Download Optical Treatment of Amblyopia in Astigmatic Children

Optical Treatment of Amblyopia in
Astigmatic Children
The Sensitive Period for Successful Treatment
Erin M. Harvey, PhD,1,2 Velma Dobson, PhD,1,3 Candice E. Clifford-Donaldson, MPH,1
Joseph M. Miller, MD, MPH1,2,4
Objective: To compare the effectiveness of eyeglass treatment of astigmatism-related amblyopia in children
younger than 8 years (range, 4.75–7.99 years) versus children 8 years of age and older (range, 8.00 –13.53 years)
over short (6-week) and long (1-year) treatment intervals.
Design: Prospective, interventional, comparative case– control study.
Participants: Four hundred forty-six nonastigmatic (right and left eye, ⬍0.75 diopters [D]) and 310 astigmatic (RE, ⱖ1.00 D) Native American (Tohono O’odham) children in kindergarten or grades 1 through 6.
Intervention: Eyeglass correction of refractive error, prescribed for full-time wear, in astigmatic children.
Main Outcome Measures: Amount of change in mean right-eye best-corrected letter visual acuity for
treated astigmatic children versus untreated, age-matched nonastigmatic children after short (6-week) and long
(1-year) treatment intervals.
Results: Astigmatic children had significantly reduced mean best-corrected visual acuity at baseline compared to nonastigmatic children. Astigmats showed significantly greater improvement in mean best-corrected
visual acuity (0.08 logarithm of the minimum angle of resolution [logMAR] unit; approximately 1 line), than the
nonastigmatic children (0.01 logMAR unit) over the 6-week treatment interval. No additional treatment effect was
observed between 6 weeks and 1 year. Treatment effectiveness was not dependent on age group (⬍8 years vs.
ⱖ8 years) and was not influenced by previous eyeglass treatment. Despite significant improvement, mean
best-corrected visual acuity in astigmatic children remained significantly poorer than in nonastigmatic children
after 1 year of eyeglass treatment, even when analyses were limited to results from highly compliant children.
Conclusions: Sustained eyeglass correction results in significant improvement in best-corrected visual
acuity in astigmatic children, including those previously believed to be beyond the sensitive period for successful
treatment. Ophthalmology 2007;114:2293–2301 © 2007 by the American Academy of Ophthalmology.
Disruption of normal visual experience during early development can lead to amblyopia, neural visual deficits characterized by reduced vision that persists after normal visual
input is restored. Uncorrected astigmatism is one condition
that can cause abnormal visual experience during early
development and can result in amblyopia. Several studies
have documented reduced best-corrected visual acuity associated with astigmatism (Invest Ophthalmol Vis Sci
25[Suppl]:217, 1984; Dissertation Abstracts International
63: No 12B p6115, 2002; Invest Ophthalmol Vis Sci 45:Eabstract 2580, 2004).1– 4 In addition, presence and severity
of visual deficits in astigmatism-related amblyopia can be
specific to stimulus orientation,1,3–13 a specific form of
amblyopia termed meridional amblyopia, the result of the
orientation-specific defocus characteristic of uncorrected
astigmatism.
The most common treatment of astigmatism-related amblyopia that occurs in the absence of strabismus or anisometropia is restoration of normal visual input through optical correction of refractive error. Few studies have focused
specifically on the effectiveness of optical treatment of
astigmatism-related amblyopia, but the available literature
Originally received: September 19, 2006.
Final revision: March 7, 2007.
Accepted: March 8, 2007.
Manuscript no. 2006-1063.
1
Department of Ophthalmology and Vision Science, University of Arizona, Tucson, Arizona.
2
College of Public Health, University of Arizona, Tucson, Arizona.
3
Department of Psychology, University of Arizona, Tucson, Arizona.
4
College of Optical Sciences, University of Arizona, Tucson, Arizona.
Presented in part at: Optical Society of America Fall Vision Meeting,
October 2005, Tucson, Arizona.
Supported by the National Eye Institute, Bethesda, Maryland (grant nos.
EY11155 [JMM], EY13153 [EMH]), and Research to Prevent Blindness,
Inc., New York, New York (unrestricted grant to the University of Arizona
Department of Ophthalmology and Vision Science [JMM], Walter E. and
Lilly Disney Award for Amblyopia Research [JMM], and Career Development Award [EMH]).
There are no conflicting relationships between any author and any product
mentioned.
Correspondence to Erin M. Harvey, PhD, University of Arizona Department of Ophthalmology and Vision Science, 655 North Alvernon Way,
Suite 108, Tucson, AZ 85711. E-mail: [email protected].
© 2007 by the American Academy of Ophthalmology
Published by Elsevier Inc.
ISSN 0161-6420/07/$–see front matter
doi:10.1016/j.ophtha.2007.03.021
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Ophthalmology Volume 114, Number 12, December 2007
suggests that successful treatment is limited to a sensitive
period. Retrospective studies, based on a small number of
astigmats, have found that astigmatic adults do not show
evidence of meridional amblyopia if astigmatism is corrected with eyeglasses before the age of 7 years and are
more likely to show evidence of meridional amblyopia if the
astigmatism is corrected after age 7 years.6,12 Consistent
with these findings, Mohindra et al7 reported that a 3-yearold astigmatic child with meridional amblyopia on initial
testing showed no evidence of meridional amblyopia after 3
months of eyeglass wear. However, in a prospective study
of eyeglass treatment of astigmatism-related amblyopia,14
we found that astigmatic 3- to 5-year-old Native American
children had significantly poorer mean best-corrected letter
visual acuity than nonastigmatic children, and there was no
significant improvement in best-corrected visual acuity after
an average eyeglass treatment duration of 4 months. These
results suggest that even when astigmatism is corrected as
early as age 3 years, astigmatism-related amblyopia may
persist. However, several alternative explanations of the
null treatment effect, including high measurement variability (because the children were cyclopleged during acuity
testing and were wearing trial frames), variability in treatment compliance, and insufficient treatment duration, prevented a definitive conclusion that these children were beyond the sensitive period for successful treatment of
astigmatism-related amblyopia.
The goal of the present study was to define more clearly
the sensitive period for successful treatment of astigmatismrelated amblyopia. We compared effectiveness of eyeglass
treatment in 2 cohorts of astigmatic children: a younger
cohort (YC; younger than age 8 years; age range, almost 5
to ⬍8 years) and an older cohort (OC; age range, 8 to ⬍14
years). If the sensitive period for successful treatment ends
before 3 to 5 years of age,14 a treatment effect in either
cohort should not be demonstrated. If the sensitive period
extends only to approximately age 7 years,6,12 a treatment
effect only in the YC should be evident. Finally, significant
treatment effects in both cohorts would suggest that the
sensitive period extends beyond age 7 years. This finding
would be contrary to previous small-sample reports regarding treatment of astigmatism-related amblyopia.6,12,14
Patients and Methods
Patients
The present study focused on members of a Native American tribe,
the Tohono O’odham, because previous research has shown that
there is a high prevalence of astigmatism15–17 and astigmatismrelated amblyopia2,3,14 among members of the tribe. Subjects
eligible for recruitment and participation were all children in
kindergarten through grade 2 (recruited during the 2003–2004
school year) and all children in grades 4 through 6 (recruited
during the 2001–2002 school year) who attended 1 of 5 elementary
schools on the Tohono O’odham Reservation in southern Arizona.
In addition, data were included from children at a sixth elementary
school on the reservation who participated in a preliminary study
during the 2000 –2001 and 2001–2002 school years in which an
identical inclusion, treatment, and outcome assessment protocol
was used (Dissertation Abstracts International 63: No 12B p6115,
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2002). Recruitment dates for the 2 cohorts were designed to
minimize the possibility of recruiting children who participated
in a previous eyeglass treatment study of preschool children
from the same population.3,18,19 Children who did not enroll
during the first year of testing of their cohort but were in
targeted grades (kindergarten– grade 2 or grades 4 – 6) during the
second year of testing for their cohort were invited to participate
and contributed baseline and initial follow-up data, but 1-year
follow-up testing was not conducted during the following year.
Although all children in the targeted grades were invited and were
eligible to participate in the study, only data from subjects meeting
specific refractive error and ophthalmic criteria were included in
analyses (see “Data Analysis and Predictions”).
The research was approved by the Institutional Review Board
of the University of Arizona and was compliant with the Health
Insurance Portability and Accountability Act. Written informed
consent was obtained from a parent or guardian prior to a child’s
participation, and written assent was obtained from children in
grades 4, 5, and 6.
Procedures
A flow chart of study procedures is provided in Figure 1. Each
child underwent a complete baseline eye examination, including
cycloplegic refraction, conducted by a pediatric ophthalmologist
(JMM) at least 40 minutes after instillation of 1 drop of proparacaine (0.5%) and 2 drops of cyclopentolate (1%) separated by an
interval of approximately 5 minutes. Eyeglasses were prescribed
for children who had 2.00 diopters (D) or more of astigmatism in
either eye, and children who had uncorrected letter acuity worse
than 20/20 and met 1 or more of the following criteria: myopia of
0.75 D or more in either meridian, hyperopia of 2.50 D or more in
either meridian, astigmatism of 1.00 D or more in either eye,
anisometropia of 1.50 D or more spherical equivalent. Refractive
error was determined by cycloplegic autorefraction (Nikon Retinomax K⫹; Nikon Inc., Tokyo, Japan; now manufactured by
Righton Manufacturing Co., Tokyo, Japan), confirmed by cycloplegic retinoscopy and, when possible, subjective refinement.
Approximately 2 to 3 weeks after the baseline eye examination,
each child participated in baseline best-corrected letter visual acuity testing. Although eyeglasses were prescribed only for children
who met the above guidelines, all children wore eyeglasses containing their refractive correction (based on cycloplegic autorefractor measurements, refined or confirmed by cycloplegic retinoscopy
or subjective refinement) for acuity testing. This allowed assessment of best-corrected visual acuity in all children and masked the
testers as to which children had been prescribed eyeglasses. Children who did not meet the prescribing criteria wore a pair of
eyeglasses from a set of stock eyeglasses that were selected with
the restriction that both the right and left lens corrections were less
than a 0.50 vector dioptric difference from the child’s refractive
error.20,21 For both prescriptions and selection of stock eyeglasses,
correction of hyperopic refractive error was reduced by one third
or by 1.00 D, whichever was greater.22 Full correction of astigmatism at the appropriate axis was given.
At the beginning of the baseline acuity testing session, each
child was fit with the appropriate set of eyeglasses. Acuity testing
then was conducted by testers who were masked to each child’s
refractive error and to results obtained at previous testing sessions.
Monocular best-corrected right eye (RE) and left eye distance
logarithm of the minimum angle of resolution (logMAR) letter
acuity was determined using 62⫻65-cm Early Treatment Diabetic
Retinopathy Study charts23 mounted in an illuminator cabinet
(Precision Vision, Inc., LaSalle, IL) at 4 m. The Early Treatment
Diabetic Retinopathy Study chart 1 (catalog item no. 2121) was
used for testing the RE, which was always tested first, and chart 2
Harvey et al 䡠 Treatment of Astigmatism-Related Amblyopia
Figure 1. Flow chart showing session types during year 01 and year 02 testing of cohorts. During year 01, kindergarten, first-, second-, fourth-, fifth-, and
sixth-grade children who enrolled participated in 3 sessions: baseline eye examination (refractive error determined by cycloplegic autorefraction confirmed
or refined by retinoscopy), baseline vision testing (best-corrected letter acuity, tested in eyeglasses containing correction determined at baseline eye
examination), and 6-week follow-up vision testing (best-corrected letter acuity, tested in eyeglasses containing correction determined at baseline eye
examination). During year 02, children who enrolled in year 01 participated in two sessions: follow-up eye examination (refractive error determined by
cycloplegic autorefraction confirmed or refined by retinoscopy), and 1-year follow-up vision testing (best-corrected letter acuity, tested in eyeglasses
containing correction determined at follow-up eye examination). In addition, during year 02, additional children in the targeted grade range were allowed
to enroll. These children completed baseline eye examination, baseline vision testing, and 6-week follow-up vision testing.
(catalog item no. 2122) was used for testing the left eye. The child
was asked to identify verbally or by matching to letters on a lap
card all 5 letters on each line of the chart, until he or she could no
longer identify any of the 5 letters on a line. Best-corrected visual
acuity was scored as the smallest letter size on which the child
correctly identified at least 3 of a maximum of 5 letters. Logarithm
of the minimum angle of resolution visual acuity scores were used
for data analyses. At the end of the baseline best-corrected visual
acuity testing session, children who were prescribed eyeglasses
were given their eyeglasses to wear and to take home and stock
glasses were collected from children who were not prescribed
eyeglasses.
A follow-up acuity testing session was conducted approximately 6 weeks after the baseline session (targeted follow-up
interval was 1 month after baseline testing, or shortly thereafter),
and a second follow-up acuity testing session was conducted
approximately 1 year after the baseline acuity testing session.
Refractive error correction for the baseline and 6-week follow-up
vision testing sessions was based on the initial eye examination
results. Refractive error correction for the 1-year follow-up vision
testing session was based on the 1-year follow-up eye examination
(identical to the baseline examination) conducted approximately 2
to 3 weeks before the 1-year follow-up visual acuity testing session.
Encouraging and Monitoring of Treatment
Compliance
On the day eyeglasses were initially dispensed (the baseline acuity
testing session), children who required eyeglasses were given a
pair and were instructed to wear them all the time. A spare pair of
eyeglasses was given to the child’s teacher to keep in the classroom. Teachers were asked to give the spare eyeglasses to the child
if they forgot to bring their other pair to school and to try to collect
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them at the end of the day so that the child would always have a
pair at school. Eyeglasses were repaired or replaced whenever they
became lost, broken, or badly scratched. A study staff member
responsible for monitoring eyeglass wear carried a spare for each
child so that they could be dispensed as soon as needed. As soon
as this spare was dispensed, a replacement spare was immediately
ordered. At the end of the school year, the child was given the
classroom spare to take home and was instructed to use them if
their other pair became lost or broken over the summer break.
Eyeglass wear was monitored by a study staff member who
made periodic visits to classrooms and by teachers who were given
daily log books to record whether children were wearing their
eyeglasses. The log books also served as a reminder to teachers to
dispense the classroom pair if the child did not have his or her
eyeglasses.
rating for their compliance rating. Confidence was rated on a scale
from 1 to 5, with 1 representing “very low confidence or little data
available” and 5 representing “very high confidence or a lot of data
available.” Children with mean compliance and mean compliance
confidence ratings of 3 or more were considered highly compliant.
Finally, secondary analysis of treatment outcome data was
conducted to determine what proportion of children identified as
amblyopes at baseline were responsive to treatment. Amblyopia
was defined as RE best-corrected letter visual acuity of 20/40 or
worse. For the astigmatic children identified as amblyopes at
baseline, analyses focused on comparing the percentage of YC
versus OC children who no longer met the criterion for amblyopia
after 1 year of treatment.
Results
Data Analysis and Predictions
All visual acuity analyses were based on RE data. Subjects were
assigned to groups based on the cycloplegic refraction results of
the baseline eye examination. The nonastigmatic control group
was composed of children with little or no astigmatism (⬍0.75 D
in the RE and the left eye), and the astigmatic group was composed
of children with high RE with-the-rule astigmatism (ⱖ1.00 D;
axis, 90⫾15°) and uncorrected letter acuity worse than 20/20
(children with 20/20 or better uncorrected visual acuity were not
prescribed eyeglasses [i.e., were untreated] per study protocol).
Data from subjects who did not meet the criteria for the nonastigmatic or the astigmatic group, subjects with any ocular abnormalities (other than high refractive error), and subjects with anisometropia (⬎1.50 D interocular difference in spherical equivalent)
were excluded from analyses.
The astigmatic group was divided further into previously untreated children (no history of eyeglass wear, per parent report) and
previously treated children (positive history of eyeglass wear, per
parent report). Subjects also were categorized by age group: children younger than 8 years (YC) versus children 8 years of age and
older (OC).
Primary analyses compared the mean change in best-corrected
visual acuity over time across groups using a repeated-measures
analysis of variance. Significant treatment effects were defined as
significantly greater improvement in mean best-corrected visual
acuity over time in the astigmatic group relative to the nonastigmatic group. A repeated-measures analysis of variance compared
mean change in measurements of best-corrected visual acuity
across cohorts (YC vs. OC) from baseline to 6 weeks to 1 year. To
increase statistical power, particularly with regard to detecting
subtle effects of previous treatment, cohort, or both on treatment
effectiveness, separate analyses evaluating change from baseline to
6 weeks also were conducted because the sample size for this
follow-up period was substantially greater than the sample size for
the 1-year follow-up period. The difference in samples size primarily was because additional children were allowed to enter the
study during the second year (when 1-year data were being collected on subjects enrolled during the first year), and these additional children provided baseline and 6-week data, but not 1-year
data.
Secondary analyses of best-corrected visual acuity data evaluated the influence of treatment compliance on outcome of treatment. All compliance data for each child were reviewed by 4 raters
(study staff members). Raters provided a compliance rating on a
scale from 1 to 5, with 1 representing “never wore eyeglasses” and
5 representing “always wore eyeglasses.” Because the amount of
compliance data available varied across subjects (e.g., some teachers recorded in the log books consistently and others recorded in
them rarely or not at all), the raters also provided a confidence
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A total of 1048 kindergarten through second-grade and fourththrough sixth-grade children were enrolled in the study. Of these
children, 250 were excluded from analyses for the following
reasons: anisometropia and ocular abnormality (n ⫽ 1), strabismus
and ocular abnormality (n ⫽ 1), history of patching (n ⫽ 1),
anisometropia and strabismus (n ⫽ 2), undilated at initial examination (n ⫽ 2; 1 declined, 1 dilated poorly), met the criteria for
astigmatic group but no data on previous treatment were available
(n ⫽ 7), strabismus (n ⫽ 11), ocular abnormality other than
strabismus (n ⫽ 11), anisometropia (n ⫽ 18), lost to follow-up
after baseline eye examination (no baseline best-corrected visual
acuity data collected, n ⫽ 39), or did not meet the criteria for either
group (nonastigmatic or astigmatic, n ⫽ 157).
Of the 798 children who provided baseline best-corrected visual acuity data and met the inclusion criteria, 94.7% (756/798)
were tested at 6 weeks (acuity testing was not completed on 4
children [⬍1%], 38 [5%] were lost to follow-up). Both 6-week and
1-year follow-up data were collected for 67.5% of children (539/
798) who provided baseline best-corrected visual acuity data (5
[1%] did not complete acuity testing at 1 year; 112 [14%] were lost
to follow-up at 6 weeks, 1 year, or both; and 142 [18%] entered the
study during the second year of testing for their cohort and contributed baseline and 6-week data, but testing at 1 year was not
attempted because testing of their cohort had ended). For the
sample of 756 children followed up for at least 6 weeks, 372
children were younger than 8 years of age and were assigned to the
YC (mean age, 6.37 years; standard deviation (SD), 0.84 year;
range, 4.75–7.99 years), and 384 children were at least 8 years of
age and were assigned to the OC (mean age, 10.55 years; SD, 1.36
years; range, 8.00 –13.53 years).
Of the 756 children who met the inclusion criteria and were
tested at 6 weeks, 446 (59.0%) met the criteria for the nonastigmatic group and 310 (41.0%) met the criteria for the astigmatic
group. Among astigmats, 93 (30.0%) had no previous eyeglass
correction and 217 (70.0%) reported a positive history of eyeglass
correction. However, only 58 (18.7%) astigmats were wearing
eyeglass correction on initial examination. For the smaller sample
of 539 children who were tested at both 6 weeks and 1 year, 320
(59.4%) met the criteria for the nonastigmatic group and 219
(40.6%) met the criteria for the astigmatic group (52 [23.7%] with
no previous eyeglass correction and 167 [76.3%] with a positive
history of eyeglass correction).
The first follow-up vision testing session (6-week follow-up)
occurred at an average of 45 days after the baseline vision testing
session (range, 18 –184 days for the 6-week follow-up sample [n ⫽
756] and ranging from 18 to 96 days for the smaller sample of
children followed 1 year [n ⫽ 539]). The 1-year follow-up vision
testing session was conducted an average of 376 days (range,
237–519 days) after the baseline vision testing session. A summary
Harvey et al 䡠 Treatment of Astigmatism-Related Amblyopia
Table 1. Sample Sizes and Mean Weeks from Baseline to Follow-up for All Children Followed up at the First (Short-Duration)
Follow-up (n ⫽ 756) and for Children Who Were Tested at Both the Short- and Long-Duration Follow-ups (n ⫽ 539)
Short Follow-up Sample
Weeks from Baseline to First
Follow-up
Short and Long Follow-up Sample
Weeks from Baseline to First
Follow-up
Weeks from Baseline
to Second Follow-up
Cohort
Group
N
Mean
Standard
Deviation
N
Mean
Standard
Deviation
Mean
Standard
Deviation
Younger cohort (⬍8 yrs)
Nonastigmats*
Astigmats†
Total
Nonastigmats*
Astigmats†
Total
Nonastigmats*
Astigmats†
Total
193
179
372
253
131
384
446
310
756
6.75
7.39
7.06
5.64
6.01
5.76
6.12
6.80
6.40
2.43
2.87
2.67
1.94
2.38
2.10
2.23
2.75
2.48
133
117
250
187
102
289
320
219
539
6.85
7.62
7.21
5.60
5.85
5.69
6.12
6.79
6.39
2.29
2.47
2.40
1.92
2.01
1.95
2.17
2.43
2.30
53.72
54.00
53.86
53.50
53.71
53.58
53.59
53.87
53.71
6.46
5.62
6.07
4.00
4.13
4.04
5.16
4.98
5.08
Older cohort (ⱖ8 yrs)
Total
*Right eye and left eye, ⬍0.75 diopters of astigmatism.
Right eye, ⱖ1.00 diopters of astigmatism.
†
of mean length of follow-up interval for each group and for each
cohort at 6 weeks and 1 year is provided in Table 1. Preliminary
analyses indicated that there were significant differences among
groups on length of follow-up. The mean 1-year follow-up interval
did not differ by cohort or by astigmatism group, but for both the
larger 6-week follow-up sample and the smaller 1 year follow-up
sample, the mean baseline to 6-week interval was significantly
longer for the YC than for the OC and was longer for astigmats
than for nonastigmats (all P⬍0.01). Therefore, repeated-measures
analyses of covariance (rather than repeated-measures analyses of
variance) were conducted to include duration of follow-up as
covariates.
Baseline Best-Corrected Letter Visual Acuity
An analysis of variance of baseline best-corrected visual acuity
data yielded a significant effect across groups (F2,750 ⫽ 151.01,
P⬍0.001) and a significant effect of cohort (F1,750 ⫽ 24.60,
P⬍0.001), reflecting significantly better best-corrected visual acuity in the OC than in the YC. The interaction between group and
cohort was not significant. Post hoc analyses comparing bestcorrected visual acuity across groups (with Bonferroni correction)
indicated that best-corrected visual acuity was significantly poorer
in the astigmatic groups (previously treated [mean logMAR visual
acuity, 0.24; SD, 0.17] and previously untreated [0.30; SD, 0.16;
P⬍0.001]) in comparison with the nonastigmatic group (mean
logMAR visual acuity, 0.04; SD 0.15), and the previously untreated astigmats had significantly poorer mean best-corrected
visual acuity than the previously treated astigmats (P⬍0.003).
When analyses were restricted only to subjects who completed
both the 6-week and 1-year follow-ups, the main effects of group
and cohort remained significant, and the group by cohort interaction neared significance (P⬍0.06; Fig 2A). Post hoc analyses
indicated that mean best-corrected visual acuity in treated astigmats was better than in untreated astigmats, but the difference no
longer reached statistical significance.
Change in Best-Corrected Letter Acuity: Baseline
versus 6 Weeks
Repeated-measures analyses of covariance yielded significant
main effects of time (F1,749 ⫽ 7.56, P⬍0.007, reflecting signifi-
cantly better best-corrected visual acuity at follow-up), group
(F2,749 ⫽ 157.43, P⬍0.001, reflecting significantly better bestcorrected visual acuity in the nonastigmatic group than in the
astigmatic groups [P⬍0.001] and better best-corrected visual acuity in the previously treated astigmats than in the previously
untreated astigmats [P⬍0.003]), and cohort (F1,749 ⫽ 37.35,
P⬍0.001, reflecting better best-corrected visual acuity in the OC
than in the YC).
There was a significant interaction between time and group
(F2,749 ⫽ 12.93, P⬍0.001). Post hoc analyses indicated that there
was significantly more improvement in the astigmatic groups
(previously treated and previously untreated) than in the nonastigmatic group (P⬍0.001), but no difference between previously
treated and previously untreated astigmats. The interaction between time, group, and cohort was not significant (P ⫽ 0.41),
indicating that there was no evidence of differences in treatment
effect between the YC and the OC.
Change in Best-Corrected Letter Acuity: Baseline
versus 6 Weeks versus 1 Year (Fig 2A)
Repeated-measures analyses of covariance on data from subjects
who completed best-corrected letter acuity measurements at baseline, 6 weeks, and 1 year (n ⫽ 539) yielded significant main effects
of time (F2,530 ⫽ 3.04, P⬍0.05, reflecting significant improvement
from baseline to 6 weeks and from 6 weeks to 1 year), group
(F2,531 ⫽ 150.60, P⬍0.001, reflecting significantly better bestcorrected visual acuity in the non-astigmatic group than in the
astigmatic groups), and cohort (F1,531 ⫽ 22.48, P⬍0.001, reflecting better best-corrected visual acuity in the OC than in the YC).
There was a significant interaction between time and group
(F4,1062 ⫽ 8.10, P⬍0.001). Post-hoc analyses indicated that there
was significantly greater mean improvement from baseline to 6
weeks in the astigmatic groups than in the non-astigmatic group
(P⬍0.001), but no difference between previously treated and previously untreated astigmats. Amount of improvement from 6
weeks to 1 year did not differ significantly among groups. The
interaction between time, group, and cohort was not significant
(P ⫽ 0.21), indicating that there was no evidence of differences in
treatment effect between the YC and the OC.
Because of the large range in the follow-up intervals for 6
weeks and 1 year (Table 1), a post hoc analysis was conducted to
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and previously untreated astigmats. The amount of improvement
from 6 weeks to 1 year did not differ significantly among groups.
Final Best-Corrected Letter Visual Acuity
(1 Year)
An analysis of covariance comparing final best-corrected visual
acuity (1 year after baseline testing) by group and cohort yielded
main effects of group (F2,531 ⫽ 92.74, P⬍0.001), indicating that
nonastigmats still had significantly better best-corrected visual
acuity than astigmats (previously treated and previously untreated)
after 1 year of treatment (P⬍0.001), and a main effect of cohort
(F1,531 ⫽ 12.80, P⬍0.001), indicating that the YC still had poorer
best-corrected visual acuity than the OC. The interaction between
group and cohort was not significant (P ⫽ 0.53).
We examined final best-corrected visual acuity data for the
nonastigmatic group in comparison with the astigmatic subjects
who were rated as highly compliant with treatment (mean compliance rating, ⱖ3, and mean confidence in compliance rating,
ⱖ3). As shown in Figure 2B, the results were similar to the overall
sample. An analysis of variance of final best-corrected letter acuity
indicated a significant main effect of group (F2,468 ⫽ 78.82;
P⬍0.001), indicating that even with analysis limited to compliant
subjects, nonastigmats still had significantly better best-corrected
visual acuity than astigmats (previously treated and previously
untreated; P⬍0.001).
Clinical Response to Treatment (Table 2)
Figure 2. Graphs showing the mean best-corrected letter acuity for children tested at baseline, 6 weeks, and 1 year for (A) the entire longitudinal
(1-year) sample of nonastigmats and astigmats and (B) the entire longitudinal (1-year) sample of nonastigmats and compliant astigmats. Open
symbols represent children in the younger cohort (YC); filled symbols
represent children in the older cohort (OC). Means are presented for
nonastigmats, astigmats with no history of previous treatment, and astigmats with a positive history of previous treatment. Bars indicate ⫾1
standard error of the mean.
determine if the pattern of results differed when analyses were
restricted to include only subjects within tighter follow-up windows who are more representative of 6-week and 1-year treatment
intervals. A repeated-measures analysis of covariance on data from
subjects who met the following criteria was conducted: (1) completed best-corrected letter acuity measurements at baseline, 6
weeks, and 1 year; (2) had 6-week follow-up data collected from
4 weeks or more to 8 weeks or less after baseline; and (3) and
1-year follow-up data collected from 10 to 14 months (ⱖ40 to ⱕ56
weeks) after baseline (n ⫽ 341). The interaction between time and
group remained significant (F4,666 ⫽ 4.30, P⬍0.003). Post hoc
analyses indicated that there was still a significantly greater mean
improvement from baseline to 6 weeks in the astigmatic groups
than in the nonastigmatic group (P⬍0.03 for previously untreated
astigmats; P⬍0.001 for previously treated astigmats) and no difference in the amount of improvement between previously treated
2298
For the YC, a significantly larger proportion of children in the
astigmatic groups (previously treated and previously untreated)
than in the nonastigmatic group met the criterion for amblyopia at
baseline (best-corrected visual acuity of 20/40 or worse;
P⬍0.001). For the OC, a significantly larger proportion of children
in the previously treated astigmatic group than in the nonastigmatic group met the criterion for amblyopia (P⬍0.001). Although
a larger percentage of OC children in the previously untreated
astigmatic group than in the nonastigmatic group met the criterion
for amblyopia at baseline, the difference did not reach significance.
The percentage of amblyopes in the previously treated versus the
previously untreated astigmatic groups at baseline did not significantly differ for either the YC or the OC.
Among astigmatic children who met the criterion for amblyopia at baseline, there was a significant reduction in the proportion
with amblyopia at 1 year for astigmatic children in the YC (both
previously treated and previously untreated) and for previously
treated astigmats in the OC (P⬍0.001). The reduction in amblyopia in the previously untreated OC astigmats was 100%, but did
not reach statistical significance because of the small sample of
previously untreated OC children who met the criterion for amblyopia at baseline (n ⫽ 2).
There was no evidence of a significantly reduced treatment
effect in the OC as compared with the YC, nor was there a
suggestion of the predicted cohort effect (a greater reduction in the
proportion of amblyopes in the YC than in the OC). In fact, the
percentage of astigmatic children who still met the criterion for
amblyopia was greater in the YC than in the OC, for both previously untreated and previously treated astigmats, although this
trend was not statistically significant.
Discussion
The results of the present study indicate that: (1) there was
significantly greater improvement in best-corrected letter
Harvey et al 䡠 Treatment of Astigmatism-Related Amblyopia
Table 2. Percentage of Children Who Met the Criterion for Amblyopia (Best-Corrected Visual Acuity of 20/40 or Worse) by Group
and by Cohort at Baselineⴱ and at 1 Year† for the Overall Longitudinal (1-Year) Sample and the Percentage of Children Who Met
the Criterion for Amblyopia at Baseline Who Remained Amblyopic at 1 Year‡
Baseline Amblyopes
Who Remained
Amblyopic at 1 Year‡
1 Year†
Baselineⴱ
Cohort
Group
N
n
%
n
%
N
n
%
Younger cohort (⬍8 yrs)
Nonastigmats
Previously untreated astigmats
Previously treated astigmats
Total
Nonastigmats
Previously untreated astigmats
Previously treated astigmats
Total
133
43
74
250
187
9
93
289
16
27
40
83
8
2
38
48
12.0
62.8
54.1
33.2
4.3
22.2
40.9
16.6
2
6
22
30
4
0
13
18
1.5
14.0
29.7
12.0
2.1
0
14.0
6.2
16
27
40
83
8
2
38
48
1
6
16
23
0
0
12
12
6.3
22.2
40.0
27.7
0
0
31.6
25.0
Older cohort (ⱖ8 yrs)
N ⫽ total no. of children in the group or cohort; n ⫽ no. of amblyopes; % ⫽ of amblyopes in the group or cohort (n/N ⫻ 100).
visual acuity from baseline to 6 weeks in the astigmatic
groups than in the nonastigmatic group, indicating a significant effect of eyeglass treatment; (2) there were no significant treatment effects observed from 6 weeks to 1 year,
suggesting that the observed treatment effects occurred primarily very early in treatment (within the first few weeks);
(3) treatment effects did not differ between cohorts, that is,
there was no evidence that older children were less responsive than younger children to treatment; and (4) astigmats
who had been treated previously with eyeglass correction
had better baseline best-corrected visual acuity than did
astigmats who had not been previously treated, but previous
treatment did not seem to reduce the improvement in bestcorrected visual acuity that occurred after eyeglass correction in the present study (treatment effect did not differ
between previously treated and untreated astigmats).
Analyses that examined reduction in prevalence of amblyopia (best-corrected visual acuity of 20/40 or worse at
presentation) as a result of treatment also showed significant
treatment effects: Most astigmatic children who met the
criterion for amblyopia at baseline no longer met the criterion after 1 year of treatment. However, based on the
percentage of nonastigmats who met the criterion for amblyopia at baseline (12.0% in the YC and 4.3% in the OC),
approximately 12% of younger astigmats and 4% of older
astigmats may have been overdiagnosed, because children
in the nonastigmatic group did not have any ocular abnormalities that might have led to amblyopia. Most likely, these
children performed poorly on the visual acuity test for
reasons unrelated to visual performance (e.g., some children, particularly younger children, may have had difficulty
with the task or were distracted during the task). This is
supported by the fact that only 1 of the nonastigmatic
children who met the criterion for amblyopia at baseline still
met the criterion at 1 year, despite the fact that no treatment
was administered. These results raise the possibility that the
visual acuity criterion for amblyopia diagnosis (20/40 or
worse) may have been too rigorous, particularly for the YC,
and that some of the astigmatic children might have been
overdiagnosed as amblyopes at baseline, leading to an overestimation of the percentage of children successfully treated
(i.e., percentage who no longer met the criterion for amblyopia). However, if we look more conservatively at our
treatment effects by reducing the percentage of children in
the YC who were treated successfully by 12% and the
percentage in the OC by 4%, the percentage of children who
were treated successfully remains substantial (66% and
48%, respectively, for previously untreated and previously
treated in the YC; 96% and 64%, respectively, for previously untreated and previously treated in the OC).
The results of the present study suggest that the introduction of clear visual input (through eyeglass correction of
astigmatic refractive error) is sufficient to result in an improvement in best-corrected visual acuity in school-age
children with astigmatism-related amblyopia and that this
treatment effect occurs over a period of approximately 6
weeks. The results also indicate that the sensitive period for
treatment of astigmatism-related amblyopia with eyeglass
correction alone extends beyond age 7 years, contrary to
previous findings in the literature on astigmatism-related
amblyopia.6,12,14
The results of the present study are not consistent with
the results of our previous study, in which we did not find
significant treatment effects as a result of eyeglass correction of astigmatism in 3- to 5-year-old children.14 A factor
that may have contributed to the difference in effects between our earlier study of preschool children and the present
study is the difference in procedures used in the 2 studies. In
the preschool study, children were tested, both at baseline
and at follow-up, after they had undergone cycloplegic
refraction and while they were wearing trial frames. In
contrast, children in the present study were tested while
wearing eyeglasses and were not cyclopleged during vision
testing. Thus, variability produced by testing under cycloplegia and with trial frames may have masked any improvement in best-corrected visual acuity that occurred between
baseline and follow-up testing in the preschool children.
The results of the present study are consistent with those
of previous studies that have demonstrated a significant
response to eyeglass treatment alone in children with anisometropic or strabismic amblyopia, or both.24 –27 For example, Moseley et al24 reported improvement in all 13 ambly-
2299
Ophthalmology Volume 114, Number 12, December 2007
opic subjects (age range, 3– 6 years) treated with eyeglass
correction alone, 5 of whom had significant astigmatism
(ⱖ1.00 D). Stewart et al25 reported a treatment response to
eyeglass correction alone in anisometropic and strabismic
amblyopes, with an average of 14 weeks to best bestcorrected visual acuity and equal gains at all ages between
age 3 and 8 years. In a randomized trial of eyeglass correction only versus eyeglass correction plus patching (atropine
also prescribed for younger [7- to 12-year-old] children) in
7- to 17-year-old children with strabismic or anisometropic
amblyopia, or both, the Pediatric Eye Disease Investigator
Group reported significant improvement with eyeglass correction alone.26 Furthermore, response to eyeglass treatment
did not seem to be dependent on age. That is, in 7- to
12-year-old children, 25% of the eyeglass correction group
were considered treatment responders (10 or more letters
improvement in visual acuity, relative to baseline acuity),
and in 13- to 17-year-old children, 23% of the eyeglass
correction group were considered treatment responders.
Treatment Effects Occur Early in Treatment
Results of the present study suggest that treatment effects
occur primarily early in treatment (within the first few
weeks; average, 6 weeks), because there were no significant
treatment effects observed from the 6-week to the 1-year
follow-up. Stewart et al25 reported an average of 1 line of
improvement in acuity in the amblyopic eye in anisometropic and strabismic amblyopes after 6 weeks of eyeglass
correction alone and 2 lines improvement after 12 weeks,
with maximum improvement shown after approximately 15
weeks. In a recent study of previously untreated 3- to
6-year-old children with anisometropic amblyopia, the Pediatric Eye Disease Investigator Group reported an average
acuity improvement of 2.9 lines with eyeglass correction
alone, with most improvement occurring within the first 5
weeks (mean improvement, 1.8 lines).27 In most subjects,
improvement occurred within the first few months: 83%
stopped improving within 15 weeks of initiating eyeglass
wear. However, the study also provided evidence to suggest
that further improvement would have occurred in some
subjects if they had been followed up for a longer period. If
no improvement occurred within a 5-week follow-up interval, subjects were classified as experiencing no further
improvement and were randomized to other treatments.
Results from children who then were randomized into the
eyeglass control group indicated that there was an average
of 1.2 lines of further improvement. It is possible that
improvement occurs more slowly after the initial treatment
period and that 5 weeks is not a sufficient duration to detect
smaller changes. However, the insufficient follow-up interval explanation for null treatment effects beyond the first 6
weeks is less likely in the present study because subjects
were followed up for an average of 1 year.
Residual Deficits: Poor Compliance, Reduced
Plasticity, or Uncorrected Refractive Errors?
Although we did find significant improvement with treatment, the results also indicated that, after 1 year of eyeglass
2300
treatment, the astigmatic groups did not reach the acuity
level of the nonastigmatic control group (Fig 2). This finding can be interpreted in 3 ways: (1) plasticity was limited
in this age range and subjects did not have the capacity to
achieve normal levels of acuity; (2) although there were
treatment effects in compliant subjects, there were null or
reduced treatment effects in poorly compliant subjects, resulting in a reduction in the overall (mean) visual performance in astigmatic children compared with nonastigmatic
children; (3) there were small residual refractive errors, for
example, spherical aberrations or coma, that were present
but not corrected with eyeglasses in the astigmatic groups,
and this failure to provide full correction limited the improvement seen in the astigmatic groups over time; or a
combination thereof. Thus, the analyses of treatment effects
reflect effectiveness (results of all treated, regardless of
compliance), rather than efficacy (results of treatment in
ideal (perfect compliance) circumstances).
Secondary analyses of best-corrected visual acuity data
for compliant astigmatic subjects did not support the hypothesis that poor treatment compliance contributed to the
failure of the astigmatic group to reach normal (nonastigmatic group) levels of best-corrected visual acuity: there
was no evidence of greater treatment effects in compliant
than in noncompliant subjects, nor did compliant subjects
reach, on average, the best-corrected visual acuity level of
the nonastigmatic group after 1 year of treatment. However,
we can not rule out the possibility that with perfect compliance and sufficient treatment duration, astigmatic subjects might have reached normal best-corrected visual acuity levels.
At this point, we can not rule out the hypothesis that
there were residual (uncorrected) refractive errors in astigmats (e.g., spherical aberrations or coma) that hindered the
improvement resulting from eyeglass wear. An ongoing
study of refractive error development and visual development in Tohono O’odham infants and young children in
which we are longitudinally measuring spherical aberrations
and coma will provide more definitive answers as to
whether there is an association between astigmatism and
higher-order aberrations.
Strengths and Limitations
An important strength of the study design is the inclusion of
a nonastigmatic control group as a normal reference to
allow us to determine if best-corrected visual performance
was significantly below normal in the treatment groups at
baseline and after treatment. In addition, comparison with a
normal control group allows us to rule out the possibility
that improvements over time in the astigmatic groups were
the result of practice effects, cognitive changes in test performance ability, or normal improvement in visual function
resulting from development.
A weakness of the present study is the absence of an
untreated astigmatic control group that was followed up
prospectively. We chose to include a nonastigmatic control
group, rather than an untreated astigmatic control group, to
avoid withholding eyeglass correction to the astigmatic
children enrolled in the study. We believed that this was
Harvey et al 䡠 Treatment of Astigmatism-Related Amblyopia
ethically appropriate for 2 reasons: (1) because eyeglass
correction of astigmatism provides a significant improvement in visual acuity to astigmatic children, even in the
presence of amblyopia,14 and (2) because we did not want to
withhold treatment that was likely to become less effective
if withheld, because the available research indicated that
astigmatism-related amblyopia becomes less responsive to
treatment as children grow older.6,12,14 Therefore, the possibility that the astigmatism groups would have improved
more than the nonastigmatic group over time with no treatment at all can not be ruled out. However, this is unlikely
for 2 reasons: (1) the observed treatment effect occurred
within just a few weeks of treatment initiation, that is,
during a time frame in which natural maturation is not likely
to have had a significant effect; and (2) if astigmatic children improved over time regardless of eyeglass treatment,
the previously untreated OC should have demonstrated
lesser deficits at baseline than the previously untreated YC,
and this was not the case (the interaction between group and
cohort was not significant at baseline).
7.
8.
9.
10.
11.
12.
13.
14.
15.
Conclusions
16.
The results of the present study provide strong evidence that
children older than age 7 years do respond to eyeglass treatment of astigmatism-related amblyopia and suggest that eyeglass treatment alone may be associated with significant reduction in amblyopia in children with bilateral ametropic
amblyopia. These findings may provide incentive for practitioners to stress more strongly to their school-age patients the
importance of eyeglass wear for the treatment of astigmatismrelated amblyopia. The present study and other recent studies
showing responsiveness to amblyopia treatment in older children also should provide incentive for further investigation into
methods of amblyopia treatment in children beyond the preschool and early elementary school years.
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