Retinal hyperreflective foci in Fabry disease

Area of Science:

• Ophthalmology
• Genetics
• Metabolic Disorders

Background:

• Fabry disease (FD) is an X-linked inherited disorder caused by a deficiency in alpha-Galactosidase A.
• This deficiency leads to the accumulation of globotriaosylceramide (Gb3) within lysosomes.
• Retinal manifestations in FD are increasingly recognized as important diagnostic and monitoring tools.

Purpose of the Study:

• To investigate novel retinal findings in patients with Fabry disease using spectral domain optical coherence tomography (SD-OCT).
• To assess the clinical relevance of these findings by correlating them with Fabry disease biomarkers.
• To compare retinal imaging features between FD patients and age-matched controls.

Main Methods:

• SD-OCT imaging of the macula was performed on 27 FD patients and 27 controls.
• Quantification of central retinal thickness, retinal nerve fiber layer, and inner retinal hyperreflective foci (HRF).
• Assessment of vessel tortuosity and correlation with lyso-Gb3 levels, a biomarker for FD.

Main Results:

• FD patients showed a significantly higher number of inner retinal HRF compared to controls.
• HRF and vessel tortuosity significantly correlated with elevated lyso-Gb3 levels (p < 0.001 and p = 0.005, respectively).
• Male patients with classic FD phenotype exhibited higher HRF and vessel tortuosity scores.

Conclusions:

• Novel intraretinal HRF were identified in the inner retinal layers of FD patients.
• These HRF correlate with lyso-Gb3 levels, potentially indicating Gb3 accumulation in the macula.
• Despite novel findings, visual acuity remained unchanged, suggesting HRF may be an early indicator without immediate functional impact.