Fractal analysis of retinal microvasculature and cardiovascular outcome: a systematic review and meta-analysis

To access associations between retinal vascular fractal dimension (FD) and the risk of the development of cardiovascular disease (CVD) in this systematic review.

PubMed, Web of science, and Cochrane Library databases were searched for cohort and cross-sectional studies with data on the association between FD and CVD risk published up to June 2025. The combined risk estimates were estimated using the random-effects model. Subgroup analysis was performed according to pre-defined characteristics. Sensitivity analysis was conducted to examined the robustness of the results. This study is registered on PROSPERO, number CRD42024591961.

Fourteen eligible studies (eight were cohort design and six were cross-sectional design) were included and analyzed. When FD was regarded as a continuous variable, the significant association between decreased FD and the incidence of the CVD (RR: 1.14, 95%CI: 1.05-1.24) was found. When FD was regarded as a categorical variable, the participants in the lower FD group at the baseline had the greater incidence risk of CVD compared to those in higher FD group (RR: 1.51, 95%CI: 1.07-2.14). Furthermore, people with reduced FD may inclined to have the established CVD (RR: 1.70, 95%CI: 1.23-2.37). The sensitivity analysis indicated that the above results are robust. We also found that when arterioles and venules were analyzed separately, the association between decreased arteriolar FD and CVD risk remained significant (cohort studies, RR: 1.08, 95%CI: 1.01-1.17; cross-sectional, RR: 1.90, 95%CI: 1.51-2.37), whereas no such association was observed in venular FD (cohort studies, RR: 0.96, 95%CI: 0.84-1.08; cross-sectional, RR: 1.42, 95%CI: 0.89-2.29).

The decreased retinal microvascular FD was significantly associated with the CVD risk, especially in retinal arteriole. The findings of this study supported that FD may be a potential marker of CVD risk including stroke and coronary heart disease. Noninvasive FD measurement may act as an adjunct to existing CVD risk stratification, facilitating early screening and diagnosis of individuals at elevated CVD risk.