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Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings

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Abstract

Purpose

To investigate the functional and structural biomarkers and their correlation with Usher syndrome (USH).

Methods

Medical records, imaging and electrophysiology test results of USH patients attending the Save Sight Institute between 2012 and 2017 were reviewed. Best corrected visual acuity (BCVA), ultra-widefield autofluorescence (UW-FAF), spectral-domain optical coherence tomography (SD-OCT), full-field electroretinogram and pattern electroretinogram (pERG) were performed. SD-OCT scans assessed central macular thickness (CMT), greatest linear diameter of preserved outer retinal layers—macular island (MI) and presence of cystoid macular edema (CME). UW-FAF images were qualitatively graded to identify hypo/hyperfluorescence patterns in the peripheral fundus.

Results

Thirty-six eyes from 18 subjects were included. Mean BCVA was 0.22 ± 0.3 LogMAR. MI extent was significantly associated with better vision (β = − 0.175 per 1000 µm; R2 = 0.487; P = 0.002; Fig. 4). A higher pERG P50 was associated with a larger macular island (β = 782 per µV; R2 = 0.238; P = 0.025), while a higher pERG N95 was associated with a smaller macular island (β = − 499 per µV; R2 = 0.219; P = 0.030). Mean CMT was 271 ± 35 μm and was significantly associated with better vision (β = − 0.083 per 10 µm; R2 = 0.612; P < 0.001). CME was diagnosed in 47.2% (n = 17) eyes. There was no significant difference in mean BCVA for those with CME (0.19 ± 0.2 LogMAR) and without CME (0.40 ± 0.5; R2 = 0.081; P = 0.17). All patients had abnormal UW-FAF. Four main patterns of change were identified (granular 55%, annular 11%, bone spicule 17% and patchy 17%). Patients with the patchy pattern demonstrated worse BCVA in comparison with those with granular (P < 0.0001) and bone spicule (P = 0.0179) patterns.

Conclusions

Structural changes identified on OCT and UW-FAF correlated with BCVA and pERG in this cohort representing different stages of the disease. These parameters could represent reliable biomarkers in therapeutic clinical trials on USH.

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Acknowledgements

The authors would like to thank Maria Korsakova for electrophysiology testing and assessment.

Funding

This study was partly funded by National Health and Medical Research Council (NHMRC) Grants APP1116360, APP1099165, APP1109056 and Ophthalmic Research Institute of Australia (ORIA).

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Authors and Affiliations

  1. The Discipline of Clinical Ophthalmology and Eye Health, Save Sight Institute, Sydney Eye Hospital, Faculty of Medicine and Health, The University of Sydney, 8 Macquarie Street, Sydney, NSW, 2001, Australia

    Nina Mustafic, Federica Ristoldo, Vuong Nguyen, Clare L. Fraser, Alessandro Invernizzi, Robyn V. Jamieson & John R. Grigg

  2. Eye Genetics Research Unit, Children’s Medical Research Institute, The Children’s Hospital at Westmead, Save Sight Institute, University of Sydney, Sydney, NSW, Australia

    Robyn V. Jamieson & John R. Grigg

  3. Department of Biomedical and Clinical Science ‘L. Sacco’, Luigi Sacco Hospital, University of Milan, Milan, Italy

    Alessandro Invernizzi

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  1. Nina Mustafic
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Correspondence to John R. Grigg.

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Conflict of interest

Author Nina Mustafic declares that she has no conflict of interest. Author Federica Ristoldo declares that she has no conflict of interest. Author Alessandro Invernizzi, declares that he has received a grant from Allergan and a Sydney Eye Hospital foundation fellowship. Author Vuong Nguyen declares that he has no conflict of interest. Author Clare Fraser declares that she has no conflict of interest. Author Robyn Jamieson declares that she is a consultant to Novartis Australia. Author John Grigg declares that he has received a speaker honorarium from Novartis Australia and is a consultant to Novartis Australia.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Sydney Eye Hospital South East Sydney Local health District Research Ethics and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Mustafic, N., Ristoldo, F., Nguyen, V. et al. Biomarkers in Usher syndrome: ultra-widefield fundus autofluorescence and optical coherence tomography findings and their correlation with visual acuity and electrophysiology findings. Doc Ophthalmol 141, 205–215 (2020). https://doi.org/10.1007/s10633-020-09765-0

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