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Analysis of the visual system in Friedreich ataxia

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Abstract

To use optical coherence tomography (OCT) and contrast letter acuity to characterize vision loss in Friedreich ataxia (FRDA). High- and low-contrast letter acuity and neurological measures were assessed in 507 patients with FRDA. In addition, OCT was performed on 63 FRDA patients to evaluate retinal nerve fiber layer (RNFL) and macular thickness. Both OCT and acuity measures were analyzed in relation to genetic severity, neurologic function, and other disease features. High- and low-contrast letter acuity was significantly predicted by age and GAA repeat length, and highly correlated with neurological outcomes. When tested by OCT, 52.7 % of eyes (n = 110) had RNFL thickness values below the fifth percentile for age-matched controls. RNFL thickness was significantly lowest for those with worse scores on the Friedreich ataxia rating scale (FARS), worse performance measure composite Z 2 scores, and lower scores for high- and low-contrast acuity. In linear regression analysis, GAA repeat length and age independently predicted RNFL thickness. In a subcohort of participants, 21 % of eyes from adult subjects (n = 29 eyes) had macular thickness values below the first percentile for age-matched controls, suggesting that macular abnormalities can also be present in FRDA. Low-contrast acuity and RNFL thickness capture visual and neurologic function in FRDA, and reflect genetic severity and disease progression independently. This suggests that such measures are useful markers of neurologic progression in FRDA.

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Acknowledgments

This study was funded by grants awarded by the Friedreich Ataxia Research Alliance (FARA), the Muscular Dystrophy Association (MDA), and the National Eye Institute (NEI).

Conflicts of interest

This study was sponsored by the Friedreich Ataxia Research Alliance (FARA), the Muscular Dystrophy Association (MDA), and the National Eye Institute (NEI). Ms. Seyer, Ms. Galetta, Mr. Wilson, Ms. Sakai, Dr. Gomez, Dr. Ashizawa, and Dr. Bushara report no disclosures. Dr. Perlman obtains salary support from clinical billing of insurance companies for treatment patients and from several research grants- FARA/MDA subcontract grant for Clinical Outcome Measures in FA; National Ataxia Foundation (NAF); Huntingtons Disease Society of America; and the CHDI Foundation, Inc. Dr. Mathews receives research support from PTC Therapeutics as a clinical trial site. She receives research support from the CDC, the NIH, Parent Project Muscular Dystrophy (PPMD), and FARA. Dr. Wilmot receives a consultant fee from Santhera Pharmaceuticals for serving on the Data Safety Monitoring Board for trials involving the drug idebenone. He also receives grant funding from FARA. Dr. Ravina is currently employed at Biogen-Idec. Dr. Zesiewicz is supported by grants from FARA, the NAF, Pfizer, Baxter, and the Bobby Allison Ataxia Research Center. She receives funds for speaking engagements by TEVA Pharmaceuticals and GE Healthcare. Dr. Subramony is a member of the Speaker’s Bureau for Athena Diagnostics and receives honoraria for such speaking engagements. He receives research support from the NAF. Dr. Delatycki receives support from the National Health and Medical Research Council in Australia, and FARA. He has a Healthscope Pathology consultancy. Ms. Brocht receives FARA salary support. Dr. Balcer is supported by grants from the NEI, National Multiple Sclerosis Society, NIH, NINDS, DAD’s Foundation, and FARA. She also holds consultancies at Biogen-Idec, Vaccinex, and Accorda. Dr. Lynch is supported by grants from the NIH, MDA/FARA (Clinical research network in Friedreich ataxia), the Trisomy 21 program of the Children’s Hospital of Philadelphia, Penwest Pharmaceuticals, and Edison Pharmaceuticals. He is a FARA board member and holds consultancies at Apopharma and Athena Diagnostics. He also holds an NMDA receptor encephalitis patent.

Ethical standard

All protocols were approved by the Institutional Review Board at the Children’s Hospital of Philadelphia and other sites. Informed consent was obtained before participation.

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Authors and Affiliations

  1. Departments of Neurology, Ophthalmology and Epidemiology, University of Pennsylvania Medical School, Philadelphia, PA, USA

    Lauren A. Seyer, Kristin Galetta, James Wilson, Reiko Sakai, Laura J. Balcer & David R. Lynch

  2. Department of Pediatrics, University of Pennsylvania Medical School, Philadelphia, PA, USA

    Lauren A. Seyer & David R. Lynch

  3. Divisions of Neurology and Pediatrics, Children’s Hospital of Philadelphia, Abramson Research Center Room 502, Philadelphia, PA, 19104, USA

    Lauren A. Seyer & David R. Lynch

  4. Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA

    Susan Perlman

  5. Department of Neurology, University of Iowa, Iowa, IA, USA

    Katherine Mathews

  6. Department of Neurology, Emory University, Atlanta, GA, USA

    George R. Wilmot

  7. Department of Neurology, University of Chicago, Chicago, IL, USA

    Christopher M. Gomez

  8. Department of Neurology, University of Rochester, Rochester, NY, USA

    Bernard Ravina & Alicia Brocht

  9. Department of Neurology, University of South Florida, Tampa, FL, USA

    Theresa Zesiewicz

  10. Department of Neurology, University of Minnesota, Minneapolis, MN, USA

    Khalaf O. Bushara

  11. Department of Neurology, University of Florida, Gainesville, FL, USA

    S. H. Subramony & Tetsuo Ashizawa

  12. Department of Neurology, Murdoch Children’s Research Institute, Melbourne, Australia

    Martin B. Delatycki

Authors
  1. Lauren A. Seyer
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  2. Kristin Galetta
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  3. James Wilson
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  4. Reiko Sakai
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  5. Susan Perlman
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  6. Katherine Mathews
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  7. George R. Wilmot
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  8. Christopher M. Gomez
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  9. Bernard Ravina
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  10. Theresa Zesiewicz
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  11. Khalaf O. Bushara
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  12. S. H. Subramony
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  13. Tetsuo Ashizawa
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  14. Martin B. Delatycki
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  15. Alicia Brocht
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  16. Laura J. Balcer
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  17. David R. Lynch
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Corresponding author

Correspondence to Lauren A. Seyer.

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Seyer, L.A., Galetta, K., Wilson, J. et al. Analysis of the visual system in Friedreich ataxia. J Neurol 260, 2362–2369 (2013). https://doi.org/10.1007/s00415-013-6978-z

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  • DOI: https://doi.org/10.1007/s00415-013-6978-z

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