Characterizing the Retinal Microvasculature in Patients with Fabry Disease: a Prospective Observational Study

Characterizing the Retinal Microvasculature in Patients with Fabry Disease: a Prospective Observational Study

This study aims to gain a deeper understanding of endothelial dysfunction in patients with Fabry disease through a prospective study of the retinal microvasculature and to identify an objective, non-invasive marker to assess disease severity and cardiovascular risk in patients.

The main questions addressed are: Do dynamic and static retinal vessel analysis parameters differ from those in healthy individuals? Can these parameters predict cardiovascular and/or Fabry-related events during follow-up? Do these parameters change during follow-up in patients with a non-stable disease?

Fabry disease is a rare genetic disorder characterized by the pathological accumulation of glycosphingolipids, specifically globotriaosylceramide (Gb3), within lysosomes in various cells of the body. This accumulation leads to damage in the cardiovascular, cerebrovascular, and renal systems and is characterized by dysfunction of endothelial cells. This dysfunction results in disturbances in the microcirculation and damage to the supplied systems, leading to a significantly increased cardiovascular risk in patients with Fabry disease. Studies have shown that these patients have a higher risk of premature death due to these risk factors compared to the general population.

Early diagnosis and adequate monitoring of enzyme replacement therapy (ERT) are crucial in reducing the risk of cardiovascular events associated with Fabry disease. Currently, LysoGb3 (lysosphingolipid globotriaosylceramide) is considered a biomarker for the diagnosis and monitoring of Fabry disease. Elevated levels of LysoGb3 have been observed in the blood of patients with Fabry disease, and its measurement has been proposed as a diagnostic tool. Additionally, measuring LysoGb3 levels before and after treatment with ERT can be used as a tool to monitor the effectiveness of the therapy in reducing the accumulation of glycosphingolipids in cells and improving symptoms and outcomes in patients with Fabry disease.

However, the performance of LysoGb3 as a predictor of cardiovascular events in patients with Fabry disease is not well understood, and more research is needed to confirm its utility in this regard.

Therefore, there is a need for additional reliable measurements of the microcirculation that can be performed non-invasively and represent a low burden for participants. The use of non-invasive markers of microcirculation can aid in the early diagnosis and monitoring of Fabry disease, which is crucial for the effective use of ERT.

In summary, this study aims to validate new microcirculation markers that can be measured non-invasively in a prospective cohort of patients with Fabry disease and to correlate these markers with established clinical and laboratory parameters. By validating these markers, the study seeks to improve the management of Fabry disease, reduce the burden on participants, and ultimately reduce the incidence of cardiovascular events associated with the disease.

Inclusion Criteria:

• Age > 18 years
• Diagnosis of Fabry disease by genetic testing or GB3 activity in leukocytes.
• Signed informed consent form

Exclusion Criteria:

• Active infection or cancer
• Surgery less than 2 weeks prior to inclusion in the study
• Known glaucoma
• Lack of capacity to give consent; lack of informed consent.
• Known epilepsy