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Selective retinal ganglion cell loss in familial dysautonomia

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Abstract

To define the retinal phenotype of subjects with familial dysautonomia (FD). A cross-sectional study was carried out in 90 subjects divided in three groups of 30 each (FD subjects, asymptomatic carriers and controls). The study was developed at the Dysautonomia Center, New York University Medical Center. All subjects underwent spectral domain optical coherence tomography (OCT) and full neuro-ophthalmic examinations. In a subset of affected subjects, visual evoked potentials and microperimetry were also obtained. We compared the retinal nerve fiber layer (RNFL) thickness from OCT between the three groups. OCT showed loss of the RNFL in all FD subjects predominantly in the maculopapillary region (63 % temporally, p < 0.0001; and 21 % nasally, p < 0.005). RNFL loss was greatest in older FD subjects and was associated with decreased visual acuity and color vision, central visual field defects, temporal optic nerve pallor, and delayed visual evoked potentials. Asymptomatic carriers of the FD gene mutation all had thinner RNFL (12 % globally, p < 0.005). OCT and clinical neuro-ophthalmological findings suggest that maculopapillary ganglion cells are primarily affected in FD subjects, leading to a specific optic nerve damage that closely resembles mitochondrial optic neuropathies. This raises the possibility that reduced IKAP levels may affect mitochondrial proteins and their function in the nervous system, particularly in the retina.

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Acknowledgments

We would like to thank all the patients and families who participated in this study. This work was supported by the Dysautonomia Foundation Inc., the National Institutes of Health (U54-NS065736-01) and The Massachusetts Lions Clubs/Research to Prevent Blindness Challenge Grant.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Dysautonomia Center, Langone Medical Center, New York University, New York, USA

    Carlos E. Mendoza-Santiesteban, Lucy Norcliffe-Kaufmann, Felicia Axelrod & Horacio Kaufmann

  2. New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA, 02111, USA

    Carlos E. Mendoza-Santiesteban & Thomas R. Hedges III

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  1. Carlos E. Mendoza-Santiesteban
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  2. Thomas R. Hedges III
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  3. Lucy Norcliffe-Kaufmann
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  4. Felicia Axelrod
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  5. Horacio Kaufmann
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Correspondence to Carlos E. Mendoza-Santiesteban.

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Mendoza-Santiesteban, C.E., Hedges III, T.R., Norcliffe-Kaufmann, L. et al. Selective retinal ganglion cell loss in familial dysautonomia. J Neurol 261, 702–709 (2014). https://doi.org/10.1007/s00415-014-7258-2

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  • DOI: https://doi.org/10.1007/s00415-014-7258-2

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