Accommodative Lag, Peripheral Aberrations, and Myopia in Children
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ACCOMMODATIVE LAG, PERIPHERAL ABERRATIONS, AND MYOPIA IN CHILDREN DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By David A. Berntsen, O.D., M.S. * * * * * The Ohio State University 2009 Dissertation Committee: Approved by Karla Zadnik, O.D., Ph.D., Advisor Donald O. Mutti, O.D., Ph.D., Co-Advisor _______________________________ Nicklaus Fogt, O.D., Ph.D. Advisor Vision Science Graduate Program ABSTRACT The Study of Theories about Myopia Progression (STAMP) is a two-year, double- masked, randomized clinical trial of myopic children 6 to 11 years old. STAMP uses progressive addition lenses (PALs) to evaluate two theories of juvenile-onset myopia progression. Eligible children have a high accommodative lag and either: (1) low myopia (less myopic than –2.25 D spherical equivalent) or (2) high myopia (more myopic that – 2.25 D spherical equivalent) with esophoria at near. The accommodative lag theory hypothesizes that hyperopic retinal blur drives myopia progression. The mechanical tension theory hypothesizes that ciliary-choroidal tension created by the ocular components restricts equatorial expansion and causes axial elongation in people with factors that produce a large globe. To test between these theories, children were randomly assigned to wear either PALs with a +2.00-D add or single vision lenses (SVLs) for one year to achieve a reduction in myopia progression in the PAL group relative to the SVL group. All children then wear SVLs for the second year to evaluate the permanence of the treatment effect; a maintained treatment effect supports the lag theory, while a rebound supports mechanical tension. The primary outcome in STAMP is central cycloplegic autorefraction. Complete ocular biometric data are being collected at six-month intervals. Over 17 months, 192 children were screened, and 85 (44%) were deemed eligible and enrolled. Of the children, 44 (52%) were female. The mean age (± SD) was 9.3 ± 1.4 ii years. The mean accommodative lag was 1.71 ± 0.37 D. The mean cycloplegic spherical equivalent refractive error was –1.95 ± 0.78 D, and the mean axial length was 24.17 ± 0.80 mm. Of those enrolled, 54 (64%) were esophoric at near. Complete baseline characteristics of the children enrolled in STAMP are described. Because the clinical trial is still in progress, the study-related findings are confidential. Central and peripheral aberrometry is performed at each visit. Results validating aberrometry-based relative peripheral refraction (RPR) measurements against measurements made with an autorefractor are presented. A method of analyzing peripheral aberration data collected from a dilated pupil is discussed and validated. A single-valued metric of image quality was calculated to describe retinal image quality at five retinal locations, centrally and in four peripheral retinal locations. When including only higher-order aberrations, image quality was best centrally and decreased in the periphery. When relative peripheral refractive error was included along with higher-order aberrations, more significant reductions in peripheral retinal image quality were present, and the greatest reductions were in the temporal and superior retina where greater amounts of astigmatism were also measured. Baseline and six-month accommodative lag data from children enrolled in STAMP were analyzed. Children in STAMP still had a significant lag of accommodation for a 4-D stimulus when tested wearing a +2.00 D bifocal add. No evidence of an effect of bifocal adaptation on accommodative lag was found. Children with greater myopia iii progression over the previous six months exhibited higher accommodative lags when tested with their full manifest correction. Myopia progression had no effect on accommodative lag when testing was performed with the child’s habitual correction. These data suggest that a child’s accommodative lag should be measured with both the full manifest and habitual corrections if attempting to relate the retinal blur experienced by the child to his or her myopia progression. iv Dedicated to my wife and children “…find the perfect future in the present.” -Nathaniel Hawthorne v ACKNOWLEDGMENTS First and foremost, I would like to thank my wife Monique. Her encouragement throughout my PhD work has been unconditional, even when late nights were required to see study patients. She has been a pillar of support through both the good times and the bad. I would not be where I am today without her personal sacrifices for both me and our family. Although life has thrown us several curves along the journey, they have only made our love stronger. I am fortunate to have had the opportunity to train with my co-advisors, Karla Zadnik and Don Mutti. Their friendships both professionally and personally have meant so much to me and have been instrumental in my professional development. They both share a love and compassion for optometric research that has been truly inspiring. There is no way to repay them for all of their time, thoughts, guidance, and encouragement along the way. Thank you for all that you have done! STAMP would not have been possible without the help of many fantastic people serving in a variety of roles. I owe an enormous “thank you” to everyone who has helped with STAMP: Masked Examiners (Bradley Dougherty, Kerri McTigue, Kathryn Richdale, Eric Ritchey, and Aaron Zimmerman), STAMP Opticians (Melissa Button, Aaron Chapman, Melissa Hill, Brandy Knight, Scott Motley, and Jeff Rohlf), Optometry Coordinating Center (Lisa Jones, G. Lynn Mitchell, Linda Barrett, Melanie Schray, and vi Austen Tanner), and Data and Safety Monitoring Committee (Mark Bullimore, Leslie Hyman, Stephen Mandel, and Mel Moeschberger). Thanks are also owed to Jeff Walline for sharing his clinical trials knowledge and to Larry Thibos and the Indiana University Visual Optics Group for all of their help with advanced optics and aberrations. I would also like to thank the members of my dissertation committee (Karla Zadnik, Don Mutti, and Nick Fogt) for their contributions and guidance during the development of this dissertation. Thanks are in order for Michael Twa and Melissa Bailey, my first officemates as a PhD student, for providing guidance as I set out on this journey. I also thank Eric Ritchey and Kathryn Richdale for their invaluable friendships throughout the moments of serenity and insanity as both Cornea and Contact Lens Fellows and PhD students. Finally, I would like to thank my parents and brother for their encouragement and support through four degrees, including two doctorates. Words cannot express my appreciation of their unconditional support of my education. This research was supported by the National Eye Institute (K12-EY015447 & T32-EY013359), Essilor of America, and two American Optometric Foundation (AOF) William C. Ezell Fellowships sponsored by the AOF Presidents Circle and the American Academy of Optometry Section on Cornea and Contact Lenses. vii VITA September 1, 1977 Born – Houston, Texas 2000 Bachelor of Science, Optometry The Honors College University of Houston 2002 Doctor of Optometry University of Houston College of Optometry 2002-2004 Fellowship, Cornea and Contact Lenses Graduate Teaching and Research Associate The Ohio State University College of Optometry 2004 Master of Science, Vision Science The Ohio State University College of Optometry 2004-2005 Fellowship, Clinical Research The Ohio State University College of Optometry College of Medicine and Public Health 2005 Postdoctoral Fellow The Ohio State University College of Optometry 2005 – present Senior Research Associate The Ohio State University College of Optometry viii PUBLICATIONS Peer-Reviewed Publications 1. Jones LA, Walline JJ, Gaume A, Rah MJ, Manny RE, Berntsen DA, Chitkara M, Kim A, Quinn N, CLIP Study Group. Purchase of contact lenses and contact-lenses-related symptoms following the Contact Lenses in Pediatrics (CLIP) Study. Cont Lens Anterior Eye. (In Press) 2. Lehman BM, Berntsen DA, Bailey MD, Zadnik K. Validation of OCT-based Crystalline Lens Thickness Measurements in Children. Optom Vis Sci. 2009;86:181- 187. 3. Walline JJ, Jones LA, Sinnott L, Chitkara M, Coffey B, Jackson JM, Manny RE, Rah MJ, Prinstein MJ, ACHIEVE Study Group. Randomized trial of the effect of contact lens wear on self-perception in children. Optom Vis Sci. 2009 Mar;86:222-232. (member of the study group) 4. Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group, Manny RE, Chandler DL, Scheiman MM, Gwiazda JE, Cotter SA, Everett DF, Holmes JM, Hyman LG, Kulp MT, Lyon DW, Marsh-Tootle W, Matta N, Melia BM, Norton TT, Repka MX, Silbert DI, Weissberg EM. Accommodative lag by autorefraction and two dynamic retinoscopy methods. Optom Vis Sci. 2009 Mar;86(3):233-43. (member of the study group) 5. Berntsen DA, Merchea MM, Richdale K, Mack CJ, Barr JT. Higher-Order Aberrations when wearing Sphere and Toric Soft Contact Lenses. Optom Vis Sci. 2009;86:115-122. 6. Berntsen DA, Mutti DO, Zadnik K. Validation of Aberrometry-Based Relative Peripheral Refraction Measurements. Ophthal Physiol Opt. 2008; 28:83-90. 7. Walline JJ,Gaume A, Jones LA, Rah MJ, Manny RE, Berntsen DA, Chitkara M, Kim A, Quinn N, CLIP Study Group. Benefits of Contact Lens Wear for Children and Teens. Eye Contact Lens. 2007;33(6, Part 1 of 2):317-321. 8. Richdale K, Berntsen DA, Mack CJ, Merchea MM, Barr JT. Visual Acuity with Spherical and Toric Soft Contact Lenses. Optom Vis Sci. 2007;84:969-975. 9. Walline JJ, Jones LA, Rah MJ, Manny RE, Berntsen DA, Chitkara M, Gaume A, Kim A, Quinn N, CLIP Study Group. Contact Lenses In Pediatrics (CLIP) Study: Chair Time and Ocular Health. Optom Vis Sci. 2007;84:896-902. 10. Berntsen, DA, Mitchell GL, Nichols JJ. Reliability of Grading Lissamine Green Conjunctival Staining. Cornea. 2006;25:695-700. ix 11. Berntsen, DA, Mitchell GL, Barr JT. The Effect of Overnight Contact Lens Corneal Reshaping on Refractive Error-Specific Quality of Life.