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Figure 1.
Flowchart showing study completion in each treatment group. Of the 188 patients in the patching group with acuity tested per protocol, 139 completed the visit within the visit window of 100 and 108 weeks after randomization, 15 completed the visit early between 78 and less than 100 weeks, and 34 completed the visit late between more than 108 and 134 weeks. Of the 175 patients in the atropine sulfate group with acuity tested per protocol, 139 completed the visit within the visit window of 100 and 108 weeks after randomization, 14 completed the visit early between 78 and less than 100 weeks, and 22 completed the visit late between more than 108 and 134 weeks.

Flowchart showing study completion in each treatment group. Of the 188 patients in the patching group with acuity tested per protocol, 139 completed the visit within the visit window of 100 and 108 weeks after randomization, 15 completed the visit early between 78 and less than 100 weeks, and 34 completed the visit late between more than 108 and 134 weeks. Of the 175 patients in the atropine sulfate group with acuity tested per protocol, 139 completed the visit within the visit window of 100 and 108 weeks after randomization, 14 completed the visit early between 78 and less than 100 weeks, and 22 completed the visit late between more than 108 and 134 weeks.

Figure 2.
Cumulative distribution of amblyopic eye visual acuity scores at the 2-year outcome examination according to treatment group at the time of randomization.

Cumulative distribution of amblyopic eye visual acuity scores at the 2-year outcome examination according to treatment group at the time of randomization.

Table 1. 
Treatment Prescribed in Phase 2 (6 Months to 2 Years) According to Treatment Group at Time of Randomization
Treatment Prescribed in Phase 2 (6 Months to 2 Years) According to Treatment Group at Time of Randomization
Table 2. 
Visual Acuity in the Amblyopic Eye at the 2-Year Outcome Examination by Treatment Group at Time of Randomization*
Visual Acuity in the Amblyopic Eye at the 2-Year Outcome Examination by Treatment Group at Time of Randomization*
Table 3. 
Visual Acuity in the Amblyopic Eye at the 2-Year Outcome Examination Stratified by Baseline Acuity in the Amblyopic Eye
Visual Acuity in the Amblyopic Eye at the 2-Year Outcome Examination Stratified by Baseline Acuity in the Amblyopic Eye
Table 4. 
Visual Acuity in the Sound Eye at 2 Years According to Treatment Group Assignment at Randomization*
Visual Acuity in the Sound Eye at 2 Years According to Treatment Group Assignment at Randomization*
Table 5. 
Binocularity Testing at the 2-Year Outcome Examination by Treatment Group Assignment at Randomization*
Binocularity Testing at the 2-Year Outcome Examination by Treatment Group Assignment at Randomization*
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National Eye Institute Office of Biometry and Epidemiology, Report on the National Eye Institute's Visual Acuity Impairment Survey Pilot Study.  Washington, DC Department of Health and Human Services1984;81- 84
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Simons  K Preschool vision screening: rationale, methodology and outcome. Surv Ophthalmol 1996;413- 30
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Attebo  KMitchell  PCumming  R  et al.  Prevalence and causes of amblyopia in an adult population. Ophthalmology 1998;105154- 159
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Pediatric Eye Disease Investigator Group, A randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120268- 278
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Holmes  JMBeck  RWRepka  MX  et al.  The amblyopia treatment study visual acuity testing protocol. Arch Ophthalmol 2001;1191345- 1353
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Moke  PSTurpin  AHBeck  RW  et al.  Computerized method of visual acuity testing: adaptation of the amblyopia treatment study visual acuity testing protocol. Am J Ophthalmol 2001;132903- 909
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Gregersen  ERindziunski  E “Conventional” occlusion in the treatment of squint amblyopia: a 10-year followup. Acta Ophthalmol (Copenh) 1965;43462- 474
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Fletcher  MCSilverman  SJBoyd  JCallaway  M Biostatistical studies: comparison of the management of suppression amblyopia by conventional patching, intensive hospital pleoptics, and intermittent office pleoptics. Am Orthopt J 1969;1940- 47
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Rutstein  RPFuhr  PS Efficacy and stability of amblyopic therapy. Optom Vis Sci 1992;69747- 754
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Levartovsky  SOliver  MGottesman  NShimshoni  M Factors affecting long term results of successfully treated amblyopia: initial visual acuity and type of amblyopia. Br J Ophthalmol 1995;79225- 228
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Leiba  HShimshoni  MOliver  MGottesmann  NLevartovsky  S Long-term follow-up of occlusion therapy in amblyopia. Ophthalmology 2001;1081552- 1555
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Sparrow  JCFlynn  JT Amblyopia: a long-term followup. J Pediatr Ophthalmol 1977;14333- 336
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Simons  KGotzler  KCVitale  S Penalization versus part-time occlusion and binocular outcome in treatment of strabismic amblyopia. Ophthalmology 1997;1042156- 2160
PubMedArticle
Clinical Trials
February 2005

Two-Year Follow-up of a 6-Month Randomized Trial of Atropine vs Patching for Treatment of Moderate Amblyopia in Children

The Pediatric Eye Disease Investigator Group*
Author Affiliations
 

W. BECKROYMD, PhD*The writing committee served as author for the Pediatric Eye Disease Investigator Group (PEDIG). A complete list of writing committee members is as follows: lead authors: Michael X. Repka, MD; David K. Wallace, MD; Roy W. Beck, MD, PhD; Raymond T. Kraker, MSPH. Additional writing committee members (alphabetical): Eileen E. Birch, PhD; Susan A. Cotter, OD; Sean Donahue, MD; Donald F. Everett, MA; Richard W. Hertle, MD; Jonathan M. Holmes, BM, BCh; Graham E. Quinn, MD, MSCE; Mitchell M. Scheiman, OD; David R. Weakley, MD.

Arch Ophthalmol. 2005;123(2):149-157. doi:10.1001/archopht.123.2.149
Abstract

Objective  To compare patching and atropine sulfate as treatments for moderate amblyopia in children 18 months after completion of a 6-month randomized trial.

Methods  In a randomized, multicenter (47 sites) clinical trial, 419 children younger than 7 years with amblyopia (20/40 to 20/100 in the affected eye) were assigned to receive either patching or atropine eye drops for 6 months. Between 6 months and 2 years, treatment was at the discretion of the investigator.

Main Outcome Measure  Visual acuity in the amblyopic eye and sound eye after 2 years.

Results  At 2 years, visual acuity in the amblyopic eye improved from baseline a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group. The difference in visual acuity between treatment groups was small: 0.01 logMAR (95% confidence interval, −0.02 to 0.04). In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20.

Conclusions  Atropine or patching for 6 months followed by best clinical care until 2 years produced similar improvement of moderate amblyopia in children between 3 and 7 years of age at enrollment. However, on average the amblyopic eye acuity was still approximately 2 lines worse than the sound eye.

Amblyopia is the most common cause of monocular visual impairment in children and young and middle-aged adults.13 Patching of the sound eye and, less commonly, atropine sulfate drops for the sound eye have been the mainstays of therapy. We conducted a randomized trial that compared patching with atropine as treatments for moderate amblyopia (20/40 to 20/100 in the affected eye) in children younger than 7 years.4 As previously reported, we found that substantial improvement in the visual acuity of the amblyopic eye occurred with both patching prescribed for at least 6 hours per day and atropine instilled daily. After 6 months, the difference between groups (approximately one-third of a line) was clinically inconsequential.

The 6-month outcome examination was designed to allow us to compare the treatments after a fixed treatment interval and not necessarily to represent the maximum treatment benefit possible from either intervention. Longer treatment is commonly prescribed to improve vision maximally and maintain the improvement, with therapy often extending for several years. Therefore, the clinical trial was designed to include a 2-year follow-up period to allow us to estimate the impact of longer amblyopia treatment on the visual acuity of both the amblyopic and sound eyes. In this study, the patients continued with the randomly assigned treatment for the first 6 months, but from 6 months until the 2-year outcome examination, the participating investigators could prescribe any type of amblyopia therapy. In this article, we evaluate the visual acuity of the amblyopic and sound eyes, binocularity, and ocular alignment at 2 years.

METHODS

The study, supported through cooperative agreements with the National Eye Institute of the National Institutes of Health (Bethesda, Md), was conducted by the Pediatric Eye Disease Investigator Group at 47 clinical sites. The protocol and informed consent forms were approved by institutional review boards, and the parent or guardian (hereafter referred to as parent) of each study patient gave written informed consent. Study oversight was provided by an independent data and safety monitoring committee. The study protocol has been detailed in prior publications and is briefly described herein.4

Eligibility criteria included age younger than 7 years, visual acuity in the amblyopic eye from 20/40 to 20/100, visual acuity in the sound eye of 20/40 or better, intereye acuity difference of 3 or more logMAR lines, and the presence or history of an amblyogenic factor that met study-specified criteria for strabismus and/or anisometropia.

During the first 6 months (phase 1), protocol-specified follow-up visits were conducted after 5, 17, and 26 weeks. Between 6 months and 2 years (phase 2), the protocol specified that patients were to be examined at least once every 6 months, with a final outcome examination at 2 years.

Both treatment groups followed a structured treatment protocol until the 6-month outcome examination. Before this examination, patients in the patching group were not to be prescribed atropine, and patients in the atropine group were not to be prescribed patching. The patching group was initially prescribed from 6 hours to full-time daily patching at investigator discretion; prescribed hours of patching were increased to full time (all waking hours or all waking hours except 1 hour) at 4 months if the amblyopic eye acuity was worse than 20/32 or had not improved from baseline by at least 3 lines. The atropine group was initially prescribed 1 drop of 1% atropine sulfate daily; for patients with hyperopia in the sound eye, the sound eye spectacle lens was changed to plano at 4 months if amblyopic eye acuity was worse than 20/32 or had not improved from baseline by at least 3 lines. After the first 6 months, treatment was prescribed at investigator discretion. Guidelines were provided to taper treatment for 3 months before being discontinued, and if amblyopia recurred, the initial successful treatment regimen was to be reinstituted.

Visual acuity in the amblyopic eye was the primary efficacy outcome measure, and acuity in the sound eye was the primary safety outcome measure. Visual acuity was measured using the Amblyopia Treatment Study (ATS) visual acuity testing protocol administered by a study-certified vision tester.5,6 Cycloplegic refractions were performed at baseline, at 6 months, and once within 6 months before the 2-year outcome visit. At the 2-year examination, a tester masked to the patient’s treatment group conducted visual acuity testing. Parents of children receiving atropine were instructed to discontinue its use at least 14 days before the examination. At the 2-year examination, if the sound eye acuity was worse than 20/20, the acuity was retested. If the acuity was still worse than 20/20 and either the cycloplegic refraction had changed or atropine had been used within the prior 2 weeks, the sound eye acuity was retested at a subsequent visit. The best visual acuity was used for data analysis.

Testing at 2 years included an assessment of ocular alignment with the simultaneous prism and cover test at distance and near fixation; an assessment of stereoacuity measured with the Randot Preschool Stereoacuity Test, Titmus fly, and Randot 2 Test (circles, animals, and random dot shapes); and an assessment of fusion suppression with the Randot Suppression Test (the R, +, and L symbols of the Randot Stereotests) and Worth 4-Dot Test (with the green lens over the amblyopic eye and the flashlight held 0.3 m from the child). The Randot Preschool Stereoacuity Test was specified as the primary outcome measure of binocularity for this study.

The primary outcome was the 2-year amblyopic eye visual acuity score measured on a logMAR scale. The randomized treatment groups were compared in an analysis-of-covariance model in which the logMAR acuity scores were adjusted for baseline acuity. Patients were included in the primary analysis if they had a visual acuity measurement in the amblyopic eye that was tested according to the ATS visual acuity testing protocol within the window of the 2-year outcome examination (±4 weeks) or, in the absence of such a visit, if they had a visual acuity measurement with the ATS visual acuity testing protocol that was not more than 6 months before or after the outcome examination target date. Patients who completed the 2-year outcome examination but had their visual acuity tested with a method other than the ATS visual acuity testing protocol were not included in the primary analysis. A secondary analysis that included the visual acuity data from all of these patients produced results similar to the primary analysis (data not shown). Interaction between baseline factors (cause of amblyopia, baseline amblyopic eye acuity, and age) and treatment group for the 2-year outcome acuity was assessed by including interaction terms in the analysis-of-covariance models.

The treatment group difference for sound eye visual acuity at 2 years was evaluated in an analysis-of-covariance model in which the sound eye acuities were adjusted for baseline acuity. Unless otherwise specified, differences in proportions between treatment groups were evaluated with a Fisher exact test, and differences in continuous outcomes between treatment groups were evaluated with an independent-sample t test. Within each treatment group, the association between the baseline amblyopic eye acuity and 2-year amblyopic eye acuity was evaluated in an analysis of variance. All reported P values are 2-tailed. Analyses were conducted using SAS statistical software, version 8.2 (SAS Institute Inc, Cary, NC).

RESULTS

The 2-year outcome examination was completed for 396 (95%) of the 419 patients enrolled. However, 6 patients completed the examination more than 6 months late, and 27 patients did not have their visual acuity measured with the ATS visual acuity testing protocol (these were patients who had moved and examinations were arranged in their new area). These 33 patients (13 in the patching group, 20 in the atropine group) were not included in the primary analysis, reducing the number of patients to 363 (87% of enrolled patients): 188 in the patching group and 175 in the atropine group (Figure 1). Of these 363 patients, the vision tester was masked to treatment group 92% of the time (92% in the patching group and 93% in the atropine group).

The 363 patients who completed the 2-year outcome examination had a mean age of 5.2 years at enrollment and 7.2 years at the 2-year examination; 47% were female. The mean visual acuity in the amblyopic eye at enrollment was 0.53 logMAR (approximately 20/63), with a mean intereye acuity difference of 4.4 lines. There were no meaningful differences in demographic or baseline clinical characteristics of the 56 patients not included in the analysis compared with the 363 patients with a visit (data not shown).

TREATMENT PRESCRIBED IN PHASE 2 (6 MONTHS TO 2 YEARS)

Most patients in both groups were prescribed amblyopia therapy during phase 2 (91% in the patching group and 85% in the atropine group) (Table 1). During the 2-year outcome examination, approximately one third of patients were still being treated for amblyopia (36% in the patching group and 37% in the atropine group).

The actual treatment regimens prescribed beyond 6 months until the 2-year outcome were related to the initial treatment assignment at randomization. Patching was prescribed for 84% of children treated with patching during the initial 6 months, whereas atropine was prescribed for 78% of children treated with atropine during the initial 6 months. Similar percentages of patients were switched to the opposite treatment (28% in the patching group and 25% in the atropine group). Both patching and atropine were prescribed, although not generally concurrently, for 21% in the patching group and 18% in the atropine group.

VISUAL ACUITY IN THE AMBLYOPIC EYE AT 2 YEARS

At the 2-year visit, visual acuity had improved from baseline by a mean of 3.7 lines in the patching group and 3.6 lines in the atropine group (mean difference between groups in logMAR acuity adjusted for baseline acuity was 0.01 [less than 1 letter]; 95% confidence interval, −0.02 to 0.04) (Figure 2 and Table 2). Eighty-six percent of patients in the patching group and 83% of patients in the atropine group had 3 or more lines of improvement from baseline and/or visual acuity in the amblyopic eye better than or equal to 20/32 (P = .56). The relative treatment effect between groups was not modified by baseline visual acuity (P for interaction = .40), cause of amblyopia (strabismus, anisometropia, and combined mechanism, P for interaction = .42), or age (P for interaction = .92).

In both treatment groups, the mean amblyopic eye acuity was approximately 20/32, 1.8 lines worse than the mean sound eye acuity, which was approximately 20/20 (Table 2). Forty-nine percent of patients in the patching group and 46% of patients in the atropine group had an intereye acuity difference of 1 line or less. In both groups, there was a greater deficit in the 2-year amblyopic eye acuity when the baseline amblyopic eye acuity was worse (P = .002 in the patching group and P<.001 in the atropine group) (Table 3).

Most of the improvement in visual acuity of the amblyopic eye was seen during the first 6 months of treatment. However, the amblyopic eyes in both groups continued to improve between 6 months and 2 years (mean change in acuity from 6 months to 2 years was 0.5 line in the patching group and 0.8 line in the atropine group, P = .08). Of the 124 patients with 20/25 or better acuity in the amblyopic eye at the 6-month examination, 23 (19%) had a reduction in the visual acuity of the amblyopic eye of 2 lines or greater at the 2-year outcome examination (14 [19%] of 75 in the patching group and 9 [18%] of 49 in the atropine group, P = .99). Of the 235 patients with 20/32 or worse acuity in the amblyopic eye at the 6-month examination, 92 (39%) improved to 20/25 or better at 2 years (43 [38%] of 112 in the patching group and 49 [40%] of 123 in the atropine group, P = .89).

A secondary analysis was performed of the outcomes for those patients who received their randomized treatment only during the 2 years of the study. Among the 135 patients in the patching group, amblyopic eye acuity at 2 years was 20/16 in 7%, 20/20 or better in 27%, and 20/25 or better in 54%, whereas among the 132 patients in the atropine group, the percentages were 14%, 31%, and 53%, respectively.

VISUAL ACUITY IN THE SOUND EYE AT 2 YEARS

Mean sound eye visual acuities were similar in the 2 treatment groups at 2 years (mean logMAR visual acuity score, −0.02 in the patching group and −0.01 in the atropine group; P = .27) (Table 4). One patient in the atropine group was actively treated in phase 2 with patching for presumed reverse amblyopia, which resolved with treatment.

Of the 17 patients in the atropine group who at 6 months had a reduction of 2 or more lines in sound eye visual acuity from baseline, 16 (94%) tested 20/20 or at least equal to baseline at the 2-year examination. The remaining patient tested 20/32 at 2 years compared with 20/25 at baseline. Of the 3 patients in the patching group who at 6 months had a reduction of 2 or more lines in sound eye visual acuity from baseline, all 3 (100%) tested 20/20 or at least equal to baseline at the 2-year examination.

OCULAR ALIGNMENT

During the study, there were no differences between treatment groups in the number of patients who developed new-onset strabismus, had an increase or decrease in a preexisting strabismus, or had surgery for preexisting strabismus between baseline and 2 years (data not shown).

STEREOACUITY AT 2 YEARS

Overall, there was no difference between treatment groups in stereopsis or suppression at the 2-year outcome examination (Table 5). However, in an unplanned post hoc subgroup analysis of patients classified at baseline to have anisometropic amblyopia (without strabismus or a history of strabismus), there was a consistent trend for stereopsis and fusion to be better at 2 years in the patching group compared with the atropine group. This trend was less apparent for the study’s primary measure of stereoacuity (Randot Preschool Stereoacuity Test). No difference was seen between treatment groups in binocular function outcomes for patients classified as having strabismic or combined-mechanism amblyopia (data not shown).

COMMENT

We compared the effectiveness at 2 years of an initial 6-month treatment of occlusion with eye patches followed by best clinical care with an initial 6-month treatment with daily topical 1% atropine sulfate followed by best clinical care in a randomized trial. The patient cohort included children younger than 7 years at randomization with moderate amblyopia (visual acuity, 20/40 to 20/100) from strabismus, anisometropia, or both. Substantial improvement in visual acuity had been observed in both treatment groups at the 6-month study examination (3.16 lines in the patching group and 2.84 lines in the atropine group).4 Additional improvement was seen in both treatment groups at 2 years. There continued to be no meaningful difference between groups in either mean visual acuity score or lines of improvement. The distributions of outcome acuities in the amblyopic eyes were remarkably similar, with 51% in the patching group and 49% in the atropine group achieving 20/25 or better.

It is noteworthy that at 2 years only approximately 50% of amblyopic eyes in both treatment groups were 20/25 or better compared with 94% of sound eyes, and, on average, in both treatment groups the amblyopic eye was 1.8 lines worse than the sound eye. The mean intraocular difference may be a slight overestimate because the study protocol specified retesting of all sound eyes with vision worse than 20/20, whereas amblyopic eyes were not retested. The difference in acuity between the sound and amblyopic eyes after 2 years was more apparent in both treatment groups when the amblyopic eye at baseline was at the worse end of the acuity range. There are several possible explanations for the persistent deficit in the amblyopic eyes. Some amblyopic eyes may never reach 20/25 because of biochemical or anatomic limitations in the eye and brain. Some eyes may have developed a recurrence of amblyopia before the 2-year outcome acuity measurement, which might improve with further treatment. Finally, for some patients the treatment may not have been of sufficient intensity or duration. These issues could be addressed by future clinical trials that evaluate the merit of increasing therapy for residual amblyopia before stopping treatment or the use of continued maintenance therapy.

In phase 2 (6 months to 2 years) of the trial, we did not mandate that patients continue with the randomized treatment assigned for the full 2 years. This was partly owing to lack of data to support atropine’s efficacy when the trial was designed and to the need to be able to switch patients with residual amblyopia to an alternate treatment regimen when they were no longer showing improvement with the assigned treatment. Therefore, after the first 6 months, treatment decisions were left to investigator judgment. The 2-year treatment group comparison essentially consisted of a 6-month protocol-defined treatment regimen followed by best clinical care. The study investigators prescribed amblyopia treatment for most of the patients between 6 months and 2 years. There was a tendency for the investigators to prescribe the same therapy used during the initial 6 months of the study for treatment during phase 2. We did not collect data on the reasons for the treatment chosen by the investigators. At 2 years, approximately one third of patients in each group were still undergoing some form of amblyopia therapy. From our data we cannot determine the duration of amblyopia treatment necessary for maximum benefit; however, it is apparent that for many patients, improvement with either patching or atropine can occur even after 6 months of treatment.

Clinicians have long been concerned about the permanence of the treatment benefit. Recidivism is commonly reported in outcome studies of children treated for amblyopia, thereby reducing the actual benefit of therapy.712 Overall, 19% of children who had a visual acuity of 20/25 or better in the affected eye at 6 months were found to have a reduction of 2 or more lines in visual acuity at 2 years. This loss occurred even while being monitored in a clinical trial designed to approximate standard clinical practice in which any amblyopia treatment was allowed. One difficulty in assessing recidivism is distinguishing between a true reduction in visual acuity and an apparent reduction due to variability of acuity testing.5 No study-specified evaluation protocol was used by the study investigators to confirm the diagnosis of a recurrence. To answer this question, we are currently conducting a separate observational study in which successfully treated children with amblyopia are monitored during a 1-year follow-up for evidence of recurrence.

In our earlier study, after 6 months of treatment, more patients in the atropine-treated group had a transient reduction in visual acuity of the sound eye.4 At 2 years, there was no difference in sound eye visual acuity between treatment groups. These data confirm our conclusion at 6 months that the acuity reductions that may have been due to atropine at that time were not permanent.

Simons and colleagues13 suggest that atropine treatment may produce better binocular vision than patching therapy. Our results do not support this hypothesis. There was no difference between the patching and atropine treatment groups in the distribution of outcomes determined by each of our measures of binocular function. In fact, a post hoc subgroup analysis limited to the patients with anisometropic amblyopia (no strabismus or history of strabismus) suggested the opposite, that binocular vision might be better in the patching group than in the atropine group. Since this subgroup analysis was not preplanned and the treatment group difference was less apparent on the study’s primary measure of binocularity (Randot Preschool Stereoacuity Test) than on the other measures, we suspect that this finding is likely due to chance or represents such a small difference that it could not be detected using the primary outcome measure despite the large sample size. There was no difference between treatment groups in the rates of development of new strabismus, deterioration of existing strabismus, or improvement of strabismus.

We could identify no sources of bias or confounding to explain our findings. The follow-up visit rate was high in both groups. Although patients, parents, and clinicians were unmasked to treatment group assignment, masking of the 2-year visual acuity tester was present in 92% of cases. In addition, visual acuity testing was performed with a standardized protocol developed for this study to reduce the opportunity for interpretation and to ensure consistency across sites. The sample size for the original clinical trial was selected to have sufficient power to evaluate the effect in treatment subgroups based on cause of amblyopia. As a result, the statistical power to detect a clinically meaningful difference in amblyopic eye acuity after 2 years of treatment and follow-up approached 100%. Thus, it is unlikely that a meaningful treatment group difference exists but was not detected in this study. We can therefore conclude with a high degree of confidence that both patching and atropine for 6 months followed by best clinical care for a period of 18 months produce an improvement in visual acuity of similar magnitude.

In summary, an initial 6-month period of prescribing either atropine or patching treatment followed by best clinical care are both effective treatments for amblyopia. However, in both treatment groups visual acuity in the amblyopic eye remained worse than 20/25 in approximately half of the patients and on average was almost 2 lines worse than the sound eye. The 2-year outcomes we report herein are too early to provide information on the ultimate outcome of treatment of amblyopia. Deterioration of acuity is reportedly common in long-term retrospective studies.11 We will reexamine many of the children in this study at ages 10 and 15 years to determine the long-term visual acuity and binocular vision outcomes.

Correspondence: Michael X. Repka, MD, Jaeb Center for Health Research, 15310 Amberly Dr, Suite 350, Tampa, FL 33647 (pedig@jaeb.org).

Submitted for Publication: January 14, 2004; final revision received October 11, 2004; accepted October 11, 2004.

Financial Disclosure: None.

Funding/Support: This study was supported by a cooperative agreement (EY11751) from the National Eye Institute, Bethesda, Md.

Box Section Ref ID

The Pediatric Eye Disease Investigator Group

CLINICAL SITES THAT PARTICIPATED IN THIS PROTOCOL

Sites are listed in order by number of patients enrolled in the study. The number of patients enrolled is noted in parentheses preceded by the site location and the site name. Personnel are listed as (I) for investigator, (C) for coordinator, and (V) for visual acuity tester.

Rockville, Md (36): Stephen R. Glaser (I), Paige E. Glaser (C), Andrea M. Matazinski (C), Misti D. Schroyer (C), Kelly A. Sirk (V).

Erie, Pa, Pediatric Ophthalmology of Erie (33): Nicholas A. Sala (I), Rhonda M. Hodde (C), Cindy E. Tanner (V), Veda L. Zeto (V).

Dallas, Tex, Pediatric Ophthalmology, PA (26): David R. Stager, Sr (I), Priscilla M. Berry (I), David R. Stager, Jr (I), Maria P. Pesheva (C), Joost Felius (C), Jennifer A. Whalen (C), Brett G. Jeffrey (C), Anna R. O’Connor (C).

Providence, RI, Pediatric Ophthalmology and Strabismus Associates (25): David Robbins Tien (I), Glenn E. Bulan (I), Heidi C. Christ (C), Lauren B. DeWaele (C).

Calgary, Alberta, Alberta Children’s Hospital (24): William F. Astle (I), Maria del Pilar Echeverri (I), Anna L. Ells (I), Trena L. Beer (C), Cheryl R. Hayduk (C), April D. Ingram (C), Catriona I. Kerr (C), Susan M. McMullen (C), Heather J. Peddie (C), Heather M. Vibert (C).

Anchorage, Alaska, Ophthalmic Associates (20): Robert W. Arnold (I), Mary Diane Armitage (C), Nancy H. Brusseau (V), Maru V. Gindling (V), Karen M. Lowe (V).

Bethesda, Md, National Eye Institute (20): Richard W. Hertle (I), Edmond J. Fitzgibbon (V), Guy E. Foster (V), Susan D. Mellow (V), William R. O’Donnell (V).

Milwaukee, Medical College of Wisconsin (18): Jane D. Kivlin (I), Mark S. Ruttum (I), Veronica R. Picard (C), Nahid Saadati (C).

Fullerton, Southern California College of Optometry (17): Susan A. Cotter (I), Carmen N. Barnhardt (I), Raymond H. Chu (I), Susan M. Shin (I), Yvonne F. Flores (C), Lourdes Asiain (C), Tal Barak (V), Connie Chu (V), Lisa Edwards (V), Monique M. Nguyen (V), Jennifer Slutsky (V), Erin Song (V).

Houston, Texas Children’s Hospital (14): Evelyn A. Paysse (I), David K. Coats (I), Kimberly G. Yen (I), Michele L. Fulton (C), Alma D. Sanchez (C).

Nashville, Tenn, Vanderbilt Eye Center (13): Sean Donahue (I), Genise G. Mofiled (C), Sandy A. Owings (C), Ronald J. Biernacki (V), Neva J. Palmer (V).

Portland, Ore, Casey Eye Institute (12): David T. Wheeler (I), Kimberley A. Beaudet (C), Christin L. Bateman (V), Michele A. Hartwell (V), Sara M. Stansell (V).

Sacramento, Calif, The Permanente Medical Group (11): James B. Ruben (I), Dipti Desai (C), Sue Ann Parrish (C), Gerald C. Louie (V), Tracy D. Louie (V).

Baltimore, Md, Wilmer Institute (10): Michael X. Repka (I), Sheena O. Broome (C), Carole R. Goodman (C), Xiaonong Liu (C).

Birmingham, University of Alabama at Birmingham School of Optometry (10): Robert P. Rutstein (I), Wendy L. Marsh-Tootle (I), Katherine K. Niemann (I), Cathy H. Baldwin (C), Kristine T. Becker-Hopkins (V), Paola M. Garjales (V), Bronwen N. Mathis (V).

Indianapolis, Indiana University Medical Center (9): Daniel E. Neely (I), David A. Plager (I), Derek Sprunger (I), Naval Sondhi (I), Jay G. Galli (C), Michele E. Whitaker (C), Donna J. Bates (V), Donna G. Harper (V), Lisa K. Keenan (V).

Miami, Fla, Bascom Palmer Eye Institute (9): Susanna M. Tamkins (I), Eva M. Olivares (C), Bruce D. Bailey (V), Nihusa P. Oviedo (V).

Atlanta, Ga, The Emory Eye Center (7): Scott R. Lambert (I), Rachel A. Reeves (C), Chris S. Bergstrom (V), David Hunter Cherwick (V), Alexander T. Elliott (V), Nicole Fallaha (V), Rebecca E. Sands (V), Lucy Yang (C).

Baltimore, Md, Greater Baltimore Medical Center (7): Mary Louise Z. Collins (I), Cheryl L. McCarus (C), Jana Mattheu (C), Jaime N. Brown (V), Dorothy B. Conlan (V).

Dallas, The University of Texas Southwestern Medical Center (6): David R. Weakley, Jr (I), Clare L. Dias (C), Anna R. O’Connor (V).

Grand Rapids, Mich, Pediatric Ophthalmology, PC (6): Patrick J. Droste (I), Robert J. Peters (I), Jan Hilbrands (C), Kelli A. Sheeran (V), Emily K. Tillman (V), Corrie L. Vanravenswaay (V).

St Louis, Mo, Cardinal Glennon Children’s Hospital (6): Oscar A. Cruz (I), Bradley V. Davitt (I), Emily A. Miyazaki (C), Angela Zimmerman Moya (C).

Waterbury, Conn, The Eye Care Group, PC (6): Andrew J. Levada (I), David N. Comstock (C), Tabitha L. Matchett (C), Angela Zimmerman Moya (C) Cheryl Schleif (V), Shelley K. Weiss (V).

Columbus, The Ohio State University (5): Marjean T. Kulp (I), Tracy L. Kitts (C), Melanie A. Ackerman (V), Michael J. Earley (V), Andrew J. Toole (V).

Philadelphia, Pennsylvania College of Optometry (5): Mitchell M. Scheiman (I), Jo Ann T. Bailey (I), Brandy J. Scombordi (I), Kathleen T. Zinzer (I), Abby M. Grossman (C), Katari D. Campbell (V), Jason R. Hochreiter (V), Karen E. Pollack (V).

Rochester, Minn, Mayo Clinic (5): Jonathan M. Holmes (I), Brian G. Mohney (I), Melissa L. Rice (I), Rebecca A. Nielsen (C), Julie A. Holmquist (V), Rose M. Kroening (V), David A. Leske (V), Marna L. Levisen (V), Deborah K. Miller (V), Debbie M. Priebe (V), Julie A. Spitzer (V).

Buffalo, NY, Children’s Hospital of Buffalo (4): Steven Awner (I), Cheryl Winkleman (V).

Wichita, Kan, Grene Vision Group (5): David A. Johnson (I), Ruth D. Dannar (C), Amy M. Wheeler (V).

Chapel Hill, University of North Carolina Department of Ophthalmology (4): David K. Wallace (I), Melissa W. Compton (C), Madonna R. Petty (V), Marguerite I. Sullivan (V).

Iowa City, The University of Iowa Hospitals and Clinics (4): Ronald V. Keech (I), Richard J. Olson (I), William E. Scott (I), Wanda I. Ottar Pfeifer (C), Sara J. Downes (V), Pamela J. Kutschke (V), Keith M. Wilken (V).

Lancaster, Pa, Family Eye Group (4): David I. Silbert (I), Eric L. Singman (I), Don Blackburn (I), Noelle S. Matta (C), Shannon M. Butler (V), Suanne E. Carner (V), Cristina M. Corradino (V), Troy J. Hosey (V), Diane M. Jostes (V), Alyson B. Keene (V), Stephanie R. Kilgore (V); Tonji L. Nelson (V); Wendy L. Piper (V); Sara L. Weit (V); Sylvia R. Wright (V).

Minneapolis, University of Minnesota (4): C. Gail Summers (I), Stephen P. Christiansen (I), Sally M. Cook (C), Ann M. Holleschau (C), Jane D. Lavoie (V), Kim S. Merrill (V).

Palm Harbor, Fla, Specialty Eye Care (4): Christine L. Burns (I), Le Ila C. Lawrence (C), Lori C. Hawkinson (V).

Tucson, University of Arizona (4): Joseph M. Miller (I), TobyAnne Aparisi (C), Sue Bulau (V), Christine M. Shelton (V).

Birmingham, Alabama Ophthalmology Associates, PC (3): Frederick J. Elsas (I), Thomas H. Metz, Jr (I), Stephanie Sandi A. Briscoe (V), Tammy R. Griffin (V), Connie C. Maddox (V), Michelle L. Mizell (V), Brooke E. Williams (V).

Mexico City, Mexico (3): Miguel Paciuc (I), Marina M. Schnadower (V), Cecilio Velasco (V).

Norfolk, Eastern Virginia Medical School (3): Earl R. Crouch, Jr (I), Kristen D. Ruark (C), Gaylord G. Ventura (V).

Salt Lake City, University of Utah/Moran Eye Center (3): Robert O. Hoffman (I), Susan F. Bracken (C), Deborah Y. Harrison (V), Pat L. Remington (V).

Temple, Tex, Scott and White Ophthalmology (3): David C. Dries (I), Lori A. Carpenter (V), Mary E. Darling (V), V. Jeanne Vengco (V).

Asheville, NC, Asheville Eye Associates (2): Robert E. Wiggins, Jr (I), Sally A. Baumgartner (C), Mary Knecht (V).

Cincinnati, Ohio, Children’s Hospital Medical Center (2): Constance E. West (I), Melissa Rickey (C), Laura E. Dickman (V), Stephanie C. Fort (V), Sarah L. Grimm (V), Laurie A. Hahn-Parrott (V), Kelli N. Kinder (V), Debbie A. Meister (V), Walker W. Motley (V), Shannen L. Nelson (V), Regina M. Poole (V), Shannon R. Walsh (V).

Philadelphia, Children’s Hospital of Philadelphia (2): Brian J. Forbes (I), Graham E. Quinn (I), David R. Phillips (V), Sonia Zhu (V).

Boston, Mass, New England College of Optometry (1): Erik M. Weissberg (I), Barry S. Kran (I), Bruce Moore (I), Nicole M. Quinn (I), Melissa A. Suckow (V).

Canton, Eye Centers of Ohio (1): Elbert H. Magoon (I), Lynn A. McAtee (C), Margie Andrews (V), Kathy Ann Earl (V), Caroline M. Hoge (V), Paula A. Kannam (V), Debby Ann Null (V), Denise Richards (V).

Charleston, Medical University of South Carolina, Storm Eye Institute (1): Richard A. Saunders (I), Amy K. Hutchinson (I), Lisa M. Langdale (C), Judy P. Hoxie (V), Kimberly D. Lenhart (V).

New York, State University of New York, College of Optometry (1): Robert H. Duckman (I), David E. FitzGerald (I).

Washington, DC, Children’s National Medical Center (1): Marijean Michele Miller (I), Mitra Maybodi (I), Cori Greger (C).

PEDIG Coordinating Center, Tampa, Fla: Roy W. Beck, Nicole M. Boyle, Christina M. Cagnina-Morales, Esmeralda L. Cardosa, Danielle L. Chandler, Quayleen Donahue, Heidi A. Gillespie, Julie A. Gillett, Karalyn L. Grant, Raymond T. Kraker, Shelly T. Mares, Holly J. McCombs, Pamela S. Moke.

National Eye Institute, Bethesda: Donald F. Everett.

PEDIG Executive Committee: Michael X. Repka (chair), Jonathan M. Holmes (vice-chair). Roy W. Beck, Eileen E. Birch, Susan A. Cotter, Donald F. Everett, Pamela S. Moke.

Amblyopia Treatment Study Steering Committee: Roy W. Beck, Eileen E. Birch, Susan A. Cotter, Donald F. Everett, Richard W. Hertle, Jonathan M. Holmes, Pamela S. Moke, Graham E. Quinn, Michael X. Repka, Mitchell M. Scheiman.

Data and Safety Monitoring Committee: William Barlow (chair), Edward G. Buckley, Barry Davis, Velma Dobson, John L. Keltner, Hana Osman, Earl A. Palmer, Dale L. Phelps.

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