Effect of a Binocular iPad Game vs Part-time Patching in Children Aged 5 to 12 Years With Amblyopia: A Randomized Clinical Trial

Key Points

Question  Is amblyopic-eye visual acuity improvement treated with a binocular iPad game not substantially worse than part-time patching?

Findings  In a noninferiority randomized clinical trial enrolling 385 children, the 16-week mean amblyopic-eye visual acuity improved 1.05 lines in the binocular group and 1.35 lines in the patching group, an adjusted treatment group difference of 0.31 lines favoring patching (upper limit of the 1-sided 95% CI, 0.53 lines, exceeding the prespecified noninferiority limit of 0.5 lines, which is an indeterminate result).

Meaning  This trial cannot establish whether binocular iPad treatment is not substantially worse than 2 hours of prescribed daily patching.

Importance  A binocular approach to treating anisometropic and strabismic amblyopia has recently been advocated. Initial studies have yielded promising results, suggesting that a larger randomized clinical trial is warranted.

Objective  To compare visual acuity (VA) improvement in children with amblyopia treated with a binocular iPad game vs part-time patching.

Design, Setting, and Participants  A multicenter, noninferiority randomized clinical trial was conducted in community and institutional practices from September 16, 2014, to August 28, 2015. Participants included 385 children aged 5 years to younger than 13 years with amblyopia (20/40 to 20/200, mean 20/63) resulting from strabismus, anisometropia, or both. Participants were randomly assigned to either 16 weeks of a binocular iPad game prescribed for 1 hour a day (190 participants; binocular group) or patching of the fellow eye prescribed for 2 hours a day (195 participants; patching group). Study follow-up visits were scheduled at 4, 8, 12, and 16 weeks. A modified intent-to-treat analysis was performed on participants who completed the 16-week trial.

Interventions  Binocular iPad game or patching of the fellow eye.

Main Outcomes and Measures  Change in amblyopic-eye VA from baseline to 16 weeks.

Results  Of the 385 participants, 187 were female (48.6%); mean (SD) age was 8.5 (1.9) years. At 16 weeks, mean amblyopic-eye VA improved 1.05 lines (2-sided 95% CI, 0.85-1.24 lines) in the binocular group and 1.35 lines (2-sided 95% CI, 1.17-1.54 lines) in the patching group, with an adjusted treatment group difference of 0.31 lines favoring patching (upper limit of the 1-sided 95% CI, 0.53 lines). This upper limit exceeded the prespecified noninferiority limit of 0.5 lines. Only 39 of the 176 participants (22.2%) randomized to the binocular game and with log file data available performed more than 75% of the prescribed treatment (median, 46%; interquartile range, 20%-72%). In younger participants (aged 5 to <7 years) without prior amblyopia treatment, amblyopic-eye VA improved by a mean (SD) of 2.5 (1.5) lines in the binocular group and 2.8 (0.8) lines in the patching group. Adverse effects (including diplopia) were uncommon and of similar frequency between groups.

Conclusions and Relevance  In children aged 5 to younger than 13 years, amblyopic-eye VA improved with binocular game play and with patching, particularly in younger children (age 5 to <7 years) without prior amblyopia treatment. Although the primary noninferiority analysis was indeterminate, a post hoc analysis suggested that VA improvement with this particular binocular iPad treatment was not as good as with 2 hours of prescribed daily patching.

Trial Registration  http://www.clinicaltrials.gov Identifier: NCT02200211

Quiz Ref IDA binocular approach to treating anisometropic and strabismic amblyopia has recently been advocated^1-6 without patching,^7,8 atropine drops,⁹ or Bangerter filters¹⁰ applied to the fellow eye. In such binocular therapy, images are presented dichoptically, with high-contrast images presented to the amblyopic eye and low-contrast images to the fellow eye to achieve a binocular percept.¹¹ This binocular treatment has been adapted to an iPad (Apple Inc) device as a “falling blocks” game that uses red-green anaglyphic glasses. Initial studies have yielded promising results,^3-5 suggesting that a larger randomized clinical trial is warranted.

The purpose of the present randomized clinical trial was to establish whether treatment of amblyopia with a binocular iPad game (prescribed 1 hour per day for 16 weeks) was not substantially worse (noninferior) than treatment with patching of the fellow eye (prescribed 2 hours per day) in children aged 5 to younger than 13 years, with 20/40 to 20/200 amblyopic-eye VA.

The study was conducted at 78 institution- or community-based clinical sites. The complete study protocol is available in Supplement 1. Eligibility criteria are listed in the eAppendix in Supplement 2.

The study was approved by the institutional review boards of all participating facilities, which are listed at the end of this article. A parent or guardian (referred to subsequently as parent) of each study participant gave written informed consent, and each participant assented to participation as required; the participants received reimbursement for travel and parking. The trial adhered to the Declaration of Helsinki guidelines.¹²

Visual acuity was measured in each eye with optimal refractive correction (if applicable) and without cycloplegia by a study-certified examiner (masked at follow-up). We used a consistent method throughout the study for each participant: either the Amblyopia Treatment Study single-surround HOTV protocol (ATS-HOTV)¹³ for participants aged 5 to younger than 7 years or the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) protocol¹⁴ for participants aged 7 to younger than 13 years. Visual acuity was converted to the logMAR scale. Additional testing at all study visits included measurement of ocular alignment with a simultaneous prism and cover test, a prism and alternate cover test, and stereoacuity (masked at follow-up) using the Randot Butterfly and Randot Preschool stereoacuity tests (Stereo Optical Co).

Follow-up visits occurred at 4, 8, 12, and 16 weeks (±1 week) after randomization (±1 week), with the primary outcome visit at 16 weeks. At each visit, a standardized questionnaire was administered to participants and their parents to assess the presence and frequency of diplopia.

Participants were randomly assigned via the PEDIG website with equal probability, using a permutated block design stratified by age group (5 to <7 years and 7 to <13 years) and site, to receive either binocular treatment (binocular group) or patching (patching group), administered via the PEDIG website.

The patching group was prescribed 2 hours of daily patching (allowing division into shorter sessions) with an adhesive-style patch (Coverlet, Opticlude, Ortopad; 3M), 7 days a week for 16 weeks. The binocular group was prescribed the binocular falling blocks iPad game for 1 hour a day (allowing division into shorter sessions), 7 days a week for 16 weeks, with instructions to perform therapy a minimum of 4 days a week if unable to play for 7 days per week. The differing durations per day (2 hours vs 1 hour) were chosen to reflect commonly used regimens with each treatment. Adherence was calculated based on an intended treatment of 7 days a week for 16 weeks.

The game was played on a study-supplied iPad device at the participants’ habitual reading distance while wearing red-green anaglyphic glasses (over the spectacles if applicable), with the green filter placed over the amblyopic eye. Participants played the game by moving the falling blocks to form solid lines, with the level of difficulty (easy, medium, and hard) set at the participant’s discretion. Although the contrast of the falling blocks for the amblyopic eye was always 100%, the contrast for the fellow eye was initially set to 20% and automatically increased or decreased by 10% increments (with a lowest level of 10%) or left unchanged from the last contrast level, based on the previous day’s game play duration and performance. The contrast changed only if 30 minutes or more of game play had occurred the previous day, increasing if 1000 points or more were scored or decreasing otherwise.

Parents recorded the number of hours the participant played the game or wore the patch each day using calendars. The iPad device automatically recorded the duration of game play, contrast, and performance.

The trial was designed as a noninferiority study. A sample size of 346 participants was computed to have 90% power with a type I error of 5% for a noninferiority limit of 0.05 logMAR (0.5 lines), assuming an SD of change of 0.15 logMAR (1.5 lines) based on prior PEDIG studies^10,15-18 and no more than 10% loss to follow-up. This noninferiority margin represents a conservative estimate of the treatment benefit of part-time patching compared with optical correction alone (based on previous studies^15,16), chosen so the effect of binocular treatment, if found to be noninferior to patching, would very likely be greater than that of optical correction alone.

The primary outcome measure was change in amblyopic-eye VA from baseline to 16 weeks (14- to <20-week window). The upper limit of a 1-sided 95% CI was computed on the treatment group difference, using an analysis of covariance model, adjusted for baseline age and VA, including only participants completing the 16-week outcome in a modified intent-to-treat analysis. Alternative approaches to the primary analysis are specified in eTable 1 in Supplement 2. The primary analysis was repeated with computation of a 2-sided 95% CI for the adjusted treatment group difference as a post hoc analysis to estimate the range of plausible values of the treatment group difference. The Wilcoxon rank sum test was used to compare the change in stereoacuity levels from baseline to 16 weeks by treatment group, and the frequency of diplopia across categories of diplopia was compared between the treatment groups using the Cochran-Armitage trend test.

In a post hoc analysis, we compared the 16-week outcomes in those who were adherent (completing >50% of the prescribed treatment) and successfully played the game (fellow-eye contrast increased to >95%) with those who were not adherent. Analyses were conducted using SAS, version 9.4 (SAS Institute Inc).

Between September 16, 2014, and August 28, 2015, a total of 385 participants were randomly assigned to the binocular group (n = 190) or the patching group (n = 195). Baseline characteristics were similar in the 2 groups (Table 1). Seven patients were subsequently found to be ineligible based on the following pre-enrollment criteria: spectacles did not meet refractive correction guidelines (n = 1), no overrefraction was performed when required (n = 1) or overrefraction outside prespecified tolerance limits (n = 1) for contact lens wear, failure to meet visual acuity stability criteria for corrective wear (n = 3), and the most recent cycloplegic refraction was performed more than 7 months before enrollment (n = 1) (Figure 1).

The 16-week primary outcome was completed by 182 children (95.8%) in the binocular group and 188 children (96.4%) in the patching group (Figure 1). Masking was maintained at 99% of the visits.

During the 16-week follow-up period, of the children who completed the examination within the prespecified analysis window, 118 children (66.7%) in the binocular group and 172 (92.5%) in the patching group reported completing more than 75% of the prescribed treatment based on calendars. However, for the binocular group, the iPad device indicated that only 39 of the 176 participants (22.2%) with log file data available performed more than 75% (median, 46%; interquartile range, 20%-72%) of the prescribed treatment. Only 2 participants in the binocular group had been prescribed less than the 1 hour per day 7 days per week intended dose during follow-up. In the binocular group, 100% contrast in the fellow eye was achieved for 35 participants (20.2%) at 4 weeks and for 86 participants (48.9%) at 16 weeks. Thirty-one (17.6%) participants had 20% contrast or worse, to the fellow eye, at 16 weeks. Nonprotocol alternative treatment was received by no participants in the patching group and 4 participants in the binocular group (1 atropine and 3 patching, 1 of whom received patching in addition to protocol binocular therapy).

Quiz Ref IDAt 16 weeks, mean amblyopic-eye VA improved from baseline by 1.08 lines (2-sided 95% CI, 0.86-1.29 lines) in the binocular group and by 1.32 lines (2-sided 95% CI, 1.14-1.51 lines) in the patching group (Figure 2, Table 2, and eFigure 1 and eTable 2 in Supplement 2). After adjusting for baseline covariates of age and VA, mean amblyopic-eye VA improved from baseline by 1.05 lines (95% CI, 0.85-1.24 lines) and 1.35 lines (95% CI, 1.17-1.54 lines) in the binocular and patching groups, respectively, resulting in a treatment group difference of 0.31 lines favoring the patching group. The upper limit of the 1-sided 95% CI of the treatment difference was 0.53 lines, which exceeded the prespecified noninferiority limit of 0.5 lines. Because we were unable to reject the null hypothesis (that binocular treatment was inferior to patching), our primary analysis was indeterminate. In a post hoc analysis, the 2-sided 95% CI for the adjusted treatment group difference was 0.04 to 0.58 lines, favoring the patching group. Results of alternative analyses were consistent with the primary analysis (eTable 1 in Supplement 2).

At 16 weeks, amblyopic-eye VA improved by 2 lines or more from baseline for 65 (34.9%) and 51 (28.8%) participants in the patching and binocular groups, respectively (adjusted difference, 5%; 2-sided 95% CI, −4% to 13%), and amblyopia resolved (VA of 20/25 or better and within 1 logMAR line of fellow eye) for 18 (9.7%) and 8 (4.5%) participants in the patching and binocular groups, respectively (adjusted difference, 2%; 2-sided 95% CI, −1% to 5%). The rate of amblyopic-eye VA improvement was not statistically different between treatment groups (P = .83) (Figure 2). At 4, 8, and 12 weeks, the mean change from baseline in the patching group was 0.76, 1.03, and 1.21 lines; and in the binocular group was 0.53, 0.76, and 0.90 lines, respectively.

The overall reduced effect of binocular treatment compared with patching on improvement of amblyopic-eye VA was paralleled in baseline subgroups (eTable 3 in Supplement 2). For both treatment groups, there was a particularly noticeable improvement in younger participants (5 to <7 years) with no prior treatment (2.5 [1.5] lines in the binocular group and 2.8 [0.8] lines in the patching group) (eTable 3 in Supplement 2).

At both 4 and 16 weeks, improvement in amblyopic-eye VA was not associated with objective measures of total hours of treatment or change in fellow-eye contrast for the binocular group overall (eFigure 2 and eFigure 3 in Supplement 2) or within baseline subgroups of age (5 to <7 years and 7 to <13 years) with or without previous treatment (eFigure 4 and eFigure 5 in Supplement 2). In addition, mean improvement in 16-week amblyopic-eye VA for participants who completed more than 50% of prescribed treatment and achieved better than 95% fellow-eye contrast was 0.9 (1.4) line (n = 51) compared with 1.2 (1.5) lines (n = 125) in those who did not fulfill these criteria.

Change in stereoacuity did not differ significantly between treatment groups for the overall cohort or for participants with no history of strabismus at baseline (eTable 4 in Supplement 2). The median change in stereoacuity from baseline to 16 weeks was 0 in both groups, and there was a similar lack of effect of binocular treatment and patching on change in stereoacuity in baseline subgroups (eTable 5 in Supplement 2).

At both 4 and 16 weeks, improvement in stereoacuity was not associated with either total hours of completed binocular treatment or change in fellow-eye contrast, either overall (eFigure 2 and eFigure 3 in Supplement 2) or within baseline subgroups of age (5 to <7 years and 7 to <13 years) with or without previous treatment (eFigure 6 and eFigure 7 in Supplement 2). At 16 weeks, median stereoacuity improvement was 0 for participants who completed more than 50% of the prescribed binocular treatment and achieved better than 95% fellow-eye contrast (n = 51) and 0 for those who did not fulfill these criteria (n = 124).

Mean improvement in fellow-eye VA, adjusted for baseline VA, differed by 0.16 lines (95% CI, 0.02-0.30 lines) favoring the binocular group (eTable 6 in Supplement 2). At 16 weeks, only 2 participants (1 participant in each treatment group) tested 2 lines worse from baseline.

The number of participants with a new tropia and/or worsening of a preexisting deviation of 10 Δ or higher was 16 (8.8%) and 11 (5.9%) in the binocular and patching groups, respectively (Fisher exact test, P = .32). Diplopia was rare in both groups (eTable 7 in Supplement 2). Three participants (1.6%) in the patching group who completed follow-up reported moderate or severe skin irritation with patching during follow-up.

Quiz Ref IDIn children aged 5 to 12 years, amblyopic-eye VA improved in both the binocular and patching groups, particularly in younger participants (5-6 years) without prior amblyopia treatment. Visual acuity improvement in the binocular group did not meet the prespecified definition for noninferiority compared with 2 hours of prescribed daily patching; therefore, our primary analysis was indeterminate. Nevertheless, a post hoc analysis suggested VA improvement with this particular binocular iPad treatment was not as good as improvement with 2 hours of prescribed daily patching.

Mean improvement in amblyopic-eye VA with binocular treatment during our 16-week study was similar in magnitude (approximately 1 logMAR line) to that previously reported in nonrandomized studies prescribing 4 hours per week of binocular treatment for 4 weeks in children aged 4 to 12 years^3,5 and in those aged 3 to 6 years.⁴ These previous studies^3-5 of binocular iPad treatment included 4 different games, one of which was the falling blocks game, and allowed concurrent patching at a different time of day at the eye care provider’s discretion, although a subanalysis of those treated with only binocular games yielded a similar magnitude of effect.⁴ Knox et al² also found a similar magnitude of improvement in children (mean [SD] age, 8.5 [1.9] years) treated with an analogous game using a head-mounted display in a supervised setting for 1 hour per day for 5 sessions during 1 week. The rate of improvement in amblyopic-eye VA was slower in the present study than in these previous studies,^3-5 which may have been attributable to a larger proportion of older participants in the present study.

When treating adults with amblyopia using binocular therapy in a supervised setting for 1 hour per day for 2 weeks, Li et al⁶ reported a mean improvement of approximately 2 logMAR lines—greater than that found in the present study of children. Nevertheless, this treatment in adults was in a laboratory setting using a head-mounted display; thus, the results cannot be directly compared.

Quiz Ref IDIn our study, investigators noted that participants often lost interest in the game after a number of days or weeks, well before the prescribed 16-week course was completed. Only 22% of our children achieved greater than 75% adherence, suggesting that adherence should be reviewed more frequently and games need to be more appealing, such as more engrossing children’s games, binocular first-person action games,¹⁹ and binocular movie viewing.²⁰

Another reason why we may not have found a greater effect of binocular treatment was the timing of the initial and final assessments. Previous studies^2-6 of binocular therapy have evaluated patients after a shorter duration of treatment. It is unclear whether active progression through contrast levels is necessary for treatment to be ongoing or whether treatment is ongoing even when equal contrast has been achieved. If active progression is needed, many of our children who achieved 100% contrast to the fellow eye would have completed treatment well before our primary outcome (86 [48.9%]) and even before 4 weeks (35 [20.2%]). We also found that 18% of participants failed to progress in contrast to the fellow eye, suggesting that the contrast starting point was not optimally set for each participant and that the initial contrast should be based on an individual measurement of suppression rather than the arbitrary 20% used here.

Regarding improvement of stereoacuity, it has been suggested¹ that the mechanism of binocular treatment of amblyopia is by reducing suppression and increasing binocularity. Stereoacuity outcomes differ between studies, with some reporting improvement^1,2 and others (like ours) reporting no improvement for most participants.^3,4 It is possible that these differences may be attributable to the type of stereoacuity test used. Improvements might be detected more easily using the Frisby test or contour tests rather than random dot tests.^21,22

It remains unclear whether the binocular iPad treatment used in our study was actually better than optical treatment alone (if needed) and, as such, whether binocular iPad treatment is actually better than sham therapy. Nevertheless, the large magnitude of the VA improvement (mean [SD], 2.5 [1.5] lines) in the younger participants (5 to <7 years) in the binocular group who had not received previous treatment suggests that binocular treatment produced a real effect, greater than what would be expected with continued optical treatment alone after achieving stable VA with spectacles.¹⁶ Regarding the effect of patching in our study, our overall mean improvement (1.3 logMAR lines) was less than we expected, but this was most likely due to the large proportion (63%) of participants who were both older (7 to <13 years) and who had received previous treatment.

There has been some concern that binocular treatment might be associated with new-onset diplopia because its mechanism of action may be via antisuppression. Nevertheless, in our study and in previous studies^3-5 of this particular form of binocular treatment, diplopia was rare.

Our study has a number of limitations regarding the assessment of adherence. For patching, we did not use occlusion dose monitors. Our adherence data relied on parental report (for patching and, in part, for binocular treatment), which may have been inaccurate. The electronic recording of adherence by the binocular game may have also included time when the game was not being played, but this would be expected to be minimal because the game sessions automatically ended after approximately 1 minute of inactivity. For binocular treatment, we allowed participants to play a minimum of 4 days per week, if they could not play 7 days per week, but reduced game play was prescribed in only 2 children. Finally, we did not monitor adherence with wearing the red-green glasses required to play the game.

In children aged 5 to 12 years, amblyopic-eye VA improved with binocular game play and with patching, but VA improvement with this particular binocular iPad treatment, when prescribed for 1 hour a day, failed to meet our study’s prespecified definition for noninferiority compared with 2 hours of prescribed daily patching; therefore, our primary analysis was indeterminate. Nevertheless, a post hoc analysis suggested that VA improvement with this particular binocular iPad treatment was not as good as with 2 hours of prescribed daily patching.

Corresponding Author: Jonathan M. Holmes, BM, BCh, Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (pedig@jaeb.org).

Accepted for Publication: September 5, 2016.

Published Online: November 3, 2016. doi:10.1001/jamaophthalmol.2016.4262

Author Contributions: Ms Lazar had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Holmes, Manh, Lazar, Beck, Birch, Kraker, Crouch, Wallace.

Acquisition, analysis, or interpretation of data: Holmes, Manh, Lazar, Birch, Kraker, Crouch, Erzurum, Khuddus, Summers, Wallace.

Drafting of the manuscript: Holmes, Manh, Lazar, Kraker.

Critical revision of the manuscript for important intellectual content: Manh, Lazar, Beck, Birch, Kraker, Khuddus, Crouch, Erzurum, Summers, Wallace.

Statistical analysis: Holmes, Manh, Lazar, Kraker.

Administrative, technical, or material support: Holmes, Kraker, Crouch, Erzurum.

Study supervision: Holmes, Manh, Beck, Kraker, Wallace.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Holmes, Lazar, Kraker, and Wallace reported receiving grants from The National Eye Institute of National Institutes of Health, Department of Health and Human Services during conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by the National Eye Institute, National Institutes of Health (NIH), Department of Health and Human Services grants EY011751, EY023198, and EY018810. Casey Eye Institute received support from NIH grant EY010572 to fund shared departmental resources for research purposes. Casey Eye Institute, Wilmer Institute, Mayo Clinic, Rainbow Babies and Children’s Hospital, and University of Minnesota received support from an unrestricted grant from Research to Prevent Blindness Inc.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The Pediatric Eye Disease Investigator Group (PEDIG) consists of the following individuals, organized by clinical site and listed in order by the number of participants enrolled. Personnel are listed as investigator (I), coordinator (C), or examiner (E). Clinical Sites:Norfolk, Virginia: Virginia Pediatric Eye Center (n = 31): Earl R. Crouch Jr, (I); Earl R. Crouch III (I), Stacy R. Martinson (I), Gaylord G. Ventura (C), Candice C. Brown (E), Cynthea M. Carlton (E), and Carolina A. Escala (E). Miami, Florida: Bascom Palmer Eye Institute (n = 19): Susanna M. Tamkins (I), Carolina Manchola-Orozco (C), Kara M. Cavuoto (E), Isaura Gomez Tamayo (E), Maria D. Martinez (E), Eva M. Olivares (E), Oriel Spierer (E), and Erin Yanowitch (E). Gainesville, Florida: Accent Physicians (n = 17): Nausheen Khuddus (I), Kathy Bryan (C), and Tammy Toskes Price (E). Rockville, Maryland: Stephen R. Glaser (n = 17): Stephen R. Glaser (I), Tara G. Missoi (I), Nancy A. Morrison (I), Kasey L. Yost (C), Deandra B. Andrade (E), and Odalis R. Flores (E). Poland, Ohio: Eye Care Associates Inc (n = 15): S. Ayse Erzurum (I), Beth J. Colon (C), Diana C. McOwen (C), Guy C. Barrett (E), and Zainab Dinani (E). Cranberry Township, Pennsylvania: Everett and Hurite Ophthalmic Association (n = 14): Darren L. Hoover (I), Pamela A. Huston (C), Christine J. Deifel (E), Jody L. Desiderio (E), Pamela M. Racan (E), and Kari E. Soros (E). Chattanooga, Tennessee: Pediatric Eye Specialists (n = 11): Edward A. Peterson (I), Zachary S. McCarty (I), Charla H. Peterson (C), and Amie Jenkins (E). Fullerton, California: Southern California College of Optometry (n = 11): Susan A. Cotter (I), Angela M. Chen (I), Raymond H. Chu (I), Silvia Han (I), Catherine L. Heyman (I), Kristine Huang (I), Sue M. Parker (C), Reena A. Patel (I), Maureen D. Plaumann (I), Carlee Y. Young (I), and Carmen N. Barnhardt (E). Houston, Texas: University of Houston College of Optometry (n = 11): Karen D. Fern (I), Heather A. Anderson (I), Debra C. Currie (I), Dashaini V. Retnasothie (I), Sylvia Landa (C), and Fawn M. Candelari (C). Portland, Oregon: Casey Eye Institute (n = 11): Allison I. Summers (I), Paula K. Rauch (C), Yelena M. Bubnov (E), Grant A. Casey (E), Rhea N. Nelson (E), and Kevin M. Woodruff (E). The Woodlands, Texas: Houston Eye Associates (11): Aaron M. Miller (I); Jorie Jackson (C); Angela C. Dillon (C); Kathleen M. Curtin (E); Maria N. Olvera (E); and Starla J. Skaggs (E). Birmingham, Alabama: University of Alabama at Birmingham School of Optometry (n = 10): Marcela Frazier (I), Kristine T. Hopkins (I), Sarah D. Lee (I), Katherine K. Weise (I), Paul Christian Spain (C), and Michelle B. Bowen (C). Baltimore, Maryland: Wilmer Institute (n = 9): Michael X. Repka (I), Courtney Kraus (I), Anya A. Trumler (I), Xiaonong Liu (C), Alex X. Christoff (E), Kyle Pearce Harrold (E), and Colin Patrick Kane (E). Cincinnati, Ohio: Cincinnati Children’s Hospital Medical Center (n = 9): Michael E. Gray (I), Melissa L. Rice (I), Daniele P. Saltarelli (I), Corey S. Bowman (C), Shemeka R. Forte (E), Amanda R. Johnson (E), Erica M. Setser (E), Miqua L. Thomas (E), and Felicia J. Timmermann (E). Boise, Idaho: St Luke’s Hospital (n = 7): Katherine A. Lee (I), Daniel R. Brooks (I), Bonita R. Schweinler (C), Lori Lynne McDaniel (E), and Larry W. Plum (E). Grand Rapids, Michigan: Helen DeVos Children’s Hospital Pediatric Ophthalmology (n = 7): Brooke E. Geddie (I), Elisabeth T. Wolinski (C), Kimberly J. Hubbard (E), and Michael N. Patton (E). Rochester, Minnesota: Mayo Clinic (n = 7): Jonathan M. Holmes (I), Suzanne M. Wernimont (C), Matthew W. Heiderscheit (E), Anita R. Hermanson (E), Julie A. Holmquist (E), Jordan J. Huisman (E), Melissa J. Hunemuller (E), Lindsay D. Klaehn (E), Marna L. Levisen (E), Laura Liebermann (E), Rebecca A. Nielsen (E), Debbie M. Priebe (E), and Casandra M. Turri (E). Spokane, Washington: Northwest Pediatric Ophthalmology, P.S. (n = 7): George F. Whitehead (I); Christina N. Nye (I), Caroline J. Shea (I), and SueAnn M. Stillman (C). Atlanta, Georgia: The Emory Eye Center (n = 6): Scott R. Lambert (I), Amy K. Hutchinson (I), Phoebe D. Lenhart (I), Judy L. Brower (C), Jayne M. Brown (E), Linda T. Curtis (E), Melanie K. Fowler (E), and Marla J. Shainberg (E). Lancaster, Pennsylvania: Conestoga Eye (n = 6): David I. Silbert (I), Noelle S. Matta (C), Karen L. Delgado (E), and Prucilla R. Shady (E). Waterbury, Connecticut: Eye Care Group, PC (n = 6): Tara H. Cronin (I), Andrew J. Levada (I), Susan H. Heaton (C), Cheryl Capobianco (E), and Lindsay Gill (E). Big Rapids, Michigan: Michigan College of Optometry at Ferris State University (n = 5): Paula S. McDowell (I), Alison M. Jenerou (I), Kerrie Rachelle Currie (C), Emily Jean Aslakson (E), and Sarah B. Hinkley (E). Chicago, Illinois: Illinois College of Optometry (n = 5): Yi Pang (I), Huizi Yin (I), and Elyse Nylin (C). Erie, Pennsylvania: Pediatric Ophthalmology of Erie (n = 5): Nicholas A. Sala (I), Allyson Sala (C), Catherine Johnson (E), and V. Lori Zeto (E). Grand Rapids, Michigan: Pediatric Ophthalmology, PC (n = 5): Patrick J. Droste (I), Robert J. Peters (I), Jan Hilbrands (C), Leslie J. Bileth (E), Andrew P. Droste (E), and Jennifer L. Mooney (E). Rochester, New York: University of Rochester Eye Institute (n = 5): Benjamin P. Hammond (I), Matthew D. Gearinger (I), Andrea Czubinski (C), and Rebecca K. Gerhart (E). Silverdale, Washington: Jason C. Cheung, MD, PS (n = 5): Jason C. Cheung (I), Tiffany M. Parypa (C), and Jacque J. Ferro (E). West Des Moines, Iowa: Wolfe Clinic (n = 5): Myra N. Mendoza (I), Sara D. Khan (I), Jill J. Frohwein (C), Lisa M. Fergus (E), Susan K. Hayes (E), and Rhonda J. Countryman (E). Chicago Ridge, Illinois: The Eye Specialists Center, LLC (n = 4): Benjamin H. Ticho (I), Megan Allen (I), Birva K. Shah (I), Deborah A. Clausius (C), Sharon L. Giers (E), Micaela N. Quebbemann (E). Cleveland, Ohio: Cole Eye Institute (n = 4): Fatema F. Ghasia (I), Diana C. McOwen (C), Susan W. Crowe (C), Angela M. Borer (E), and Rachael Briggs (E). Fall River, Massachusetts: Center for Eye Health, Inc (n = 4): John P. Donahue (I), Samantha J. Pape (C), Danielle K. Berry (E), Linda M. Cabeceiras (E), Mary E. Silvia (E), and Samantha Teixeira (E). Houston, Texas: University of Texas–Robert Cizik Eye Clinic (n = 4): Kartik S. Kumar (I), Ephrem K. Melese (C), and Laura A. Baker (E). Marlton, New Jersey: Michael F. Gallaway, OD, PC (n = 4): Michael F. Gallaway (I), Debbie L. Killion (C), Tammy Lynn Thomas (E), Beth Zlock (E). Portland, Oregon: Pacific University College of Optometry (n = 4): Richard London (I), Ryan C. Bulson (I), Jayne L. Silver (C), and James J. Kundart (E). Rio Rancho, New Mexico: City of Vision Eye Care (n = 4): Lisa M. Edwards (I), Carolyn Sue Marquez (C), Jessica Noel Marquez (E), and Tristan Lee Martinez (E). Wilmette, Illinois: Pediatric Eye Associates (n = 4): Lisa C. Verderber (I), Deborah R. Fishman (I), Roberta A. Forde (C), Sarah Ahn (E), and Adam J. Julian (E). Aberdeen, North Carolina: Family Eye Care of the Carolinas (n = 3): Michael J. Bartiss (I), Tennille F. McGaw (C), Leah M. Kelly (E), and Lauren E. Simmons (E). Arnold, Maryland: Ophthalmology Associates of Greater Annapolis (n = 3): John M. Avallone (I), Charlene R. Bryant (C), and Wanda E. Peyton (E). Chicago, Illinois: Ann & Robert H. Lurie Children’s Hospital of Chicago (n = 3): Bahram Rahmani (I), Sudhi P. Kurup (I), Magdalena Stec (I), Hawke H. Yoon (I), Janice B. Zeid (I), Hantamalala Ralay Ranaivo (C), Kristyn M. Magwire (E), Erika A. Talip (E), and Vivian Tzanetakos (E). Durham, North Carolina: Duke University Eye Center (n = 3): Laura B. Enyedi (I), David K. Wallace (I), Sarah K. Jones (C), Courtney E. Fuller (E), and Namita Kashyap (E). Houston, Texas: Texas Children’s Hospital (n = 3): Evelyn A. Paysse (I), Amit R. Bhatt (I), Kimberly G. Yen (I), Lingkun Kong (C), and Melynda T. Homann (E). Kansas City, Missouri: Children’s Mercy Hospitals and Clinics (n = 3): Amy L. Waters (I), Christina M. Twardowski (I), Rebecca J. Dent (C), Lori L. Soske (C), Lezlie L. Bond (E), and Cindy J. Cline (E). Kingston, Ontario, Canada: Children’s Eye Research Center (n = 3): Brian W. Arthur (I) and Lesley E. MacSween (E). Mayfield Heights, Ohio: Rainbow Babies and Children’s Hospital (n = 3): Faruk H. Orge (I), Alicia Marie Baird (C), and Veronica Marie Bontempo (E). Munster, Indiana: The Eye Specialist Center, LLC (n = 3): Birva K. Shah (I), Micaela N. Quebbemann (C), and Deborah Ann Clausius (E). Omaha, Nebraska: University of Nebraska Medical Center (n = 3): Donny W. Suh (I), Carolyn Chamberlain (C), Whitney R. Brown (E), Joel O. Rivas (E), and Dimitra M. Triantafilou (E). Pittsburgh, Pennsylvania: UPMC Children’s Eye Center of Children’s Hospital of Pittsburgh (n = 3): Ken K. Nischal (I), Ellen B. Mitchell (I), Lauren Bolling (C), Bianca Blaha (E), Whitney Churchfield (E), and Christina Fulwylie (E). Aurora, Colorado: University of Colorado Health Science Center (n = 2): Emily A. McCourt (I), Daniel E. Smith (I), Nanastasia Welnick (C), Susan James (E), and Sarah E. Peck (E). Bloomington, Indiana: Indiana University School of Optometry (n = 2): Don W. Lyon (I), Kristy M. Dunlap (C), Vidhyapriya Sreenivasan (E), and Yifei Wu (E). Charleston, South Carolina: Medical University of South Carolina, Storm Eye Institute (n = 2): Edward W. Cheeseman (I), Carol U. Bradham (C), Paige P. Edwards (E), and Carole M. Lemieux (E). Columbus, Ohio: Pediatric Ophthalmology Associates (n = 2): Don L. Bremer (I), Richard P. Golden (I), Mary Lou McGregor (I), Meghan C. McMillin (C), Sara Ann Oravec (C), Andrea Nicole Gearhart (E), and Benita Nechell Mansperger (E). Dubuque, Iowa: Medical Associates Clinic PC (n = 2): Timothy J. Daley (I), Shannon R. Walsh (C), and Cheyanne M. Hoeger (E). Fort Lauderdale, Florida: Nova Southeastern University College of Optometry, The Eye Institute (n = 2): Michael Au (I), Jacqueline Rodena (I), Yin C. Tea (I), Nadine Girgis Hanna (I), Erin Jenewein (I), and Surbhi Bansal (C). Little Rock, Arkansas: Arkansas Children’s Hospital/University of Arkansas Medical Sciences (n = 2): Robert Scott Lowery (I), Paul H. Phillips (I), Brita S. Deacon (I), Kelly D. To (C), and Shawn L. Cupit (E). Minneapolis, Minnesota: University of Minnesota (n = 2): Raymond G. Areaux (I), Sara J. Downes (I), Ann M. Holleschau (C), Kathy M. Hogue (E), Andrea M. Kramer (E), and Kim S. Merrill (E). Montreal, Quebec, Canada: Centre Hospitalier de l'Université–Sainte-Justine (n = 2): Rosanne Superstein (I), Maryse Thibeault (C), Emma Chilliet (E), and Charlotte Riguidel (E). Philadelphia, Pennsylvania: Salus University/Pennsylvania College of Optometry (n = 2): Erin C. Jenewein (I), Mitchell M. Scheiman (I), Karen E. Pollack (C), Michael F. Gallaway (E), Jenny Myung (E), and Ruth Y. Shoge (E). Seattle, Washington: Seattle Children's Hospital (n = 2): Vivian Manh (I), Lyndsey A. Tews (C), Amy Gladstone (E), and Jennifer Vincent (E). Spokane, Washington: Spokane Eye Clinic (n = 2): Jeffrey D. Colburn (I), Eileen Dittman (C), Dylan C. Waidelich (E), and Marilyn M. Westerman (E). Wheaton, Illinois: Wheaton Eye Clinic (n = 2): Noha S. Ekdawi (I), Darin L. Strako (C), Brittany Freese (E), and Maria T. Jimenez (E). Baltimore, Maryland: Greater Baltimore Medical Center (n = 1): Mary Louise Z. Collins (I), Allison A. Jensen (I), Maureen A. Flanagan (C), Saman Bhatti (E), Cheryl L. McCarus (E), and Srianna Narain (E). Boston, Massachusetts: Boston Medical Center (n = 1): Jenna R. Titelbaum (I), Jean E. Ramsey (I), Stephen P. Christiansen (I), Kate Hutton McConnell (C), Kelly M. Castle (E), and Jennifer E. Lambert (E). Boston, Massachusetts: Harvard Vanguard Medical Associates (n = 1): Mei L. Mellott (I), Troy L. Kieser (C), and Linette Miranda (E). Calgary, Alberta, Canada: Alberta Children's Hospital (n = 1): William F. Astle (I), Emi N. Sanders (C), Zuzana Ecerova (E), Charlene D. Gillis (E), Catriona I. Kerr (E), Shannon L. Steeves (E), and Heather N. Sandusky (E). Concord, New Hampshire: Concord Ophthalmologic Associates (n = 1): Christie L. Morse (I), Melanie L. Christian (C), and Caroline C. Fang (E). Glendale, Arizona: Midwestern University Eye Institute (n = 1): Paula A. Handford (I), Alicia E. Feis (I), Christina A. Esposito (I), and Tracy A. Bland (C). Hurricane, West Virginia: Marshall University (n = 1): Deborah L. Klimek (I), Ginger Peters (C), Amanda C. Conley (E), Sara E. Miramontes (E), and Sonya G. Walls (E). Indianapolis, Indiana: Riley Hospital for Children (n = 1): Kathryn M. Haider (I), Michele E. Whitaker (C), Adam J. Harshbarger (E), and Jingyun Wang (E). Iowa City, Iowa: University of Iowa Hospitals and Clinics (n = 1): Scott A. Larson (I), Xiaoyan Shan (C), Tara L. Bragg (E), and Miriam Di Menna (E). Jacksonville, Florida: Nemours Children’s Specialty Care (n = 1): John W. Erickson (I), Charlotte Ann Louise Reaser (C), and Gracie Sylvester (E). Lincoln, Nebraska: Eye Surgical Associates (n = 1): Donald P. Sauberan (I), Jody C. Hemberger (C), and Gail Walker (E). Nashville, Tennessee: Vanderbilt Eye Center (n = 1): Sean P. Donahue (I), Lori Ann F. Kehler (I), Scott T. Ruark (C), Lisa A. Fraine (E), and Ronald J. Biernacki (E). New Haven, Connecticut: Yale University Medcal School, Department. of Ophthalmology and Visual Science (n = 1): Jennifer A. Galvin (I), Margaret B. Therriault (C), Jaime Harrison (E), and Christine C. Medina (E). New York, New York: State University of New York, College of Optometry (n = 1): Marilyn Vricella (I), Erica L. Schulman-Ellis (I), Valerie Leung (C), and Rochelle Mozlin (E). Oklahoma City, Oklahoma: Dean McGee Eye Institute (n = 1): Tammy L. Yanovitch (I), Keven W. Lunsford (C), Lauren Ukleya (C), Shannon Almeida (E), Vanessa K. Drummond (E), Sonny William Icks (E), and Lauren Pendarvis (E). Saint Paul, Minnesota: Associated Eye Care (n = 1): Susan Schloff (I), Kristi D. Neuenfeldt (E), and Cheera M. Sundgaard (E). Schaumburg, Illinois: Advanced Vision Center (n = 1): Ingryd J. Lorenzana (I), Beata Wajs (C), Angelyque L. Lorenzana (E), and Yesenia Meza (E). Toms River, New Jersey: Ocean Eye Institute (n = 1): Michael J. Spedick (I), Katelyn Karausky (C), Emily Guyer (E), Mary A. Lizardo (E), Dena Mitchell (E), and Pamela Stokes (E). PEDIG Coordinating Center:Tampa, Florida: Raymond T. Kraker, Roy W. Beck, Darrell S. Austin, Nicole M. Boyle, Courtney L. Conner, Danielle L. Chandler, Trevano W. Dean, Quayleen Donahue, Brooke P. Fimbel, Graham M. Hardt, James E. Hoepner, Joseph D. Kaplon, Elizabeth L. Lazar, B. Michele Melia, Gillaine Ortiz, Diana E. Rojas, Jennifer A. Shah, and Rui Wu. ATS18 Planning Committee: Jonathan M. Holmes (co-chair), Vivian Manh (co-chair), Eileen B. Birch, Susan A. Cotter, Robert F. Hess (consultant), Kristine B. Hopkins, Raymond T. Kraker, Elizabeth L. Lazar, David A. Leske, Donald W. Lyon, B. Michele Melia, Michael X. Repka, and David K. Wallace. National Eye Institute: Donald F. Everett. PEDIG Executive Committee: David K. Wallace (chair), William F. Astle (2013-2015), Roy W. Beck, Eileen E. Birch, Susan A. Cotter (2011-2014, 2015-present), Eric R. Crouch (2014-2015), Laura B. Enyedi (2014-present), Donald F. Everett, Jonathan M. Holmes, Raymond T. Kraker, Scott R. Lambert (2013-2015), Katherine A. Lee (2014-present), Ruth E. Manny, Michael X. Repka, Jayne L. Silver (2014-present), Katherine K. Weise (2014-present), and Lisa C. Verderber (2015-present). Amblyopia Treatment Study Steering Committee: Eileen E. Birch, Trevano W. Dean, Donald F. Everett, Michael E. Gray (2016-present), Jonathan M. Holmes, Raymond T. Kraker, Marjean T. Kulp, Sylvia Landa, Elizabeth L. Lazar, Vivian Manh, Diana McOwen (2014-2015), B. Michele Melia, Evelyn A. Paysse, Donny W. Suh, Allison I. Summers (2016-present), Rosanne Superstein (2014-2015), and David K. Wallace. Data and Safety Monitoring Committee: Marie Diener-West (chair), John D. Baker, Barry Davis, Donald F. Everett, Dale L. Phelps, Stephen W. Poff, Richard A. Saunders, and Lawrence Tychsen.

Disclaimer: Dr Beck is a deputy editor of JAMA Ophthalmology but was not involved in the editorial review or the decision to accept the manuscript for publication.