ATS9: Trial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00315328
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 233
• Locations: 2
• Arms: 2
• Duration (Months): 29
• Patients Per Site: 116.5
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

The purpose of this study is:

• To compare the effectiveness of weekend atropine plus near activities and daily patching plus near activities for moderate amblyopia (20/40 to 20/100) and severe amblyopia (20/125 to 20/400) in improving vision in the amblyopic eye of 7 to <13 year olds.

• To determine the maximum improvement in vision of the amblyopic eye with each treatment.

• To determine whether amblyopia is associated with structural abnormalities of optic nerve fiber layer.

Condition or Disease	Intervention/Treatment	Phase
Amblyopia	Drug: Atropine; Device: Patching; Procedure: Near activities	Phase 3

Detailed Description

Although there is consensus that amblyopia can be treated effectively in young children, many eye care practitioners believe that treatment beyond a certain age is ineffective. Some clinicians have believed that a treatment response is unlikely after the age of 6 or 7 years, while others have considered age 9 or 10 years to be the upper age limit for successful treatment. The American Academy of Ophthalmology Preferred Practice Pattern for amblyopia recommends treatment up to age 10 years. The opinion that amblyopia treatment is ineffective in older children may have arisen because the age of 6 to 7 years is thought to be the end of the "critical period" for visual development in humans. This belief, however, was not based on adequate prospectively-collected data.

To address this issue of the response of amblyopia to treatment in children 7 years and older, the Pediatric Eye Disease Investigator Group (PEDIG) conducted a randomized trial of 507 patients (aged 7 to <18 years) with amblyopic eye visual acuity ranging from 20/40 to 20/400. Patients were provided with optimal optical correction and then randomized to a Treatment Group (2 to 6 hours per day of prescribed patching of the sound eye combined with near visual activities for all patients plus atropine one drop per day in the sound eye for 7 to <13 year olds) or an Optical Correction Group (optical correction alone). Patients whose amblyopic eye acuity improved 10 or more letters (2 lines) by 24 weeks were considered responders. In the 7 to <13 year olds (N=404), 53% of the Treatment Group were responders compared with 25% of the Optical Correction Group (P<0.001). In the 13 to <18 year olds (N=103), the responder rates were 25% and 23% respectively overall (adjusted P=0.22), but 47% and 20% respectively among patients not previously treated with patching and/or atropine for amblyopia (adjusted P=0.03). Most patients, including responders, were left with a residual visual acuity deficit.

The use of multiple modalities (patching, atropine, near visual activities) in the treatment regimen for the 7 to <13 year olds in this trial (ATS3) was an effort to maximize the therapeutic response. Patients age 13 years and older were prescribed patching but not atropine because of concern that the continual optical blur from the atropine could have a deleterious effect on their ability to drive and perform other activities. Prescribed patching was 2 to 6 hours a day to limit patch wear to non-school hours and because our prior studies of 3 to <7 year olds demonstrated that as little as two hours of patching a day (when combined with near visual activities) is as effective as a greater number of hours. Instructing patients to perform at least one hour of near activities while wearing the patch was based on the unproven clinical opinion that near activities can augment the effect of the occlusion therapy. A PEDIG pilot study suggested that near activities are beneficial and this question of benefit of near activities is currently being studied in another randomized clinical trial. Atropine placed in the sound eye once a day and two days a week has been demonstrated in younger children to be beneficial to the acuity of the amblyopic eye, presumably due to its cycloplegic effect of blurring vision in the sound eye especially at near fixation. In a study comparing daily and weekend atropine, daily atropine was not found to be superior.

The unanswered question from this completed clinical trial is whether prescribing patching or atropine alone could have produced a response similar to the combination therapy, or whether in this age group, one treatment is better than the other. A poll of PEDIG investigators at an investigator meeting on January 15, 2005 indicated that very few are following the treatment regimen used in the prior study (ATS3); rather, most are prescribing monotherapy-either patching or atropine-as the initial treatment for amblyopia in the 7 to <13 year age range. Thus, a trial comparing atropine and patching as amblyopia treatments in 7 to <13 year olds is needed.

The study has been designed as a simple trial that, other than the type of amblyopia therapy being determined through the randomization process, approximates standard clinical practice. The two treatment regimes are: 1) Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day without the aid of reading glasses (with increase to daily atropine at 5 weeks if acuity not improved by at least 5 letters) and 2) Patching 2 hours per day plus near activities for one hour while patching (with increase to 4 hours per day for moderate amblyopes and > 4 hours per day for severe amblyopes at 5 weeks if acuity not improved by at least 5 letters).

Optional Ancillary Study As part of the optic nerve imaging ancillary study, retinal nerve fiber layer imaging using optical coherence tomography will be performed on some patients. This will be optional for patients at participating sites. The procedure is not part of standard care. The subject's pupils will need to be dilated, if not already dilated as part of the exam. Testing of both eyes can be completed in about 15 minutes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 233 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial Comparing Patching Versus Atropine for Amblyopia in 7 to < 13 Year Olds
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Patching Patching 2 hours per day plus near activities for one hour while patching (with increase to 4 hours per day for moderate amblyopes and >4 hours per day for severe amblyopes at 5 weeks if acuity not improved at least 5 letters)	Device: Patching; Patching 2 hours per day; Other Names: Coverlet, 3M Opticlude, Ortopad® ; Procedure: Near activities; near visual activities for at least one hour per day
Active Comparator: Atropine Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day (with increase to daily atropine at 5 weeks if acuity not improved by at least 5 letters)	Drug: Atropine; Atropine 1% each weekend day in the sound eye; Procedure: Near activities; near visual activities for at least one hour per day

Outcome Measures

Primary Outcome Measures

1. Distribution of Visual Acuity in the Amblyopic Eye at 17 Weeks [17 weeks]

   Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.

2. Mean Visual Acuity in the Amblyopic Eye at 17 Weeks [17 weeks]

   Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.

3. Distribution of Change in Visual Acuity in the Amblyopic Eye From Baseline to 17 Weeks [Baseline to 17 weeks]

   Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.

4. Mean Change in Visual Acuity in the Amblyopic Eye From Baseline to 17 Weeks [Baseline to 17 weeks]

   Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.

Secondary Outcome Measures

1. Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With All Causes of Moderate Amblyopia [17 or 19 weeks]

   The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.

2. Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Anisometropic Participants With Moderate Amblyopia Only [17 or 19 weeks]

   The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.

3. Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With Moderate Amblyopia From Strabismus Only or Combined Mechanism [17 or 19 weeks]

   The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.

4. Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With All Causes of Moderate Amblyopia [17 or 19 weeks]

   Stereoacuity is scored as seconds of arc with values of: <800, 800, 400, 200, 100, 60, 40. The lower the arc second value, the better the score (i.e. 40 arc sec is best stereoacuity; <800 is the worst). A change score was defined as the difference between baseline and outcome in score level (i.e. moving from 800 at baseline to 400 at outcome is one level change, moving from 800 to 200 is two levels, etc.) change in levels was categorized as "within one level" meaning change was -1, 0, or +1.

5. Amblyopia Treatment Index - Social Stigma (Moderate Amblyopia Only) [17 weeks]

   Questionnaire scores on the Social Stigma subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.

6. Amblyopia Treatment Index - Compliance (Moderate Amblyopia Only) [17 weeks]

   Questionnaire scores on the compliance subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.

7. Amblyopia Treatment Index - Adverse Effects Scale (Moderate Amblyopia Only) [17 weeks]

   Questionnaire scores on the adverse events subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.

8. Distribution of Visual Acuity in the Fellow Eye at 17 Weeks [17 weeks]

   Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.

9. Mean Visual Acuity in the Fellow Eye at 17 Weeks [17 weeks]

   Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.

10. Distribution of Change in Visual Acuity in the Fellow Eye From Baseline to 17 Weeks [Baseline to 17 weeks]

    Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.

11. Mean Change in Visual Acuity in the Fellow Eye From Baseline to 17 Weeks [Baseline to 17 weeks]

    Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 7 to 12 years old (inclusive)

• Amblyopia associated with strabismus, anisometropia, or both

• Visual acuity in the amblyopic eye 19 to 71 letters on Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS©) (20/40 to 20/400 inclusive)

• Visual acuity in the sound eye 79 letters or better on E-ETDRS© (20/25 or better)

• Interocular difference >=15 letters (3 lines)

• Spectacles, if needed, worn for at least 16 weeks or visual acuity documented to be stable

Inclusion Criteria for Optional Ancillary Study:

• Enrolled into the main study

• Refractive error in both eyes between -0.25 and +5.00D, inclusive (to avoid the need to adjust for refractive error)

• Birth weight >1500 grams

• No history of Central Nervous System (CNS) disease (e.g. intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), meningitis, developmental abnormalities of the brain, hydrocephalus, cerebral palsy, hypoxic ischemic encephalopathy

Exclusion Criteria:

• Amblyopia treatment (other than spectacles) in the last 6 months

• Myopia (more than -0.25D spherical equivalent) in either eye

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pennsylvania College of Optometry	Philadelphia	Pennsylvania	United States	19141
2	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Jaeb Center for Health Research
• National Eye Institute (NEI)

Investigators

• Study Chair: Richard W. Hertle, M.D., University of Pittsburgh
• Study Chair: Mitchell M. Scheiman, O.D., Pennsylvania College of Optometry

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• PubMed Abstract
• PubMed Central HHS Public Access - Full Text

Publications

• Felius J, Chandler DL, Holmes JM, Chu RH, Cole SR, Hill M, Huang K, Kulp MT, Lazar EL, Matta NS, Melia M, Wallace DK; Pediatric Eye Disease Investigator Group. Evaluating the burden of amblyopia treatment from the parent and child's perspective. J AAPOS. 2010 Oct;14(5):389-95. doi: 10.1016/j.jaapos.2010.07.009.
• Pediatric Eye Disease Investigator Group. Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial. Arch Ophthalmol. 2009 Jan;127(1):22-30. doi: 10.1001/archophthalmol.2008.520.
• Repka MX, Kraker RT, Beck RW, Birch E, Cotter SA, Holmes JM, Hertle RW, Hoover DL, Klimek DL, Marsh-Tootle W, Scheiman MM, Suh DW, Weakley DR; Pediatric Eye Disease Investigator Group. Treatment of severe amblyopia with weekend atropine: results from 2 randomized clinical trials. J AAPOS. 2009 Jun;13(3):258-63. doi: 10.1016/j.jaapos.2009.03.002.
• Repka MX, Kraker RT, Tamkins SM, Suh DW, Sala NA, Beck RW; Pediatric Eye Disease Investigator Group. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol. 2009 Jul;148(1):143-7. doi: 10.1016/j.ajo.2009.01.015. Epub 2009 Mar 27.

• Responsible Party: Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT00315328
• Other Study ID Numbers: NEI-119; 2U10EY011751
• First Posted: Apr 18, 2006
• Last Update Posted: Jun 24, 2016
• Last Verified: May 1, 2016

• Keywords provided by Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research: Amblyopia; Atropine; Patching
• Additional relevant MeSH terms: Amblyopia; Atropine

Study Results

Participant Flow

Recruitment Details	Between August 2005 and July 2007, 233 subjects were randomized at 39 certified sites (193 with moderate amblyopia 20/40 to 20/100 in a primary cohort, and an additional 40 with severe amblyopia 20/125 to 20/400 that were followed as a secondary cohort).
Pre-assignment Detail	Subjects must have been wearing optimal spectacle correction for a minimum of 16 weeks or until stability of visual acuity was documented (no improvement in amblyopic eye visual acuity at 2 consecutive visits at least 4 weeks apart) before enrollment and randomization.

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Period Title: Overall Study
STARTED	98	95	18	22
5 Week Visit	91	89	17	19
COMPLETED	84	88	13	20
NOT COMPLETED	14	7	5	2

Baseline Characteristics

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia	Total
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).	Total of all reporting groups
Overall Participants	98	95	18	22	233
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.9 (1.5)	9.1 (1.6)	9.5 (1.5)	9.2 (1.8)	9.0 (1.6)
Age, Customized (participants) [Number]
7 to <8 years	35 35.7%	28 29.5%	6 33.3%	9 40.9%	78 33.5%
8 to <9 years	24 24.5%	26 27.4%	0 0%	4 18.2%	54 23.2%
9 to <10 years	17 17.3%	16 16.8%	5 27.8%	3 13.6%	41 17.6%
10 to <11 years	8 8.2%	10 10.5%	4 22.2%	2 9.1%	24 10.3%
11 to <12 years	8 8.2%	7 7.4%	2 11.1%	1 4.5%	18 7.7%
12 to <13 years	6 6.1%	8 8.4%	1 5.6%	3 13.6%	18 7.7%
Sex: Female, Male (Count of Participants)
Female	48 49%	54 56.8%	4 22.2%	12 54.5%	118 50.6%
Male	50 51%	41 43.2%	14 77.8%	10 45.5%	115 49.4%
Race/Ethnicity, Customized (participants) [Number]
White	68 69.4%	56 58.9%	16 88.9%	18 81.8%	158 67.8%
African-American	8 8.2%	11 11.6%	2 11.1%	1 4.5%	22 9.4%
Hispanic or Latino	20 20.4%	23 24.2%	0 0%	3 13.6%	46 19.7%
Asian	0 0%	1 1.1%	0 0%	0 0%	1 0.4%
More than one race	1 1%	2 2.1%	0 0%	0 0%	3 1.3%
Not reported	1 1%	2 2.1%	0 0%	0 0%	3 1.3%
Cause of Amblyopia (participants) [Number]
Strabismus	28 28.6%	33 34.7%	4 22.2%	4 18.2%	69 29.6%
Anisometropia	46 46.9%	31 32.6%	6 33.3%	9 40.9%	92 39.5%
Strabismus and anisometropia	24 24.5%	31 32.6%	8 44.4%	9 40.9%	72 30.9%
Distance Visual Acuity in Amblyopic Eye (participants) [Number]
20/400 (18 to 22 letters) (worse)	0 0%	0 0%	0 0%	1 4.5%	1 0.4%
20/320 (23 to 27 letters)	0 0%	0 0%	0 0%	1 4.5%	1 0.4%
20/250 (28 to 32 letters)	0 0%	0 0%	2 11.1%	4 18.2%	6 2.6%
20/200 (33 to 37 letters)	0 0%	0 0%	8 44.4%	3 13.6%	11 4.7%
20/160 (38 to 42 letters)	0 0%	0 0%	5 27.8%	4 18.2%	9 3.9%
20/125 (43 to 47 letters)	0 0%	0 0%	3 16.7%	9 40.9%	12 5.2%
20/100 (48 to 52 letters)	6 6.1%	13 13.7%	0 0%	0 0%	19 8.2%
20/80 (53 to 57 letters)	15 15.3%	13 13.7%	0 0%	0 0%	28 12%
20/63 (58 to 62 letters)	24 24.5%	22 23.2%	0 0%	0 0%	46 19.7%
20/50 (63 to 67 letters)	33 33.7%	28 29.5%	0 0%	0 0%	61 26.2%
20/40 (68 to 72 letters) (best)	20 20.4%	19 20%	0 0%	0 0%	39 16.7%
Distance Visual Acuity in Fellow Eye (participants) [Number]
20/32 (73 to 77 letters) (worse)	0 0%	0 0%	0 0%	0 0%	0 0%
20/25 (78 to 82 letters)	17 17.3%	20 21.1%	1 5.6%	6 27.3%	44 18.9%
20/20 (83 to 87 letters)	43 43.9%	47 49.5%	8 44.4%	5 22.7%	103 44.2%
20/16 (88 to 92 letters)	36 36.7%	26 27.4%	9 50%	11 50%	82 35.2%
20/12 (93 to 97 letters) (best)	2 2%	2 2.1%	0 0%	0 0%	4 1.7%
Prior Treatment for Amblyopia at Enrollment (participants) [Number]
None	71 72.4%	68 71.6%	13 72.2%	18 81.8%	170 73%
Patching	16 16.3%	16 16.8%	2 11.1%	3 13.6%	37 15.9%
Atropine	2 2%	0 0%	1 5.6%	0 0%	3 1.3%
Patching and atropine	9 9.2%	11 11.6%	2 11.1%	1 4.5%	23 9.9%
Refractive Error in Amblyopic Eye (spherical equivalent) (participants) [Number]
< 0 Diopters (D)	2 2%	2 2.1%	0 0%	0 0%	4 1.7%
0 to < +1.00D	8 8.2%	10 10.5%	1 5.6%	1 4.5%	20 8.6%
+1.00 to < +2.00D	13 13.3%	6 6.3%	2 11.1%	2 9.1%	23 9.9%
+2.00 to < +3.00D	10 10.2%	8 8.4%	1 5.6%	3 13.6%	22 9.4%
+3.00 to < +4.00D	23 23.5%	16 16.8%	2 11.1%	4 18.2%	45 19.3%
>= +4.00D	42 42.9%	53 55.8%	12 66.7%	12 54.5%	119 51.1%
Refractive Error in Fellow Eye (spherical equivalent) (participants) [Number]
< 0 Diopters (D)	1 1%	2 2.1%	0 0%	0 0%	3 1.3%
0 to < +1.00D	32 32.7%	29 30.5%	4 22.2%	9 40.9%	74 31.8%
+1.00 to < +2.00D	33 33.7%	17 17.9%	8 44.4%	5 22.7%	63 27%
+2.00 to < +3.00D	13 13.3%	9 9.5%	1 5.6%	2 9.1%	25 10.7%
+3.00 to < +4.00D	7 7.1%	6 6.3%	2 11.1%	2 9.1%	17 7.3%
>= +4.00D	12 12.2%	32 33.7%	3 16.7%	4 18.2%	51 21.9%
Distance Visual Acuity in Amblyopic Eye (ETDRS letter score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ETDRS letter score]	62.4 (5.7)	61.7 (6.6)	37.5 (5.0)	37.5 (7.5)	57.9 (11.1)
Distance Visual Acuity in Fellow Eye (ETDRS letter score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ETDRS letter score]	86.0 (3.6)	85.7 (3.4)	87.0 (3.5)	85.5 (4.0)	85.9 (3.6)
Intereye Acuity Difference (ETDRS letter score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ETDRS letter score]	23.5 (6.8)	24.0 (7.0)	49.5 (5.5)	47.5 (9.5)	28.0 (11.7)
Refractive Error in Amblyopic Eye (spherical equivalent (diopter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopter]	3.57 (2.07)	4.10 (2.19)	4.97 (2.50)	4.18 (1.99)	3.95 (2.16)
Refractive Error in Fellow Eye (spherical equivalent) (diopter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopter]	1.84 (1.74)	2.56 (2.22)	2.12 (1.76)	1.98 (2.11)	2.17 (2.00)

Outcome Measures

1. Secondary Outcome

Title	Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With All Causes of Moderate Amblyopia
Description	The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.
Time Frame	17 or 19 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	0	0
Failed black & white shape identification pretest	1 1%	4 4.2%
>800 arcsec (worse)	26 26.5%	34 35.8%
800 arcsec	9 9.2%	3 3.2%
400 arcsec	9 9.2%	14 14.7%
200 arcsec	10 10.2%	10 10.5%
100 arcsec	9 9.2%	12 12.6%
60 arcsec	7 7.1%	2 2.1%
40 arcsec (best)	13 13.3%	9 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests were used to assess treatment group differences in the change in Randot Preschool stereoacuity levels ( from baseline to the outcome examination).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Anisometropic Participants With Moderate Amblyopia Only
Description	The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.
Time Frame	17 or 19 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	42	28	0	0
Failed black & white shape identification pretest	0 0%	0 0%
>800 arcsec (worse)	5 5.1%	6 6.3%
800 arcsec	3 3.1%	1 1.1%
400 arcsec	5 5.1%	4 4.2%
200 arcsec	7 7.1%	4 4.2%
100 arcsec	9 9.2%	8 8.4%
60 arcsec	6 6.1%	0 0%
40 arcsec (best)	7 7.1%	5 5.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests used to assess treatment group differences in change in Randot Preschool stereoacuity levels ( from baseline to the outcome examination) among those with anisometropia only.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With Moderate Amblyopia From Strabismus Only or Combined Mechanism
Description	The Randot Preschool Stereotest measures stereopsis from 800 to 40 seconds of arc on patients as young as 2 years of age. This Stereotest is designed as a matching game in which the patient matches pictures in a test booklet wearing special glasses. A subject can fail the pretest (not see any pictures) or can score >800 (the worst), 800, 400, 200, 100, 60, or 40 (the best) seconds of arc. If two shapes are identified correctly the patient progresses to the next lower stereoacuity level. A failed test occurs when the patient cannot identify any shapes.
Time Frame	17 or 19 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	42	60	0	0
Failed black & white shape identification pretest	1 1%	4 4.2%
>800 arcsec (worse)	21 21.4%	28 29.5%
800 arcsec	6 6.1%	2 2.1%
400 arcsec	4 4.1%	10 10.5%
200 arcsec	3 3.1%	6 6.3%
100 arcsec	0 0%	4 4.2%
60 arcsec	1 1%	2 2.1%
40 arcsec (best)	6 6.1%	4 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests were used to assess treatment group differences in the change in Randot Preschool stereoacuity levels ( from baseline to the outcome examination) among patients with strabismus or combined mechanism only.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Stereoacuity Measured by the Randot Preschool Test at 17 or 19 Weeks- Participants With All Causes of Moderate Amblyopia
Description	Stereoacuity is scored as seconds of arc with values of: <800, 800, 400, 200, 100, 60, 40. The lower the arc second value, the better the score (i.e. 40 arc sec is best stereoacuity; <800 is the worst). A change score was defined as the difference between baseline and outcome in score level (i.e. moving from 800 at baseline to 400 at outcome is one level change, moving from 800 to 200 is two levels, etc.) change in levels was categorized as "within one level" meaning change was -1, 0, or +1.
Time Frame	17 or 19 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	0	0
>= 2 levels worse	4 4.1%	9 9.5%
Within 1 level	57 58.2%	54 56.8%
>= 2 levels better	17 17.3%	18 18.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atropine-Moderate Amblyopia
	Comments	To evaluate WITHIN each treatment group whether stereoacuity changed from baseline to outcome a Wilcoxon sign-rank test was performed to evaluate whether the distribution of change from baseline was zero
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia
	Comments	To evaluate WITHIN each treatment group whether stereoacuity changed from baseline to outcome a Wilcoxon sign-rank test was performed to evaluate whether the distribution of change from baseline was zero
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Amblyopia Treatment Index - Social Stigma (Moderate Amblyopia Only)
Description	Questionnaire scores on the Social Stigma subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects who completed the 17wk amblyopia treatment index questionnaire evaluating the impact of treatment on the child and family.

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	66	64	0	0
Mean (Standard Deviation) [Units on a scale]	2.37 (0.75)	1.91 (0.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests were used to assess treatment group differences in the parent questionnaire subscale scores at 17 weeks - Social Stigma subscale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Positive mean favors atropine group.

6. Secondary Outcome

Title	Amblyopia Treatment Index - Compliance (Moderate Amblyopia Only)
Description	Questionnaire scores on the compliance subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects who completed the 17wk amblyopia treatment index questionnaire evaluating the impact of treatment on the child and family.

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	66	64	0	0
Mean (Standard Deviation) [Units on a scale]	2.59 (0.93)	2.03 (0.82)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests were used to assess treatment group differences in the parent questionnaire subscale scores at 17 weeks - Compliance subscale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Positive mean favors atropine group.

7. Secondary Outcome

Title	Amblyopia Treatment Index - Adverse Effects Scale (Moderate Amblyopia Only)
Description	Questionnaire scores on the adverse events subscale of the Amblyopia Treatment Index. Questions were evaluated on a likert type scale as strongly agree (5) to strongly disagree (1), with a higher number indicating worse response.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects who completed the 17wk amblyopia treatment index questionnaire evaluating the impact of treatment on the child and family.

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	66	64	0	0
Mean (Standard Deviation) [Units on a scale]	2.28 (0.68)	2.22 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	Wilcoxon rank sum tests were used to assess treatment group differences in the parent questionnaire subscale scores at 17 weeks - Adverse events subscale.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Primary Outcome

Title	Distribution of Visual Acuity in the Amblyopic Eye at 17 Weeks
Description	Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

Primary analysis includes only patients who completed the 17 week exam between 13 and 26 weeks following randomization. No imputation was done if missed exam; analysis followed the intent to treat principle.

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
20/400 (18 to 22 letters) (worse)	0 0%	0 0%	0 0%	0 0%
20/320 (23 to 27 letters)	0 0%	0 0%	0 0%	1 4.5%
20/250 (28 to 32 letters)	0 0%	0 0%	0 0%	3 13.6%
20/200 (33 to 37 letters)	0 0%	0 0%	3 16.7%	3 13.6%
20/160 (38 to 42 letters)	1 1%	0 0%	1 5.6%	3 13.6%
20/125 (43 to 47 letters)	0 0%	1 1.1%	4 22.2%	2 9.1%
20/100 (48 to 52 letters)	3 3.1%	4 4.2%	1 5.6%	2 9.1%
20/80 (53 to 57 letters)	3 3.1%	6 6.3%	4 22.2%	3 13.6%
20/63 (58 to 62 letters)	5 5.1%	12 12.6%	0 0%	1 4.5%
20/50 (63 to 67 letters)	13 13.3%	14 14.7%	0 0%	1 4.5%
20/40 (68 to 72 letters)	20 20.4%	15 15.8%	0 0%	0 0%
20/32 (73 to 77 letters)	19 19.4%	21 22.1%	0 0%	0 0%
20/25 (78 to 82 letters)	14 14.3%	10 10.5%	0 0%	1 4.5%
20/20 (83 to 87 letters)	6 6.1%	4 4.2%	0 0%	0 0%
20/16 (88 to 92 letters) (best)	0 0%	1 1.1%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	95% confidence interval constructed on the treatment group difference in proportion with amblyopic eye visual acuity 20/25 or better at 17 weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.07
	Confidence Interval	() 95%; -0.03 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Primary Outcome

Title	Mean Visual Acuity in the Amblyopic Eye at 17 Weeks
Description	Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
Mean (Standard Deviation) [ETDRS letter score]	71.0 (8.9)	69.2 (9.2)	46.0 (6.0)	45.0 (14.0)

10. Primary Outcome

Title	Distribution of Change in Visual Acuity in the Amblyopic Eye From Baseline to 17 Weeks
Description	Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.
Time Frame	Baseline to 17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
>=15 letters worse	1 1%	0 0%	0 0%	0 0%
10 to 14 letters worse	0 0%	2 2.1%	0 0%	0 0%
5 to 9 letters worse	0 0%	3 3.2%	0 0%	2 9.1%
+/- 4 letters	23 23.5%	22 23.2%	2 11.1%	6 27.3%
5 to 9 letters better	22 22.4%	26 27.4%	4 22.2%	4 18.2%
10 to 14 letters better	17 17.3%	20 21.1%	2 11.1%	3 13.6%
>=15 letters better	21 21.4%	15 15.8%	5 27.8%	5 22.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	95% confidence interval constructed on the treatment group difference of the proportion improving 15 or more letters from baseline to 17 weeks.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	() 95%; -0.02 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	Mean Change in Visual Acuity in the Amblyopic Eye From Baseline to 17 Weeks
Description	Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.
Time Frame	Baseline to 17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
Mean (Standard Deviation) [ETDRS letter score]	8.6 (7.8)	7.6 (7.5)	9.0 (6.5)	7.5 (10.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	The trial was designed to evaluate whether patching and atropine are equivalent treatments for amblyopia in children 7 to 12 years old. The sample size was computed based on a standard deviation of 17-week visual acuity scores of 10 letters, correlation between outcome and baseline visual acuity scores of 0.30 and 10% loss to follow up.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Treatment equivalence was to be declared if the ends of the 2 1-sided 95% confidence intervals constructed on the difference between adjusted mean visual acuity scores were completely contained within the designated equivalence interval of +/- 5 letters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.2
	Confidence Interval	() 95%; -0.7 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Distribution of Visual Acuity in the Fellow Eye at 17 Weeks
Description	Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
20/50 (63 to 67 letters) (worse)	0 0%	0 0%	0 0%	0 0%
20/40 (68 to 72 letters)	0 0%	0 0%	0 0%	1 4.5%
20/32 (73 to 77 letters)	2 2%	4 4.2%	0 0%	1 4.5%
20/25 (78 to 82 letters)	5 5.1%	12 12.6%	1 5.6%	2 9.1%
20/20 (83 to 87 letters)	31 31.6%	42 44.2%	4 22.2%	4 18.2%
20/16 (88 to 92 letters)	42 42.9%	29 30.5%	5 27.8%	11 50%
20/12 (93 to 97 letters) (best)	4 4.1%	1 1.1%	3 16.7%	1 4.5%

13. Secondary Outcome

Title	Mean Visual Acuity in the Fellow Eye at 17 Weeks
Description	Visual acuity was measured in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best.
Time Frame	17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
Mean (Standard Deviation) [ETDRS letter score]	87.3 (3.8)	85.8 (3.9)	88.5 (5.0)	86.5 (6.5)

14. Secondary Outcome

Title	Distribution of Change in Visual Acuity in the Fellow Eye From Baseline to 17 Weeks
Description	Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.
Time Frame	Baseline to 17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
>=10 letters worse	0 0%	0 0%	0 0%	1 4.5%
5 to 9 letters worse	4 4.1%	7 7.4%	1 5.6%	2 9.1%
+/- 4 letters	69 70.4%	72 75.8%	8 44.4%	11 50%
5 to 9 letters better	11 11.2%	9 9.5%	4 22.2%	4 18.2%
>=10 letters better	0 0%	0 0%	0 0%	2 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patching-Moderate Amblyopia, Atropine-Moderate Amblyopia
	Comments	95% confidence interval constructed on the treatment group difference of mean change in fellow eye visual acuity from baseline to 17 weeks, adjusted for baseline fellow eye visual acuity.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.4 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Mean Change in Visual Acuity in the Fellow Eye From Baseline to 17 Weeks
Description	Visual acuity was measured at baseline and 17 weeks in each eye using the electronic early treatment diabetic retinopathy study (E-ETDRS) method which resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. A difference between the scores at baseline and 17 weeks was calculated. A positive difference indicates acuity was better at 17 weeks than at baseline; a negative difference indicates acuity was worse at 17 weeks.
Time Frame	Baseline to 17 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patching-Moderate Amblyopia	Atropine-Moderate Amblyopia	Patching-Severe Amblyopia	Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).	Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)	Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
Measure Participants	84	88	13	20
Mean (Standard Deviation) [ETDRS letter score]	1.5 (3.1)	0.3 (3.5)	1.0 (3.0)	1.0 (5.0)

Adverse Events

Time Frame	Adverse events were collected through the 17 week outcome visit.
Arm/Group Title	Patching-Moderate Amblyopia		Atropine-Moderate Amblyopia		Patching-Severe Amblyopia		Atropine-Severe Amblyopia
Arm/Group Description	Patching 2 hours per day plus near activities for one hour while patching among patients with moderate amblyopia (20/40 to 20/100)		Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with moderate amblyopia (20/40 to 20/100).		Patching 2 hours per day plus near activities for one hour while patching among patients with severe amblyopia (20/125 to 20/400)		Atropine 1% once each weekend day in the sound eye plus near activities for at least one hour every day among patients with severe amblyopia (20/125 to 20/400).
All Cause Mortality
	Patching-Moderate Amblyopia		Atropine-Moderate Amblyopia		Patching-Severe Amblyopia		Atropine-Severe Amblyopia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Patching-Moderate Amblyopia		Atropine-Moderate Amblyopia		Patching-Severe Amblyopia		Atropine-Severe Amblyopia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/95 (0%)		0/18 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Patching-Moderate Amblyopia		Atropine-Moderate Amblyopia		Patching-Severe Amblyopia		Atropine-Severe Amblyopia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		14/95 (14.7%)		0/18 (0%)		5/22 (22.7%)
Eye disorders
Light sensitivity	0/98 (0%)		14/95 (14.7%)		0/18 (0%)		3/22 (13.6%)
General disorders
Systemic	0/98 (0%)		0/95 (0%)		0/18 (0%)		2/22 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.