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Inner retinal hyper-reflective foci number correlates with flood-illumination adaptive optics ophthalmoscopy grading and systemic organ involvement in patients with Fabry disease

Eye volume 39, pages 1578–1583 (2025)Cite this article

Subjects

Abstract

Objectives

To determine the correlation of inner retinal hyper-reflective foci (HRFs) number with Flood-illumination Adaptive Optics Ophthalmoscopy (FIAOO) grading and systemic organ involvement in a cohort of patients with Fabry disease (FD).

Methods

Observational and cross-sectional study. Thirty-two eyes of 16 genetically proven FD patients (11 females) were included in the analysis. Data regarding therapeutic regimen and organ involvement (heart, kidney, and brain) of each patient were reviewed. Patients underwent full ophthalmological examination including best-corrected visual acuity, retinography, spectral domain optical coherence tomography and FIAOO imaging grading of retinal vessels. The number of inner-retinal HRFs was determined within the central 2500 μm at the foveal level in each patient and correlation with ocular imaging findings and systemic involvement parameters was assessed through Spearman correlation analysis and Generalized Linear Models (GLM) with a robust Huber White standard error estimation.

Results

Inner retinal HRFs number showed a significant association with male gender, use of enzyme replacement therapy and presence of retinal vessel tortuosity (all p < 0.001). Severity of NHYA class and presence of cornea verticillata reached a quasi-significant association (p = 0.089 and p = 0.07, respectively). Increase of FIAOO grading was associated to increased HRFs number (p < 0.001) and increase in estimated glomerular filtration rate was inversely associated with HRFs number (p = 0.04).

Conclusions

Inner retinal HRF number correlated with organ involvement and ocular imaging findings in FD patients. They may represent a biomarker of disease severity in diagnosed patients and their presence should enhance the suspect of FD in the appropriate clinical setting.

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Fig. 1: Detection of inner retinal hyper-reflective foci in a patient with Fabry Disease.
Fig. 2: Flood-illumination Adaptive Optics Ophthalmoscopy grading in patients with Fabry Disease.
Fig. 3: Association of inner retinal hyperreflective foci and other study variables.

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Author information

Author notes

  1. These authors contributed equally: Daniela Bacherini, Stefano Mercuri.

Authors and Affiliations

  1. Department of Neurosciences, Psychology, Drug Research, and Child Health, Eye Clinic, University of Florence, AOU Careggi, 50139, Florence, Italy

    Daniela Bacherini, Stefano Mercuri, Andrea Sodi, Gianni Virgili & Fabrizio Giansanti

  2. Ophthalmology Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168, Rome, Italy

    Gloria Gambini & Stanislao Rizzo

  3. Ophthalmology Unit, Catholic University “Sacro Cuore”, 00168, Rome, Italy

    Gloria Gambini & Stanislao Rizzo

  4. Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy

    Clara Rizzo

  5. Consiglio Nazionale delle Ricerche, Istituto di Neuroscienze, Pisa, Italy

    Stanislao Rizzo

  6. Torino, Eye Clinic, 18152 ASL Torino, 10134, Turin, Italy

    Francesco Faraldi

  7. Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Florence, Italy

    Lino Cirami & Egrina Dervishi

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Contributions

Conception or design of the work: DB, SM, AS, GV, FG. Acquisition, analysis, or interpretation of data for the work: DB, SM, AS, GV, FG. Drafting the work or reviewing it critically for important intellectual content: DB, SM, AS, GG, CR, SR, FF, LC, ED, GV, FG. Final approval of the version to be published: DB, SM, AS, GG, CR, SR, FF, LC, ED, GV, FG.

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Correspondence to Stefano Mercuri.

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Bacherini, D., Mercuri, S., Sodi, A. et al. Inner retinal hyper-reflective foci number correlates with flood-illumination adaptive optics ophthalmoscopy grading and systemic organ involvement in patients with Fabry disease. Eye 39, 1578–1583 (2025). https://doi.org/10.1038/s41433-025-03721-5

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