Pediatric Eye Disease Investigator Group (PEDIG) Writing Committee* . Randomized Trial to Evaluate Combined Patching and Atropine for Residual Amblyopia. Arch Ophthalmol. 2011;129(7):960-962. doi:10.1001/archophthalmol.2011.174
*Authors/Group Information: David K. Wallace, MD, MPH (lead author); Raymond T. Kraker, MSPH (lead author); Roy W. Beck, MD, PhD, Susan A. Cotter, OD, MS; Patricia L. Davis, MD; Jonathan M. Holmes, BM, BCh; Michael X. Repka, MD, MBA; Donny W. Suh, MD.
Many children fail to achieve normal visual acuity after treatment for amblyopia.1,2 This remaining deficit may be called residual amblyopia. We conducted a randomized trial to determine whether an intensive final push with combined patching and atropine sulfate can improve visual acuity in children with residual amblyopia.
A parent or guardian of each study subject gave written informed consent. The protocol is available at http://www.pedig.net. Eligible subjects were aged 3 to younger than 10 years and had strabismic and/or anisometropic amblyopia, best-corrected visual acuity of 20/32 to 20/63 in the amblyopic eye, interocular visual acuity difference of 2 or more lines, and no improvement in visual acuity in the amblyopic eye between 2 consecutive visits at least 6 weeks apart while patching 6 hours per day or using daily atropine. Spectacles, if prescribed (based on investigator discretion), met the criteria in eTable 1. All subjects wore spectacles except 4 with purely strabismic amblyopia. Additional eligibility criteria are listed in eTable 1. Subjects were randomized with equal probability to the following: (1) treatment with 6 hours of prescribed daily patching combined with daily atropine (intensive group); or (2) a reduction of current treatment for 4 weeks with 2 hours of prescribed daily patching or once-weekly atropine followed by spectacles alone if needed (weaning group). Randomization was accomplished using a permuted-blocks design stratified by site and by current treatment with patching or atropine. The primary outcome was masked assessment of visual acuity by isolated crowded Amblyopia Treatment Study HOTV (for subjects aged 3 to <7 years)3 or Electronic Early Treatment Diabetic Retinopathy Study (for subjects aged 7 to <10 years)4 optotypes at 10 weeks. Subjects in the intensive treatment group discontinued using atropine 2 weeks before this examination.
The planned sample size was 240. After a recruitment period of 18 months, 55 subjects had been randomized at 18 sites. The study was stopped on recommendation of the data and safety monitoring committee because of slow recruitment and a conditional power analysis indicating that the study was unlikely to find a statistically significant benefit of intensive treatment if the study continued.
Between October 1, 2007, and March 30, 2009, 27 subjects were randomized to the intensive group and 28 were randomized to the weaning group. The average age was 6.9 years; 25 subjects (45%) were female; and 40 subjects (73%) were white. At the time of enrollment, 39 subjects (71%) were being treated with patching and 16 (29%) were being treated with daily atropine. The 2 groups appeared balanced with respect to baseline characteristics (eTable 2), except that those in the intensive group were more likely than those in the weaning group to have anisometropia or combined mechanism as the cause of amblyopia (17 subjects [63%] vs 12 subjects [43%], respectively) and had more hyperopia in the amblyopic eye (mean spherical equivalent, 5.39 vs 4.24 diopters, respectively).
At the 10-week primary outcome examination, visual acuity in the amblyopic eye improved 2 or more lines from enrollment in 3 of the 27 subjects (11%) in the intensive treatment group and 6 of the 27 subjects (22%) in the weaning group (difference in proportions = −10%; 95% confidence interval, −30% to +9%) (Table). Improvement in visual acuity in the amblyopic eye averaged 0.5 logMAR line in both groups (treatment group difference in mean logMAR lines adjusted for baseline visual acuity = 0.0; 95% confidence interval, −0.7 to +0.7) (Table). After adjusting for sex, cause of amblyopia, refractive error in the amblyopic eye, and visual acuity testing method (Amblyopia Treatment Study HOTV testing protocol3 vs Electronic Early Treatment Diabetic Retinopathy Study testing protocol4), results were similar (data not shown).
For children with amblyopia who have already stopped improving with 6 hours of prescribed daily patching or with daily atropine, we found that an intensive final push of combined treatment with patching and atropine did not produce a better visual acuity outcome after 10 weeks compared with a control group in whom treatment was gradually discontinued. Despite our small sample size, it is unlikely that a meaningful effect was missed, since both the upper and lower limits of the 95% confidence interval for the mean difference between treatment groups were less than 1 line.
This study evaluated a select group of children with mild residual amblyopia (visual acuity of 20/32-20/63 inclusive) who had a substantial amount of previous amblyopia treatment. Our results should not be generalized to children with more severe residual amblyopia or those who have stopped improving after less intense treatment.
Correspondence: David K. Wallace, MD, MPH, c/o Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (email@example.com).
Author Contributions: The authors had full access to all of the data in the study, and Dr Wallace takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Funding/Support: This study was supported by grant EY011751 from the National Eye Institute, National Institutes of Health, US Department of Health and Human Services.
Role of the Sponsor: The funding organization had no role in the design or conduct of the study.
Trial Registration: clinicaltrials.gov Identifier: NCT00506675
Previous Presentation: This paper was presented at the 36th Annual Meeting of the American Association for Pediatric Ophthalmology and Strabismus; April 17, 2010; Orlando, Florida.
Authors/Writing Committee David K. Wallace, MD, MPH (lead author); Raymond T. Kraker, MSPH (lead author); Roy W. Beck, MD, PhD; Susan A. Cotter, OD, MS; Patricia L. Davis, MD; Jonathan M. Holmes, BM, BCh; Michael X. Repka, MD, MBA; and Donny W. Suh, MD.
Clinical Sites That Participated in This Protocol
Sites are listed in order by the number of patients enrolled into the study (shown in parentheses). Personnel are listed as (I) for investigator, (C) for coordinator, and (V) for visual acuity examiner. *Center received support used for this project from an unrestricted grant from Research to Prevent Blindness Inc, New York, New York.
Wolfe Clinic, West Des Moines, Iowa (11): Donny W. Suh (I), Marilee McNeece (C), Autumn J. Swallow (C), Ashley D. Andreassen (V), Rhonda J. Countryman (V), Lisa M. Fergus (V); Progressive Eye Care, Lisle, Illinois (10): Patricia L. Davis (I), Katie R. Hulett (C), Carrie S. Bloomquist (V); Bascom Palmer Eye Institute, Miami, Florida (5): Susanna M. Tamkins (I), Eva M. Olivares (C), Marlon Parra (C), Sonia M. Fernandez (V), Lidia E. Salinas (V); Duke University Eye Center, Durham, North Carolina (4): David K. Wallace (I), Sarah K. Jones (C), Courtney E. Fuller (V), Cassandra W. Headen (V); Everett and Hurite Ophthalmic Association, Cranberry Township, Pennsylvania (3): Darren L. Hoover (I), Pamela A. Huston (C), Barbara R. Fuchs (V), Pamela M. Racan (V); Southern California College of Optometry, Fullerton (3): Susan A. Cotter (I), Carmen N. Barnhardt (I), Raymond H. Chu (I), Lisa M. Edwards (I), Tawna L. Roberts (I), Sue M. Parker (C); Pediatric Ophthalmology and Strabismus Associates, Providence, Rhode Island (3): David Robbins Tien (I), Myra B. McGuinness (C), Colleen M. Bailey (V), Diana Gonzalez (V); Intermountain Eye Centers, Boise, Idaho (2): Katherine A. Lee (I), Bonita R. Schweinler (C), Derek Beck (V); Pediatric Ophthalmology, Dallas, Texas (2): David R. Stager (I), Mary K. Alters (C), Joost Felius (C), June M. Gartlir (V); Family Eye Group, Lancaster, Pennsylvania (2): David I. Silbert (I), Noelle S. Matta (C), Darlene R. Crick (V); Pacific University College of Optometry, Portland, Oregon (2): Richard London (I), James J. Kundart (I), Jayne L. Silver (C), Garnet M. Yokoi (V); Stephen R. Glaser, MD, PC, Rockville, Maryland (2): Stephen R. Glaser (I), Monica M. Pacheco (I), Christen Y. Addison (C), Tracey L. Coussens (C); University of Alabama at Birmingham School of Optometry, Birmingham (1): Marcela Frazier (I), Kristine T. Hopkins (I), Michael P. Hill (C); Alberta Children's Hospital, Calgary, Alberta, Canada (1): William F. Astle (I), Ania M. Hebert (C), Heather N. Sandusky (C), Melissa K. Racine (V); Concord Eye Care PC, Concord, New Hampshire (1): Christie L. Morse (I), Caroline C. Fang (C); Pediatric Ophthalmology of Erie, Erie, Pennsylvania (1)*: Nicholas A. Sala (I), Benjamin H. Whitling (I), Rhonda M. Hodde (C); Eastern Virginia Medical School, Norfolk (1): Earl R. Crouch (I), Eric R. Crouch III (I), Gaylord G. Ventura (C), Cynthia M. Carlton (V); Mayo Clinic, Rochester, Minnesota (1)*: Jonathan M. Holmes (I), Rebecca A. Nielsen (C), Deborah K. Miller (V).
PEDIG Coordinating Center (as of October 23, 2009)
Raymond T. Kraker, Roy W. Beck, Nicole M. Boyle, Christina M. Cagnina-Morales, Debora A. Cagnina, Danielle L. Chandler, Laura E. Clark, Elise R. Diamond, Quayleen Donahue, Brooke Fimbel, Nicole C. Foster, Heidi A. Gillespie, Brett M. Kaminski, Elizabeth L. Lazar, Stephanie V. Lee, Lee Anne Lester, B. Michele Melia, Pamela S. Moke, Michael Philips, Diana E. Rojas, Sydney L. Shrader.
National Eye Institute, Bethesda, Maryland
Donald F. Everett.
Amblyopia Treatment Study Steering Committee
Roy W. Beck, Eileen E. Birch, Donald F. Everett, Jonathan M. Holmes, Michael X. Repka, Susan A. Cotter, Richard W. Hertle, Don W. Lyon, Mitchell M. Scheiman, David R. Weakley, David K. Wallace, Graham E. Quinn, Robert P. Rutstein, Michael P. Hill (2007), Eva M. Olivares (2009), Pamela A. Huston (2008-2009).
PEDIG Executive Committee
Jonathan M. Holmes (chair), Raymond T. Kraker, Darron A. Bacal (2009), Roy W. Beck, Eileen E. Birch, Stephen P. Christiansen, Susan A. Cotter, Donald F. Everett, Darren L. Hoover, Pamela A. Huston, Katherine A. Lee (2008-2009), Noelle S. Matta (2008-2009), David G. Morrison, Michael X. Repka, Robert P. Rutstein (2009), Nicholas A. Sala (2009), Mitchell M. Scheiman (2008), David K. Wallace.
PEDIG Data and Safety Monitoring Committee
Marie Diener-West (chair), John D. Baker, Barry Davis, Velma Dobson, Donald F. Everett, Dale L. Phelps, Stephen Poff, Richard A. Saunders, Lawrence Tychsen.