Longitudinal assessment of the retinal phenotype in patients with Fabry disease undergoing continuous enzyme replacement and/or chaperone therapy

Abstract Purpose Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by deficiency of the enzyme α-galactosidase A. This study describes the long-term evolution of retinal findings in genetically confirmed FD patients, who have been receiving enzyme replacement therapy (ERT) or pharmacological chaperone therapy (PCT). Methods This retrospective observational study included 42 eyes of 21 patients, who underwent comprehensive ophthalmic examination including best-corrected visual acuity (BCVA) testing, tonometry, slit-lamp biomicroscopy of the anterior eye segment, fundus examination and spectral-domain optical coherence tomography (OCT) imaging. Longitudinal analysis focused on the central retinal thickness (CRT), peripapillary retinal nerve fiber layer (RNFL) thickness, intraretinal hyperreflective foci (HRF), and retinal vessel tortuosity. Results Over a median follow-up period of 6.5 years, BCVA remained stable in all patients. Serum lyso-globotriaosylceramide (lyso-Gb3) levels demonstrated strong correlations with intraretinal HRF and retinal vessel tortuosity but no significant change during the observation period was observed. Longitudinal assessment showed no significant change of HRF, retinal vessel tortuosity or CRT over time, whereas a significant reduction of RNFL thickness was observed, although these values remained within the normal range. Conclusion Long-term treatment with ERT or PCT in FD is associated with a largely stable retinal phenotype. Retinal imaging parameters remain structurally preserved over time, with only mild RNFL thinning observed, suggesting limited progressive retinal neurodegeneration.