Retinal vessel traits and their association with diabetic retinopathy and cognitive decline in a population with type 2 diabetes

Abstract

Background People with diabetes are at an increased risk of developing vascular disease, which is the leading cause of morbidity and mortality in this population. The retina is one of the few places in the body that offers noninvasive visualisation of the vascular system and thus provides a rich platform to evaluate local and systemic vascular disease. Recent advancements in retinal image analysis tools allow us to evaluate the retinal microvasculature in a more efficient and unbiased way compared to manual methods. Local retinal changes may provide insight into vascular disease prior to overt pathological changes. Aim The aim of this thesis was to explore and evaluate retinal vessel traits in relation to various manifestations of vascular disease, specifically diabetic retinopathy and cognitive decline, using prospectively collected data. In addition to undertaking this research, this PhD project also aimed to contribute to the collection of primary data from in ongoing longitudinal cohort in order to provide data not only for this project, but for many other future and ongoing projects. Methods Edinburgh Type 2 Diabetes Study is a cohort of 1,066 adults aged 60-75 years with type 2 diabetes living in the Lothian region of Scotland. Data were collected through research clinics as well as record linkage. Diabetic retinopathy status was obtained from the national screening programme and to evaluate cognitive decline, dementia diagnosis was obtained from a combination of medical records, death records and self-report. Cognitive decline was also evaluated using cognitive status derived from a battery of cognitive tests administered at baseline and then again after 10 years. Retinal images were analysed using VAMPIRE software for central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar and venular tortuosity, fractal dimension and density. Results A total of 83 participants (11.6%) developed retinopathy over 10 years. After controlling for a wide number of cardiometabolic, diabetic and vascular risk factors, there was evidence of an association between increased venular tortuosity and incident retinopathy (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.15 to 1.98, p = 0.003), as well as decreased standardised fractal dimension and incident retinopathy (OR 0.75, 0.58 to 0.96, p = 0.025). Of the total 1066, 106 (9.9%) were determined to have a dementia diagnosis after 10 years of follow-up. Cognitive decline, as measured by cognitive testing after 10 years, controlling for baseline cognitive status, was measured in the 581 returning participants. There were no independent associations between the retinal vessel traits and cognitive decline, using either dementia or the general intelligence factor, after controlling for various covariates. There was, however, evidence of age-related decreases in fractal dimension and density over the course of the study. Conclusions This thesis has provided evidence from the ET2DS that venular tortuosity and fractal dimension are independently associated with diabetic retinopathy. The independent associations were modest and need to be contextualised within the heterogeneity that exists within the supporting literature as well as replicated in other studies, but they provide exciting support for the use of the retinal vessel traits in future risk prediction modelling for diabetic retinopathy. There was no evidence of an association between the reported retinal vessel traits and cognitive decline. Novel findings regarding age-related decreases in fractal dimension and density are important as more information is coming to light regarding the vessel traits and their associations with vascular disease.