Download VEP asymmetry in albinism

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
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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.
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VEPs IN CONGENITAL NYSTAGMUS AND ALDINISM / Apkorion ond Shollo-Hoffmon
No. 9
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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.
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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
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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-
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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
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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-
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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.
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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
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