Abstract
purpose. To determine the maturational course of nasotemporal asymmetry in
infantile esotropia and to define the relationships among the symmetry
of the motion visual evoked potential (MVEP), eye alignment, fusion,
and stereopsis.
methods. Sixty healthy term infants and 34 infants with esotropia participated.
Nasotemporal MVEP asymmetry was assessed by the presence of a
significant F1 response component with an inter-ocular
phase difference of approximately 180° and by an amplitude“
asymmetry index.” Fusion was evaluated using the 4 p.d.
base out prism test. Random dot stereoacuity was assessed in infants
with forced-choice preferential looking (FPL) using the Infant Random
Dot Stereocards. Eye alignment was assessed by the alternate prism and
cover or the modified Krimsky test.
results. Normal infants 2 to 3 months of age exhibited marked nasotemporal MVEP
asymmetry, which rapidly diminished by 6 to 8 months. Neonates did not
exhibit MVEP asymmetry. There was good concordance between fusion and
MVEP symmetry and between stereopsis and MVEP symmetry; the concordance
between MVEP symmetry and orthoposition of the visual axes was
significantly poorer. The same proportion of normal and young esotropic
infants showed symmetrical MVEPs. Regardless of the age at surgery,
most patients with infantile esotropia had asymmetrical MVEPs after
surgery.
conclusions. These data support a strong link between fusion and MVEP symmetry
during both normal maturation and in infantile esotropia. Furthermore,
the finding that the youngest infants with esotropia do not differ
significantly from normal suggests that the nasotemporal asymmetry
found in older patients with infantile esotropia does not represent an
arrest of maturation but, rather, a pathologic change of the motion
pathways.
The maturation of motion processing in the human visual cortex
can be assessed by means of the motion visual evoked potential (MVEP),
which appears to selectively access binocular motion pathways. An
initial study of the MVEP in 11 normal infants 6 to 26 weeks of age
reported nasotemporal asymmetries that diminished as the visual
system’s response to motion matured.
1 A subsequent
cross-sectional study of 22 infants 25 to 104 weeks of age verified
that normal infants over 25 weeks of age show little residual
asymmetry.
2
“Persistence” of nasotemporal asymmetry was reported in 15 patients
with infantile esotropia who had been surgically aligned after 2 years
of age.
1 Unlike esotropic patients with infantile onset,
those with late onset do not show pronounced nasotemporal asymmetries
in the MVEP.
3 Treatment of infantile esotropia with
full-time alternate occlusion and surgery during the first 2 years of
life has been shown to decrease or abolish the nasotemporal asymmetries
in most patients, whereas later treatment had little or no effect on
nasotemporal asymmetry.
1 2 4 Taken together, these data
are consistent with an early critical period during which abnormal
binocular experience can interfere with the maturation of the binocular
motion pathways tapped by the MVEP.
Although the association between early abnormal binocular
experience and nasotemporal asymmetry is clear, it is not known whether
the asymmetry truly represents persistence of an infantile state or,
rather, a pathologic change due to prolonged abnormal experience. In
addition, the interrelationships among eye alignment, fusion,
stereopsis, and the MVEP have not been well defined. All show rapid
development during the first months of life, all are sensitive to
disruption by early abnormal sensory experience, and all are responsive
to treatment during the first 2 years of life. The aims of the present
study were to determine the maturational course of nasotemporal
asymmetry and to define the relationships among the symmetry of the
MVEP, eye alignment, fusion, and stereopsis.
Sixty healthy term infants 0.5 to 10 months of age participated in
study 1. None had a family history of strabismus or hereditary eye
disease. Thirty-four infants with infantile esotropia participated in
studies 2 and 3. All of the patients were diagnosed with constant
esotropia of at least 30 p.d. at 3 to 6 months of age, and the
angle of deviation was found to be maintained or increased during
follow-up before surgery. All were otherwise healthy infants. None of
the infants had significant refractive errors. Only nonamblyopic
infants were recruited for the study because phase delays in VEP
responses associated with amblyopia might confound measurement of
interocular phase differences associated with nasotemporal asymmetry.
Twenty of the infants were tested before surgery and 28 infants after
surgery (14 infants were tested both pre- and post-surgery). No
treatment other than surgery was provided to these patients.
Informed consent was obtained from one or both parents before the
child’s participation. This research protocol observed the tenets of
the Declaration of Helsinki and was approved by the Institutional
Review Board of the University of Texas Southwestern Medical Center.
Data were grouped by age into 8 categories: newborns (<1 month
old) and 1.5, 2.5, 3.5, 4.5, 5.5, 8, and 10 months. Between 5 and 10
infants contributed data to each age group. Sample MVEP records for
three infants are shown in
Figure 1 . Response amplitude and phase are plotted in polar coordinates for each
of the 10-second trials obtained for each eye. The youngest infant
shown has small response amplitudes overall, variable first harmonic
responses, and small but reliable second harmonic responses with
similar phase for the two eyes. The 2.5-month-old infant has a sizeable
first harmonic component, which is approximately 180° out of phase
for the two eyes, and a small but reliable second harmonic response
with similar phase for the two eyes. The 4.5-month-old infant had
little first harmonic response and a robust second harmonic response
with similar phase for the two eyes.
Mean data are summarized in
Figure 2 . Both measures of asymmetry (the “bow tie” and the asymmetry index)
show rapid change from asymmetry toward symmetry between 1.5 and 8
months. Also shown in
Figure 2 are data from 9 infants who were tested
longitudinally on 4 to 6 visits between 1.5 to 6 months of age; these
asymmetry index data show the same general trend as the group averages.
In contrast to the monotonic decline during months 1.5 to 8, the group
of 5 neonates aged 0.5 to 1 month showed a qualitatively different
pattern of response (namely, robust F
2 responses). None of the 5 neonates showed evidence of a “bow tie,”
and their asymmetry indices ranged from 0.17 to 0.38, with a mean of
0.26.
In a subset of 19 normal infants, eye alignment and fusion responses to
4 p.d. base out prisms were measured on 2 to 4 visits. At 1.5 and
2 months of age, 89% of infants had asymmetrical MVEPs and
intermittent exotropia and failed to show fusional eye movements on the
4 p.d. base out prism test. By 4.5 months, 78% of the infants had
symmetrical MVEPs, orthoposition of the visual axes, and fusional eye
movements on the 4 p.d. base out test. There was good concordance
between the response to the 4 p.d. base out prism and the symmetry
of the MVEP, with only one discordant pair in 52 test pairs. The
concordance between MVEP symmetry and orthoposition of the visual axes
was significantly poorer (10 of 52 pairs discordant;χ 2 = 6.51, P = 0.011).
In a subset of 15 normal infants aged 3 to 5 months, both random dot
stereopsis and MVEPs were measured. Of 8 infants who had random dot
stereoacuity ≤ 400 seconds, 7 had symmetrical MVEPs. Of 7 infants
who had no random dot stereopsis, 6 had asymmetrical MVEPs. These
proportions are significantly different by the Fisher exact test
(P = 0.01).
The prevalence of “bow ties” and the mean asymmetry index at
the first postoperative visit is shown in
Figure 4 as a function of age along with the normative data replotted from
Figure 1 . Eleven of the infants had their first postoperative visit at
9 to 11 months of age (8.6 ± 1.1 weeks postop), 10 infants had
their first postoperative visit at 12 to 14 months of age (20.7 ±
4.2 weeks postop), and 5 infants had their first postoperative visit at
15 to 24 months of age (34.1 ± 11.2 weeks postop). For all 3
groups, the proportion of treated esotropic infants with “bow ties”
was statistically higher than the proportion found in the normative
cohort (Fisher exact test;
P < 0.008). For all 3
groups, the asymmetry index was significantly higher than normal as
well (
P < 0.001 by
t-test). Similar trends
can be seen in the longitudinal data sets from 11 infants who were
tested on 2 to 4 visits postoperatively
(Fig. 4) ; all but one of the
asymmetry indices obtained from these infants during 29 visits were
abnormal.
For 14 of the infants, both pre- and postsurgery data were available.
Eleven infants had a “bow tie” presurgery; six retained the “bow
tie” postoperatively. Of the three infants who had no “bow tie”
presurgery, one developed a “bow tie” postoperatively. The mean
change in the asymmetry index postoperatively was not significantly
different from zero (−0.06 ± 0.28). Eight infants showed a
decrease in their asymmetry index ranging from −0.05 to −0.69,
whereas 6 infants showed an increase ranging from +0.01 to +0.63.
Clinical variables that might contribute to binocular vision outcomes
were examined. Infants who were surgically aligned by 10 months of age
had significantly lower postoperative asymmetry indices than those who
were aligned at 11 to 18 months of age (t = 2.64; P < 0.05). There were no significant differences in
asymmetry indices between infants who developed a dissociated vertical
deviation and those who did not (Mann–Whitney test; P = 0.22). The proportion of treated esotropic infants who demonstrated
fusion with “bow ties” was statistically lower than the proportion
found among infants who failed to demonstrate fusion (Fisher exact
test; P = 0.008). Infants who demonstrated fusion after
surgery (n = 4) also had significantly lower
postoperative asymmetry indices than those who did not demonstrate
fusion (t = 2.12; P < 0.05). There
were no significant differences in asymmetry indices between infants
who developed stereopsis (n = 4) and those who did not
develop stereopsis (t-test; P = 0.54).
The MVEP data from 60 normal infants aged 0.5 to 10 months provide
a well-defined range for comparison with data from pediatric patients.
As noted by others,
1 2 4 infants aged 2 to 3 months
exhibited marked nasotemporal asymmetry that rapidly diminished by 6 to
8 months. A novel finding in the present study is that neonates did not
exhibit nasotemporal asymmetry. This finding is consistent with the
report that neonates can detect motion but cannot discriminate its
direction
8 (i.e., direction selective mechanisms may not
be present at birth). Given the concordance between MVEPs and fusion
during normal development, the lack of nasal-temporal asymmetry in
neonates is consistent with the observation that, despite the absence
of stereopsis, simultaneous perception with two eyes may be present at
birth. This finding suggests that substantial reorganization of
directionally selective binocular pathways occurs
postnatally.
9
The concordance of MVEP symmetry with sensory fusion and
stereopsis but not with eye alignment supports a link between these
aspects of binocular sensory function in normal infants. Although every
attempt was made to obtain data only when the infant was alert and
fixating, it is possible that eye alignment varied during the course of
conducting multiple tests and that the eye alignment assessed during
the alternate prism and cover test did not always reflect alignment
status during the fusion and stereopsis tests. Thus, it is possible
that the two infants who were judged to have intermittent exotropia
during the alignment examination had straight eye during the fusion
test. Likewise, the eight infants who were judged orthophoric on the
alignment examination may have exhibited intermittent exotropia during
the fusion test.
Among infantile esotropes evaluated during the first weeks after onset,
the same proportion of normal and esotropic infants show symmetrical
responses, and, in the youngest infants the asymmetry index is near
normal. These data conflict with an earlier report of abnormal MVEPs
before treatment,
2 but patients in that study were
evaluated at an average of 4 months after the onset of esotropia (all
had onset by 4 months and were first evaluated at an average age of 8
months), whereas patients in the present study were evaluated at an
average of 1 month after onset. The finding that the initial course of
maturation of MVEPs in young esotropes appears to be normal is
reminiscent of our earlier finding that the same proportions of normal
and esotropic infants (aligned with prisms) are able to demonstrate
stereopsis at 3 to 5 months of age.
10 Both observations
support the hypothesis that early treatment may be beneficial in
preventing major abnormalities in this aspect of binocular sensory
function.
Regardless of the age at surgery, most patients with infantile
esotropia exhibited “bow ties” and abnormal asymmetry indices after
surgery. These outcome data were gathered from patients at 5 to 60
weeks postoperatively, so it is possible that there may be further
long-term changes in the asymmetry index. The rare patients who
achieved symmetry after surgery had had surgery during the first 10
months of life, achieved good alignment outcomes, and exhibited fusion.
Early surgery for infantile esotropia also has been reported to be
associated with better stereoacuity outcomes.
11 12 13 In
addition, a strong relationship between fusion (by the 4 p.d.
prism test) and nasotemporal symmetry has been reported in a large
group of older children treated for infantile esotropia, accommodative
esotropia, intermittent strabismus, or other common pediatric eye
disorders who had a wide spectrum of binocular sensory
function.
14
Overall, the data presented here support a strong link between
fusion and MVEP symmetry during both normal maturation and in infantile
esotropia. Furthermore, the finding that pediatric patients with
infantile esotropia do not differ significantly from normal immediately
after the onset of strabismus suggests that the nasotemporal asymmetry
found in such patients may not represent a persistence of the normal
infantile state but, rather, a pathologic disruption of motion pathways
as a result of prolonged abnormal binocular sensory experience.
Supported by NIH Grant EY05236 (EB) and a Fight for Sight Postdoctoral Fellowship, PD98011 (SF).
Submitted for publication July 20, 1999; revised December 15, 1999; accepted January 5, 2000.
Commercial relationships policy: N.
Corresponding author: Eileen E. Birch, Retina Foundation of the Southwest, 9900 N. Central Expressway, Suite 400, Dallas, TX 75231.
ebirch@retinafoundation.org
Norcia A, Garcia H, Humphry R, Holmes A, Hamer R, Orel–Bixler D. Anomalous motion VEPs in infants and in infantile esotropia. Invest Ophthalmol Vis Sci
. 1991;32:436–439.
[PubMed]Norcia A, Hamer R, Jampolsky A, Orel–Bixler D. Plasticity of human motion processing mechanisms following surgery for infantile esotropia. Vision Res
. 1995;35:3279–3296.
[CrossRef] [PubMed]Hamer R, Norcia A, Orel–Bixler D, Hoyt C. Motion VEPs in late-onset esotropia. Clin Vis Sci. 1993;8:55–62.
Jampolsky A, Norcia A, Hamer R. Preoperative alternate occlusion decreases motion processing abnormalities in infantile esotropia. J Pediatr Ophthalmol Strabismus
. 1994;31:6–17.
[PubMed]Victor J, Mast J. A new statistic for steady-state evoked potentials. Electroenceph Clin Neurophysiol
. 1991;78:378–388.
[CrossRef] [PubMed]Von Noorden G. Atlas of Strabismus. 1977;70–71. CV Mosby St. Louis.
Birch E, Salamão S. Infant random dot stereoacuity cards. J Pediatr Ophthalmol Strabismus
. 1998;35:86–90.
[PubMed]Wattam–Bell J. Visual motion processing in one-month-old infants. Vision Res
. 1996;36:1671–1685.
[CrossRef] [PubMed]Held R. Development of cortically mediated visual processes in human infants. von Euler C Forssberg H Lagercrantz H eds. Neurobiology of Early Infant Behavior. 1988;155–164. Stockton Press New York.
Birch E, Stager D. Monocular acuity and stereopsis in infantile esotropia. Invest Ophthalmol Vis Sci
. 1985;26:1624–1630.
[PubMed]Birch E, Stager D, Everett M. Random dot stereoacuity following surgical correction of infantile esotropia. J Pediatr Ophthalmol Strabismus
. 1995;32:231–235.
[PubMed]Wright K, Edelman P, McVey J, Terry A, Lin M. High grade stereoacuity after early surgery for congenital esotropia. Arch Ophthalmol. 1993;112:913–919.
Ing M. Outcome study of surgical alignment before 6 months of age for congenital esotropia. Ophthalmology
. 1995;102:2041–2045.
[CrossRef] [PubMed]Fawcett S, Birch E. Motion VEPs, stereopsis, and bifoveal fusion in children with strabismus. Invest Ophthalmol Vis Sci.
. 2000;41:411–416.
[PubMed]