# Endothelial dysfunction in Fabry disease: retinal biomarkers link cardiac GLA gene variants with chronic inflammation

## TL;DR

The study finds retinal microcirculation changes in Fabry disease patients linked to heart-related gene variants and inflammation, suggesting a non-invasive way to assess cardiovascular risk.

## Contribution

This study introduces retinal vessel analysis as a novel non-invasive biomarker for cardiovascular risk in Fabry disease.

## Key findings

- FD patients showed impaired retinal microcirculation compared to healthy controls.
- Cardiac-associated GLA variants correlated with narrower retinal arterioles and higher inflammation.
- Retinal biomarkers are linked to endothelial dysfunction and cardiovascular risk in FD.

## Abstract

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by variants in the alpha-galactosidase A gene (GLA). Cardiac complications are a major cause of mortality, but the large number of variants complicate early identification of at-risk patients. In this study, we assessed the microcirculation using Retinal Vessel Analysis (RVA) in 63 FD patients age- and gender-matched to 60 healthy controls, analyzing associations between RVA parameters, cardiac involvement, and GLA variants. FD patients showed reduced venular flicker-induced dilation, narrower retinal arterioles, and a lower arteriolar-to-venular ratio. Impaired retinal microcirculation was associated with cardiac involvement, and patients with cardiac-associated GLA variants exhibited narrower retinal arterioles. Markers of inflammation and endothelial dysfunction (ED) were significantly higher in FD patients. Higher inflammatory levels correlated with altered retinal microcirculation in patients carrying cardiac-associated GLA variants. RVA detects microvascular ED in FD patients and may serve as a non-invasive biomarker for cardiovascular risk stratification. Registration:
https://clinicaltrials.gov/study/NCT06758648; Unique identifier: NCT06758648.