The intersubject CVs of the peak times and amplitudes did not differ when the parameters were grouped by side or by higher and lower values for both the PERG and the PVEPs (Tables 1, 2). Mean (±SD); CV; 5, 25, 50 (median); 75 and 95 percentiles; and maximum values of percentage differences are shown in Table 3.
For the PVEP P100 and PERG P50 peak times, the maximum percentage interocular differences were less than 7%. The percentage side differences of the PERG P50 and N95 and the PVEP P100 and N135 amplitudes were as high as 50%, but in more than 95% of the cases (regarded as a cutoff point), the interocular amplitude differences were less than 30.5%. The latter can be used as the threshold of the normal interocular difference in clinical practice. The usefulness of interocular differences is supported by its lower variability than that of the monocular responses (Table 4).
The lateral correspondence of the longer and shorter peak times of P50 and P100 with the χ2 test was 0.015 (p = 0.9), and the power of the test was 0.049. The differences in the PERG and PVEP amplitudes of right and left eyes were not related. For the PERG P50 and PVEP P100 amplitudes, the χ2 value was 0.008 (p = 0.93), with the power of the test 0.048; whereas for the PERG P50 and PVEP N135 amplitudes, the χ2 value was 0.236 (p = 0.63), with the power of the test 0.073. For the PERG N95 and PVEP P100 amplitudes, the χ2 value was 0.686 (p = 0.41), with the power of the test 0.122; and for the PERG N95 and PVEP P100 amplitudes, the χ2 value was less than 0.001 (p = 0.98), with the power of the test 0.047.
Determination of the interocular differences in the PERG and PVEP parameters in normal subjects may be useful in the evaluation of monocular macular pathologies or asymmetric macular ganglion cell or optic nerve diseases. Clinically, PERG can be used in a patient with an abnormal VEP to establish whether a retinal (macular) disorder is present and, therefore, to differentiate between a macular and an optic nerve dysfunction as a cause of the VEP abnormality. It can also directly demonstrate retinal ganglion cell dysfunction.2 In the event of a high interocular difference, the side difference may be interpreted as abnormal.
Previous histological and imaging studies revealed an interocular difference as high as 8% in the foveolar cone density.12 Asymmetry in macular thickness was detected by optical coherence tomography as 6.4 ± 14.7 μm (average foveal thickness, 207 ± 24 μm vs. 200 ± 23 μm).13 With regard to the normal retinal nerve fiber layer thickness measured by optical coherence tomography, the side difference was approximately 9 to 12 μm, depending on the scanning algorithm applied.14 These data may explain the visual acuity differences determined by psychophysical methods and the PERG and PVEP amplitude differences.
The retinal blood flow of the macula has been shown to display no interocular difference in the absence of light stimulation of the eyes.15,16 We found no previously published studies involving light stimulation. A recent article on hemispheric asymmetry from the aspect of lateralization of the visual evoked response revealed a general dominance of the right occipital lobe in the visual process. In addition, functional transcranial Doppler demonstrated a higher blood flow velocity in the right posterior cerebral arteries in response to white light stimuli.17
The occipital blood flow (visual evoked flow responses) was found to correlate with the VEP N145 amplitude of the PVEP on hemifield visual stimulation and showed a side difference.18 In this study, there was a tendency to an increase in the N145 amplitude on the dominant side in young subjects.
Other groups have shown that pattern stimulation can cause amplitude and latency disparities of VEP between the dominant and nondominant eyes, providing electrophysiological evidence of lateralization in the nervous system at a cortical level.19 The PERG side difference was independent of the eye dominance.20 Our study was not aimed at finding dependences on eye dominance.
An interocular difference of the full-field ERG was described earlier.21 In 95% of that cohort, the interocular difference in the five standard ISCEV stimuli was in the range 27 to 36%, which is similar to the interocular difference of the PERG and PVEP parameters in our study (the amplitude difference was approximately 30%). We have previously reported an interocular difference of multifocal ERG of 21.55% on binocular stimulation and of 18.69% on monocular stimulation.22
Our present study revealed interocular side differences in both the PERG and PVEP parameters. If retinal anatomical differences were responsible for the lateralization, for example, differences in retinal ganglion cell density and the corresponding area of the visual cortex, the PERG and PVEP parameters would correlate, or the side correspondence would be higher. These two examinations test the consecutive elements of the visual pathway. If the PERG of one eye is influenced by a pathological or anatomical cause, the subsequent PVEP on stimulation of the same eye would be influenced in a similar way. The side differences we observed are therefore presumed to be independent of the electrophysiological method used and to be attributable to normal variability.
It is possible that artifacts, such as biological or technical noise, may contribute to side differences. Although it was beyond the scope of this report, biological noise could be examined by the repeated testing of subjects on separate visits. Technical noise could be caused by differences in electrode characteristics or amplifier characteristics. This possibility could be assessed by reversing the electrodes and recording channels between the eyes on retesting within a session. We used the same electrodes as in the daily routine, in which such technical noise is not observed (unpublished data). On the other hand, for PVEPs, the electrodes were placed in the midline, and technical noise was therefore unlikely to cause any side difference.
On determination of the normative values, an interocular difference should be considered regardless of its cause. If the differences previously described are neglected, misinterpretation of the results might occur in the event of the existence of some monocular pathology.
Department of Ophthalmology
Albert Szent-Györgyi Clinical Center
University of Szeged
H-6720, Szeged Korányi Fasor 10-11
This study was supported by grant K83810 OTKA/Hungary.
We thank Dr. Goran Petrovski and David Durham for proofreading this manuscript. We are also grateful to Ms. Kati Majer for her kind technical help.
Received June 8, 2013; accepted December 12, 2013.
1. Holder GE. Pattern electroretinography (PERG) and an integrated approach to visual pathway diagnosis. Prog Retin Eye Res 2001; 20: 531–61.
2. Holder GE, Brigell MG, Hawlina M, Meigen T, Vaegan, Bach M. ISCEV standard for clinical pattern electroretinography—2007 update. Doc Ophthalmol 2007; 114: 111–6.
3. Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, Vaega. Visual evoked potentials standard (2004). Doc Ophthalmol 2004; 108: 115–23.
4. Froehlich J, Kaufman DI. Improving the reliability of pattern electroretinogram recording. Electroencephalogr Clin Neurophysiol 1992; 84: 394–9.
5. Jacobi PC, Walter P, Brunner R, Krieglstein GK. Reproducibility and intraindividual variability of the pattern electroretinogram. Ger J Ophthalmol 1994; 3: 216–9.
6. Shors TJ, Ary JP, Eriksen KJ, Wright KW. P100 amplitude variability of the pattern visual evoked potential. Electroencephalogr Clin Neurophysiol 1986; 65: 316–9.
7. Abe Y, Kuroiwa Y. Amplitude asymmetry of hemifield pattern reversal VEPs in healthy subjects. Electroencephalogr Clin Neurophysiol 1990; 77: 81–5.
8. Mellow TB, Liasis A, Lyons R, Thompson D. When do asymmetrical full-field pattern reversal visual evoked potentials indicate visual pathway dysfunction in children? Doc Ophthalmol 2011; 122: 9–18.
9. Nightingale S, Mitchell KW, Howe JW. Visual evoked cortical potentials and pattern electroretinograms in Parkinson’s disease and control subjects. J Neurol Neurosurg Psychiatry 1986; 49: 1280–7.
10. Porciatti V, Ventura LM. Normative data for a user-friendly paradigm for pattern electroretinogram recording. Ophthalmology 2004; 111: 161–8.
11. Vaegan, Anderton PJ, Millar TJ. Multifocal, pattern and full field electroretinograms in cats with unilateral optic nerve section. Doc Ophthalmol 2000; 100: 207–29.
12. Curcio CA, Sloan KR, Kalina RE, Hendrickson AE. Human photoreceptor topography. J Comp Neurol 1990; 292: 497–523.
13. El-Ashry M, Hegde V, James P, Pagliarini S. Analysis of macular thickness in British population using optical coherence tomography (OCT): an emphasis on interocular symmetry. Curr Eye Res 2008; 33: 693–9.
14. Budenz DL. Symmetry between the right and left eyes of the normal retinal nerve fiber layer measured with optical coherence tomography (an AOS thesis). Trans Am Ophthalmol Soc 2008; 106: 252–75.
15. Kimura I, Shinoda K, Tanino T, Ohtake Y, Mashima Y, Oguchi Y. Scanning laser Doppler flowmeter study of retinal blood flow in macular area of healthy volunteers. Br J Ophthalmol 2003; 87: 1469–73.
16. Rawji MH, Flanagan JG. Intraocular and interocular symmetry in normal retinal capillary perfusion. J Glaucoma 2001; 10: 4–12.
17. Roje-Bedeković M, Lovrenčić-Huzjan A, Bosnar-Puretić M, Serić V, Demarin V. Hemispheric asymmetry of visual cortical response by means of functional transcranial Doppler. Stroke Res Treat 2012; 2012: 615406.
18. Topcuoglu MA, Aydin H, Saka E. Occipital cortex activation studied with simultaneous recordings of functional transcranial Doppler ultrasound (fTCD) and visual evoked potential (VEP) in cognitively normal human subjects: effect of healthy aging. Neurosci Lett 2009; 452: 17–22.
19. Seyal M, Sato S, White BG, Porter RJ. Visual evoked potentials and eye dominance. Electroencephalogr Clin Neurophysiol 1981; 52: 424–8.
20. Kamis U, Gunduz K, Okudan N, Gokbel H, Bodur S, Tan U. Relationship between eye dominance and pattern electroretinograms in normal human subjects. Int J Neurosci 2005; 115: 185–92.
21. Rotenstreich Y, Fishman GA, Anderson RJ, Birch DG. Interocular amplitude differences of the full field electroretinogram in normal subjects. Br J Ophthalmol 2003; 87: 1268–71.
22. Palffy A, Janaky M, Fejes I, Horvath G, Benedek G. Interocular amplitude differences of multifocal electroretinograms obtained under monocular and binocular stimulation conditions. Acta Physiol Hung 2010; 97: 326–31.
Keywords:© 2014 American Academy of Optometry
pattern electroretinography; visual evoked potential; interocular difference