Retinal hyperreflective foci in Fabry disease

Abstract

Background: Fabry disease (FD) is an X-linked inherited storage disorder caused by deficiency of lysosomal alpha-Galactosidase A. Here we describe new retinal findings in patients with FD assessed by Spectral domain optical coherence tomography (SD-OCT) and their possible clinical relevance.

Methods: 54 eyes of 27 FD patients and 54 eyes of 27 control subjects were included. The ophthalmic examination included visual acuity testing, tonometry, slit lamp and fundus examination. SD-OCT imaging of the macula was performed in all subjects. Central retinal thickness and retinal nerve fiber layer analysis were quantified. Vessel tortuosity was obtained by a subjective scoring and mathematically calculated. Inner retinal hyperreflective foci (HRF) were quantified, clinically graded and correlated with a biomarker of Fabry disease (lyso-Gb3).

Results: In comparison to an age-matched control group, a significant amount of HRF was identified in macular SD-OCT images in FD patients. These HRF were localized within the inner retinal layers. Furthermore, lyso-Gb3 levels correlated significantly with the quantitative evaluation of HRF (p < 0,001). In addition, the vessel tortuosity was remarkably increased in FD patients compared to control persons and correlated significantly with lyso-G3 levels (p = 0.005). A further subanalysis revealed significantly higher HRF and vessel tortuosity scores in male patients with the classic FD phenotype.

Conclusions: The observational, cross sectional, comparative study describes novel intraretinal findings in patients with FD. We were able to identify suspicious HRF within the inner retinal layers. These findings were not accompanied by functional limitations, as visual acuity remained unchanged. However, HRF correlated well with lyso-Gb3, a degradation product of the accumulating protein Gb3 and might potentially indicate Gb3 accumulation within the highly metabolic and densely vascularized macula.

Keywords: Fabry disease; Hyperreflective foci; Retina; SD-OCT; Vessel tortuosity.

Fig. 1

A representative central SD-OCT slice of the right eye of a healthy control person is shown in (a). The macular SD-OCT slide of a left eye of FD patient (b) shows significant HRF. A magnification of the parafoveal region, highlights numerous HRFs (red arrows) within the inner retinal layers (c). Quantification was performed by counting an area of 300 μm temporal (red box) and nasal to the foveal center

Fig. 2

A cSLO image of a patient with FD. Retinal vessel tortuosity was analysed by measuring the true length (a) and the end-to-end length (b) of the retinal vessels and dividing a/b

Fig. 3

Subanalysis of the impact of the clinical course (classical or oligosymptomatic form) and gender of the FD cohort on calculated (a) and subjective (b) vessel tortuosity scores and quantitative (c) and subjective (d) scores of HRF. Male patients with the classic phenotype (n = 9) revealed significantly higher scores in calculated vessel tortuosity (p = 0.0081), subjective vessel tortuosity (p = 0.0018), quantitative score of HRF (p = 0.0015) and subjective score of HRT (p = 0.00098) in comparison with females with the classic phenotype (n = 7). No statistical difference was detected in the evaluated vessel tortuosity and HRF scores between the male (n = 5) and female FD patients (n = 6) with oligosymptomatic phenotype. Statistical analyses of data were performed with the Wilcoxon signed rank test. n.s.: not significant; *p < 0.05; **p < 0.01; ***p < 0.001