Retinal vessel tortuosity as a prognostic marker for disease severity in Fabry disease

Yevgeniya Atiskova,Martin Stephan Spitzer,Jan Wildner,Nicole Muschol,Simon Dulz,Charlotte Aries

doi:10.1186/s13023-021-02080-0

Yevgeniya Atiskova, Martin Stephan Spitzer + Show 4 more

Open Access

https://doi.org/10.1186/s13023-021-02080-0

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Abstract

PurposeThe aim of this case control study was to evaluate the prognostic value of automatically quantified retinal vessel tortuosity from fundus images and vessel density from OCT-A in Fabry disease and to evaluate the correlation of these with systemic disease parameters.MethodsAutomatically quantified perimacular retinal vessel tortuosity (MONA REVA software), acquired by fundus imaging, and perifoveal retinal vessel density, acquired by optic coherence tomography angiography (OCT-A) were compared between 26 FD patients and 26 controls. Gender and FD phenotype were analyzed to the obtained retinovascular data and correlated to the Mainz severity score index (MSSI) and plasma lyso-Gb3.ResultsAutomatically quantified retinal vessel tortuosity indices of FD patients were significantly lower, reflecting an increased vessel tortuosity, compared to controls (p = 0.008). Males with a classical phenotype showed significantly lower retinal vessel tortuosity indices compared to males with an oligosymptomatic phenotype and females with a classical or oligosymptomatic phenotype (p < 0.001). The retinal vessel tortuosity index correlated significantly with systemic disease severity parameters [global MSSI (r = − 0.5; p < 0.01), cardiovascular MSSI (r = − 0.5; p < 0.01), lyso-Gb3 (r = − 0.6; p < 0.01)].ConclusionWe advocate fundus imaging based automatically quantified retinal vessel tortuosity index over OCT-A imaging as it is a quick, non-invasive, easily assessable, objective and reproducible marker.

Highlights

Fabry disease (FD) is a rare X-chromosomal inherited lysosomal storage disorder affecting the glycosphingolipid metabolism
We recently reported on intraretinal hyperreflective foci in FD patients identified by optical coherence tomography (OCT) imaging [14]
We have shown that automatically quantified retinal vessel tortuosity indices of FD patients were significantly lower, reflecting a significantly increased vessel tortuosity, compared to the control group

Summary

Introduction

Fabry disease (FD) is a rare X-chromosomal inherited lysosomal storage disorder affecting the glycosphingolipid metabolism. Pathogenic variants of the α-Galactosidase A (GLA) gene located at chromosome Xq22 result in decreased activity of the lysosomal enzyme GLA [2, 3]. Glycosphingolipid accumulation in lysosomes of multiple tissues results in non-specific symptoms such as acroparesthesia, cutaneous angiokeratomas, Atiskova et al Orphanet J Rare Dis (2021) 16:485. Approved therapeutic options for the treatment of FD are intravenously applied recombinant enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta [4, 10] and for specific GLA mutations an oral chaperon therapy with migalastat is available [11]. An early diagnosis of FD leads to early access to disease-specific follow-up programs and treatment protocols affecting the prognosis significantly [10]. Ocular signs of FD such as cornea verticillata, subcapsular cataract formation and vessel tortuosity of the conjunctival and retinal vessels can be observed prior or parallel to systemic symptoms and can contribute to finding the diagnosis [12, 13]

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