Retinal venular tortuosity and fractal dimension predict incident retinopathy in adults with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

Abstract

Aims/hypothesis Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes. Methods In the prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60–75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years. Results The incidence of diabetic retinopathy was 11.4% (n = 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98; p = 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96; p = 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA1c, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640, p = 0.013), but no such benefit was found with fractal dimension. Conclusions/interpretation Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted. Graphical abstract

A Study of the Association Between Retinal Vessel Geometry and Optical Coherence Tomography Angiography Metrics in Diabetic Retinopathy

“… 8 , 11 However, other studies indicate no association between the vascular tortuosity and DR severity, consistent with our results. 13 Although there are few studies evaluating branching coefficient or junctional exponent deviation in DR, it has been reported that JEa decreased in severe DR, consistent with our finding. 11 In contrast, most studies of OCTA parameter change according to DR severity report consistent results 14 : lower VAD, lower VLD, decreased FAZ circularity, and enlarged FAZ area, similar to our findings.…”

“… 11 Several studies indicate conflicting results regarding the association between the DR severity and the vascular fractal dimension. 13 In addition, the fractal dimension was calculated without distinguishing between the arteriole and the venule in many studies.…”

Retinal microvascular associations with cardiometabolic risk factors differ by diabetes status: results from the UK Biobank

“…In our previous work on the diagnostic criteria for type 2 diabetes, we showed that the association of each glucose measure with retinopathy was linear in several populations, with no evidence of a threshold [46,47]. Given that changes in the retinal microvascular architecture predict the development of diabetic retinopathy, it is not surprising to find evidence of this linear association among those without diabetes [48]. Once you have diabetes, it appears that the degree of glycaemic control does not influence venular tortuosity much; perhaps the venular tortuosity damage has already been done by the time of clinical diagnosis.…”

Artificial Intelligence and Corneal Confocal Microscopy: The Start of a Beautiful Relationship

“…Torp et al [ 98 ] demonstrated that retinal venular fractal dimension predicted disease activity 6 months after panretinal photocoagulation, suggesting it may serve as a biomarker of treatment efficacy. The challenges of utilising the fractal dimension in DR have been described by Forster et al [ 99 ]. Thus, with the progression of DR, different vascular changes can result in opposing fractal indices, with an initial decrease followed by increased fractal dimensions in proliferative DR [ 100 ].…”