Retinal microvascular alterations reflect cerebral small vessel disease burden in frontotemporal dementia: a multimodal OCTA–MRI Study

Frontotemporal dementia (FTD) is a neurodegenerative disorder with a suspected vascular component. However, the relationship between retinal and cerebral microvascular alterations in FTD remains underexplored. This study investigates retinal microvasculature and its association with cerebral small vessel disease (SVD) markers in FTD using optical coherence tomography angiography (OCTA) and MRI. In this cross-sectional study, 33 patients with clinically diagnosed FTD and 43 cognitively unimpaired controls (CU) underwent multimodal imaging, including OCTA and 3.0T MRI. Retinal vessel density and choriocapillaris perfusion were quantified using OCTA, while cerebral SVD markers, such as white matter hyperintensities (WMH) and perivascular spaces (PVS), were evaluated through both visual and automated methods. The correlation between retinal and cerebral microvascular changes was assessed using statistical models adjusting for potential confounders. FTD patients demonstrated significantly reduced retinal and choriocapillaris perfusion compared to CU (all p < 0.001). Notably, decreased superficial vascular complex (SVC) density correlated with higher WMH and PVS volumes. Choriocapillaris perfusion showed the highest diagnostic accuracy (AUC = 0.993) for distinguishing FTD from CU. Furthermore, OCTA metrics, particularly reduced SVC density, were significantly associated with increased SVD burden, indicating a link between retinal microvascular changes and cerebral small vessel pathology in FTD. Our findings support a retina–brain microvascular axis in FTD, where retinal microvascular alterations may reflect cerebral SVD burden. These results highlight the potential of OCTA as a noninvasive biomarker for monitoring vascular contributions to frontotemporal neurodegeneration. The study provides a framework that using OCTA-derived metrics may help improve early diagnosis, disease stratification, and monitoring of vascular involvement in FTD.