Retinal hemodynamic and caliber biomarkers for the assessment of cerebral small vessel disease burden: insights from fundus fluorescein angiography.

BACKGROUND

Retinal microvasculature serves as a promising window to assess cerebral small vessel disease (CSVD). However, the association between comprehensive fundus fluorescein angiography (FFA) biomarkers and the total CSVD burden score remains to be fully elucidated.

AIMES: To investigate the relationship between the total CSVD burden score and FFA-derived retinal biomarkers, and to identify independent retinal indicators for evaluating CSVD severity.

METHODS

This retrospective study enrolled 120 patients. The CSVD burden score was evaluated based on lacunes of presumed vascular origin, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. FFA parameters included dynamic hemodynamic indicators (arm-retinal circulation time [ARCT], retinal circulation time [V1-ARCT], retinal venous transit time [V2-V1]) and static vascular caliber indicators (central retinal artery equivalent [CRAE], central retinal vein equivalent [CRVE], arteriolar-to-venular ratio [AVR]), as well as arteriovenous nicking and vascular leakage. Correlation and multivariable regression analyses were performed.

RESULTS

Across CSVD burden groups, significant differences were detected in age, hypertension, hyperlipidemia, key neuroimaging markers, ARCT, V1-ARCT, CRAE, CRVE, and AVR, whereas gender, diabetes, arteriovenous nicking, vascular leakage, and V2-V1 showed no significant differences. Spearman analysis showed that the CSVD burden score was negatively correlated with CRAE and AVR, and positively correlated with CRVE and V1-ARCT. Multivariable analysis identified CRAE, CRVE, and V1-ARCT as independent factors associated with the CSVD burden score: lower CRAE, higher CRVE, and prolonged V1-ARCT were related to higher CSVD burden.

CONCLUSION

Static vascular caliber (CRAE, CRVE) and dynamic retinal circulation time (V1-ARCT) are independently associated with CSVD burden. The combined use of these FFA biomarkers provides a promising tool for the early assessment and noninvasive monitoring of CSVD, supporting further clinical translation.