ATS16: Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old

• Sponsor: Jaeb Center for Health Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00944710
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 73
• Locations: 2
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 36.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study is designed to evaluate the effectiveness of adding a plano lens to weekend atropine after visual acuity has stabilized with weekend atropine but amblyopia is still present. Children ages 3 to <8 years with visual acuity of 20/50 to 20/400 in the amblyopic eye will be enrolled in a run-in phase with weekend atropine until no improvement, followed by randomization of eligible patients to weekend atropine treatment with a plano lens over the sound eye versus without a plano lens over the sound eye. The primary objective is to determine if adding a plano lens to weekend atropine will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.

Condition or Disease	Intervention/Treatment	Phase
Amblyopia	Drug: Atropine; Device: Plano lens; Drug: Atropine	Phase 3

Detailed Description

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children.1 Many practitioners prescribe weekend atropine as initial therapy for amblyopia. However, many children fail to achieve normal visual acuity in the amblyopic eye after treatment with this regimen. In a randomized trial conducted by PEDIG comparing atropine regimens, 58 of 83 patients with moderate amblyopia (70%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of treatment with weekend atropine.2 In another PEDIG randomized trial comparing atropine with a plano lens versus without a plano lens for initial treatment of amblyopia, 60 of 84 patients with moderate amblyopia (71%) had amblyopic eye visual acuity of 20/32 or worse after 16 weeks of treatment with weekend atropine.3 When improvement stops after initial therapy and amblyopia is still present, treatment options include increasing the dosage of current treatment, switching to another treatment, maintaining the same treatment and dosage, or combining treatments. Many clinicians will add a plano lens over the sound eye to atropine treatment, in part because families using atropine have become comfortable with its use. This option is limited to children with hypermetropia in the sound eye. However, it is unknown whether adding a plano lens over the sound eye will improve amblyopic eye visual acuity more than continuing atropine alone in patients who have shown no improvement after initial treatment with atropine. In a PEDIG randomized trial comparing patching to atropine for initial treatment of amblyopia, a plano lens was prescribed for the sound eye for 55 patients who had not improved to 20/30 or at least 3 lines after 4 months of daily atropine use.1, 4 Their mean acuity improvement prior to using the plano lens was 1.0 line, compared with 1.6 lines after prescribing the plano lens. We are unaware of any reports of the response of treatment of amblyopia still present after initial treatment with weekend atropine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intensified treatment Weekend atropine 1% with plano lens over the sound eye	Drug: Atropine; Weekend atropine 1%; Device: Plano lens; plano lens over the sound eye
Active Comparator: Control Weekend atropine 1%	Drug: Atropine; Weekend atropine 1%

Outcome Measures

Primary Outcome Measures

1. Distribution of 10-week Amblyopic-Eye Visual Acuity [10 weeks after randomization]

   The masked 10-week amblyopic eye visual acuity scores were tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.

2. Mean 10-week Amblyopic-Eye Visual Acuity [10 weeks after randomization]

   The primary outcome analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.

3. Distribution of the Change in Amblyopic-Eye Visual Acuity [Randomization to 10 weeks]

   The change in 10-week amblyopic eye visual acuity scores since randomization was tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.

4. Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization [Randomization to 10 weeks]

   The change in 10-week amblyopic eye visual acuity was computed for both treatment groups and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.

Secondary Outcome Measures

1. Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization [10 weeks after randomization]

   The proportion of participants who achieved 20/25 or better visual acuity since randomization was computed at the 10-week outcome. The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity was 20/25 or better since randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

2. Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization [10 weeks after randomization]

   The proportion of participants who improved at least 2 logMAR lines since randomization was computed at the 10-week outcome. The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity improved at least 2 logMAR lines since randomization using logistic regression, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

3. Spectacle Compliance at 10 Weeks by Treatment Group [10 weeks after randomization]

   The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

4. Average Spectacle Compliance by Treatment Group [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

   The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

5. Atropine Compliance at 10 Weeks by Treatment Group [10 weeks after randomization]

   The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

6. Average Atropine Compliance by Treatment Group [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

   The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

7. Distribution of Interocular Difference at 12-week Exam [12 weeks after randomization]

   Distribution of Interocular Difference Between Eyes at 12-week Exam

8. Mean Interocular Difference at 12-week Exam [12 weeks after randomization]

   Mean Interocular Difference Between Eyes at 12-week Exam

9. Distribution of 12-week Fellow-Eye Visual Acuity [12 weeks after randomization]

   Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity.

10. Mean Fellow-Eye Visual Acuity at 12-week Exam [12 weeks after randomization]

11. Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [12 weeks after randomization]

12. Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [12 weeks after randomization]

13. Distribution of Baseline Characteristics at the 10-week Outcome [10 weeks after randomization]

    The number of participants was tabulated by treatment group within categorical levels of prespecified baseline subgroup factors for participants with 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to principles specified in the primary outcome analysis.

14. Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome [10 weeks after randomization]

    Mean amblyopic eye visual acuity at randomization was computed by treatment group within categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

15. Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics [10 weeks after randomization]

    A treatment comparison of mean amblyopic eye visual acuity change since randomization was performed at the 10-week outcome according to categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

16. Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of best post-randomization (10 weeks or later) visual acuity scores in the amblyopic eye was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)

17. Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. A treatment comparison of mean amblyopic eye visual acuity at the visit of best post-randomization visual acuity (10 weeks or later) was performed using an analysis of covariance, adjusting for amblyopic eye visual acuity at randomization.

18. Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit [Randomization to 10 weeks or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of change in best post-randomization (10 weeks or later) visual acuity in the amblyopic eye since randomization was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)

19. Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The mean change in amblyopic eye visual acuity since randomization was computed for both treatment groups based on the visit of best post-randomization visual acuity (10 weeks or later) using the initial visual acuity score (if a retest was obtained.)

20. Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines Based on Visual Acuity at Best Outcome Visit [10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)]

21. Distribution of Randot Preschool Stereoacuity Score at 12 Weeks [12 weeks after randomization]

    Distribution of Randot Preschool Stereoacuity Score at 12 Weeks; Participants with a Randot Preschool test of >800 seconds of arc were classified as having a stereoacuity of 3000 seconds of arc if the Titmus fly test was positive or as nil if the Titmus fly test was negative.

22. Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia [12 weeks after randomization]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 7 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Major Eligibility Criteria for Run-in Phase

• Age 3 to < 8 years

• Amblyopia associated with strabismus, anisometropia, or both

• Visual acuity in the amblyopic eye between 20/50 and 20/400 inclusive

• Visual acuity in the sound eye 20/32 or better and inter-eye acuity difference >3 logMAR lines

• Amblyopia treatment within the past 6 months subject to the following stipulations:

• No more than 6 weeks of any amblyopia treatment other than spectacles (except for patients being treated with atropine who are entering the study on treatment)

• No simultaneous treatment with patching and atropine

• No use of atropine in combination with the sound eye spectacle lens reduced by more than 1.50 D

• Maximum level of treatment within the past 6 months:

• Patching: up to 2 hours daily

• Atropine: up to once daily

• Wearing spectacles with optimal correction (if amblyopic eye acuity is 20/80 or better, then VA must be stable in glasses; if amblyopic eye acuity is 20/100 or worse, then spectacles and atropine can be initiated simultaneously).

• Hypermetropia and spectacle correction in sound eye of +1.50 D or more

Eligibility Criteria for Randomization:

• Amblyopic eye acuity of 20/40 to 20/160 with an inter-ocular difference of >2 lines, or amblyopic eye acuity of 20/32 with 3 lines of IOD.

• Compliance with weekend atropine treatment based on investigator judgment.

Exclusion Criteria:

• Currently using vision therapy or orthoptics

• Ocular cause for reduced visual acuity (nystagmus per se does not exclude the patient if the above visual acuity criteria are met)

• Prior intraocular or refractive surgery

• Known allergy to atropine or other cycloplegic drugs

• Down Syndrome present

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern California College of Optometry	Fullerton	California	United States	92831
2	Duke University Eye Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

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

Investigators

• Study Chair: David K. Wallace, M.D., Duke University Eye Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT00944710
• Other Study ID Numbers: NEI-144; 2U10EY011751
• First Posted: Jul 23, 2009
• Last Update Posted: Mar 6, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Jaeb Center for Health Research: Amblyopia; atropine; Plano lens
• Additional relevant MeSH terms: Amblyopia; Atropine

Study Results

Participant Flow

Recruitment Details	Between November 2009 and August 2013, 73 participants from 20 sites were randomly assigned to either augmenting weekend atropine by changing the lens over the fellow eye to plano (n=33) or continuing with weekend atropine with best spectacle correction (n=40).
Pre-assignment Detail	Prior to being considered for the randomized trial, participants who had not completed at least 12 weeks of atropine were enrolled into a run-in phase and treated with weekend atropine 1% ophthalmic solution and spectacles based upon a recent cycloplegic refraction, with follow up every 6 weeks until no improvement

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Period Title: 10-week Primary Outcome
STARTED	40	33
COMPLETED	40	33
NOT COMPLETED	0	0
Period Title: 10-week Primary Outcome
STARTED	40	33
COMPLETED	40	33
NOT COMPLETED	0	0
Period Title: 10-week Primary Outcome
STARTED	40	33
Eligible to Enter Post 10-week Phase	24	26
COMPLETED	23	22
NOT COMPLETED	17	11

Baseline Characteristics

Arm/Group Title	Control	Intensified Treatment	Total
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye	Total of all reporting groups
Overall Participants	40	33	73
Age (Count of Participants)
<=18 years	40 100%	33 100%	73 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.8 (1.5)	5.8 (1.4)	5.8 (1.4)
Age, Customized (participants) [Number]
3 to <4 years	5 12.5%	4 12.1%	9 12.3%
4 to <5 years	8 20%	6 18.2%	14 19.2%
5 to <6 years	9 22.5%	9 27.3%	18 24.7%
6 to <7 years	7 17.5%	5 15.2%	12 16.4%
>=7 years	11 27.5%	9 27.3%	20 27.4%
Sex: Female, Male (Count of Participants)
Female	22 55%	19 57.6%	41 56.2%
Male	18 45%	14 42.4%	32 43.8%
Race/Ethnicity, Customized (participants) [Number]
White	33 82.5%	29 87.9%	62 84.9%
African American	3 7.5%	1 3%	4 5.5%
Hispanic	4 10%	3 9.1%	7 9.6%
Region of Enrollment (participants) [Number]
United States	40 100%	33 100%	73 100%
Duration of Atropine Treatment Prior to Randomization (participants) [Number]
12 to <15 weeks	11 27.5%	5 15.2%	16 21.9%
15 to <21 weeks	6 15%	9 27.3%	15 20.5%
21 to <27 weeks	13 32.5%	9 27.3%	22 30.1%
27 to 84 weeks	10 25%	10 30.3%	20 27.4%
Duration of Atropine Treatment Prior to Randomization (weeks) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [weeks]	24.0 (11.2)	26.4 (14.6)	25.0 (12.8)
Cause of Amblyopia (participants) [Number]
Strabismus	9 22.5%	13 39.4%	22 30.1%
Anisometropia	10 25%	6 18.2%	16 21.9%
Strabismus and Anisometropia	21 52.5%	14 42.4%	35 47.9%
Distance Visual Acuity in the Amblyopic Eye at Randomization (participants) [Number]
20/160	2 5%	1 3%	3 4.1%
20/125	2 5%	2 6.1%	4 5.5%
20/100	5 12.5%	1 3%	6 8.2%
20/80	2 5%	6 18.2%	8 11%
20/63	9 22.5%	8 24.2%	17 23.3%
20/50	7 17.5%	8 24.2%	15 20.5%
20/40	11 27.5%	6 18.2%	17 23.3%
20/32	2 5%	1 3%	3 4.1%
Distance Visual Acuity in the Amblyopic Eye at Randomization (logMAR) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR]	0.48 (0.19)	0.48 (0.16)	0.48 (0.18)
Distance Visual Acuity in the Fellow Eye at Randomization (participants) [Number]
20/32	5 12.5%	6 18.2%	11 15.1%
20/25	13 32.5%	9 27.3%	22 30.1%
20/20	16 40%	13 39.4%	29 39.7%
20/16	6 15%	5 15.2%	11 15.1%
Distance Visual Acuity in the Fellow Eye at Randomization (logMAR) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR]	0.04 (0.09)	0.05 (0.10)	0.05 (0.09)
Interocular Eye Visual Acuity Difference at Randomization (logMAR lines) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [logMAR lines]	4.4 (1.8)	4.4 (1.7)	4.4 (1.7)
Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment (participants) [Number]
0 to <+1.00 D	0 0%	0 0%	0 0%
+1.00 to <+2.00 D	0 0%	1 3%	1 1.4%
+2.00 to <+3.00 D	1 2.5%	1 3%	2 2.7%
+3.00 to <+4.00 D	6 15%	5 15.2%	11 15.1%
+4.00 D or more	33 82.5%	26 78.8%	59 80.8%
Spherical Equivalent Refractive Error in Amblyopic Eye at Enrollment (diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopters]	5.73 (1.62)	5.84 (1.89)	5.78 (1.74)
Spherical Equivalent Refractive Error in Fellow Eye at Enrollment (participants) [Number]
+1.50 to <+2.00 D	5 12.5%	5 15.2%	10 13.7%
+2.00 to <+3.00 D	6 15%	2 6.1%	8 11%
+3.00 to <+4.00 D	7 17.5%	9 27.3%	16 21.9%
+4.00 D or more	22 55%	17 51.5%	39 53.4%
Spherical Equivalent Refractive Error in Fellow Eye at Enrollment (diopters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [diopters]	3.95 (1.60)	4.55 (2.28)	4.22 (1.95)

Outcome Measures

1. Primary Outcome

Title	Distribution of 10-week Amblyopic-Eye Visual Acuity
Description	The masked 10-week amblyopic eye visual acuity scores were tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
20/200	0 0%	1 3%
20/160	2 5%	0 0%
20/125	1 2.5%	2 6.1%
20/100	4 10%	0 0%
20/80	5 12.5%	4 12.1%
20/63	3 7.5%	4 12.1%
20/50	6 15%	6 18.2%
20/40	11 27.5%	4 12.1%
20/32	3 7.5%	6 18.2%
20/25	3 7.5%	5 15.2%
20/20	1 2.5%	1 3%
20/16	0 0%	0 0%

2. Secondary Outcome

Title	Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization
Description	The proportion of participants who achieved 20/25 or better visual acuity since randomization was computed at the 10-week outcome. The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity was 20/25 or better since randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis includes data from participants who completed a 10-week exam.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Number [participants]	4 10%	6 18.2%

3. Secondary Outcome

Title	Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization
Description	The proportion of participants who improved at least 2 logMAR lines since randomization was computed at the 10-week outcome. The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity improved at least 2 logMAR lines since randomization using logistic regression, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Number [participants]	8 20%	9 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intensified Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Binomial regression
	Comments	adjusted for visual acuity at randomization
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; -10 to 30
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Spectacle Compliance at 10 Weeks by Treatment Group
Description	The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Excellent	39 97.5%	30 90.9%
Good	1 2.5%	1 3%
Fair	0 0%	1 3%
Poor	0 0%	1 3%

5. Secondary Outcome

Title	Average Spectacle Compliance by Treatment Group
Description	The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Excellent	39 97.5%	30 90.9%
Good	1 2.5%	2 6.1%
Fair	0 0%	0 0%
Poor	0 0%	1 3%

6. Secondary Outcome

Title	Atropine Compliance at 10 Weeks by Treatment Group
Description	The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Excellent	38 95%	31 93.9%
Good	2 5%	2 6.1%
Fair	0 0%	0 0%
Poor	0 0%	0 0%

7. Secondary Outcome

Title	Average Atropine Compliance by Treatment Group
Description	The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Excellent	39 97.5%	29 87.9%
Good	1 2.5%	4 12.1%
Fair	0 0%	0 0%
Poor	0 0%	0 0%

8. Primary Outcome

Title	Mean 10-week Amblyopic-Eye Visual Acuity
Description	The primary outcome analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Mean (Standard Deviation) [logMAR]	0.42 (0.22)	0.37 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intensified Treatment
	Comments	The primary analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis was a 2-sided test for efficacy to test the null hypothesis of no treatment difference, assuming 90% power and a type I error rate of 5%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments	The ANCOVA model included amblyopic eye visual acuity at randomization as an adjustment covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Positive values favor the Intensified Treatment group

9. Primary Outcome

Title	Distribution of the Change in Amblyopic-Eye Visual Acuity
Description	The change in 10-week amblyopic eye visual acuity scores since randomization was tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.
Time Frame	Randomization to 10 weeks

Outcome Measure Data

Analysis Population Description

The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
3 or more lines worse	0 0%	0 0%
2 lines worse	1 2.5%	2 6.1%
1 line worse	4 10%	3 9.1%
No change	14 35%	6 18.2%
1 line improved	12 30%	13 39.4%
2 lines improved	7 17.5%	2 6.1%
3 or more lines improved	1 2.5%	7 21.2%

10. Primary Outcome

Title	Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization
Description	The change in 10-week amblyopic eye visual acuity was computed for both treatment groups and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data. The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.
Time Frame	Randomization to 10 weeks

Outcome Measure Data

Analysis Population Description

The primary outcome analysis followed the intent-to-treat principle and included data from 10-week visual acuity exams completed between 8 and 15 weeks (inclusive) with no imputation for missing data.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Mean (Standard Deviation) [logMAR lines]	0.6 (1.1)	1.1 (1.8)

11. Secondary Outcome

Title	Distribution of Interocular Difference at 12-week Exam
Description	Distribution of Interocular Difference Between Eyes at 12-week Exam
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
0 or less lines	3 7.5%	2 6.1%
1 line	2 5%	2 6.1%
2 lines	6 15%	8 24.2%
3 lines	6 15%	8 24.2%
4 lines	5 12.5%	4 12.1%
5 lines	5 12.5%	5 15.2%
6 or more lines	12 30%	4 12.1%

12. Secondary Outcome

Title	Mean Interocular Difference at 12-week Exam
Description	Mean Interocular Difference Between Eyes at 12-week Exam
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Mean (Standard Deviation) [logMAR lines]	4.3 (2.6)	3.3 (2.0)

13. Secondary Outcome

Title	Distribution of 12-week Fellow-Eye Visual Acuity
Description	Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity.
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
20/40	1 2.5%	0 0%
20/32	0 0%	4 12.1%
20/25	10 25%	7 21.2%
20/20	19 47.5%	14 42.4%
20/16	10 25%	8 24.2%

14. Secondary Outcome

Title	Mean Fellow-Eye Visual Acuity at 12-week Exam
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Mean (Standard Deviation) [logMAR]	0.01 (0.09)	0.02 (0.10)

15. Secondary Outcome

Title	Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
3 or more lines worse	1 2.5%	0 0%
2 lines worse	0 0%	0 0%
1 line worse	1 2.5%	2 6.1%
No change	23 57.5%	22 66.7%
1 line improved	12 30%	7 21.2%
2 lines improved	3 7.5%	2 6.1%
3 or more lines improved	0 0%	0 0%

16. Secondary Outcome

Title	Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Mean (Standard Deviation) [change in lines]	0.4 (0.9)	0.3 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intensified Treatment
	Comments	A treatment group difference in fellow-eye visual acuity change at the 12-week exam was evaluated using an ANCOVA model, adjusting for the fellow-eye visual acuity at randomization.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Distribution of Baseline Characteristics at the 10-week Outcome
Description	The number of participants was tabulated by treatment group within categorical levels of prespecified baseline subgroup factors for participants with 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to principles specified in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Gender: Female	21 52.5%	19 57.6%
Gender: Male	18 45%	14 42.4%
Race/Ethnicity: White (non-Hispanic)	32 80%	29 87.9%
Race/Ethnicity: Non-White/Hispanic	7 17.5%	4 12.1%
Age at randomization: 3 to <4 years	5 12.5%	4 12.1%
Age at randomization: 4 to <5 years	7 17.5%	6 18.2%
Age at randomization: 5 to <6 years	9 22.5%	9 27.3%
Age at randomization: 6 to <7 years	7 17.5%	5 15.2%
Age at randomization: 7 years or older	11 27.5%	9 27.3%
Amblyopic-eye VA at randomization: 20/80 or worse	11 27.5%	10 30.3%
Amblyopic-eye VA at randomization: 20/63	9 22.5%	8 24.2%
Amblyopic-eye VA at randomization: 20/50	7 17.5%	8 24.2%
Amblyopic-eye VA at randomization: 20/40 or better	12 30%	7 21.2%
Cause of amblyopia: Strabismus	8 20%	13 39.4%
Cause of amblyopia: Anisometropia	10 25%	6 18.2%
Cause of amblyopia: Combined mechanism	21 52.5%	14 42.4%
Atropine duration prior to randomization:12-<15wks	11 27.5%	5 15.2%
Atropine duration prior to randomization:15-<21wks	6 15%	9 27.3%
Atropine duration prior to randomization:21-<27wks	12 30%	9 27.3%
Atropine duration prior to randomization:27-84 wks	10 25%	10 30.3%
Fellow-eye SE RE at enrollment: <+3.00 Diopters(D)	10 25%	7 21.2%
Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D	12 30%	13 39.4%
Fellow-eye SE RE at enrollment: +4.50 to +6.00 D	12 30%	4 12.1%
Fellow-eye SE RE at enrollment: >+6.00 D	5 12.5%	9 27.3%

18. Secondary Outcome

Title	Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome
Description	Mean amblyopic eye visual acuity at randomization was computed by treatment group within categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles of the primary outcome analysis.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Gender: Female	0.51 (0.19)	0.46 (0.14)
Gender: Male	0.45 (0.19)	0.51 (0.19)
Race/Ethnicity: White (non-Hispanic)	0.50 (0.19)	0.49 (0.17)
Race/Ethnicity: Non-White/Hispanic	0.41 (0.18)	0.43 (0.05)
Age at randomization: 3 to <4 years	0.58 (0.22)	0.48 (0.17)
Age at randomization: 4 to <5 years	0.50 (0.13)	0.58 (0.23)
Age at randomization: 5 to <6 years	0.46 (0.21)	0.42 (0.10)
Age at randomization: 6 to <7 years	0.43 (0.18)	0.50 (0.12)
Age at randomization: 7 years or older	0.48 (0.21)	0.48 (0.18)
Cause of amblyopia: Strabismus	0.48 (0.23)	0.46 (0.16)
Cause of amblyopia: Anisometropia	0.42 (0.13)	0.35 (0.11)
Cause of amblyopia: Combined mechanism	0.51 (0.20)	0.56 (0.15)
Atropine duration prior to randomization:12-<15wks	0.54 (0.23)	0.38 (0.11)
Atropine duration prior to randomization:15-<21wks	0.53 (0.23)	0.51 (0.18)
Atropine duration prior to randomization:21-<27wks	0.43 (0.12)	0.53 (0.12)
Atropine duration prior to randomization:27-84 wks	0.46 (0.18)	0.47 (0.19)
Fellow-eye SE RE at enrollment: <+3.00 Diopters(D)	0.41 (0.20)	0.49 (0.20)
Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D	0.50 (0.18)	0.51 (0.16)
Fellow-eye SE RE at enrollment: +4.50 to +6.00 D	0.53 (0.17)	0.45 (0.24)
Fellow-eye SE RE at enrollment: >+6.00 D	0.48 (0.25)	0.47 (0.11)

19. Secondary Outcome

Title	Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics
Description	A treatment comparison of mean amblyopic eye visual acuity change since randomization was performed at the 10-week outcome according to categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.
Time Frame	10 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis included participants who completed 10-week exams between 8 and 15 weeks (inclusive) according to the principles of the primary outcome analysis.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Gender: Female	0.2 (1.0)	1.2 (1.6)
Gender: Male	1.0 (1.0)	1.1 (2.0)
Race/Ethnicity: White (non-Hispanic)	0.5 (1.1)	1.1 (1.8)
Race/Ethnicity: Non-White/Hispanic	0.9 (1.2)	1.0 (2.2)
Age at randomization: 3 to <4 years	0.2 (0.8)	1.3 (1.3)
Age at randomization: 4 to <5 years	04 (1.5)	0.7 (2.4)
Age at randomization: 5 to <6 years	0.8 (1.3)	1.2 (1.4)
Age at randomization: 6 to <7 years	0.3 (0.5)	2.4 (2.0)
Age at randomization: 7 years or older	0.9 (0.9)	0.6 (1.7)
Amblyopic-eye VA at randomization: 20/80 or worse	0.5 (0.7)	1.0 (2.4)
Amblyopic-eye VA at randomization: 20/63	0.4 (1.3)	1.5 (1.7)
Amblyopic-eye VA at randomization: 20/50	1.0 (1.3)	1.3 (1.7)
Amblyopic-eye VA at randomization: 20/40 or better	0.5 (1.1)	0.7 (1.0)
Cause of amblyopia: Strabismus	0.1 (1.1)	1.7 (1.8)
Cause of amblyopia: Anisometropia	0.8 (0.9)	1.0 (1.9)
Cause of amblyopia: Combined mechanism	0.7 (1.1)	0.6 (1.6)
Atropine duration prior to randomization:12-<15wks	1.1 (0.7)	1.2 (1.8)
Atropine duration prior to randomization:15-<21wks	-0.3 (1.0)	1.7 (2.2)
Atropine duration prior to randomization:21-<27wks	0.6 (1.3)	1.2 (1.5)
Atropine duration prior to randomization:27-84 wks	0.6 (0.8)	0.5 (1.6)
Fellow-eye SE RE at enrollment: <+3.00 Diopters(D)	0.7 (1.3)	1.0 (2.7)
Fellow-eye SE RE at enrollment: +3.00 to <+4.50 D	0.7 (1.2)	1.0 (1.2)
Fellow-eye SE RE at enrollment: +4.50 to +6.00 D	0.4 (0.9)	1.3 (2.6)
Fellow-eye SE RE at enrollment: >+6.00 D	0.6 (1.1)	1.3 (1.4)

20. Secondary Outcome

Title	Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit
Description	Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of best post-randomization (10 weeks or later) visual acuity scores in the amblyopic eye was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

The analysis includes data from participants who completed the 10-week exam and/or a later visit.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
20/200	0 0%	1 3%
20/160	2 5%	0 0%
20/125	1 2.5%	0 0%
20/100	3 7.5%	1 3%
20/80	6 15%	1 3%
20/63	1 2.5%	4 12.1%
20/50	8 20%	5 15.2%
20/40	10 25%	3 9.1%
20/32	3 7.5%	10 30.3%
20/25	5 12.5%	5 15.2%
20/20	1 2.5%	3 9.1%
20/16	0 0%	0 0%

21. Secondary Outcome

Title	Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit
Description	Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. A treatment comparison of mean amblyopic eye visual acuity at the visit of best post-randomization visual acuity (10 weeks or later) was performed using an analysis of covariance, adjusting for amblyopic eye visual acuity at randomization.
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

The analysis includes data from participants who completed the 10-week exam and/or a later visit.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Mean (Standard Deviation) [logMAR]	0.40 (0.23)	0.29 (0.22)

22. Secondary Outcome

Title	Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit
Description	Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of change in best post-randomization (10 weeks or later) visual acuity in the amblyopic eye since randomization was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)
Time Frame	Randomization to 10 weeks or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

The analysis includes data from participants who completed the 10-week exam and/or a later visit.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
3 or more lines worse	0 0%	0 0%
2 lines worse	1 2.5%	1 3%
1 line worse	4 10%	3 9.1%
No change	12 30%	3 9.1%
1 line improved	12 30%	6 18.2%
2 lines improved	9 22.5%	6 18.2%
3 or more lines improved	2 5%	14 42.4%

23. Secondary Outcome

Title	Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit
Description	Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The mean change in amblyopic eye visual acuity since randomization was computed for both treatment groups based on the visit of best post-randomization visual acuity (10 weeks or later) using the initial visual acuity score (if a retest was obtained.)
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

The analysis includes data from participants who completed the 10-week exam and/or a later visit.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	30
Mean (Standard Deviation) [logMAR lines]	0.8 (1.2)	1.9 (1.8)

24. Secondary Outcome

Title	Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines Based on Visual Acuity at Best Outcome Visit
Time Frame	10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	39	33
Number [participants]	11 27.5%	20 60.6%

25. Secondary Outcome

Title	Distribution of Randot Preschool Stereoacuity Score at 12 Weeks
Description	Distribution of Randot Preschool Stereoacuity Score at 12 Weeks; Participants with a Randot Preschool test of >800 seconds of arc were classified as having a stereoacuity of 3000 seconds of arc if the Titmus fly test was positive or as nil if the Titmus fly test was negative.
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis includes all participants who completed the 12-week exam.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	40	33
Failed pretest	4 10%	2 6.1%
>800 arcsec: Nil	7 17.5%	10 30.3%
>800 arcsec: 3000 arcsec	14 35%	12 36.4%
800 arcsec	7 17.5%	3 9.1%
400 arcsec	4 10%	3 9.1%
200 arcsec	0 0%	1 3%
100 arcsec	1 2.5%	1 3%
60 arcsec	2 5%	1 3%
40 arcsec	1 2.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intensified Treatment
	Comments	The distribution of 12-week Randot Preschool Stereoacuity scores was compared between treatment groups using a Wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

26. Secondary Outcome

Title	Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia
Time Frame	12 weeks after randomization

Outcome Measure Data

Analysis Population Description

The analysis includes participants with anisometropic amblyopia (no strabismus) who completed the 12-week exam.

Arm/Group Title	Control	Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%	Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
Measure Participants	10	6
Failed pretest	0 0%	0 0%
>800 arcsec: Nil	1 2.5%	1 3%
>800 arcsec: 3000 arcsec	2 5%	2 6.1%
800 arcsec	3 7.5%	1 3%
400 arcsec	2 5%	0 0%
200 arcsec	0 0%	0 0%
100 arcsec	0 0%	1 3%
60 arcsec	1 2.5%	1 3%
40 arcsec	1 2.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Intensified Treatment
	Comments	The distribution of 12-week Randot Preschool Stereoacuity scores was compared between treatment groups using a Wilcoxon rank sum test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Control		Intensified Treatment
Arm/Group Description	Weekend atropine 1% Atropine: Weekend atropine 1%		Weekend atropine 1% with plano lens over the sound eye Atropine: Weekend atropine 1% Plano lens: plano lens over the sound eye
All Cause Mortality
	Control		Intensified Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		Intensified Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Control		Intensified Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/40 (12.5%)		9/33 (27.3%)
Eye disorders
Light Sensitivity	1/40 (2.5%)		6/33 (18.2%)
New ocular deviation or worsening of preexisting deviation by at least 10 PD	4/40 (10%)		3/33 (9.1%)

Limitations/Caveats

A potential study limitation is that compliance with patching was based on discussions with the parent and by reviewing study calendars maintained by the parent, which not an objective measure of compliance.

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.