Patients with Fabry disease exhibit vascular injuries affecting heart, brain, kidneys, and retina. 20 The pathophysiology of this vasculopathy remains incompletely elucidated, with current hypotheses suggesting endothelial dysfunctions, alterations in cerebral perfusion, and a pro-thrombotic phenotype arising from alpha-galactosidase A deficiency. 21
In patients with Fabry disease, diverse ocular manifestations have been observed, with occasional findings indicating vascular occlusive disorders arising from compromised choroidal and retinal vasculature. 6
The objective of this study is to investigate vascular differences between Fabry patients and healthy controls, encompassing for the first time not only arterial stiffness but also exploring ocular aspects through the assessment of retinal angiopathy (specifically CSP-VD, DCP-VD, and CC-VD) and retinal arterial compromise (RI-CRA), using reliable non-invasive methods.
In our analysis, arterial stiffness resulted higher in the Fabry group than in the control group, aligning with findings from several prior studies. 22 This observation correlates with an increased incidence of cardiovascular events and challenges in peripheral microcirculation in this particular patient population. 23 Alterations in arterial stiffness and blood pressure metrics are increasingly investigated, suggesting a potential role not only in delaying the decline in kidney functions but also in contributing to retinal neurodegeneration. 24,25
Comparison of data between the two cohorts, FD and controls, revealed a significant decrease in VD across the superficial, deep, and choriocapillaris plexuses. Our study identified the choriocapillaris as the most compromised, consistent with the knowledge that it is particularly vulnerable to damage in the presence of systemic diseases involving vascular complications. 26–28
Alongside alterations in VD, the information obtained through ColorDoppler revealed a noteworthy increase in the resistive index of the central retinal artery in Fabry patients.
The resistive index is a measure of vascular resistance, and changes in this index can indicate alterations in blood flow characteristics within the central retinal artery. In diabetic retinopathy increased vascular resistance in the central retinal artery has been investigated and resulted from both macrovascular and microvascular changes associated with the pathology. 29
This elevation is reflective of the compromised retinal circulation and impaired autoregulation in the context of diabetes and has been considered as a bioimaging biomarker for the severity of the disease 16
In our study, for the first time an increase in the resistive index of the central retinal artery has been registered in Fabry patients, probably due to the glycolipid accumulation leading to structural changes, potentially impacting blood flow dynamics and increasing vascular resistance.
Investigating and comparing RI changes in the central retinal artery can contribute to a deeper understanding of the vascular alterations specific to the analysed condition.
It's essential to consider the potential implications of RI changes in guiding treatment strategies and predicting the risk of vision-related complications, such as the risk of thrombosis, which encompasses central retinal artery occlusion and retinal vein occlusion. 30–32 Notably, the individuals under examination did not exhibit symptomatic ocular complications; rather, the sole indicators of ocular vasculopathy were observed in the form of conjunctival vessel tortuosity (in 19 patients) and retinal vessel tortuosity (in 15 patients). In essence, these patients could be characterized from an ocular standpoint as being in a subclinical stage. The highlighted alteration in VD prompts consideration of the potential value in longitudinally monitoring these individuals. Eco ColorDoppler and OCTA emerge as early preferences, offering non-invasive and cost-effective means to delineate vascular changes in the absence of overt pathology.
This study is subject to certain limitations, notably the relatively small number of patients analyzed, a factor attributed to the rarity of the disease. Additionally, the short-term follow-up period raises a need for further investigations to evaluate longitudinal changes and potential correlations between ocular alterations and the emergence of signs and symptoms of pathology. Despite these limitations, the study gains strength from its innovative approach, employing for the first time a combination of eco ColorDoppler and OCTA in Fabry patients.
In conclusion, our study has revealed that FD patients exhibit not only the anticipated significant increase in arterial stiffness compared to healthy subjects but also an elevation in the resistive index of the central retinal artery and a reduction in retinal microvasculature density. These findings suggest the presence of subclinical ocular damage in these patients, underscoring the importance of ongoing monitoring. A focused screening for organ damage in FD patients is strongly recommended, emphasizing the necessity to identify parameters that can serve as pivotal benchmarks in assessing ocular vascular involvement. Such non-invasive bioimaging biomarkers might also serve to monitor the latest therapies available for Fabry patients, such as the enzyme replacement therapy, to assess treatment response and adjust therapy as needed. Certainly, further studies are needed to elucidate how variations in these parameters over time are associated with the pathology progression.