Is the arteriovenous ratio a biomarker of progression from diabetes to diabetic retinopathy?

Purpose : In order to shed light on the vascular alterations during diabetes and diabetic retinopathy (DR), the central retinal artery and vein equivalents (CRAE and CRVE) and the arteriovenous ratio (AVR) were calculated, investigating the hypothesis that the vascular changes that occur during the final stages of diabetes and early stages of DR are distinct and significant.

Methods : Fifty diabetic patients that progressed to DR were included, coming from a UK DR screening database. For each patient, four images were analyzed, in four different time intervals; three, two and one year before DR and the first year of DR. In total, two hundred retinal fundus images (3216-by-2316 pixels) were used. Initially, the images were processed in order to define the AVR region, separate and measure the arteries and veins, and include only the six largest for each of them. In total, 1200 veins (300 for each of the 4 groups) and 1200 arteries (similarly) were measured. For the analysis, a repeated measures Anova was used, after meeting the assumptions of normality and sphericity.

Results : Significant results were observed in all the main effects (image 1). There was an overall significant increase on the group means of the AVR along with the progression of diabetes (F (3,147)=3.04, p-value=0.03). An opposite significant trend was observed for the CRVE and to a lesser extend the CRAE, when evaluated individually (F (3,147)=5.46, p-value=0.002 and F (3,147)=4.10, p-value=0.009, respectively). In addition, post-hoc exploration of the differences among the means was needed. In all three cases, significant differences were observed for the pairs 3 years pre-DR/1st year of DR and 2 years pre-DR/1st year of DR (AVR: a) p-value=0.02, b) p-value=0.03, CRAE: a) p-value=0.003, b) p-value=0.009, and CRVE: a) p-value=0.001, b) p-value=0.002. More details, including effect sizes and power of study can be found on the included table.

Conclusions : CRVE, CRAE and their ratio are important biomarkers of progression to DR. This study, which included an extensive number of patients,
showed that these biomarkers could be used to monitor the progression of diabetes. Therefore, supported by the findings of this comprehensive study, it would be useful, in addition to the routine checks of the retina for lesions, to start evaluating the geometry as well.