Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study
Authors: Paterson Euan N. , Cardwell Chris , MacGillivray Thomas J. , Trucco Emanuele , Doney Alexander S. , Foster Paul , Maxwell Alexander P. , McKay Gareth J. ,   on behalf of The UK Biobank Eye and Vision Consortium, Aslam Tariq , Barman Sarah , Barrett Jenny , Bishop Paul , Blows Peter , Bunce Catey , Carare Roxana , Chakravarthy Usha , Chan Michelle , Chianca Antonietta , Cipriani Valentina , Crabb David , Cumberland Philippa , Day Alexander , Desai Parul , Dhillon Bal , Dick Andrew , Egan Cathy , Ennis Sarah , Foster Paul , Fruttiger Marcus , Gallacher John , Garway-Heath David , Gibson Jane , Gore Dan , Guggenheim Jeremy , Hammond Chris , Hardcastle Alison , Harding Simon , Hogg Ruth , Hysi Pirro , Keane Pearse A. , Khaw Sir Peng Tee , Khawaja Anthony , Lascaratos Gerassimos , Lotery Andrew , Luthert Phil , MacGillivray Tom , Mackie Sarah , Martin Keith , McGuinness Bernadette , McKay Gareth , McKibbin Martin , Mitry Danny , Moore Tony , Morgan James , Muthy Zaynah , O’Sullivan Eoin , Owen Chris , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Rahi Jugnoo , Rudnicka Alicja , Self Jay , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Thaung Caroline , Thomas Dhanes , Trucco Emanuele , Tufail Adnan , Ugarte Marta , Vitart Veronique , Vernon Stephen , Viswanathan Ananth , Williams Cathy , Williams Katie , Woodside Jayne , Yates Max , Yip Jennifer , Zheng Yalin , Zhu Haogang , Tapp Robyn , Atan Denize , Doney Alexander 
Published: February 2021

Abstract
Background
Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD.

Methods
Retinal microvascular parameters (fractal dimension [FD] – a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR < 3 mg/mmol (ACR stage A1) were categorised as controls. Participants were matched on age, sex and ethnic background.

Results
Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03–1.34 for arterioles and OR 1.24, CI 1.05–1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR.

Conclusions
This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.