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Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH)

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Abstract

Purpose

As part of a long-term, prospective study of prenatal and clinical risk factors for optic nerve hypoplasia (ONH) at Children’s Hospital Los Angeles, pattern ERGs (PERGs) were evaluated for prognostic value using an automated objective and robust analytical method.

Methods

Participants were 33 children with ophthalmoscopically diagnosed ONH [disc diameter-to-disc macula ratio (DD/DM) less than 0.35 in one or both eyes on fundus photographs]. Using cycloplegia and chloral hydrate sedation in one session before 26 months of age, we recorded PERGs to checkerboard reversal using five check sizes. Participants were followed with clinical and psychometric testing until 5 years of age. PERGs were analysed using automated robust statistics based on magnitude-squared coherence and bootstrapping optimized to objectively quantify PERG recovery in the challenging recordings encountered in young patients. PERG measures in the fixating or better-seeing eyes were compared with visual outcome data.

Results

PERG recording was complete to at least three check sizes in all eyes and to all five sizes in 79%. Probability of recording a PERG that is significantly different from noise varied with check size from 73% for the largest checks to 30% for the smallest checks (p = 0.002); smaller waveforms were associated with earlier implicit times. The presence of significant PERGs in infancy is associated with better visual outcomes; the strongest association with visual outcome was for the threshold check size with a significant N95 component (ρ = 0.398, p = 0.02).

Conclusions

Automated statistically robust signal-processing techniques reliably and objectively detect PERGs in young children with ONH and show that congenital deficits of retinal ganglion cells are associated with diminished or non-detectable PERGs. The later negativity, N95, was the best indicator of visual prognosis and was most useful to identify those with good visual outcomes (≤0.4 LogMAR). Although PERGs reflect function of the inner layers of the central retina, they lack the specificity required to determine prognosis reliably in individual cases.

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Notes

  1. This cohort does not include any cases published by laboratory in previous studies.

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Acknowledgements

We thank the participants the clinical registry and their families.

Funding

This work is supported by One Small Voice Foundation and the Children’s Hospital Los Angeles grant UL1TR000130, from the National Center for Advancing Translational Sciences (NCATS) at the NIH. The sponsors had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. School of Optometry and Vision Sciences, University of Waterloo, Waterloo, Canada

    Daphne McCulloch

  2. Vision Sciences, Glasgow Caledonian University, Glasgow, Scotland, UK

    Daphne McCulloch

  3. The Vision Center at Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Pamela Garcia-Filion, Cassandra Fink & Mark S. Borchert

  4. Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, UK

    Anthony C. Fisher & Antonio Eleuteri

Authors
  1. Daphne McCulloch
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  2. Pamela Garcia-Filion
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  3. Cassandra Fink
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  4. Anthony C. Fisher
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  5. Antonio Eleuteri
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  6. Mark S. Borchert
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Corresponding author

Correspondence to Daphne McCulloch.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony, or patent-licensing arrangements), or conflicting non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. The article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from parents or legal guardians for all individual participants included in the study.

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McCulloch, D., Garcia-Filion, P., Fink, C. et al. Predictive value of N95 waveforms of pattern electroretinograms (PERGs) in children with optic nerve hypoplasia (ONH). Doc Ophthalmol 135, 97–106 (2017). https://doi.org/10.1007/s10633-017-9603-0

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  • DOI: https://doi.org/10.1007/s10633-017-9603-0

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