Measurement of an Elasticity Map in the Human Cornea.

Cornea Measurement of an Elasticity Map in the Human Cornea Eric R. Mikula, 1 James V. Jester, 1,2 and Tibor Juhasz 1,2 1 Gavin Herbert Eye Institute, University of California, Irvine, California, United States Department of Biomedical Engineering, University of California, Irvine, California, United States Correspondence: Eric R. Mikula, Hewitt Hall, 843 Health Sciences Road, Building 843, 2nd Floor, Room 2121, Irvine, CA 92697, USA; emikula@uci.edu. Submitted: September 22, 2015 Accepted: February 13, 2016 Citation: Mikula ER, Jester JV, Juhasz T. Measurement of an elasticity map in the human cornea. Invest Ophthalmol Vis Sci. 2016;57:3282–3286. DOI:10.1167/iovs.15-18248 P URPOSE . The biomechanical properties of the cornea have an important role in determining the shape of the cornea and visual acuity. Since the cornea is a nonhomogeneous tissue, it is thought that the elastic properties vary throughout the cornea. We aim to measure a map of corneal elasticity across the cornea. M ETHODS . An acoustic radiation force elasticity microscope (ARFEM) was used to create a map of corneal elasticity in the human cornea. This ARFEM uses a low frequency, high intensity acoustic force to displace a femtosecond laser-generated microbubble, while using a high frequency, low intensity ultrasound to monitor the position of the microbubble within the cornea. From the displacement of the bubble and the magnitude of the acoustic radiation force, the local value of corneal elasticity is calculated in the direction of the displacement. Measurements were conducted at 6 locations, ranging from the central to peripheral cornea at anterior and posterior depths. R ESULTS . The mean anterior elastic moduli were 4.2 6 1.2, 3.4 6 0.7, and 1.9 6 0.7 kPa in the central, mid, and peripheral regions, respectively, while the posterior elastic moduli were 2.3 6 0.7, 1.6 6 0.3, and 2.9 6 1.2 kPa in the same radial locations. C ONCLUSIONS . We found that there is a unique distribution of elasticity axially and radially throughout the cornea. Keywords: elasticity, ARFEM, corneal biomechanics, ultrasound T he biomechanical properties of the cornea, along with the underlying corneal microstructure, help determine the shape of the corneal surface, and, thus, also determine visual acuity. Since the cornea provides nearly two-thirds of the refractive power of the eye, understanding corneal biome- chanics is useful when considering refractive errors in the eye, such as keratoconus and post-LASIK ectasia. Further- more, a better knowledge of corneal mechanical properties can provide insight into the corneal response to refractive surgery or ultraviolet A (UVA) cross-linking procedures. Numerous methods have been used to evaluate corneal elasticity, including strip testing, globe inflation, atomic force microscopy, and various ultrasonic methods. Earlier methods, such as globe inflation and strip testing, treated the cornea as a homogenous material, measuring a bulk material property and not localized elastic moduli. 1–8 However, the cornea is a complex, nonhomogenous tissue composed of different layers and varying microstructure radially. There is significant interweaving of stromal lamellae in the central anterior cornea, while this interweaving is absent in the posterior. 9–12 Additionally, the interweaving in the anterior cornea affects the biomechanical properties and interlamellar cohesive strength increases with lamellar interweaving. 13,14 Recently, atomic force microscopy was used to probe varying biomechanical properties through the thickness of the cornea. 15 It was found that Bowman’s layer was nearly three times stiffer than the anterior stroma. Similarly, the trans- verse shear modulus in the anterior cornea was significantly higher than central and posterior layers using torsional rheometry. 16 A study using needle indentation found that the elastic modulus in the anterior cornea was nearly twice that of the posterior. 17,18 Furthermore, this same study also revealed that collagen fiber branching-point density was four times higher in the anterior third of the cornea than in the posterior third. These studies have shown that there is some depth dependence in corneal elasticity. As the cornea approaches the limbus and transitions into sclera tissue, there also is a transition in the microstructure of the tissue. Furthermore, x-ray scattering data suggest that collagen fibril orientation shifts from a preferred orthogonal orientation in the central cornea to a preferred circumferential orientation near the limbus. 19 The nonhomogenous structure of the cornea, through its thickness and radially towards the sclera, suggests that the elastic modulus will vary throughout the cornea. To date, there still is no consensus on regional corneal elastic modulus distribution, especially in the radial direction. Recently, we used acoustic radiation force elastic micros- copy (ARFEM) to measure localized elastic moduli in the human cornea. 20 Acoustic radiation force elastic microscopy uses a low frequency, high intensity acoustic force to displace a femtosecond laser-generated microbubble within the cornea, while using a high frequency, low intensity ultrasound to track the position of the microbubble within the tissue. 21 Importantly, the elasticity measurement is localized to the exact position of the microbubble, which can be created at any position within the cornea. This feature makes ARFEM ideal for probing biomechanical properties throughout the cornea. In this study, ARFEM was used to measure elasticity at varying positions through- out the cornea, with the goal of creating a map of corneal elastic moduli. iovs.arvojournals.org j ISSN: 1552-5783 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.