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Documenta Ophthalmologica
Published in: Documenta Ophthalmologica 3/2016

01-12-2016 | Original Research Article

VEP analysis methods in children with optic nerve hypoplasia: relationship to visual acuity and optic disc diameter

Authors: John P. Kelly, James O. Phillips, Avery H. Weiss

Published in: Documenta Ophthalmologica | Issue 3/2016

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Abstract

Purpose

Assessing vision in young children with optic nerve hypoplasia (ONH) is challenging due to multi-directional infantile nystagmus, the range of optic nerve loss, and cognitive delay. This study examined visual evoked potential (VEP) responses and averaging techniques in children with ONH. The assumption is that EEG epochs with inconsistent temporal phase would be associated with nystagmus, signal reduction due to axon loss, and visual inattention.

Methods

A retrospective chart review was performed on 44 children (average age 2.2 years; SD 1.9). Optic disc diameter was estimated by ophthalmoscopy. Visual function was measured under binocular viewing and then compared to the eye with the larger optic disc to exclude secondary amblyopia. Visual acuity was measured by Teller cards or by recognition optotypes, and both measures were converted into log minimum angle of resolution (logMAR). VEPs were recorded to onset/offset of horizontal gratings and to reversing checkerboards. Signal-to-noise ratios (SNRs) were estimated from phase consistency across epochs in the Fourier domain. VEPs were also averaged after (1) correction of epochs for phase shifts across a limited bandwidth, or (2) selection of only epochs showing phase consistency.

Results

Optic disc diameter, logMAR, VEP amplitudes, and VEP SNR were all significantly inter-correlated. Optic disc diameter correlated best with VEP SNR (Spearman rho = 0.82; p < 0.001). Age-corrected logMAR correlated with optic disc diameter and VEP SNR (Spearman rho = −0.695 and 0.70, respectively; p < 0.001). VEP latency poorly correlated with optic disc diameter or logMAR. Correction of phase shifts or selection of epochs based on phase consistency significantly increased VEP amplitude and SNR for children with optic disc diameters <1000 microns. Correction of phase inconsistency did not improve the correlation of VEP parameters with optic disc diameter or with logMAR.

Conclusions

In ONH, the size of the optic nerve is correlated with VEP SNR and logMAR. The results imply a direct relationship between the reduction in optic nerve axons and generalized reduction in visual function. Our calculation of VEP SNR provides objective assessment of optic nerve function that is independent of subjective scoring of VEP peaks.
Appendix
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Literature
1.
Hatton D, Schwietz E, Boyer B, Rychwalski P (2007) Babies count: the national registry for children with visual impairments, birth to 3 years. J AAPOS 11:351–355CrossRefPubMed
2.
Walton DS, Robb RM (1970) Optic nerve hypoplasia: a report of 20 cases. Arch Ophthalmol 84:572–578CrossRefPubMed
3.
4.
Skarf B, Hoyt CS (1984) Optic nerve hypoplasia in children. Association with anomalies of the endocrine and CNS. Arch Ophthalmol 102:62–67CrossRefPubMed
5.
Hellstrom A, Wiklund LM, Svensson E (1999) The clinical and morphologic spectrum of optic nerve hypoplasia. J AAPOS 3:212–220CrossRefPubMed
6.
Taylor D (2007) Developmental abnormalities of the optic nerve and chiasm. Eye (Lond) 21:1271–1284CrossRef
7.
Fink C, Vedin AM, Garcia-Filion P, Ma NS, Geffner ME, Borchert M (2012) Newborn thyroid-stimulating hormone in children with optic nerve hypoplasia: associations with hypothyroidism and vision. J AAPOS 16:418–423CrossRefPubMedPubMedCentral
8.
Provis JM, Van Driel D, Billson FA, Russel P (1985) Human fetal optic nerve: overproduction and elimination of retinal axons during development. J Comp Neurol 238:92–100CrossRefPubMed
9.
10.
Hoyt CS, Good WV (1992) Do we really understand the difference between optic nerve hypoplasia and atrophy? Eye 6:201–204CrossRefPubMed
11.
Garcia-Filion P, Borchert M (2013) Optic nerve hypoplasia syndrome: a review of the epidemiology and clinical associations. Curr Treat Options Neurol 15:78–89CrossRefPubMedPubMedCentral
12.
Brennan D, Giles S (2014) Ocular involvement in fetal alcohol spectrum disorder: a review. Curr Pharm Des 20:5377–5387CrossRefPubMed
13.
Thomas PQ, Dattani MT, Brickman JM et al (2001) Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet 10:39–45CrossRefPubMed
14.
Yang Z, Ding K, Pan L, Deng M, Gan L (2003) Math5 determines the competence state of retinal ganglion cell progenitors. Dev Biol 2003(264):240–254CrossRef
15.
Bejarano-Escobar R, Álvarez-Hernán G, Morona R, González A, Martín-Partido G, Francisco-Morcillo J (2015) Expression and function of the LIM-homeodomain transcription factor Islet-1 in the developing and mature vertebrate retina. Exp Eye Res 138:22–31CrossRefPubMed
16.
Samuel A, Rubinstein AM, Azar TT, Ben-Moshe Livne Z, Kim SH, Inbal A (2016) Six3 regulates optic nerve development via multiple mechanisms. Sci Rep 6:20267CrossRefPubMedPubMedCentral
17.
Macgregor S, Hewitt AW, Hysi PG et al (2010) Genome-wide association identifies ATOH7 as a major gene determining human optic disc size. Hum Mol Genet 19:2716–2724CrossRefPubMedPubMedCentral
18.
Khor CC, Ramdas WD, Vithana EN et al (2011) Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area. Hum Mol Genet 20:1864–1872CrossRefPubMed
19.
Springelkamp H, Mishra A, Hysi PG et al (2015) Meta-analysis of genome-wide association studies identifies novel loci associated with optic disc morphology. Genet Epidemiol 39:207–216CrossRefPubMedPubMedCentral
20.
Sprague JB, Wilson WB (1981) Electrophysiologic findings in bilateral optic nerve hypoplasia. Arch Ophthalmol 99:1028–1029CrossRefPubMed
21.
Borchert M, McCulloch D, Rother C, Stout AU (1995) Clinical assessment, optic disk measurements, and visual-evoked potential in optic nerve hypoplasia. Am J Ophthalmol 120:605–612CrossRefPubMed
22.
Weiss AH, Kelly JP (2003) Acuity, ophthalmoscopy, and visually evoked potentials in the prediction of visual outcome in infants with bilateral optic nerve hypoplasia. J AAPOS 7:108–115CrossRefPubMed
23.
McCulloch DL, Garcia-Filion P, Fink C, Chaplin CA, Borchert MS (2010) Clinical electrophysiology and visual outcome in optic nerve hypoplasia (ONH). Br J Ophthalmol 94:1017–1023CrossRefPubMed
24.
Odom JV, Bach M, Brigell M, Holder GE, McCulloch DL, Mizota A, Tormene AP (2016) ISCEV standard for clinical visual evoked potentials: (2016 update. Doc Ophthalmol 133:1–9CrossRefPubMed
25.
Weiss AH, Kelly JP, Phillips JO (2011) Relationship of slow-phase velocity to visual acuity in infantile nystagmus associated with albinism. J AAPOS 15:33–39CrossRefPubMed
26.
Arlt A, Zangemeister WH (1990) Influence of slow eye movements and nystagmus on pattern induced visual evoked potentials. Neuro-Ophthalmology 10:241–251CrossRef
27.
Saunders KJ, Brown G, McCulloch DL (1998) Pattern-onset visual evoked potentials: more useful than reversal for patients with nystagmus. Doc Ophthalmol 94:265–274CrossRef
28.
Hoffmann MB, Seufert PS, Bach M (2004) Simulated nystagmus suppresses pattern-reversal but not pattern-onset visual evoked potentials. Clin Neurophysiol 115:2659–2665CrossRefPubMed
29.
Kuba M, Kubova Z, Kremláček J, Langrova J (2007) Motion-onset VEPs: characteristics, methods, and diagnostic use. Vis Res 47:189–202CrossRefPubMed
30.
Gur M, Beylin A, Snodderly DM (1997) Response variability of neurons in primary visual cortex (V1) of alert monkeys. J Neurosci 17:2914–2920PubMed
31.
Thornton ARD (2008) Evaluation of a technique to measure latency jitter in event-related potentials. J Neurosci Methods 168:248–255CrossRefPubMed
32.
Kremláček J, Hulan M, Kuba M, Kubová Z, Langrová J, Vít F, Szanyi J (2012) Role of latency jittering correction in motion-onset VEP amplitude decay during prolonged visual stimulation. Doc Ophthalmol 124:211–223CrossRefPubMed
33.
Kelly JP, Darvas F, Weiss AH (2014) Waveform variance and latency jitter of the visual evoked potential in childhood. Doc Ophthalmol 128:1–12CrossRefPubMed
34.
Kelly JP, Crognale MA, Weiss AH (2003) ERGs, cone-isolating VEPs and analytical techniques in children with cone dysfunction syndromes. Doc Ophthalmol 106:289–304CrossRefPubMed
35.
Mezer E, Bahir Y, Leibu R, Perlman I (2004) Effect of defocusing and of distracted attention upon recordings of the visual evoked potential. Doc Ophthalmol 109:229–238CrossRefPubMed
36.
Jonas JB, Schmidt AM, Muller-Bergh JA, Schlötzer-Schrehardt UM, Naumann GO (1992) Human optic nerve fiber count and optic disc size. Invest Ophthalmol Vis Sci 33:2012–2018PubMed
37.
Quigley HA, Coleman AL, Dorman-Pease ME (1991) Larger optic nerve heads have more nerve fibers in normal monkey eyes. Arch Ophthalmol 109:1441–1443CrossRefPubMed
38.
Saadati HG, Hsu HY, Heller KB, Sadun AA (1998) A histopathologic and morphometric differentiation of nerves in optic nerve hypoplasia and Leber hereditary optic neuropathy. Arch Ophthalmol 116:911–916CrossRefPubMed
Metadata
Title
VEP analysis methods in children with optic nerve hypoplasia: relationship to visual acuity and optic disc diameter
Authors
John P. Kelly
James O. Phillips
Avery H. Weiss
Publication date
01-12-2016
Publisher
Springer Berlin Heidelberg
Published in
Documenta Ophthalmologica / Issue 3/2016
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-016-9566-6