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

Atiskova, Yevgeniya; Wildner, Jan; Spitzer, Martin S.; Aries, Charlotte; Muschol, Nicole; Dulz, Simon

doi:10.1186/s13023-021-02080-0

Cited by 6 publications

(7 citation statements)

References 30 publications

(50 reference statements)

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“…VT in patients with FD is speculated to be a result of intracytoplasmic storage of Gb3 within the endothelial cells, which can lead to endothelial proliferation and weakening of the vessel walls [1,13,32]. Hence, this could lead to a higher retinal VTI in these patients [46]. The finding of our study confirms data from previous studies where cohorts of patients with FD were analyzed to assess retinal VT with different methods [1,46].…”

Section: Discussionsupporting

confidence: 79%

Assessment of Retinal Vessel Tortuosity Index in Patients with Fabry Disease Using Optical Coherence Tomography Angiography (OCTA)

Hangartner,

Bajka,

Wiest

et al. 2023

Diagnostics

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Vessel tortuosity (VT) is a parameter used to assess retinal involvement in patients affected by systemic diseases such as Fabry disease (FD). In this study, we assessed a retinal VT index (VTI) using optical coherence tomography angiography (OCTA) in a group of patients with FD (FD cohort) compared to a healthy control group (HC cohort). This is a single-center, retrospective study analysis of all consecutive patients with genetically tested and confirmed FD who underwent regular ophthalmological visits from December 2017 to January 2020 at the Department of Ophthalmology at the University Hospital of Zurich, Switzerland. VTI was calculated for each OCTA image and the results were compared between FD and HC cohort. A total of 56 participants, 32 (male:female ratio 12:20) in the FD cohort and 24 (male:female ratio 13:11) in the HC cohort. Classic onset was determined in 18 patients. Overall, mean VTI (±SD) was 0.21 (±0.07). Male patients with classic-onset FD had a significantly higher mean VTI (0.33, SD ± 0.35) compared to all other subgroups (p-value < 0.05). Further investigations of retinal VTI in patients with FD could be helpful to use OCTA as a noninvasive screening and follow-up modality to assess disease progression in affected patients.

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Section: Discussionsupporting

confidence: 79%

Assessment of Retinal Vessel Tortuosity Index in Patients with Fabry Disease Using Optical Coherence Tomography Angiography (OCTA)

Hangartner,

Bajka,

Wiest

et al. 2023

Diagnostics

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“…DNA damage-associated targets have already been investigated in human FD studies [33,34] reporting that lyso-Gb3, a deacylated form of Gb3, induces cellular stress, leading to FD human kidney cell DNA damage. FD patients also display neurovascular involvement such as cerebral stroke and microangiopathy [35][36][37]. Thus, we investigated different EC properties in control EC and EC derived from FD patients reporting either pain attacks (P1) or no pain (P2).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell Dysfunction and Hypoxia as Potential Mediators of Pain in Fabry Disease: A Human-Murine Translational Approach

Klug,

Spitzel,

Hans

et al. 2023

IJMS

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Fabry disease (FD) is caused by α-galactosidase A (AGAL) enzyme deficiency, leading to globotriaosylceramide accumulation (Gb3) in several cell types. Pain is one of the pathophysiologically incompletely understood symptoms in FD patients. Previous data suggest an involvement of hypoxia and mitochondriopathy in FD pain development at dorsal root ganglion (DRG) level. Using immunofluorescence and quantitative real-time polymerase chain reaction (qRT PCR), we investigated patient-derived endothelial cells (EC) and DRG tissue of the GLA knockout (KO) mouse model of FD. We address the question of whether hypoxia and mitochondriopathy contribute to FD pain pathophysiology. In EC of FD patients (P1 with pain and, P2 without pain), we found dysregulated protein expression of hypoxia-inducible factors (HIF) 1a and HIF2 compared to the control EC (p < 0.01). The protein expression of the HIF downstream target vascular endothelial growth factor A (VEGFA, p < 0.01) was reduced and tube formation was hampered in the P1 EC compared to the healthy EC (p < 0.05). Tube formation ability was rescued by applying transforming growth factor beta (TGFβ) inhibitor SB-431542. Additionally, we found dysregulated mitochondrial fusion/fission characteristics in the P1 and P2 EC (p < 0.01) and depolarized mitochondrial membrane potential in P2 compared to control EC (p < 0.05). Complementary to human data, we found upregulated hypoxia-associated genes in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). At protein level, nuclear HIF1a was higher in the DRG neurons of old GLA KO mice compared to WT mice (p < 0.01). Further, the HIF1a downstream target CA9 was upregulated in the DRG of old GLA KO mice compared to WT DRG (p < 0.01). Similar to human EC, we found a reduction in the vascular characteristics in GLA KO DRG compared to WT (p < 0.05). We demonstrate increased hypoxia, impaired vascular properties, and mitochondrial dysfunction in human FD EC and complementarily at the GLA KO mouse DRG level. Our data support the hypothesis that hypoxia and mitochondriopathy in FD EC and GLA KO DRG may contribute to FD pain development.

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“…In contrast to other studies Atiskova et al reported no difference in perifoveal vessel density when comparing FD patients with controls [ 23 ]. A study by Dogan et al reported a reduction of deep capillary vascular density in FD but no difference in superficial capillary vascular density in FD and controls [ 21 ].…”

Section: Discussionmentioning

confidence: 59%

Correlation of retinal vascular characteristics with laboratory and ocular findings in Fabry disease: exploring ocular diagnostic biomarkers

Lindziute,

Kaufeld,

Hufendiek

et al. 2023

Orphanet J Rare Dis

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Background The goal of this study was to evaluate macular microvascular changes in patients with Fabry disease (FD) using optical coherence tomography angiography (OCTA) and to explore their correlation with laboratory and ocular findings. Methods A total of 76 eyes (38 patients) and 48 eyes of 24 healthy controls were enrolled in this prospective study. Vessel Area Density (VAD) and Foveal Avascular Zone (FAZ) area were calculated on 2.9 × 2.9 mm OCTA images scanned with the Heidelberg Spectralis II (Heidelberg, Germany). VAD was measured in three layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP). All scans were analyzed with the EA-Tool (Version 1.0), which was coded in MATLAB (The MathWorks Inc, R2017b). FAZ area was manually measured in full-thickness, SVP, ICP and DCP scans. Results Average VAD in SVP, ICP and DCP was higher in Fabry disease patients than in controls (49.4 ± 11.0 vs. 26.5 ± 6.2, 29.6 ± 7.4 vs. 20.2 ± 4.4, 32.3 ± 8.8 vs. 21.7 ± 5.1 respectively, p < 0.001). Patients with cornea verticillata (CV) had a higher VAD in ICP and DCP compared to patients without CV (p < 0.01). Patients with increased lysoGb3 concentration had a higher VAD in DCP when compared to patients with normal lysoGb3 concentration (p < 0.04). There was no difference in VAD in patients with and without vascular tortuosity. However, a significantly higher VAD was observed in patients with vascular tortuosity compared to controls (p < 0.03). Conclusions Increased lysoGb3 and VAD in DCP could be reliable biomarkers of disease activity. Cornea verticillata could be adopted as a predictive biomarker for VAD changes and disease progression. The combination of cornea verticillata and increased VAD may serve as a diagnostic biomarker for Fabry disease, however due to the discrepancies in VAD values in various studies, further research has to be done to address this claim.

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

Cited by 6 publications

References 30 publications

Assessment of Retinal Vessel Tortuosity Index in Patients with Fabry Disease Using Optical Coherence Tomography Angiography (OCTA)

Assessment of Retinal Vessel Tortuosity Index in Patients with Fabry Disease Using Optical Coherence Tomography Angiography (OCTA)

Endothelial Cell Dysfunction and Hypoxia as Potential Mediators of Pain in Fabry Disease: A Human-Murine Translational Approach

Correlation of retinal vascular characteristics with laboratory and ocular findings in Fabry disease: exploring ocular diagnostic biomarkers

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