Over the past two decades, there have been multiple software systems developed to measure retinal vessel caliber from fundus photographs. The Retinal Analysis (RA; version 6.51; Department Ophthalmology & Visual Science, University of Wisconsin, Madison, WI)
12–14 was a pioneer computer-assisted software program, that was originally used in studies such as the Atherosclerosis Risk in Communities study,
15 Cardiovascular Health Study,
16 Rotterdam study,
17 Beaver Dam Eye Study,
18 Blue Mountains Eye Study,
19 Wisconsin Epidemiologic Study of Diabetic Retinopathy,
9 the Handan Eye Study
20 (
Supplementary Table S1). This software program, however, requires significant user input and manual tracing of vessels (
Fig. 1A). Another widely used system that was subsequently developed with automated detection and identification of arterioles and venules was the Integrative Vessel Analysis (IVAN; University of Wisconsin, Madison;
Fig. 1B),
21,22 used also in some of the earlier studies such as the Wisconsin Epidemiologic Study of Diabetic Retinopathy
23 and the Beaver Dam Eye Study,
24 and in later studies such as the Multi-Ethnic Study of Atherosclerosis,
21 Singapore Malay Eye Study,
25 Singapore Prospective Study Program
26 Age, Gene/Environment Susceptibility-Reykjavik Study
27 (
Supplementary Table S1). Finally, the Singapore I Vessel Assessment (SIVA; version 3.0; National University of Singapore),
28,29 improved on more automation features, including automated detection of the optic disc center, optic disc edge, and automated detection and identification of arterioles and venules. The SIVA software also provided a more global representation of the overall retinal vascular network, with measurements over a wider measurement area (up to 2 disc diameters) and additional geometry parameters such as branching angles, bifurcation, fractal dimension, and tortuosity (
Fig. 1C).
29,30 Together, these three retinal vessel software systems have been used in population- and clinic-based studies totaling more than 100,000 participants (
Supplementary Table S1).