Investigating Early Worsening of Diabetic Retinopathy with Rapid Improvement in Glycaemic Control

Precis
Early worsening of diabetic retinopathy following rapid improvement in glycaemic control is a well-recognised phenomenon. This studentship will investigate the risk factors for early worsening of retinopathy, characterise changes in retinal structure and function following initiation of tight glycaemic control and document responses to intravitreal therapies.

Background
Tight glycaemic control is a major clinical goal for patients with diabetes due to unequivocal evidence that it reduces incidence of microvascular complications. However, improving glycaemic control carries risks. Early worsening of diabetic retinopathy (DR) following rapid improvement in glycaemic control was noted in the Diabetes Complications and Control Trial [1]. Little is known about the mechanism of this well-recognised phenomenon or responses to intervention.

Project aims
1. To investigate risk factors for early worsening of DR associated with rapid improvement in glycaemic control
2. To characterise systemic biomarkers, retinal structure and function during initiation of intensive glycaemic control
3. To assess ophthalmic biomarkers of diabetic neuropathy using Corneal Confocal Microscopy (CCM) in relation to early worsening of DR
4. To document the effect of intravitreal anti-vascular endothelial growth factor (VEGF) therapy (given for maculopathy) in subjects with early worsening of DR associated with tight glycaemic control

Aim 1 will be achieved through an observational, retrospective case-control study of subjects who demonstrate rapid, substantial lowering of HbA1c who are enrolled in the ongoing ‘Individualised Screening for Diabetic Retinopathy’ 7 year cohort study. Aims 2, 3 and 4 will be addressed in an observational, prospective cohort study of subjects with type 2 diabetes, high HbA1c and pre-existing DR attending the Royal Liverpool University Hospital Diabetes Clinic for conversion to insulin therapy.

Environment
The Department of Eye and Vision Science at the University of Liverpool has an excellent track record in delivering world-leading vision research. The proposed study will take place in the Clinical Eye Research Centre, a partnership between the Department and the regional clinic service in St Paul’s Eye Unit at the Royal Liverpool University Hospital. The project will benefit from expertise in image analysis from the Liverpool Ophthalmic Reading Centre.

The successful candidate will benefit from 4 experienced and complementary supervisors. Professor Simon Harding (primary supervisor) leads a programme of word leading research at the Department of Eye and Vision Science. Dr Philip Burgess (co-supervisor) is a Clinical Lecturer in Ophthalmology with a focus on interventions for retinal vascular disease. Dr Uazman Alam (co-supervisor) is a Senior Clinical Lecturer in Diabetes and Endocrinology with expertise in the study of diabetic microvascular complications including corneal neuropathy [2]. Dr Amira Stylinides (co-supervisor) is a Consultant Medical Ophthalmologist with a special interest in diabetic retinopathy. The student will work within a multidisciplinary team with extensive experience in retinal image analysis, biostatistics and mechanisms of retinal vascular disease.

Training and Support
This project is suitable for either a clinician wishing to undertake a higher degree (MD or PhD) or a non-clinician scientist as a PhD. The candidate will obtain skills in retinal imaging techniques, data collection and management, epidemiological analysis and writing clinical papers. Image analysis training will be provided within the Department of Eye and Vision Science. Statistical support and training will be provided by the Institute of Aging and Chronic Disease. All University of Liverpool postgraduate students undertake the PGR Development Programme which aims to enhance their skills for a successful research experience and career.

The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. We offer a supportive working environment with flexible family support for all our staff and students and applications for part-time study are encouraged. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

We are seeking a highly-motivated and driven student who will benefit from an enthusiastic and stimulating training experience. Clinical candidates should have a medical degree (MBChB). Non clinician scientists will have an honours degree at 2.1 or above in a relevant life science/biomedical subject. For all candidates a Master’s degree in a relevant area would be an advantage. Candidates whose first language is not English should have an IELTS score of 6.5 or equivalent.