Precision Medicine Doctoral Training Programme

Exploring the eye as a site for virtual biopsy to detect and track of chronic kidney disease (iCase)

Project Details - Exploring the eye as a site for virtual biopsy to detect and track of chronic kidney disease (iCase)

Supervisor(s): Dr Tom MacGillivray, Dr Neeraj Dhaun, Prof Bal Dhillon & Dr Alan Fleming
Centre/Institute: Centre for Clinical Brain Sciences
Industrial Partner: Optos

Background

CKD affects 6-11% of the world’s population [1]. Hypertension is an independent risk factor for CKD progression and is a frequent finding in patients with CKD. Around a quarter of the world’s adult population is hypertensive, a number that is projected to rise to nearly 30% by 2025 [2]. Renal microvascular changes are important in the development of CKD. Currently, these can only be assessed reliably through renal biopsy, which is not without risk. However, the kidney and eye are remarkably similar in their developmental, structural and pathogenic pathways [3]. Transparency of the ocular media offers a unique opportunity to directly visualize and image microvasculature within the eye that may be affected in systemic diseases such as hypertension and CKD. Optical coherence tomography (OCT) is a non-invasive and rapid method for cross- sectional imaging of the retina and choroid. Our preliminary data suggest chorioretinal thinning in CKD and that choroidal thickness associates strongly with measures of kidney injury, systemic and renal inflammation as well as endothelial dysfunction [4]. Retinal imaging metrics may reflect renal (and systemic) injury and could have utility in detection and tracking of kidney disease over time. Our industrial partner, Optos, is a leading medical technology company based in Scotland specialising in the retina and is developing state-of-the-art OCT instrumentation.

Aims

Hypothesis: OCT will provide a virtual biopsy to aid in the assessment of patients with CKD.

Specifically:

  1. Segment the chorioretinal layers and map the choroidal vasculature in 3D by developing novel post-processing methodologies for OCT.

  2. Investigate new choroidal vascular metrics relating to abnormalities in patients with CKD and compare to healthy volunteers and patients with a similar degree of hypertension but without CKD.

  3. Explore whether severity of chorioretinal abnormalities correlates with the degree of CKD and endothelial dysfunction as measured by standard clinical biomarkers.

  4. Ascertain whether the retina is a viable site for biomarker discovery of disease activity.

The student will be in a unique position to leverage an exciting and rich dataset that has been acquired over the past 2 years from >200 participants. These include healthy volunteers (~60 subjects), those with hypertension (~50 subjects), those with CKD (~70 subjects) and those with CKD who have received a kidney transplant and therefore, their kidney function has returned to a healthy level (~30 subjects).

The student will be in a unique position to leverage an exciting and rich dataset that has been acquired over the past 2 years from >200 participants. These include healthy volunteers (~60 subjects), those with hypertension (~50 subjects), those with CKD (~70 subjects) and those with CKD who have received a kidney transplant and therefore, their kidney function has returned to a healthy level (~30 subjects).

Training Outcomes

The student will join a vibrant interdisciplinary academic-clinical team with a strong and successful industrial collaboration with a proven record of accomplishment in delivering successful educational experiences. This includes three CASE-style studentships that saw students spending time in Optos. The student will engage with multiple aspects of eye imaging in patients at increased cardiovascular risk from acquisition to post-processing and analysis.

They will also feed into the VAMPIRE project, a joint initiative between the Universities of Edinburgh and Dundee that is building a world-class virtual centre of expertise in retinal biomarkers. The student, with support from members of the VAMPIRE team, will learn about machine learning algorithms (e.g. random forest, neural networks) and apply these as a cutting- edge means of utilising retinal measures to classify the clinical status of study participants. The student will gain key skills by attending appropriate courses (such as those offered by the Education Programme at the Edinburgh CRF on statistical analysis, etc.) and accessing on-line materials offered by the Edinburgh Imaging Academy (e.g. anatomy, physics, biomechanics). They will also interact with the expert members of our group. By the end of the project, the student will be expert in retinal imaging biomarkers of renal and systemic vascular health and will have investigated conventional clinical biomarkers and novel retinal endpoints.

References

  1. Meguid El Nahas A, Bello AK. Chronic kidney disease: the global challenge. Lancet. 2005 Jan 22-28;365(9456):331-40
  2. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23.
  3. Wong CW, Wong TY, Cheng CY, Sabanayagam C. Kidney and eye diseases: common risk factors, etiological mechanisms, and pathways. Kidney Int. 2014 Jun;85(6):1290-302.
  4. Balmforth C, van Bragt JJMH, Ruijs T, et al. Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction. JCI Insight. 2016;1(20):e89173.

Apply Now

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  • The deadline for 18/19 applications is 5pm on Wednesday 10th January 2018.
  • Please note all applications for the Precision Medicine DTP should be submitted to University of Edinburgh, even those applying for a project at the University of Glasgow.
  • Applicants must apply to a specific project, ensure you include details of the project you are applying to in Section 4 of your application. We encourage you to contact the primary supervisor prior to making your application.  
  • As you are applying to a specific project, you are not required to submit a Research Proposal as part of your application. 
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