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Investigative Ophthalmology & Visual Science, Vol. 29, No. 7, July 1988 Copyright © Association for Research in Vision and Ophthalmology Normal Visual Pathway Routing in Dissociated Vertical Deviation Christine Boylan,* Richard Anthony Clement,* and Anne Howrief Flash visually evoked cortical potentials have been recorded in three groups of age- and sex-matched subjects; one comprised of subjects with dissociated vertical deviation, one comprised of subjects with oculocutaneous albinism and one group of controls. The latency of the major positive (P2) component did not show statistically significant contralateral lateralization on monocular stimulation in either the dissociated vertical deviation group or the control group. Contralateral lateralization was found in the albino group at a statistically significant level (P < 0.01). It is concluded that subjects with dissociated vertical deviation do not possess the typical albino optic pathway misrouting that has been reported. Invest Ophthalmol Vis Sci 29:1165-1167,1988 The visual system of albinos is characterized by a misrouting of optic nerve fibers. Somefibersfrom the temporal retina are misrouted at the chiasma and cross over to terminate in the contralateral rather than the ipsilateral hemisphere. This has been shown anatomically1 and electrophysiologically when the visually evoked cortical potential (VECP) shows contralateral lateralization on monocular stimulation.2"8 Recent VECP studies using half-field pattern reversal stimulation in subjects with dissociated vertical deviation (DVD) have concluded that these individuals possess the albino-type misrouting,910 although there is no anatomical confirmation of such a defect. Albino-type misrouting can be demonstrated with full-field stimulation using a simple flash stimulus. In albinos, monocular responses show contralateral lateralization of the major positive component at a statistically significant level; the latency is shorter over the hemisphere contralateral to the eye stimulated.7 To investigate the possibility of misrouting in subjects with DVD a study was undertaken with the method already used successfully in albinos.7'8 months. One had an exotropia first noticed at 18 months of age. The optokinetic responses had been tested in four of the subjects. Three showed a definite abnormal uniocular response when the drum was rotated in a nasotemporal direction, and one subject had a reduced response. Flash VECPS were recorded from Ol (left hemisphere) and O2 (right hemisphere) referred to C3 and C4 respectively (10/20 system11). Flash stimulation was provided by a Grass PS22 photostimulator (Grass, Quincy, MA) at setting 2 (1363 nits) with a flash rate of 1.8 per second. The initial 500 msec of the responses to 50flasheswere averaged by a Nicolet Pathfinder II (Nicolet, Madison, WI), bandpass 0.5-30 Hz. Binocular and monocular responses were recorded; care was taken to ensure complete occlusion of the nonstimulated eye. For comparison, two other groups of age- and sex-matched subjects were examined under identical conditions. One group consisted of five control subjects with normal visual acuities (6/6 or better) and no known ophthalmologic or neurologic defects, and one group consisted of five oculocutaneous albinos. Informed consent to undertake examination was obtained in all cases from the subjects and their parents prior to the study. Materials and Methods Five subjects with DVD ranging in age from 6-14 (mean 9.8) years were examined. Four had esotropia, three with onset from birth and one with onset at 4 Results The DVD group showed the typical flash VECP waveform. The major component was a positive component at around 110 msec (P2) preceded by Nl and PI components. The responses recorded from one subject are shown in Figure 1. In common with the previous study7 the P1-N2 and N2-P2 peak to peak amplitudes and the PI, N2 and P2 latencies were measured over both hemispheres on monocular and binocular stimulation in each subject of the three From the *Department of Vision Sciences, University of Aston, and the tOrthoptic Department, Birmingham and Midland Eye Hospital, Birmingham, United Kingdom. Submitted for publication: November 2, 1987; accepted December 17, 1987. Reprint requests: Dr. C. Boylan, Department of Vision Sciences, University of Aston, Aston Triangle, Birmingham, B4 7ET, England. 1165 Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933371/ on 05/12/2017 1166 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / July 1988 groups. Two-way analysis of variance was carried out using the hemisphere as one treatment and the stimulation condition (binocular, right or left eye) as the Binocular Vol. 29 DVD group 116 114 112 110 108 106 104 102 100 RE BIN H Right hemisphere 0 Left hemisphere \S Right hemisphere © Left hemisphere H Right hemisphere LE 02-C4 Control group 116 114 112 110 108 106 104 102 100 01 -C3 RE BIN LE Albmo group 100 msec 116-| 114 112110108106104102100- >P 12] Left hemisphere r • RE BIN LE Fig. 2. Graphic illustration of the results of two-way analysis of variance of the P2 latency data in the DVD, control and albino groups. There is no significant interaction effect in the control or DVD groups. There is a significant interaction effect in the albinos (P < 0.01). P2 has a shorter latency over the hemisphere contralateral to the eye stimulated. RE = right eye, LE = left eye, BIN = binocular. 01 -C3 Left eye 02-C4 01 -C3 second. The albino group showed a significant interaction effect for the latency of the P2 component, the latency being shorter over the hemisphere contralateral to the eye stimulated (F2,8 = 16.385, P < 0.01). There was no significant interaction effect for any of the measured variables in either the control group or the DVD group. A comparison of the interaction effects of the P2 latencies in the three groups is shown in Figure 2. Discussion Fig. 1. TheflashVECPs recorded from the two.hemispheres of a subject with DVD, on binocular and monocular stimulation. The responses illustrate the noise-free nature of the recordings obtained and show the typical flash VECP waveform of a major positive component (P2) preceded by Nl and PI components. The DVD group examined did not show the VECP lateralization that is characteristic of albino-type misrouting as confirmed in this and a previous study.7 The lateralization on monocular stimulation in the DVD group did not differ from that found Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933371/ on 05/12/2017 VISUAL PATHWAY IN DVD / Boy Ian er ol. No. 7 within an age- and sex-matched control group. The responses recorded from the DVD group had the usual flash VECP waveform, latencies and amplitudes and were not delayed as reported for the pattern reversal response.910 Without further anatomical evidence to the contrary, we conclude that misrouting does not occur in subjects with DVD. This finding of normal optic projections in DVD is in contrast to previous results910 and may be because of the following reasons. On methodological grounds, the most direct test of albino-type misrouting involves monocular full-field stimulation rather than half-field stimulation.4"6 Because of the gross asymmetry in the cortical projections, a clear lateralization of the VECP is observed when stimulation is swapped from one eye to the other. The use of full-field stimulation avoids the need to interpret the lateralization that occurs with half-field stimulation in terms of the "paradoxical" lateralization that occurs in normal subjects.12 On technical grounds, the pattern reversal VECP is not the appropriate technique for revealing misrouting; the nystagmus present with albinism has been shown to result in very poor responses.4"6 Finally, previous studies of DVD subjects910 described lateralization of the amplitude of the PI00 component but did not give any statistical analysis of the results. In many of the albinos studied here and previously,7 individual traces did show amplitude lateralization but, due to the inherent variability of the VECP amplitude, the lateralization was not statistically significant. Although the neural misrouting found in albinos is an exciting discovery, one must proceed with caution when hypothesizing the existence of this misrouting in other conditions. It was shown early on that misrouting is not associated with congenital squint.13 At present, it appears that the type of misrouting found in albinos is specifically linked to a lack of melanin in the retinal pigment epithelium.14"16 Key words: dissociated vertical deviation, visually evoked cortical potential, oculocutaneous albinism, misrouting Acknowledgments The authors would like to thank Paul Furlong and Vivica Van der Vliet for their technical assistance and the orthop- 1167 tists and consultant ophthalmologists at the Birmingham and Midland Eye Hospital for arranging for us to see the subjects. References 1. Guillery RW, Okoro AN, and Witkop CJ: Abnormal visual pathways in the brain of a human albino. Brain Res 96:373, 1975. 2. Creel D, Witkop CJ, and King RA: Asymmetric visually evoked potentials in human albinos: Evidence for visual system anomalies. Invest Ophthalmol 6:430, 1974. 3. Creel D, O'Donnell FE, and Witkop CJ: Visual system anomalies in human ocular albinos. Science 201:931, 1978. 4. Creel D, Spekreijse H, and Reits D: Visual evoked potential (VEP) methods of detecting misrouted optic projections. Doc Ophthalmol Proc Ser 27:157, 1981. 5. Creel D, Spekreijse H, and Reits D: Evoked potentials in albinos: Efficacy of pattern stimuli in detecting misrouted fibers. Electroencephalogr Clin Neurophysiol 52:595, 1981. 6. Apkarian P, Reits D, Spekreijse H, and van Dorp D: A decisive electrophysiological test for human albinism. Electroencephalogr Clin Neurophysiol 55:513, 1983. 7. Boylan C, Clement RA, and Harding GFA: Lateralization of the flash visual-evoked potential in human albinos. Invest Ophthalmol Vis Sci 25:1448, 1984. 8. Boylan C, Clement RA, and Harding GFA: Lateralisation of the flash visually evoked cortical potential in albino babies. Electroencephalogr Clin Neurophysiol 60:500, 1985. 9. Fitzgerald A: Evidence of abnormal optic nerve fibre projections in patients with dissociated vertical deviation (DVD)—a preliminary report. Australian Orthop J 20:23, 1983. 10. Fitzgerald A and Billson FA: Dissociated vertical deviation: Evidence of abnormal visual pathway projection. Br J Ophthalmol 68:801, 1984. 11. Jasper HH: Report of the committee on methods of clinical examination in electroencephalography. Electroencephalogr Clin Neurophysiol 10:370, 1958. 12. Barrett G, Blumhardt L, Halliday AM, and Kriss A: A paradox in the lateralisation of the visual evoked response. Nature 261:253, 1976. 13. McCormack GL: Electrophysiological evidence for normal optic nerve fiber projection in normally pigmented squinters. Invest Ophthalmol 14:931, 1975. 14. Silver J and Sapiro J: Axonal guidance during development of the optic nerve: The role of pigmented epithelia and other extrinsic factors. J Comp Neurol 202:521, 1981. 15. Witkop CJ, Jay B, Creel D, and Guillery RW: Optic and otic abnormalities in oculocutaneous and ocular albinism. Birth Defects 18:299, 1982. 16. Creel DJ, Bendel CM, Wiesner GL, Wirtschafter JD, Arthur DC, and King RA: Abnormalities of the central visual pathways in Prader-Willi syndrome associated with hypopigmentation. New Engl J Med 314:1606, 1986. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933371/ on 05/12/2017