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.
Similar content being viewed by others
References
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 11:351–355
Walton DS, Robb RM (1970) Optic nerve hypoplasia: a report of 20 cases. Arch Ophthalmol 84:572–578
Frisen L, Holmegaard L (1978) Spectrum of optic nerve hypoplasia. Br J Ophthalmol 62:7–15
Skarf B, Hoyt CS (1984) Optic nerve hypoplasia in children. Association with anomalies of the endocrine and CNS. Arch Ophthalmol 102:62–67
Hellstrom A, Wiklund LM, Svensson E (1999) The clinical and morphologic spectrum of optic nerve hypoplasia. J AAPOS 3:212–220
Taylor D (2007) Developmental abnormalities of the optic nerve and chiasm. Eye (Lond) 21:1271–1284
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 16:418–423
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 238:92–100
Zeki SM, Dutton GN (1990) Optic nerve hypoplasia in children. Br J Ophthalmol 74:300–304
Hoyt CS, Good WV (1992) Do we really understand the difference between optic nerve hypoplasia and atrophy? Eye 6:201–204
Garcia-Filion P, Borchert M (2013) Optic nerve hypoplasia syndrome: a review of the epidemiology and clinical associations. Curr Treat Options Neurol 15:78–89
Brennan D, Giles S (2014) Ocular involvement in fetal alcohol spectrum disorder: a review. Curr Pharm Des 20:5377–5387
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 10:39–45
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):240–254
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 138:22–31
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 6:20267
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 19:2716–2724
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 20:1864–1872
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 39:207–216
Sprague JB, Wilson WB (1981) Electrophysiologic findings in bilateral optic nerve hypoplasia. Arch Ophthalmol 99:1028–1029
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 120:605–612
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 7:108–115
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 94:1017–1023
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 133:1–9
Weiss AH, Kelly JP, Phillips JO (2011) Relationship of slow-phase velocity to visual acuity in infantile nystagmus associated with albinism. J AAPOS 15:33–39
Arlt A, Zangemeister WH (1990) Influence of slow eye movements and nystagmus on pattern induced visual evoked potentials. Neuro-Ophthalmology 10:241–251
Saunders KJ, Brown G, McCulloch DL (1998) Pattern-onset visual evoked potentials: more useful than reversal for patients with nystagmus. Doc Ophthalmol 94:265–274
Hoffmann MB, Seufert PS, Bach M (2004) Simulated nystagmus suppresses pattern-reversal but not pattern-onset visual evoked potentials. Clin Neurophysiol 115:2659–2665
Kuba M, Kubova Z, Kremláček J, Langrova J (2007) Motion-onset VEPs: characteristics, methods, and diagnostic use. Vis Res 47:189–202
Gur M, Beylin A, Snodderly DM (1997) Response variability of neurons in primary visual cortex (V1) of alert monkeys. J Neurosci 17:2914–2920
Thornton ARD (2008) Evaluation of a technique to measure latency jitter in event-related potentials. J Neurosci Methods 168:248–255
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 124:211–223
Kelly JP, Darvas F, Weiss AH (2014) Waveform variance and latency jitter of the visual evoked potential in childhood. Doc Ophthalmol 128:1–12
Kelly JP, Crognale MA, Weiss AH (2003) ERGs, cone-isolating VEPs and analytical techniques in children with cone dysfunction syndromes. Doc Ophthalmol 106:289–304
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 109:229–238
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 33:2012–2018
Quigley HA, Coleman AL, Dorman-Pease ME (1991) Larger optic nerve heads have more nerve fibers in normal monkey eyes. Arch Ophthalmol 109:1441–1443
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 116:911–916
Funding
The Peter LeHaye, Barbara Anderson, and William O. Rogers Endowment Funds provided financial support in the form of an unrestricted grant. The sponsor had no role in the design or conduct of this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
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 or comparable ethical standards.
Informed consent
For this type of study formal consent is not required.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Kelly, J.P., Phillips, J.O. & Weiss, A.H. VEP analysis methods in children with optic nerve hypoplasia: relationship to visual acuity and optic disc diameter. Doc Ophthalmol 133, 159–169 (2016). https://doi.org/10.1007/s10633-016-9566-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10633-016-9566-6