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Investigative Ophthalmology & Visual Science, Vol. 32, No. 9, August 1991 Copyright © Association for Research in Vision and Ophthalmology VEP Projections in Congenital Nystogmus; VEP Asymmetry in Albinism: A Comporison Study Patricia Apkarian* and Josephine Shallo-Hoffmannf Visual evoked potential (VEP) asymmetry in which a preponderance of nasal and temporal retina afferents project to the contralateral hemisphere after full-field monocular stimulation is considered specific to albinism. Some reports, however, suggest that patients with congenital nystagmus (CN) share the albino-like visual pathway anomaly. To examine the clinical specificity of albino misrouting, VEP topography was assessed in ten patients with congenital nystagmus and in ten age-matched albino patients. As an additional control, the VEP response profiles from eight albino patients with no nystagmus were also evaluated. The results are definitive; VEP contralateral asymmetry reflecting temporal retinal misprojection is evinced only in albino patients. Furthermore, ocular-motor instabilities in CN cannot be readily attributed to albino-type misrouted retinal-cortical projections. Invest Ophthalmpl Vis Sci 32:2653-2661,1991 Visual evoked potential (VEP) asymmetry in which the potential distribution across the occiput lateralizes to the left hemisphere after full-field right-eye stimulation and to the right hemisphere after left-eye stimulation, is generally considered to be an obligate characteristic in albinism.1-2 Iris diaphany, foveal and macular hypoplasia, fundus hypopigmentation, high refractive errors, strabismus, nystagmus, and reduced visual acuity are also characteristic,3'4 although nonspecific, albino features. The frequent absence of one or more of these ophthalmic symptoms (with the exception of foveal hypoplasia), is common to the albino condition.3"5 The phenotypic variability of the ocular anomalies that are associated with albinism and their concomitant lack of specificity frequently hamper diagnosis since the classic oculocutaneous albino, devoid of hair and skin pigmentation, typically constitutes, contrary to popular opinion, the less prevalent of albino phenotypes in most nonisolate populations.2'3 Fortunately, diagnostic ambiguity is readily precluded by application of the VEP albino misrouting test.6"9 While it is proposed that contralateral VEP hemispheric asymmetry of the type described is pathognomonic to albinism,1-6 comparable VEP profiles are suggested in patients with hereditary or idiopathic congenital nystagmus (CN).10"12 If the latter is correct, From the *Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands and the f Department of Strabismology and Neuro-ophthalmology, University of Gottingen Eye Hospital, Gottingen, Germany. Submitted for publication: November 19, 1990; accepted March 29,1991. Reprint requests: Patricia Apkarian, PhD, Academic Medical Center, Ophthalmology Department—A2, Meibergdreef 9, 1105 AZ Amsterdam ZO, The Netherlands. the specificity and clinical viability of the VEP misrouting test is compromised. Moreover, with a presumptive presence of albino VEP asymmetry in patients with CN, some authors foster the idea that the ocular instabilities associated with CN are related to the condition of albino-type misrouted optic pathway projections.1314 The ocular-motor instabilities of CN, or of albinism, may result from some form of congenital misdirection of visual afferents that effect aberrant ocular-motor organization.15"20 However, there is no evidence to purport that the former, ie, patients with CN, share the specific form of optic pathway misprojections documented anatomically and electrophysiologically in all albino mammals thus far studied.21"24 In addition to establishing the presence of abnormal optic pathway projections across species, early albino investigations also prompted speculation regarding the possible pathophysiology of ocular-motor disorders associated with eye alignment.1822 As a result, several electrophysiologic studies questioning the relationship between albino-like optic pathway decussation and various forms of strabismus, including alternating esotropia and exotropia,25 congenital esotropia with and without abduction nystagmus,26 and dissociated vertical deviation with latent nystagmus,27 were also performed. The negative misrouting results of the latter studies confirmed, in support of initial conclusions,25 that the albino anomaly is not an appropriate model for the ocular-motor disturbances associated with squint. In addition to the negative correlation between strabismus and the albino visual pathway defect, a negative relationship between VEP misrouting and hereditary or idiopathic CN has also been reported.8'28"31 However, despite the fact that 2653 Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 2654 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Augusr 1991 studies from several independent laboratories have shown an absence of misrouting findings in patients with CN, the question regarding the relationship between albino misrouting and hereditary or idiopathic CN remains controversial.1314 One reason for the prevailing ambiguity may be that in most of these studies, VEP evaluation in patients with CN was typically a secondary issue rather than one of focal importance. This investigation readdressed the question of VEP misrouting in patients with CN by concentrating on this single issue. This study compared the cortical topography of the VEP in a group of patients with hereditary or idiopathic CN with a group of age-matched albino patients. To stress the primary nature of misrouted optic pathway projections and the concomitant VEP correlate, a control group of albino patients without nystagmus who readily evince VEP albino asymmetry is also shown. Our results are definitive; patients with CN do not show albino-type VEP asymmetry. Materials and Methods Patients The 28 patients included in this study were preselected from a group of 374 patients tested for VEP albino misrouting because they had one or more albino-like features and/or a positive albino family history. Included in this group were 225 clinically diagnosed albino patients, 18 of whom had no nystagmus, and 16 patients with hereditary or idiopathic CN. Patients with nystagmus and concomittant neurologic or ophthalmic disorders, including congenital malformations or syndromes, optic nerve atrophy or hypoplasia, maculopathy or retinal dystrophies, aniridia or achromatropisa, were excluded from further consideration. In addition, this selection was restricted to patients whose VEP data were readily computer-compatible for quantitative analysis. After these restrictions, a subsample of ten patients with CN remained. For comparison, ten age-matched albino patients were also objectively selected. Eight albino patients without nystagmus whose data were also computer compatible were included as a control group. All patients underwent detailed genetic and ophthalmic evaluation at the Ophthalmogenetics Department of the Netherlands Ophthalmic Research Institute to which they were typically referred by their district ophthalmologists for diagnostic confirmation, pedigree registration, and genetic counseling. Electrophysiologic evaluation was performed with informed consent after full explanation of the nature and purpose of the proceedings. Tables 1 and 2 show the clinical histories and the VEP test results of the patients. All CN and albino Vol. 32 patients listed in Table 1 had manifest nystagmus. However, in the cases in which strabismus accompanied CN, we cannot exclude the possibility that the nystagmus reflects latent manifest nystagmus (LMN) rather than CN per se.32 Further, although all albino patients listed in Table 2 evinced no detectable nystagmus on repeated clinical examination, we also cannot exclude the complete absence of ocular-motor instability. For example, whereas none of the patients reported in Table 2 had clinically detectable manifest or latent nystagmus, patient 110.1 evinced a gazeevoked nystagmus on extreme lateral gaze. The condition of albinism without nystagmus and/or measurable ocular misalignment has been previously reported5-30; eye movement recordings with electromagnetic coil techniques demonstrating the absence of nystagmus in some albino patients have also been described.17 In the tables, acuity values are denoted first in the right eye, then in the left eye. The patient with CN, 101.7 (Table 1) was strabismic; postoperative ocular alignment, however, was not documented. The term (alt) refers to alternating. Albino 101.6 (Table 1) was genotyped tyrosinase negative (after hairbulb test and tyrosinase assay); the remaining albino patients with an autosomal recessive mode of inheritance can be considered tyrosinase positive, although albino genotyping, can be ambiguous.33-34 Further, the presence or absence of fundus hypopigmentation is not restrictive. In the cases presented, complete fundus hypopigmentation of the periphery and posterior pole is not a prerequisite for a positive (present) score. Although all albino patients listed in Table 1 had iris diaphany, the absence of this feature does not a priori exclude the condition of albinism35 (see also albino 109.8, Table 2). Finally, patient 103.7, whose clinical history is shown at a test age of only 10 weeks, was also seen at 1.7 yr of age. At that time, there was still no clinical evidence of nystagmus; visual acuity during follow-up was estimated to be about 0.5 right (OD) and left eyes (OS). Visual Evoked Potentials (VEPs) Right- and left-eye pattern onset/offset evoked potentials were recorded from five tinned, copper-cup electrodes positioned (with collodian) in a row across the occiput, 1 cm above the inion and about 3 cm apart. The reference electrode was placed at the midline, frontal cortex (Fz); in some patients, linked ears served as reference. The common ground was located near the vertex. Bandwidth of the electroencephalogram (EEG) amplifiers (Nihon Kohden) was set at 0.5-70 Hz. An additional Butterworth filter introduced a phase shift in peak latency of about 7 msec. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 VEPs IN CONGENITAL NYSTAGMUS AND ALDINISM / Apkorion ond Shollo-Hoffmon No. 9 2655 Table 1. Clinical status: congenital nystagmus Case no. Age (yr) 115.7 115.8 111.4 114.1 111.2 101.7 108.1 106.9 104.3 120.4 5.7 5.7 9.3 9.8 18.4 18.8 21.1 28.8 46.9 67.9 Visual acuity Fundus hypopigment Foveal reflex 0.2, 0.3 0.7, 0.6 O O O O O O • O O O 4ft 4» 4 4• 4ft 4ft 4ft C) 4 4 Visual acuity Fundus hypopigment Foveal reflex Iris diaphany Ocular alignment OCC-Aut Rec OCC-Aut Rec OCC-Aut Rec OA-X Chrom OA-X Chrom OA-X Chrom OCC-Aut Rec 4ft 4ft 4ft 4ft 4ft 4ft 4ft OA-X Chrom 4» O C C - A u t Rec O A - X Chrom 4ft 4ft 0.1,0.1 0.1,0.2 0.4,0.5 0.5,0.5 0.3,0.2 0.4,0.2 0.3,0.3 0.3,0.3 0.1,0.1 0.1,0.2 4ft 4ft 4» C) 4» 4ft 4» 4ft 4ft 4ft O O O O O O O O O O 4ft 4ft 4ft 4ft 41 4ft 4ft 4ft 4ft 4ft Clinical diagnosis VEP asymmetry CN-Idiopathic CN-Idiopathic O O CN-X Chrom CN-X Chrom CN-Idiopathic CN-Idiopathic CN-Idiopathic CN-X Chrom o o o o o o o o CN-Idiopathic CN-Aut Dom 0.3, 0.4 0.4, 0.5 0.2, 0.2 1.0, 1.0 0.6, 0.6 0.4, 0.5 0.4, 0.6 0.6, 0.6 Iris diaphany • • » oo • • • O > > o o Ocular alignment csotropia esotropia orthophoria cxotropia orthophoria orthophoria orthophoria orthophoria orthophoria Clinical status: albinos with nystagmus Case no. Age (yr) Clinical diagnosis 106.7 103.3 106.5 5.8 9.3 110.4 104.2 110.6 103.8 102.8 101.6 116.9 5.7 9.7 18.1 18.4 22.2 28.9 41.5 68.9 VEP asymmetry exotropia orthophoria orthophoria esotropia (alt] exotropia exotropia esotropia (alt] orthophoria esotropia (alt] exotropia CN, congenital nystagmus; X-Chrom, X chromosomal; Aut-Dom, autosomal dominant; Aut-Rec, autosomal recessive; OA, ocular albino; OCC, oculocutaneous albino. • , present; O, absent; *, unknown. The filtered signals were sampled at a rate of 200 Hz and averaged with an Apple II microcomputer; all cummulative signals were displayed in real time, and the averages were stored on disk. The evoked potential stimulus consisted of a checkerboard pattern of 80% contrast generated on a Tetraco video monitor. The mode of stimulus presentation was full-field, pattern onset (40 msec)/offset (460 msec) at a constant mean luminance of 90 cd/m2. Viewing distance was typically 150 cm, pattern size 55', and field size 10°. During each session, slight test modifications were implemented when necessary. For example, for all patients, the luminance flash VEP was recorded, as were responses to larger and smaller pattern sizes. We report the VEP responses to the standard VEP misrouting test which emphasizes the 55' paradigm. The only exception are the VEP responses from the 10-week-old infant (patient 103.7), who yielded a measurable pattern response only for a large pattern size of 220'. For testing the Table 2. Clinical status: albinos with no nystagmus Case no. Age (yr) Clinical diagnosis 103.7 114.3 106.8 104.4 119.2 113.8 110.1 109.8 0.2 3.3 4.9 OCC-Aut Rec OCC-Aut Rec Alb-Unspec OCC-Aut Rec 5.5 9.1 10.0 24.3 32.6 OCC-Aut Rec OCC-Aut Rec OCC-Aut Rec OCC-Aut Rec VEP asymmetry 4ft 4ft 4ft ft ft ft ft ft Visual acuity ** 0.3,0.3 0.5,0.5 0.4,0.4 0.5,0.3 1.0,0.7 0.8,0.8 0.8,0.6 Fundus hypopigment ^ » > » OCC-Aut Rec, oculocutaneous autosomal recessive albino; Alb-Unspec, albino type unspecified. • , present; O, absent; *, unknown. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 Foveal reflex O O O O O O O O Iris diaphany Ocular alignment * exotropia (alt) csotropia exophoria exotropia (alt) exotropia (alt) esophoria exophoria esotropia O 2656 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Augusr 1991 infant and younger children, in general,fixationat the stimulus plane was facilitated by games and toys and by temporarily halting the signal averaging and replacing the checkerboard stimulus with a popular children's video program. When the child resumed appropriate fixation, the stimulus replaced the video portion of the program and recording proceeded while the auditory portion, with speakers directly behind the TV monitor, continued to play. This procedure redirected the children's attention to the screen. Data Analysis The topographic distribution of the recorded signals was evaluated by visual inspection and quantitative analysis. Visual inspection of the potential distribution across the occiput was aided by a difference potential in which a right hemispheric response was subtracted from that of a left (Figs. 1, 2, bottom traces). Polarity reversals of the difference potentials from left- to right-eye stimulation are indicative of asymmetry of the VEP amplitude. VEP amplitude at a latency corresponding to the first major positive peak was also plotted as a function of electrode, yielding functions of VEP hemispheric topography as shown in Figures 1 and 2. For the more mature response profiles, the positive peak within a latency window from about 80-110 msec corresponding to the positive C, component was selected.36-37 For the infant and younger children whose pattern onset responses consist primarily of a single positive peak, the topography functions were determined at the typically longer latency, major peak deflection.6 The range of the latency window in patients younger than 6 yr old was from about 100-190 msec. VEP latency and amplitude (voltage difference between a given latency response and baseline averaged over 40 msec after stimulus onset) were calculated with the aid of a software cursor program developed for this purpose. Topography values of amplitude as a function of the electrode array provided an estimate of hemispheric lateralization/eye/stimulus condition. The amplitude function was split into left-half (amplitudes derived from electrodes positioned across the left hemisphere) and right-half (amplitudes derived from electrodes positioned across the right hemisphere) functions, where the surface area under the respective half-curves (Ls and Rs) was then estimated. The measurement of hemispheric amplitude lateralization was calculated after the method of Varner et al.38 That is, the lower surface for each homologous pair was divided by the higher surface area, yielding a ratio value. If the left-half area amplitude was greater than that of the right half (Ls > Rs), hemispheric lateralization was defined as the right half pair divided by Vol. 32 the left (lateralization = Rs/Ls). For all remaining conditions, lateralization was defined as 2 minus the lefthalf pair divided by the right-half pair (lateralization = 2 - (Ls/Rs)). This subtraction procedure produces hemispheric ratios that are symmetric about the value of 1. Thus, an interhemispheric ratio of 0 indicates left-hemispheric lateralization, ie, the peak of the potential distribution across the electrode array is located at the leftmost electrode derivation. A value of 1 indicates interhemispheric symmetry with the peak of the potential distribution falling at the midline electrode, and finally, a ratio of 2 indicates right-hemispheric lateralization. Comparing the hemispheric lateralization of the response following left-eye stimulation with that following right-eye stimulation yields the symmetry index (symmetry index = lateralization [OS] - lateralization [OD]). A symmetry index of 2 reflects maximum contralateral asymmetry, ie, the peak of the potential distribution after left-eye stimulation lateralizes to the right hemisphere; after stimulation of the right eye, the peak of the potential distribution lateralizes to the left hemisphere. A symmetry index of 0 reflects no difference in lateralization between the left- and right-eye potential distributions. Negative values reflect ipsilateral asymmetry. As contralateral asymmetry is the condition of importance in detecting the misrouting associated with albinism, symmetry index values of zero and less than zero have been combined (Figs. 3, 4). The abcissa are thus labeled asymmetry index. This latter procedure was implemented to facilitate data presentation. All statistical analyses, however, were performed with the full range of symmetry values. Results Figure 1 shows the left (OS) and right (OD) eye pattern onset responses recorded across the occiput for an albino (upper traces) and a patient with Xlinked CN (lower traces). The bottom traces represent the difference potentials. After full-field monocular stimulation, the response profile from the albino shows contralateral asymmetry, with the peak of the potential distribution lateralizing to the right hemisphere after left-eye stimulation and vice versa after right-eye stimulation. The difference potentials reflect this asymmetry in the form of a polarity reversal (see arrows). A quantitative description of this particular form of VEP asymmetry is shown to the right in the graph labeled, "VEP Topography," in which amplitudes at the latency values indicated have been plotted across the electrode array from the left (electrode position 1) to right (electrode position 5) hemisphere. The classic crossover of the two monocular distributions from the albino response profile is in strong contrast to that of the patient with CN. The VEP topogra- Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 No. 9 VEPs IN CONGENITAL NYSTAGMUS AND ALDINISM / ApKorion and Shallo-Hoffman 2657 ALBINISM OS OD VEP TOPOGRAPHY OS o OD • 1 2 L-R 3 4 5 electrode position OS 95 ms OD 100 ms pt(101.6) CONGENITAL NYSTAGMUS OS VEP TOPOGRAPHY OS O OD • L-R 1 2 3 4 5 electrode position O S 9 9 ms O D 9 6 ms pt(106.9) Fig. 1. Albino visual evoked potential (VEP) asymmetry in the left (OS) and right eye (OD) pattern onset responses from an adult albino; normal VEP projections in the monocular pattern onset responses from an adult with congenital nystagmus (CN). The upper five traces of each column are derived from electrodes positioned from left (trace 1) to right occiput (trace 5). Bottom trace is obtained by subtracting trace 4 (R) from trace 2 (L). Contralateral asymmetry in the upperfiguresis shown by the polarity reversal of the difference potentials (sec arrows) and by the crossover of the CI component measured at the time instant indicated and plotted as a function of electrode for OD and OS. VEP topography for the patient with CN shows a slight interocular amplitude difference and midline response attenuation. phy from the patient with CN remains relatively stable from left- to right-eye stimulation. The most noticeable change is a slight decrease in response amplitude of the C, (or approximately 100 msec) compo- nent from right- and left-eye stimulation. This interocular amplitude difference, clearly shown in the corresponding topography plot, is expected from the existing interocular acuity difference (Table 1, patient Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 2658 Vol. 32 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / Augusr 1991 ALBINISM WITHOUT NYSTAGMUS OS OD VEP TOPOGRAPHY 2 L-R 3 4 5 electrode position OD 90 ms OS 90 ms pt(109.81) CONGENITAL NYSTAGMUS OS OD VEP TOPOGRAPHY 8- OS O OD • 2 L-R 3 4 electrode position OS 90 ms OD 90 ms pt(101.7) Fig. 2. VEP intcrocular hemispheric asymmetry in the responses and topography plot from an albino without nystagmus. Note also the interocular amplitude differences. No albino VEP asymmetry is shown by the patient with congenital nystagmus (CN) but rather a right hemispheric response dominance for both OD and OS responses. For more details, see Figure I. 106.9) with OS acuity greater than OD acuity. However, despite the interocular VEP amplitude differences, evidence of albino VEP asymmetry in either the VEP responses or topographic representation is clearly absent. The albino whose VEP responses are shown in Figure 2 also has an interocular acuity difference. In this case, OD acuity is better than OS acuity (see Table 2, patient 109.8) and is reflected in more robust VEP amplitudes for OD as seen in the raw traces and the topography plot. The difference potential (see arrows) shows a polarity reversal, and VEP responses from the left eye show peak response lateralization at electrode positions 4 and 5 (right occiput), whereas VEP ampli- Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 VEPs IN CONGENITAL NYSTAGMUS AND ALDINISM / Apkarion and Shallo-Hoffman No. 9 (P < 0.001). As the latency of asymmetry detection with pattern stimulation changes with age, it is best to perform statistical analyses between age-matched groups. However, despite maturational differences, a statistically significant difference (P < 0.001) was also found between the group of patients with CN and the albino control patients with no nystagmus (Fig. 4). Finally, based on nonparametric statistical analyses (Kolmogorov-Schmirnov) of the significantly different frequency distributions of asymmetry indices between the patients with CN and albino patients with or without nystagmus, statistically significant (P < 0.001) albino asymmetry can be considered for index values of greater than 0.7. Actual asymmetry values for the CN patients depicted did not exceed 0.3. PATTERN VEP Lateralization OS - Lateralization OD Albinos Congenital Nystagmus 4- E O) CO V> o 3 CO o O 2- Discussion 0) n E 1- 3 w 2659 "7 0 i i I I I 0.4 0.8 1.2 1.6 2 Hemispheric Asymmetry Index The genetic anomaly in albinism precludes normal melanogenesis of neural ectoderm derivatives, ie, the retinal pigment epithelium and the optic tract, resulting in a course of developmental anomalies that include abnormal central-retinal ganglion cell differentiation and the consequent inappropriate guidance, Fig. 3. Asymmetry index distributions for patients with congenital nystagmus (dark shading) and age-matched albinos (light shading). Values greater than 0.7 indicate significant albino asymmetry. The two groups show no overlap. PATTERN VEP Lateralization OS - Lateralization OD tudes from the dominant right eye peak at electrodes 1 and 2 (left occiput). This albino control, who does not have nystagmus, also demonstrates the predicted albino VEP asymmetry. The topography plots (Figs. 1, 2) of albino asymmetry can be compared with an example of nonalbino VEP asymmetry for the monocular amplitude distributions from a second patient with CN (Fig. 2). This patient shows a right hemispheric response dominance rendering potential distributions across the scalp that are asymmetric. The asymmetry, however, is not contralateral for each eye. In this case, regardless of the eye of stimulation, the responses lateralize to the right hemisphere. This finding does not constitute an example of albino VEP contralateral asymmetry. Summaries of VEP contralateral asymmetry for the three patient groups are presented in Figures 3 and 4. The asymmetry index for each patient was calculated as described in the Materials and Methods section and is shown in histogram form. In Figure 3, the asymmetry indices from ten patients with CN are compared with ten age-matched albino patients. Visual inspection alone reveals no overlap between the two distributions. One-tailed student t-test shows a statistically significant difference between patients with CN and age-matched albino patients with nystagmus Albino Controls No Nystagmus 400 o 3- < "5 n E 3 1 - i i i \ r 0 0.4 0.8 1.2 1.6 2 Hemispheric Asymmetry Index Fig. 4. Asymmetry index distribution for albino control patients without nystagmus. All albinos in this group (N = 8) with an age range spanning from 10 weeks to about 33 yr show significant albino contralateral asymmetry. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933160/ on 06/15/2017 2660 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / Augusr 1991 projection, and organization of retinal-fugal fibers.39-40 One result of this inborn error of metabolism and its seemingly preprogramed developmental course is that a preponderance of temporal retinal fibers erroneously decussate at the optic chiasm, disrupting normal retinotopic mapping and corresponding functional substrates throughout the visual system. Thus, the two obligate features in albinism, by definition are misrouted contralateral optic pathway projections and incomplete cone-receptor and ganglion cell migration within the central retina.41"43 Auxilliary but not necessarily specific nor prerequisite visual system anomalies, including irisdiaphany, fundus hypopigmentation, and ocularmotor instabilities, are secondary features, the severity of which depends on the degree, extent, and prenatal timing of the albino gene expression. The consequent pigment cell anomalies may be restricted to the neural ectoderm derivatives effecting ocular albinism or may extend to neural endoderm derivatives as well, thus yielding various forms of oculocutaneous albinism. However, regardless of the specific albino genotype or phenotype, all forms of albinism share the optic pathway misrouting readily revealed in the potential distributions of the scalp-recorded VEP6-9184445; the VEP topography shows contralateral asymmetry between the two eyes, indicative of the anomalous projections from the temporal retinae. It is unlikely that patients with CN also share this VEP correlate of albino-type optic pathway misrouting. This study shows the absence of albino VEP asymmetry in patients with hereditary or idiopathic CN. A comparison of the monocular full-field VEP response profiles from a group of CN patients with a group of age-matched albino patients shows normal VEP retinal-cortical projections in the patients with CN and contralateral asymmetric VEP projections in the albinos. Introduction of a control group of atypical albinos who do not evince nystagmus, further emphasizes the dissociation between the primary albino visual pathway anomaly of temporal retinal-cortical misprojections and the secondary condition of ocular-motor instability. One source of confusion resulting in erroneous reports of VEP asymmetry in nonalbino patients may be the individual differences in cortical neuroanatomy46 and correspondingly, the wide variation in hemispheric lateralization. Responses that lateralize across the occiput are typically described as asymmetric. However, it is important to distinguish between the generalized asymmetric VEP and the specific form of contralateral albino VEP asymmetry. For the latter, a comparison of the interocular VEP projections is critical. An understanding of the albino visual pathway anomaly should clarify any existing confu- Vol. 32 sion and render the VEP misrouting test a sensitive and reliable diagnostic probe for detection and differential diagnosis of albinism. Key words: albinism, congenital nystagmus (CN), visual evoked potentials (VEPs), VEP misrouting References 1. Apkarian P, Rcits D. Spckrcijsc H, and Dorp van D: A decisive clectrophysiological test for human albinism. ElectrocnccphalogrClin Ncurophysiol 55:513, 1983. 2. Dorp van DB, Hacringcn van NJ, Delleman JW, Apkarian P, and WesterhofW: Albinism: phenotype or genotype? Doc Ophthalmol 56:183, 1983. 3. Kinncar PE, Jay B, and Witkop CJ Jr: Albinism. Surv Ophthalmol 30:75, 1985. 4. Taylor WOG: Visual disabilities of oculocutaneous albinism and their alleviation. Trans Ophthalmol Soc (UK) 98:423, 1978. 5. Sicgel IM: Ophthalmological findings in tyrosinasc positive oculocutaneous albinism. Perspectives in Ophthalmology 3:17, 1979. 6. 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