A stronger association of diabetes mellitus with impaired hyperaemia using a novel ECG-gated device compared with peripheral arterial tonometry.

PURPOSE: Impaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system. METHODS: In total, 119 controls and 120 participants with diabetes mellitus partook in this cross-sectional study. The EndoPAT2000 system assessed digital reactive hyperaemia under fasting conditions. A mydriatic ECG-gated fundoscope with a novel flicker module acquired digital retinal images of the left eye before, during and after flicker stimulation. An inhouse semi-automated software measured retinal vessel diameters using a validated protocol with two observers repeating measurements in a subset of 10 controls and 10 participants with diabetes mellitus. Intra- and inter-observer reliability analyses occurred by the interclass correlation coefficient. A receiver operating characteristic curve established associations of variables with diabetes mellitus. RESULTS: Diabetes mellitus was more strongly associated with flicker-stimulated retinal arteriolar calibre change from baseline (AUC 0.81, 95% CI 0.75-0.87, p < 0.0001) than reactive hyperaemia index. Median flicker-stimulated arteriolar calibre change from baseline (controls: 2.74%, IQR 1.07 vs diabetes mellitus: 1.64%, IQR 1.25, p < 0.0001) and reactive hyperaemia index (controls: 1.87, IQR 0.81 vs diabetes mellitus: 1.60, IQR 0.81, p = 0.003) were lower in diabetes mellitus than controls. Intra- and inter-observer reliability coefficients were high from 0.87 to 0.93. CONCLUSIONS: Impaired flicker-stimulated retinal arteriolar calibre change from baseline is more highly correlated with diabetes mellitus in this study than a reduced reactive hyperaemia index.

Comparison of experiences and preferences following non-invasive cardiovascular risk procedures: a cross-sectional survey in participants with and without diabetes mellitus.

Aims: Endothelial dysfunction is an early risk marker of cardiovascular disease in diabetes mellitus. Timely screening is important in reducing cardiovascular disease-associated morbidity and mortality. This cross-sectional study investigates the acceptability and preferability of non-invasive cardiovascular risk procedures (EndoPAT2000 system and the ECG-gated fundoscope) in participants with diabetes mellitus compared to controls. Methods: A self-administered Likert scale-based questionnaire was completed by 106 controls and 117 participants with diabetes mellitus, identified through stratified random sampling, upon conclusion of an Australian Heart Eye sub-study conducted at Westmead Hospital, NSW, Australia from 2012 to 2014. Pearson's χ 2 test, independent-samples t-test and regression analysis were performed. Results: Study participants who responded to the questionnaire had no preference for procedures (controls: 2.4 ± 1.1 vs diabetes mellitus: 2.5 ± 0.9, p = 0.38) but had an overall more negative experience with most aspects of the ECG-gated fundoscope than the EndoPAT2000 system. Of those with diabetes mellitus, participants who provided poorer self-rated health expressed discomfort with the mydriatic drops (ß 0.27, 95%CI 0.001 - 0.54, p = 0.049) and the fundoscope's green light filter (ß 0.27, 95%CI 0.07 - 0.47, p = 0.009), as well as maintaining still (ß 0.40, 95%CI 0.08 - 0.72, p = 0.02) and not blinking (ß 0.38, 95%CI 0.07 - 0.70, p = 0.02) during photo acquisition. These participants were also less willing to repeat the ECG-gated fundoscope procedure (ß 0.29, 95%CI 0.07 - 0.52, p = 0.01). Conclusions: Participants with diabetes mellitus, especially with poorer self-rated health, had a more negative experience with the ECG-gated fundoscope than the EndoPAT2000 system. Difficulties experienced under examination by the ECG-gated fundoscope appear related to the procedural design, which requires amendments improving patient comfort and compliance.

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes.

Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes.Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules.Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88-1.17% vs ECG-gated: 0.39, 95%CI 0.29-0.49%, p < .0001) than venular (ungated 0.62, 95%CI 0.53-0.73% vs ECG-gated: 0.26, 95%CI 0.19-0.35%, p < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively.Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.