Wallace DK, Lazar EL, Crouch ER, Hoover DL, Kraker RT, Tamkins SM, for the Pediatric Eye Disease Investigator Group. Time Course and Predictors of Amblyopia Improvement With 2 Hours of Daily Patching. JAMA Ophthalmol. 2015;133(5):606-609. doi:10.1001/jamaophthalmol.2015.6
For children with amblyopia secondary to strabismus and/or anisometropia, many clinicians initiate treatment with spectacles alone, if needed.1,2 When improvement of the amblyopic eye stops after a period of treatment with spectacles alone, prescription of 2 hours of daily patching is often the next step.2,3 Our purpose was to evaluate the amount and time course of amblyopia improvement with 2 hours of prescribed daily patching in children aged 3 years but younger than 8 years, and to determine predictors of improvement in visual acuity (VA) and amblyopia resolution.
Analyses were limited to children aged 3 years but younger than 8 years with strabismic and/or anisometropic amblyopia and no prior amblyopia treatment except spectacles (if needed) who participated in the run-in phase of a clinical trial (protocol at http://www.pedig.net).4 The protocol and Health Insurance Portability and Accountability Act–compliant informed consent forms were approved by the institutional review boards of all institutions involved in this multicenter study, and a parent or guardian of each participant gave written informed consent. Before enrollment, children requiring spectacles wore them for 16 weeks or more or until there was no improvement in VA of the amblyopic eye between 2 consecutive visits. At enrollment, 2 hours of daily patching was prescribed for 12 weeks or more and until there was no improvement in VA of the amblyopic eye between 2 consecutive visits at least 6 weeks apart, confirmed by a retest. We analyzed VA outcomes for 196 children who had a minimum follow-up of 11 weeks: 135 with moderate amblyopia (VA of 20/50 to 20/80 in the affected eye) and 61 with severe amblyopia (VA of 20/100 to 20/400 in the affected eye). We evaluated the relationship between improvement at best VA during the run-in phase and baseline factors of age, amblyopic-eye VA, and cause of amblyopia (strabismus, anisometropia, or both) by fitting an analysis of covariance model. We used logistic regression to evaluate the relationship between these baseline factors and achieving amblyopia resolution (amblyopic-eye VA of 20/25 or better and ≤1 line interocular difference).
The median duration of prescribed patching until there was no improvement in VA of the amblyopic eye was 20.2 weeks (20.0 and 22.1 weeks in the moderate and severe amblyopia groups, respectively), and ranged from 11.0 to 50.3 weeks. Children with moderate amblyopia improved an average of 2.9 logMAR lines (95% CI, 2.7-3.2), and those with severe amblyopia improved an average of 4.9 logMAR lines (95% CI, 4.4-5.4) (Table 1). Visual acuity in the amblyopic eye improved to 20/25 or better and was within 1 line of the fellow eye for 33% (95% CI, 25%-42%) of children with moderate amblyopia and 11% (95% CI, 5%-22%) of those with severe amblyopia. Nearly half of the children with either moderate (47%) or severe (48%) amblyopia achieved their best amblyopic-eye VA observed during the run-in phase at the visit 12 weeks (range, 8 to <14 weeks) after initiation of patching. Greater improvement in VA of the amblyopic eye was associated with worse baseline VA (P < .001) and younger age (P = .03) at enrollment but not with amblyopia cause (P = .47) (Table 1). Better VA in the amblyopic eye at enrollment was the only predictor of achieving amblyopia resolution (Table 2).
Children in this study were treated with 2 hours of daily patching until no improvement in VA was observed between 2 visits, but as previously reported, no improvement from results of a previous examination is insufficient to establish maximum or stable VA.2,4 Nonetheless, our data show that 2 hours of daily patching often leads to robust improvement in VA, and younger children tend to improve more with patching. Children with worse VA when starting patching tend to improve more, but those with better baseline VA are more likely to achieve amblyopia resolution. Taken together with results from prior studies, we conclude that it is reasonable to initiate patching at a dosage of 2 hours each day, even for children with severe amblyopia.5 If there is no improvement between 2 visits, reasonable options include increasing the prescribed patching dose to 6 hours per day4 or continuing 2 hours of prescribed patching, knowing that VA stability is not established by VA test results showing no improvement from the previous visit.
Corresponding Author: David K. Wallace, MD, MPH, Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (firstname.lastname@example.org).
Published Online: February 19, 2015. doi:10.1001/jamaophthalmol.2015.6.
Author Contributions: Dr Wallace and Ms Lazar had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Wallace, Lazar, Crouch, Kraker, Tamkins.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Wallace, Lazar, Tamkins.
Critical revision of the manuscript for important intellectual content: Lazar, Crouch, Hoover, Kraker, Tamkins.
Statistical analysis: Wallace, Lazar, Kraker.
Obtained funding: Wallace, Kraker.
Administrative, technical, or material support: Crouch, Hoover, Kraker, Tamkins.
Study supervision: Crouch, Kraker.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: This study was supported through a cooperative agreement from the National Eye Institute of the National Institutes of Health, Department of Health and Human Services (grants EY011751 and EY018810).
Role of the Funder/Sponsor: The funding source 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.
Previous Presentation: This study was presented in part at the annual meeting of the Association for Vision in Research and Ophthalmology; May 7, 2013; Seattle, Washington.
Clinical Sites: The following PEDIG members participated in the study and are listed by clinical site. Sites are listed in order by number of subjects enrolled into the run-in phase and number randomized (number in run-in/number randomized). Personnel are listed as (I) for Investigator, (C) for Coordinator, or (E) for Visual Acuity Examiner. *Center received support utilized for this project from an unrestricted grant from Research to Prevent Blindness Inc, New York, New York. ** Center received support utilized for this project from the UK National Institute for Health Research, through the Northumberland, Tyne and Wear Comprehensive Local Research Network. *** Center received support utilized for this project from the Ohio Lions Eye Research Fund.
Miami, FL—Bascom Palmer Eye Institute (38/10): Susanna M. Tamkins (I), Mariana Nunez (C), Courtney E. Ewert (E), Lernik X. Mesropian (E), Mallika X. Patel (E), Raynold Crespo (E), Priya X. Joshi (E), Eva M. Olivares (E), Marlon Parra (E), Anna S. Yi (E); Norfolk, VA—Eastern Virginia Medical School (32/11): Earl R. Crouch (I), Earl R. Crouch III (I), Gaylord G. Ventura (C), Cynthia M. Carlton (E); West Des Moines, IA—Wolfe Eye Clinic (32/20): Donny W. Suh (I), Jody L. Jackson (C), Rhonda J. Countryman (E), Shannon L. Craig (E), Lisa M. Fergus (E), Susan K. Hayes (E), Autumn Parrino (E); Cranberry, PA—Everett and Hurite Ophthalmic Association (30/5): Darren L. Hoover (I), Pamela A. Huston (C), Christine J. Deifel (E), Pamela M. Racan (E), Jasbir K. Sayal (E), Kari E. Soros (E); Columbus, OH—Pediatric Ophthalmology Associates Inc. (22/12):*** Don L. Bremer (I), David L. Rogers (I), Cybil M. Cassady (I), Gary L. Rogers (I), Richard P. Golden (I), Rae R. Fellows (C), Rich E. Cox (E), Laura J. Shenberger (E), Angela R. Young (E), Lisa J. Vanover (E), Michelle L. Hurst (E), Meghan C. McMillin (E), Amy J. Wagner (E); Fullerton, CA—Southern California College of Optometry (22/13): Susan A. Cotter (I), Angela M. Chen (I), Lisa M. Edwards (I), Paula A. Handford (I), Raymond H. Chu (I), Catherine L. Heyman (I), Sue M. Parker (C), Carmen N. Barnhardt (E), Kristine Huang (E); Rockville, MD—Stephen R. Glaser, M.D., P.C. (16/7): Stephen R. Glaser (I), Monica M. Pacheco (I), Laura L. Graham (C), Markita G. Miller (E), Noga Senderowitsch (E), Aliza C. Shabanowitz (E); Erie, PA—Pediatric Ophthalmology of Erie (14/8): Nicholas A. Sala (I), Jeanine M. Romeo (C), Rhonda M. Hodde (E), Cindy E. Tanner (E), Veda L. Zeto (E); Salt Lake, City UT—Rocky Mountain Eye Care Associates (14/8): David B. Petersen (I), J. R. McMurtrey (C); Newcastle upon Tyne, United Kingdom—Newcastle upon Tyne Hospitals NHS Foundation Trust (10/4:)** Michael P. Clarke (I), Christine J. Powell (C), Laura C. Crawford (E); Boise, ID—St. Luke’s Hospital (9/4): Katherine A. Lee (I), Bonita R. Schweinler (C), Larry W. Plum (E), Derek Beck (E); Concord, NH—Concord Eye Care P.C. (8/4):Christie L. Morse (I), Melanie L. Christian (C), Caroline C. Fang (E), Virginia X. Karlsson (E); Colorado Springs, CO—The Children’s Eye Center (6/6): Dave H. Lee (I), Kelly A. Martinez (E), Colleen M. Schwanz (E), Amanda H. Williams (E), Maria M. Busemeyer (E); Dallas, TX—Pediatric Ophthalmology, P.A. and the Center for Adult Strabismus (6/4): Cynthia L. Beauchamp (I), David R. Stager (I), Angela X. Goodloe (C), Jennifer A. Whalen (E); Durham, NC—Duke University Eye Center (6/2): Laura B. Enyedi (I), David K. Wallace (I), Terri L. Young (I), Sarah K. Jones (C), Cassandra W. Headen (E), Courtney E. Wilkins (E); Birmingham, AL—University of Alabama at Birmingham School of Optometry (6/4): Robert P. Rutstein (I), Marcela Frazier (I), Katherine K. Weise (I), Ross B. Roegner (C), Michael P. Hill (E), Kristine T. Hopkins (E), Wendy L. Marsh-Tootle (E); Schaumburg, IL—Advanced Vision Center (6/4): Ingryd J. Lorenzana (I), Claudia I. Ortiz (C), Yesenia Meza (E); Chicago Ridge, IL—The Eye Specialists Center, L.L.C. (5/3): Benjamin H. Ticho (I), Deborah A. Clausius (C), Megan Allen (E), Sharon L. Giers (E), Lindsay A. Horan (E); Durham, NC—North Carolina Eye, Ear, Nose, & Throat (5/3): Joan T. Roberts (I), Heather M. Klem (C), Marguerite J. Sullivan (E), Lynelle G. Perez (E); Cleveland, OH—Cole Eye Institute (5/4:)* Elias Traboulsi (I), Paul J. Rychwalski (I), Susan W. Crowe (C), Rachael Briggs (E), Angela M. Borer (E); Baltimore, MD—Greater Baltimore Medical Center (4/4): Mary Louise Z. Collins (I), Allison A. Jensen (I), Maureen A. Flanagan (C), Jennifer E. Lambert (E), Dorotea R. Maranto (E); Memphis, TN—Southern College of Optometry (4/0): Janette D. Dumas (I), Marc B. Taub (I), Kelly D. Dasinger (C); Arnold, MD—Ophthalmology Associates of Greater Annapolis (4/1): John M. Avallone (I), Charlene R. Bryant (C), Wanda E. Peyton (E); Lisle, IL—Progressive Eye Care (4/3): Patricia L. Davis (I), Indre M. Rudaitis (E), Charita L. Smith (E), Sarah J. Velazquez (E), Carrie S. Bloomquist (E); Tomball, TX—Houston Eye Associates (4/0): Aaron M. Miller (I), Jorie L. Jackson (C), Luis Arguijo (E), Suzanne S. LaRiviere (E); Houston, TX—Texas Children’s Hospital, Department of Ophthalmology (3/2): Evelyn A. Paysse (I), David K. Coats (I), Lingkun X. Kong (C), Paul G. Steinkuller (E); Lancaster, PA—Family Eye Group (3/1): David I. Silbert (I), Noelle S. Matta (C), Darlene R. Crick (E); Wilmette, IL—Pediatric Eye Associates (3/1): Deborah R. Fishman (I), JoAnn Spieker (C), Aliza Julian (E); Portland, OR—Casey Eye Institute (3/0): Daniel J. Karr (I), Allison I. Summers (I), Paula K. Rauch (C), Yelena M. Bubnoz (E), Albert Romo (E); Columbus, OH—The Ohio State University (3/0): Marjean T. Kulp (I), Freda D. Dallas (C); Portland, OR—Pacific University College of Optometry (3/2): Richard London (I), James J. Kundart (I), Jayne L. Silver (C), Tonya M. Tira (E); Kansas City, MO—Children’s Mercy Hospitals and Clinics (3/1): Amy L. Langford (I), Rebecca J. Dent (C), Amy R. Sullivan (E); San Francisco, CA—University of California, San Francisco Department of Ophthalmology (3/1):* Tina Rutar (I), Alejandra de Alba Campomanes (I), Patricia W. Tam (C); Silverdale, WA—Jason C. Cheung, M.D., PS (3/1): Melissa L. Rice (I), Jason C. Cheung (I), Tiffany M. Parypa (C), Jacque J. Ferro (E), Andria E. Goddard (E); Salt Lake City, UT—University of Utah Health Care, Moran Eye Center (2/1): Robert O. Hoffman (I), Marielle P. Young (I), Scott A. Larson (I), Elisa M. Robertson (C), Jason K. Taylor (E); Philadelphia, PA—Salus University/Pennsylvania College of Optometry (2/1): Mitchell M. Scheiman (I), Karen E. Pollack (C), Elise B. Ciner (E); Marlton, NJ—Michael F. Gallaway, O.D. (2/1): Michael F. Gallaway (I), Debbie L. Killion (C), Beth Zlock (E); Bloomington, IN—Indiana University School of Optometry (2/1): Don W. Lyon (I), Vivian M. Wong (I), Kristy M. Dunlap (C), Tawna L. Roberts (E); Lincoln, NE—Eye Surgical Associates (2/1): Donald P. Sauberan (I), Jody C. Hemberger (C), Gail Walker (E), Jenni A. Craf, (E); Chattanooga, TN—Pediatric Eye Specialists (2/0): Edward A. Petersen (I), Zachary S. McCarty (I), Charla H. Petersen (C), Amie Jenkins (E); Boston, MA—Harvard Vanguard Medical Associates (2/1): Justin B. Smith (I), Mei L. Mellott (I), Troy L. Kieser (C), Kate A. Palitsch (E); Baltimore, MD—Wilmer Ophthalmological Institute, John Hopkins University (1/0):* Michael X. Repka (I), Alex Christoff (C), Xiaonong Liu (C), Carole R. Goodman (E); Calgary, Alberta, Canada—Alberta Children’s Hospital (1/1): William F. Astle (I), Emi N. Sanders (C), Heather N. Sandusky (E); Rochester, MN—Mayo Clinic (1/1):* Jonathan M. Holmes (I), Tomohiko Yamada (I), Rebecca A. Nielsen (C), Debbie M. Priebe (E), Janet L. Westergaard (E); St. Louis, MO—St. Louis Children’s Hospital Eye Center (1/1): James R. Hoekel (I), Marlo L. Galli (C), Tracey Fast (E); Grand Rapids, MI—Pediatric Ophthalmology, P.C. (1/1): Patrick J. Droste (I), Robert J. Peters (I), Jan Hilbrands (C), Misha K. Mennega (E); Chicago IL—Illinois College of Optometry (1/1): Yi Pang (I), Megan Allen (I), Anesu H. Mvududu (C); Albuquerque, NM—Children’s Eye Center of New Mexico (1/1): Todd A. Goldblum (I), Angela Alfaro (C), Chastity R. Escobedo (E); Wilmington, DE—Delaware Vision Academy, L.L.C. (1/1): Don D. Blackburn (I), Tracy Tunis (C), Florence Greene (E); Wilmington, NC—Eye Associates of Wilington, P.A. (1/1): David A. Johnson (I), Kelly L. Moulton (C), Kellie Drake (E); New Haven, CT—Yale School of Medicine, Department of Ophthalmology and Visual Science (1/1): Jennifer A. Galvin (I), Daniel J. Salchow (I), Margaret B. Therriault (C).
PEDIG Coordinating Center: Raymond T. Kraker, Roy W. Beck, Katie R. Aylor, Christina M. Cagnina-Morales, Danielle L. Chandler, Laura E. Clark, Quayleen Donahue, Brooke P. Fimbel, Nicole C. Foster, James E. Hoepner, Curtis R. Koh, Elizabeth L. Lazar, Stephanie V. Lee, B. Michele Melia, Diana E. Rojas.
National Eye Institute—Bethesda, MD: Donald F. Everett.
Amblyopia Treatment Study Steering Committee: Eileen E. Birch, Susan A. Cotter, Donald F. Everett, Nicole C. Foster, Jonathan M. Holmes, Raymond T. Kraker, Marjean T. Kulp, Elizabeth L. Lazar, David B. Petersen, Michael X. Repka, Gaylord G. Ventura (2011-13), Lisa C. Verderber (2011-12), David K. Wallace.
PEDIG Executive Committee: Jonathan M. Holmes (chair), Darron A. Bacal (2009-10), Roy W. Beck, Eileen E. Birch, Stephen P. Christiansen (2009-10), Susan A. Cotter (2009-Present), Eric R. Crouch III (2010-11), Laura B. Enyedi (2011-13), Donald F. Everett, Darren L. Hoover (2008, 2011-Present), Pamela A. Huston (2009-10), Jorie L. Jackson (2011-12), Raymond T. Kraker, Marjean T. Kulp (2010-12), Aaron M. Miller (2011-12), David G. Morrison (2008-9), David Petersen (2011- Present), Michael X. Repka, David L. Rogers (2011-13), Robert P. Rutstein (2009-10), Nicholas A. Sala (2009-10), Benjamin H. Ticho (2010-11), David K. Wallace (2009-Present).
PEDIG Data and Safety Monitoring Committee: Marie Diener-West (chair), John D. Baker, Barry Davis, Donald F. Everett, Dale L. Phelps, Stephen Poff, Richard A. Saunders, Lawrence Tychsen