers in the area of Food for Health theme, as it aims to develop a multiple biomarker approach to the assessment of adherence to the Mediterranean Diet and explore links with healthy ageing.This theme includes biomarkers for dietary exposure/dietary pattern, and the work described is validating dietary assessment methods and developing novel biomarker approaches to the assessment of the Mediterranean diet pattern in both observational and intervention studies. A second topic is described as research underpinning the relationship between diet and disease. The proposal is focused on assessing the link between adherence to a Mediterranean diet and healthy ageing in older people, as defined by maintenance of cognitive function (avoidance of cognitive decline), maintenance of muscle mass, function and physical strength (avoidance of sarcopenia and frailty), retinal vessel health (avoidance of eye disease), and cardiometabolic health (avoidance of cardiovascular disease), and is therefore relevant to this topic. A further topic focuses on biomarkers indicative of the health promoting properties of food. Again the proposal is directly relevant, focusing on the use of retinal vessel health as an early indicator of cerebrovascular disease risk, cognitive decline and dementia risk. |
Impact | This collaboration brings together investigators from clinical and research backgrounds across several disciplines including public health, dementia, nutrition, food science vision and medical statistics. |
Start Year | 2014 |
Description | Measuring Mediterranean Diet adherence and its association with healthy ageing: the NICOLA and TILDA studies |
Organisation | Trinity College Dublin |
Country | Ireland |
Sector | Academic/University |
PI Contribution | This collaboration is based on a funding application for 2.014 million euros to the Investigator Programme for Science Foundation Ireland 2014 to look at the potential of a Mediterranean diet (MD) on healthy ageing. The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) and The Irish Longitudinal Study of Ageing (TILDA) are comprehensive and complementary longitudinal studies of ageing in Ireland, which represent an ideal resource to determine how the MD pattern is associated with healthy ageing. I had responsibility for Work package 5: assessment of retinal vascular health in TILDA and NICOLA study using SIVA software to identify and measure retinal microvasculature parameters from digital photographs. This application is currently under review. |
Collaborator Contribution | This proposal is directly relevant to human nutrition under the Diagnostics and Biomarkers in the area of Food for Health theme, as it aims to develop a multiple biomarker approach to the assessment of adherence to the Mediterranean Diet and explore links with healthy ageing.This theme includes biomarkers for dietary exposure/dietary pattern, and the work described is validating dietary assessment methods and developing novel biomarker approaches to the assessment of the Mediterranean diet pattern in both observational and intervention studies. A second topic is described as research underpinning the relationship between diet and disease. The proposal is focused on assessing the link between adherence to a Mediterranean diet and healthy ageing in older people, as defined by maintenance of cognitive function (avoidance of cognitive decline), maintenance of muscle mass, function and physical strength (avoidance of sarcopenia and frailty), retinal vessel health (avoidance of eye disease), and cardiometabolic health (avoidance of cardiovascular disease), and is therefore relevant to this topic. A further topic focuses on biomarkers indicative of the health promoting properties of food. Again the proposal is directly relevant, focusing on the use of retinal vessel health as an early indicator of cerebrovascular disease risk, cognitive decline and dementia risk. |
Impact | This collaboration brings together investigators from clinical and research backgrounds across several disciplines including public health, dementia, nutrition, food science vision and medical statistics. |
Start Year | 2014 |
Description | Retinal Evaluation in Alzheimer's Disease and Mild Cognitive Impairment |
Organisation | Queen's University Belfast |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Alzheimer's Disease (AD) is often preceded by mild cognitive impairment (MCI); this is defined as a transitional state between normal ageing and dementia; it is a syndrome defined by clinical, cognitive and functional criteria in which the patient has cognitive decline but which does not interfere with ability to function independently. This collaboration will seek to evaluate the potential of retinal microvascular changes to identify individuals at increased risk of MCI and AD. This grant application is currently under review with the Northern Ireland HSC R&D Office (£39,984). The main workpackage, for which I will have responsibility will assess the retinal microvasculature and compare to clinical functional measures of cognition. |
Collaborator Contribution | This collaborative study combines basic research scientists and clinicians specialising in geriatric medicine. |
Impact | This collaboration is multidisciplinary with 2 clinical academics and 2 basic academic research scientists with backgrounds in vision and public health. |
Start Year | 2014 |
Description | Retinal Evaluation in Alzheimer's Disease and Mild Cognitive Impairment |
Organisation | Queen's University Belfast |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Alzheimer's Disease (AD) is often preceded by mild cognitive impairment (MCI); this is defined as a transitional state between normal ageing and dementia; it is a syndrome defined by clinical, cognitive and functional criteria in which the patient has cognitive decline but which does not interfere with ability to function independently. This collaboration will seek to evaluate the potential of retinal microvascular changes to identify individuals at increased risk of MCI and AD. This grant application is currently under review with the Northern Ireland HSC R&D Office (£39,984). The main workpackage, for which I will have responsibility will assess the retinal microvasculature and compare to clinical functional measures of cognition. |
Collaborator Contribution | This collaborative study combines basic research scientists and clinicians specialising in geriatric medicine. |
Impact | This collaboration is multidisciplinary with 2 clinical academics and 2 basic academic research scientists with backgrounds in vision and public health. |
Start Year | 2014 |
Description | Retinal Evaluation of Cerebral Variation in Dementia (REoCViD) |
Organisation | Eyenuk |
Country | United States |
Sector | Private |
PI Contribution | I am the principal investigator on this funding application to the MRC DPFS programme (£638,215). The initial application was well received but not shortlisted for a full application. Nevertheless, the review panel made some recommendations on the application which will be resubmitted on December 2nd 2014. |
Collaborator Contribution | Our study will capture retinal images and use data from a randomised controlled trial to evaluate the potential of a medication commonly prescribed for hypertension, in those with vascular dementia (n=580), a calcium channel blocking drug which may offer clinical benefit to those with dementia who currently have limited therapeutic options. Should the biomarkers proposed in our study prove useful, this will result in significantly reduced clinical monitoring costs and may offer an opportunity for earlier intervention. Crucially, the expertise offered by our collaborating industrial partner (EyeNuk), provides a level of proficiency to translate this proof of concept application into a delivery vehicle with real clinically potential within the community. |
Impact | This multi-disciplinary collaboration brings together experts from dementia research (both clinical and non-clinical), vision research and medical imaging. Crucially it brings together academics and the commercial sector to maximise the potential of the research outputs to deliver in a translational and clinically relevant manner. |
Start Year | 2014 |
Description | Retinal Evaluation of Cerebral Variation in Dementia (REoCViD) |
Organisation | National University of Singapore |
Country | Singapore |
Sector | Academic/University |
PI Contribution | I am the principal investigator on this funding application to the MRC DPFS programme (£638,215). The initial application was well received but not shortlisted for a full application. Nevertheless, the review panel made some recommendations on the application which will be resubmitted on December 2nd 2014. |
Collaborator Contribution | Our study will capture retinal images and use data from a randomised controlled trial to evaluate the potential of a medication commonly prescribed for hypertension, in those with vascular dementia (n=580), a calcium channel blocking drug which may offer clinical benefit to those with dementia who currently have limited therapeutic options. Should the biomarkers proposed in our study prove useful, this will result in significantly reduced clinical monitoring costs and may offer an opportunity for earlier intervention. Crucially, the expertise offered by our collaborating industrial partner (EyeNuk), provides a level of proficiency to translate this proof of concept application into a delivery vehicle with real clinically potential within the community. |
Impact | This multi-disciplinary collaboration brings together experts from dementia research (both clinical and non-clinical), vision research and medical imaging. Crucially it brings together academics and the commercial sector to maximise the potential of the research outputs to deliver in a translational and clinically relevant manner. |
Start Year | 2014 |
Description | Retinal Evaluation of Cerebral Variation in Dementia (REoCViD) |
Organisation | Queen's University Belfast |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am the principal investigator on this funding application to the MRC DPFS programme (£638,215). The initial application was well received but not shortlisted for a full application. Nevertheless, the review panel made some recommendations on the application which will be resubmitted on December 2nd 2014. |
Collaborator Contribution | Our study will capture retinal images and use data from a randomised controlled trial to evaluate the potential of a medication commonly prescribed for hypertension, in those with vascular dementia (n=580), a calcium channel blocking drug which may offer clinical benefit to those with dementia who currently have limited therapeutic options. Should the biomarkers proposed in our study prove useful, this will result in significantly reduced clinical monitoring costs and may offer an opportunity for earlier intervention. Crucially, the expertise offered by our collaborating industrial partner (EyeNuk), provides a level of proficiency to translate this proof of concept application into a delivery vehicle with real clinically potential within the community. |
Impact | This multi-disciplinary collaboration brings together experts from dementia research (both clinical and non-clinical), vision research and medical imaging. Crucially it brings together academics and the commercial sector to maximise the potential of the research outputs to deliver in a translational and clinically relevant manner. |
Start Year | 2014 |
Description | Retinal Evaluation of Cerebral Variation in Dementia (REoCViD) |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am the principal investigator on this funding application to the MRC DPFS programme (£638,215). The initial application was well received but not shortlisted for a full application. Nevertheless, the review panel made some recommendations on the application which will be resubmitted on December 2nd 2014. |
Collaborator Contribution | Our study will capture retinal images and use data from a randomised controlled trial to evaluate the potential of a medication commonly prescribed for hypertension, in those with vascular dementia (n=580), a calcium channel blocking drug which may offer clinical benefit to those with dementia who currently have limited therapeutic options. Should the biomarkers proposed in our study prove useful, this will result in significantly reduced clinical monitoring costs and may offer an opportunity for earlier intervention. Crucially, the expertise offered by our collaborating industrial partner (EyeNuk), provides a level of proficiency to translate this proof of concept application into a delivery vehicle with real clinically potential within the community. |
Impact | This multi-disciplinary collaboration brings together experts from dementia research (both clinical and non-clinical), vision research and medical imaging. Crucially it brings together academics and the commercial sector to maximise the potential of the research outputs to deliver in a translational and clinically relevant manner. |
Start Year | 2014 |
Description | UK BioBank |
Organisation | UK Biobank |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | I am a member of the UK BioBank Vision Consortium and the UK BioBank Vision and Cognition Research Group. This collaboration is ongoing to investigate data collected by UK BioBank to evaluate retinal measures as potential biomarkers for multiple microvascular conditions, including diabetes, chronic kidney disease, cardiovascular disease, dementia, cognition and nutrition. |
Collaborator Contribution | Provision of data and analysis tools. |
Impact | No direct outputs from my involvement yet although several listed as collaborations (G McKay). |
Start Year | 2015 |
Description | Analysis of retinal vasculature for MACE risk stratification in patients with diabetes. Royal Society Science+ meeting, London |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Conference presentation |
Year(s) Of Engagement Activity | 2018 |
Description | Association between retinal microvascular caliber and chronic kidney disease: participant-level and aggregate-data meta-analyses. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Association between retinal microvascular caliber and chronic kidney disease: participant-level and aggregate-data meta-analyses. The Association for Research in Vision and Ophthalmology, Honolulu, USA, |
Year(s) Of Engagement Activity | 2018 |
Description | Association between venular tortuosity and impaired renal function in an ageing population. American Society of Nephrology, Washington, DC, USA, 6-10th November 2019. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at the annual American Society of Nephrology meeting |
Year(s) Of Engagement Activity | 2019 |
Description | Association of retinal vessel caliber and iris color. The Association for Research in Vision and Ophthalmology 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Moore E, McGowan A, Patterson CC, Silvestri V, Silvestri G, Maxwell AP, McKay GJ. Association of retinal vessel caliber and iris color (2014). The Association for Research in Vision and Ophthalmology, Orlando, USA, 4-8th May. |
Year(s) Of Engagement Activity | 2014 |
Description | Association of venular tortuosity with impaired renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing. British and Irish Longitudinal Study meeting, Manchester, UK, 3-4th February 2020. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at the British and Irish Longitudinal Study meeting, Manchester, UK, 3-4th February 2020. |
Year(s) Of Engagement Activity | 2020 |
Description | Big data meeting RCUK 2016 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | A joint Research Council UK Transatlantic data science workshop held at the National Institute of Health in Bethesda, Washington DC, USA. Approximately 60 participants participated in the two day work shop to focus on opportunities associated with access to big data to improve health outcomes. The meeting was streamed live across the internet. |
Year(s) Of Engagement Activity | 2016 |
Description | Classification of hypertension using nasal annular arteriole-venule ratio in ultra-widefield ophthalmic imaging. Joint Hypertension 2018 Scientific Sessions. Chicago |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Conference presentation of study data |
Year(s) Of Engagement Activity | 2018 |
Description | Detailed Retinal Microvascular Analysis Predicts Cardiovascular Outcomes in Diabetic Patients. European Society of Cardiology Congress, Munich, Germany |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | European Society of Cardiology Congress, Munich, Germany |
Year(s) Of Engagement Activity | 2018 |
Description | Dietary patterns and retinal vessel calibre in the Irish Nun Eye Study. 12th European Nutrition Conference 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Neville CE, Montgomery S, Silvestri G, McGowan A, Cardwell CR, McEvoy CT, Woodside JV, Maxwell AP, McKay GJ (2015). Dietary patterns and retinal vessel calibre in the Irish Nun Eye Study. 12th European Nutrition Conference, Berlin, Germany, October 13-23rd |
Year(s) Of Engagement Activity | 2015 |
Description | Evaluation of retinal microvascular variation in hypertension and chronic kidney disease. American Society of Nephrology 2014 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | McGowan A, Patterson CC, Silvestri G, Silvestri V, Moore E, Maxwell AP, McKay GJ (2014). Evaluation of retinal microvascular variation in hypertension and chronic kidney disease. American Society of Nephrology, Philadelphia, PA, USA, November 13-16th |
Year(s) Of Engagement Activity | 2014 |
Description | Expert Panel member - diabetic kidney disease EU 2015 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited EU IMI 2 expert panel member to advise on diabetic kidney disease outcomes and research priority areas. |
Year(s) Of Engagement Activity | 2015 |
Description | Grey matter atrophy, retinal vessel dilatation and reduction in aortic distensibility in COPD: The relationship between multi-organ vascular measures. British Thoracic Society, London, UK |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Grey matter atrophy, retinal vessel dilatation & reduction in aortic distensibility in COPD: The relationship between multi-organ vascular measures. British Thoracic Society, London, UK |
Year(s) Of Engagement Activity | 2017 |
Description | Helsinki visit #1 Oct 2012 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | This visit to the Helsinki project collaborator enabled the identification and prioritisation of patients with type 1 diabetes likely to meet our inclusion criteria for the study. Previously, the image capture process for participant retinal image capture was deemed insufficient. Following this visit, amendments were made to the ascertainment protocol to improve the quality of the retinal images acquired for participating subjects. |
Year(s) Of Engagement Activity | 2012 |
Description | Helsinki visit #2 June 2013 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The FinnDiane group facilitated a 2 day invited symposium on diabetes and its complications. This incorporated the leading international researchers across the field of type 1 and type 2 diabetes and the various associated complications. This meeting provided an opportunity to hold face-to-face collaborative discussions with key collaborators and stakeholders within the project to consider the options for initiating the amalgamation of data from the various studies as part of the proposed project's meta-analysis of data. |
Year(s) Of Engagement Activity | 2013 |
Description | Higher fruit intake is associated with albuminuria in a nested United Kingdom Biobank case control cohort. American Society of Nephrology, Washington, DC, USA, 6-10th November 2019. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at the annual American Society of Nephrology meeting |
Year(s) Of Engagement Activity | 2019 |
Description | Invited presentation - Singapore Eye Research Institute |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | My data was presented and discussed. Key findings were highlighted and some areas for consideration discussed during and after the presentation with various members of the audience. A number of key collaborative contacts were established and joint funding applications are ongoing as a consequence. |
Year(s) Of Engagement Activity | 2014 |
Description | MRC Centre of Excellence in Public Health Away Day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other audiences |
Results and Impact | Meeting of a wide range of individuals with a range in discussing the advancement of public health issues. |
Year(s) Of Engagement Activity | 2016 |
Description | Retinal Thickness is not Associated with Renal Function in Diabetes. American Diabetes Association |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | American Diabetes Association annual meeting, Orlando, Florida |
Year(s) Of Engagement Activity | 2018 |
Description | Retinal microvascular evaluation in Alzheimer's disease. The Association for Research in Vision and Ophthalmology 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | McKay GJ, McGowan A, Maxwell AP, Cardwell CR, Cheung CY, Silvestri V, Craig D, Passmore P, Silvestri G, Williams MA (2015). Retinal microvascular evaluation in Alzheimer's disease. The Association for Research in Vision and Ophthalmology, Denver, USA, 3-7th May. |
Year(s) Of Engagement Activity | 2015 |
Description | Retinal vessel calibre - a potential biomarker for chronic kidney disease. British Renal Society and the Renal Association, Glasgow, UK Presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Oral poster presentation with follow-up discussions with several interested parties. Follow-up enquiries on potential collaborative funding opportunities. |
Year(s) Of Engagement Activity | 2014 |
Description | Screening for hypertension using retinal vascular calibre in ultra-widefield fundus imaging. British and Irish Hypertension Society Annual Scientific Meeting, Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Conference presentation |
Year(s) Of Engagement Activity | 2018 |
Description | Semi-automatic measurements of retinal fundus camera images: caveats from the VAMPIRE experience. Medical Image Understanding and Analysis (MIUA), Edinburgh, Scotland |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Semi-automatic measurements of retinal fundus camera images: caveats from the VAMPIRE experience. Medical Image Understanding and Analysis (MIUA), Edinburgh, Scotland |
Year(s) Of Engagement Activity | 2017 |
Description | Singapore Collaborative Visit |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Discussions were had on the best way to analyse this type of data and appropriate confounding factors that should be considered. Different types of analysis software were evaluated and extensive training undertaken. Collaborative discussions on future research opportunities were held. Several joint grant applications were submitted for funding. |
Year(s) Of Engagement Activity | 2014 |
Description | The impact of blood pressure on retinal vascular traits. A Mendelian randomisation study in patients with type 2 diabetes. Royal Society Science+ meeting, London, |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Conference presentation |
Year(s) Of Engagement Activity | 2018 |