Corneal Biomechanics: From Theory to Practice

While lecturing in recent months at a number of prominent institutions, I asked some of the residents and fellows whether and how they might benefit from a book on corneal biomechanics. The typical response was the look of a deer caught in the headlights as they tried to intuit the “appropriate” answer, but had little understanding or insight as to why this would be an important and useful knowledge base for them now, or in the future. I then posed the question differently. “Would a book that explained corneal biomechanical principles and testing devices and their application in detecting eyes at risk for developing keratoconus and post-LASIK ectasia, understanding the biomechanical impact of specific types of keratorefractive surgery and riboflavin UV-A corneal collagen cross-linking, and the impact of corneal biomechanics on the fidelity of intraocular pressure measurement and risk for glaucoma progression be of interest?” Framed in this context, the answer I got was a resounding, “Yes!” Therein lies a fundamental disconnect that highlights both the opportunity and need to educate all ophthalmologists about this nascent field.

This comprehensive book is strengthened by the breadth of contributions from leading experts around the world and provides an important resource for ophthalmologists at all levels of training and experience. It gives a panoramic snapshot of our understanding of corneal biomechanics today, bridging the gap between theoretical principles, testing devices that are commercially available and in development as well as current and potential future clinical applications.

While there has been a long-held appreciation that all types of keratorefractive surgery have an impact and interdependence on corneal biomechanics and wound healing, the initial finite element analyses that were applied to understand radial keratotomy were limited by incorrect assumptions that the cornea was a linear, elastic, homogenous, isotropic material.¹ With the advent of excimer laser vision correction, critical observations indicated that Munnerlyn’s theoretic ablation profiles did not account for either lower or higher order (e.g. spherical aberration) refractive outcomes,² suggesting that there were important components missing from the equation—e.g., corneal biomechanics and wound healing. In a seminal editorial, Roberts³ pointed out that the cornea is not a piece of plastic, but rather a material with viscoelastic qualities. Since that time, much has been learned about spatial and depth- related patterns of collagen orientation and interweaving, as well as the biomechanical response to different keratorefractive surgeries that sever tension-bearing lamellae, as the cornea responds to and redistributes stress induced by IOP, hydration, eye rubbing, blinking and extraocular muscle forces.^3-6 The first reports of post-LASIK ectasia⁷ highlighted the need to identify a biomechanical signature of early keratoconus as well as corneas at high risk of developing ectasia irrespective of their current topography or tomography. The introduction of two instruments into clinical use—the Ocular Response Analyzer (ORA) and the Corneal Visualization Scheimpflug Technology (Corvis ST)—that allow measurement of various biomechanical metrics further catapulted the field. The availability of these instruments in routine clinical settings allowed the systematic study of the effect of age, collagen disorders, collagen cross-linking, corneal rings, flaps of various depths, contour, sidecut angulation, pockets, and flockets, just to name of few. Future application of biomechanics to the sclera may improve our understanding of the development and prevention of myopia, as well as scleral surgeries and treatments under development for presbyopia.

It was appreciated by Goldmann and Schmidt that corneal thickness and curvature would influence the measurement of applanation tonometry. The recent ability to measure some corneal biomechanical metrics have led to IOP measurement that may be more immune both to their influence and the impact of central corneal thickness (CCT). Certain chapters in this book explain how a thin cornea could be stiffer than a thick one and that stiffness is also impacted by IOP, thereby precluding simplistic attempts to adjust IOP measurements using nomograms based upon CCT alone. Also highlighted is how corneal hysteresis, the ability of the cornea to absorb and dissipate energy during the bidirectional applanation response to a linear Gaussian air puff, appears to be an independent risk factor for glaucoma progression and rate of progression.^9,10

This comprehensive book starts out with a section devoted to outlining basic biomechanical principles and theories, teaching us the language of what Dupps¹¹ has referred to as “mechanospeak”, thus providing a context and common vocabulary to better comprehend the following chapters. By first defining basic concepts such as stress-strain relationships and creep, this theoretical basis is later applied to explain the pathogenesis of corneal diseases, e.g., explaining how a focal abnormality in corneal biomechanical properties precipitates a cycle of decompensation and localized thinning and steepening, clinically expressed as ectasia progression. These early chapters further detail biomechanical differences between in-vivo and ex-vivo testing, between human and animal corneas and sclera, and between methods of testing. The second section provides a thorough description of two FDA-approved devices to measure corneal biomechanics in the clinic (i.e., the ORA and the Corvis ST), as well as an overview of potential future technologies, including OCT with air puff stimulus, ocular pulse elastography, and Brilloiun microscopy. The third and final section of the book is a thorough treatise on how to interpret the metrics derived from the waveform provided by available clinical devices; their adjunct use in ectasia risk screening; the comparative biomechanical impact of various keratorefractive surgeries and corneal procedures such as PRK, LASIK, SMILE, and corneal collagen cross-linking; the impact of corneal biomechanics on IOP measurement; and potential biomechanical markers of enhanced susceptibility to glaucoma progression.

This compendium of our current knowledge of corneal biomechanics, its measurement and application, provides a strong foundation to more fully understand advances in keratorefractive and corneal surgery, diseases, and treatments, all of which are interdependent on and influence inherent corneal biomechanical properties and behavior. Both the robust aspects and limitations of our current understanding are presented, including the challenge of creating accurate and predictive finite element models that incorporate the impact of IOP, corneal thickness, geometry, and scleral properties on corneal biomechanics. This book provides a key allowing clinical ophthalmologists and researchers to grasp the basics and nuances of this exciting field and to shape it as it evolves in the future.

Jay S. Pepose, MD, PhD
Founder and Medical Director, Pepose Vision Institute; Professor of Clinical Ophthalmology, Washington University School of Medicine, St. Louis, Missouri

Cynthia J. Roberts, PhD

Dr. Roberts received a B.S. Degree in Nursing with Distinction from the University of Iowa in 1979, and worked as a Registered Nurse for several years at the University of Iowa Hospitals and Clinics before enrolling in engineering. She received an M.S. degree in Electrical Engineering in 1986, and a PhD in Biomedical Engineering in 1989, both from The Ohio State University. Dr. Roberts is currently a Professor in Ophthalmology and Biomedical Engineering at The Ohio State University, and holds the Martha G. and Milton Staub Chair for Research in Ophthalmology. Her research focus is ‘Ophthalmic Engineering’ or the application of engineering principles and problem–solving techniques to the maintenance and improvement of vision. Corneal topography was her first area of research within ophthalmology. Her other research interests include ocular biomechanics in refractive surgery, cornea and glaucoma; intraocular pressure measurement error; the in–vivo assessment of corneal biomechanical properties using ultrasonic and dynamic imaging techniques; ophthalmic imaging applications including intraoperative topography–guided surgery, Scheimpflug tomography, and optical coherence tomography with both cornea and retinal applications. She is well published in these areas and has many international collaborators. Dr. Roberts serves on the editorial boards of the Journal of Refractive Surgery, the Journal of Cataract and Refractive Surgery, and the International Journal of Keratoconus and Ectatic Corneal Diseases. She has given many invited lectures internationally, and multiple courses in corneal topography and corneal biomechanics, in both the United States and in Europe. Dr. Roberts received the inaugural Barrequer Medal from the Brazilian Society of Refractive Surgery in 2008 with a lecture entitled ‘Biomechanical Customization: The Next Generation of Refractive Surgery.’ She was inducted as a Fellow in the American Institute for Medical and Biological Engineering in 2009, and was recognized by the American Academy of Ophthalmology with an Achievement Award in 2012.

Jun Liu;, MD

un Liu, PhD, obtained BS and MS degrees in Biomedical Engineering from Zhejiang University, China, in 1994 and 1997. She obtained a PhD in Biomedical Engineering from The Ohio State University (OSU) in 2002. Her graduate work focused on the design and testing of ultrasound techniques and nano-mechanics models for cancer diagnosis and early detection. After completing her PhD, Dr. Liu held a Research Scientist position at OSU Department of Ophthalmology and began directing her research to ocular biomechanics. During the same period, she held an appointment at OSU Department of Veterinary Biosciences where she worked on novel nanoparticle agents for ultrasonic imaging of cancer. In 2005, Dr. Liu started a tenure-track position at OSU Department of Biomedical Engineering. She has closely collaborated with clinicians and her work has been published in both engineering and medical journals. Dr. Liu’s research has been reported by OSU Research News, the Advance magazine for medical imaging professionals, and the Medical Physics web. Dr. Liu serves as a reviewer for many archival journals including Investigative Ophthalmology and Visual Science, Experimental Eye Research, Physics in Medicine and Biology, and Journal of Biomechanical Engineering. She has been a proposal reviewer for the National Institutes of Health, National Science Foundation, the British Fight for Sight Organization, the Sweden Research Council, and the Hong Kong Innovation and Technology Fund. Dr. Liu has served as a Principal Investigator or Co-Investigator for research grants funded by the National Institutes of Health (two RO1s, PI), the National Science Foundation (NSEC, Co-I), the American Health Assistant Foundation (PI), the Susan G. Komen Breast Cancer Foundation (PI), and the Columbus Foundation (PI). Dr. Liu has taught undergraduate and graduate courses in Biomedical Engineering, and has served as a research adviser for graduate, undergraduate, and medical students. Dr. Liu’s current research interests focus on the role of biomechanics in ocular diseases and health, and her laboratory has developed advanced ultrasound techniques to characterize the 3D and in vivo biomechanical properties of ocular tissue.

Foreword

About the editors

About the authors

Section 1: Basics

1. Definitions and concepts
Joel R. Palko, Jun Liu

2. Ex vivo mechanical testing of the cornea
Hugh Morris, Jun Liu

3. Laser interferometry
Abby Wilson, John Tyrer, John Marshall

4. Comparison of porcine and human cornea and sclera mechanical behavior
Benjamin Cruz Perez, Jun Liu

Section 2: Devices

5. Ocular response analyzer
David Luce, David Taylor

6. Measuring biomechanical properties in vivo: the Corvis® ST
Sven Reisdorf
Corvis corrected IOP algorithm
Ahmed Elsheikh

7. OCT with air puff stimulus
Susana Marcos, Carlos Dorronsoro, Karol Karnowski, Maciej Wojtkowski

8. Ocular pulse elastography
Hong Chen, Elias R. Pavlatos, Jun Liu

9. Brillouin microscopy
Giuliano Scarcelli, Seok Hyun Yun

Section 3: Applications

10. Interpreting dynamic corneal response parameters of the Corvis ST
Cynthia J. Roberts, Ashraf M. Mahmoud, Kristen Ann V. Mendoza, Renato Ambrósio Jr.

11. Corneal biomechanics: IOP measurement error and potential biomarker in glaucoma
Aachal Kotecha

12. Incorporating corneal hysteresis in a glaucoma practice
Michael D. Greenwood, Justin A. Schweitzer, John P. Berdahl

13. Corneal collagen cross-linking
Paolo Vinciguerra,Riccardo Vinciguerra, Cynthia J. Roberts

14. Biomechanics in ectasia detection: ORA and Corvis ST
Renato Ambrósio Jr., Fernando Faria Correia, Isaac Ramos, Marcella Q. Salomão, Allan Luz, Bernard T. Lopes

15. Comparison of corneal biomechanics after PRK, LASIK and small-incision lenticule extraction (SMILE)
Dan Z. Reinstein, Timothy J. Archer, Marine Gobbe, J. Bradley Randleman

16. Interpreting corneal biomechanical parameters in refractive surgery
Naveen Mysore, William J. Dupps Jr.

Index

Index of Authors