The influence of hydration on different mechanical moduli of the cornea

  • Theo G. SeilerEmail author
  • Peng Shao
  • Beatrice E. Frueh
  • Seok-Hyun Yun
  • Theo Seiler
Basic Science



To determine the interrelation of different elastic moduli of the cornea and to investigate their dependency on corneal hydration.


Rabbit eyes were divided into four groups. Corneas were excised and mounted into a Barron artificial anterior chamber. Various corneal hydration steady states were achieved with different dextran T-500 concentrations in the anterior chamber, as well as on the corneal anterior surface. The treatment-solutions of each group contained either 5, 10, 15, or 20% w/w dextran. Ultrasound pachymetry was used to measure central corneal thickness. Brillouin microscopy of the central cornea determined the longitudinal bulk modulus by means of Brillouin frequency shift. Subsequently, a 5-mm-wide central strip was taken for extensiometry to measure the tangential elastic modulus.


The longitudinal bulk modulus was 1.2-times higher in corneas dehydrated with 20% dextran compared to those hydrated with 5% dextran. In contrast, the tangential elastic modulus increased by 4.4 times. The obtained longitudinal bulk moduli were two orders of magnitude bigger than the tangential elastic moduli. Regression analysis of longitudinal bulk modulus and tangential elastic modulus revealed a quadratic relation. The bulk modulus seemed to be independent of tension, whereas the elastic modulus was tension-dependent. Greater corneal hydration led to significantly thicker pachymetry.


Corneal biomechanics are highly dependent on the level of corneal hydration. Surprisingly, tangential elastic moduli were more sensitive to hydration changes than longitudinal bulk moduli. A quadratic relation was found between both moduli.


Cornea Biomechanics Hydration Brillouin Stress strain Extensiometry Tangential elastic modulus Longitudinal elastic modulus 



The authors thank Irene E. Kochevar, PhD; Marleen Engler, BSc; and Eric Beck, BSc for their support.


T. G. Seiler was supported by an unrestricted grant from the Swiss National Science Foundation. The sponsor had no role in the design or conduct of this research.

Compliance with ethical standards

Conflict of interest

S.H. Yun is a co-founder of Intelon Inc., Boston, MA. T. Seiler and P. Shao are scientific consultants of Intelon Inc. T.G. Seiler and B.E. Frueh certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed.


  1. 1.
    Maurice DM (1984) The cornea and the sclera. In: Davson H (ed) The Eye, Vol 1b, 3rd edn. Academic Press, Orlando, pp 1–158Google Scholar
  2. 2.
    Palko JR, Liu J (2016) Definitions and concepts. In: Roberts CJ, Liu J (eds) Corneal Biomechanics. Kugler Publications, Amsterdam, pp 1–24Google Scholar
  3. 3.
    Hatami-Marbini H, Maulik R (2016) A biphasic transversely isotropic poroviscoelastic model for the unconfined compression of hydrated soft tissue. J Biomech Eng 138:4032059CrossRefPubMedGoogle Scholar
  4. 4.
    Thomsen L (1986) Weak elastic anisotropy. Geophysics 51:1954–1966CrossRefGoogle Scholar
  5. 5.
    Dias J, Ziebarth NM (2015) Impact of hydration media on ex vivo corneal elasticity measurements. Eye Contact Lens 41:281–286CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Liu J, Roberts CJ (2005) Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg 31:146–155CrossRefPubMedGoogle Scholar
  7. 7.
    Spoerl E, Huhle M, Seiler T (1998) Induction of cross-links in corneal tissue. Exp Eye Res 66:97–103CrossRefPubMedGoogle Scholar
  8. 8.
    Hoeltzel DA, Altman P, Buzard K, Choe K (1992) Strip extensiometry for comparison of the mechanical response of bovine, rabbit, and human corneas. J Biomech Eng 114:202–215CrossRefPubMedGoogle Scholar
  9. 9.
    Hammer A, Richoz O, Mosquera SA, Tabibian D, Hoogewoud F, Hafezi F (2014) Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Invest Ophth Vis Sci 55:2881–2884CrossRefGoogle Scholar
  10. 10.
    Seiler TG, Fischinger I, Senfft T, Schmidinger G, Seiler T (2014) Intrastromal application of riboflavin for corneal crosslinking. Invest Ophthalmol Vis Sci 55:4261–4265CrossRefPubMedGoogle Scholar
  11. 11.
    Hatami-Marbini H, Rahimi A (2015) Evaluation of hydration effects on tensile properties of bovine corneas. J Cataract Refract Surg 41:644–651CrossRefPubMedGoogle Scholar
  12. 12.
    Boyce BL, Jones RE, Nguyen TD, Grazier JM (2007) Stress-controlled viscoelastic tensile response of bovine cornea. J Biomech 40:2367–2376CrossRefPubMedGoogle Scholar
  13. 13.
    Elsheikh A, Alhasso D, Rama P (2008) Biomechanical properties of human and porcine corneas. Exp Eye Res 86:783–790CrossRefPubMedGoogle Scholar
  14. 14.
    Elsheikh A, Anderson K (2005) Comparative study of corneal strip extensometry and inflation tests. J R Soc Interface 2:177–185CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gloster J, Perkins ES, Pommier ML (1957) Extensibility of strips of sclera and cornea. Br J Ophthalmol 41:103–110CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mikula ER, Jester JV, Juhasz T (2016) Measurement of an elasticity map in the human cornea. Invest Ophthalmol Vis Sci 57:3282–3286CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Scarcelli G, Pineda R, Yun SH (2012) Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci 53:185–190CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Webb JN, Su JP, Scarcelli G (2017) Mechanical outcome of accelerated corneal crosslinking evaluated by Brillouin microscopy. J Cataract Refract Surg 43:1458–1463CrossRefPubMedGoogle Scholar
  19. 19.
    Dias JM, Ziebarth NM (2013) Anterior and posterior corneal stroma elasticity assessed using nanoindentation. Exp Eye Res 115:41–46CrossRefPubMedGoogle Scholar
  20. 20.
    Seifert J, Hammer CM, Rheinlaender J, Sel S, Scholz M, Paulsen F, Schäffer TE (2014) Distribution of Young's modulus in porcine corneas after riboflavin/UVA-induced collagen cross-linking as measured by atomic force microscopy. PLoS One 9:e88186CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jue B, Maurice DM (1986) The mechanical properties of the rabbit and human cornea. J Biomech 19:847–853CrossRefPubMedGoogle Scholar
  22. 22.
    Boyce BL, Grazier JM, Jones RE, Nguyen TD (2008) Full-field deformation of bovine cornea under constrained inflation conditions. Biomaterials 28:3896–3904CrossRefGoogle Scholar
  23. 23.
    Kling S, Marcos S (2013) Effect of hydration state and storage media on corneal biomechanical response from in vitro inflation tests. J Refract Surg 29:490–497CrossRefPubMedGoogle Scholar
  24. 24.
    Hjortdal JO (1996) Regional elastic performance of the human cornea. J Biomech 29:931–942CrossRefPubMedGoogle Scholar
  25. 25.
    Scarcelli G, Kling S, Quijano E, Pineda R, Marcos S, Yun SH (2013) Brillouin microscopy of collagen crosslinking: noncontact depth-dependent analysis of corneal elastic modulus. Invest Ophthalmol Vis Sci 54:1418–1425CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Vaughan JM, Randall JT (1980) Brillouin scattering, density and elastic properties of the lens and cornea of the eye. Nature 284:489–491CrossRefPubMedGoogle Scholar
  27. 27.
    Soergel F, Jean B, Seiler T, Bende T, Mücke S, Pechhold W, Pels L (1995) Dynamic mechanical spectroscopy of the cornea for measurement of its viscoelastic properties in vitro. Ger J Ophthalmol 4:151–156PubMedGoogle Scholar
  28. 28.
    Petsche SJ, Chernyak D, Martiz J, Levenston ME, Pinsky PM (2012) Depth-dependent transverse shear properties of the human corneal stroma. Invest Ophthalmol Vis Sci 53:873–880CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Spiru B, Kling S, Hafezi F, Sekundo W (2017) Biomechanical differences between femtosecond Lenticule extraction (FLEx) and small incision Lenticule extraction (SmILE) tested by 2D-Extensometry in ex vivo porcine eyes. Invest Ophthalmol Vis Sci 58:2591–2595CrossRefPubMedGoogle Scholar
  30. 30.
    Scarcelli G, Yun SH (2016) Brillouin microscopy. In: Roberts CJ, Liu J (eds) Corneal Biomechanics. Kugler Publications, Amsterdam, pp 147–164Google Scholar
  31. 31.
    Reiß S, Burau G, Stachs O, Guthoff R, Stolz H (2011) Spatially resolved Brillouin spectroscopy to determine the rheological properties of the eye lens. Biomed Opt Express 2:2144–2159CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hedbys BO, Mishima S (1966) The thickness-hydration relationship of the cornea. Exp Eye Res 5:221–228CrossRefPubMedGoogle Scholar
  33. 33.
    Hatami-Marbini H, Etebu E (2013) Hydration dependent biomechanical properties of the corneal stroma. Exp Eye Res 116:47–54CrossRefPubMedGoogle Scholar
  34. 34.
    Palko JR, Tang J, Cruz Perez B, Pan X, Liu J (2014) Spatially heterogeneous corneal mechanical responses before and after riboflavin-ultraviolet-a crosslinking. J Cataract Refract Surg 40:1021–1031CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Müller LJ, Pels E, Schurmans LR, Vrensen GF (2004) A new three-dimensional model of the organization of proteoglycans and collagen fibrils in the human corneal stroma. Exp Eye Res 78:493–501CrossRefPubMedGoogle Scholar
  36. 36.
    Nguyen TD, Jones RE, Boyce BL (2008) A nonlinear anisotropic viscoelastic model for the tensile behavior of the corneal stroma. J Biomech Eng 130:041020CrossRefPubMedGoogle Scholar
  37. 37.
    Fratzl P, Daxer A (1993) Structural transformation of collagen fibrils in corneal stroma during drying. An x-ray scattering study. Biophys J 64:1210–1214CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Meek KM, Fullwood NJ, Cooke PH, Elliott GF, Maurice DM, Quantock AJ, Wall RS, Worthington CR (1991) Synchrotron x-ray diffraction studies of the cornea, with implications for stromal hydration. Biophys J 60:467–474CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ko MW, Leung LK, Lam DC, Leung CK (2013) Characterization of corneal tangent modulus in vivo. Acta Ophthalmol 91:e263–e269CrossRefPubMedGoogle Scholar
  40. 40.
    Singh M, Li J, Han Z, Wu C, Aglyamov SR, Twa MD, Larin KV (2016) Investigating elastic anisotropy of the porcine cornea as a function of intraocular pressure with optical coherence Elastography. J Refract Surg 32:562–567CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Sperlich K, Reiß S, Bohn S, Stolz H, Guthoff RF, Jünemann A, Stachs O (2017) Effect of the age-related corneal elasticity on applanation tonometry. Klin Monatsbl Augenheilkd 234:1472–1476CrossRefPubMedGoogle Scholar
  42. 42.
    Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE (2006) Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet a light. J Cataract Refract Surg 32:279–283CrossRefPubMedGoogle Scholar
  43. 43.
    Elsheikh A, Brown M, Alhasso D, Rama P, Campanelli M, Garway-Heath D (2008) Experimental assessment of corneal anisotropy. J Refract Surg 24:178–187PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Theo G. Seiler
    • 1
    • 2
    • 3
    Email author
  • Peng Shao
    • 1
  • Beatrice E. Frueh
    • 2
  • Seok-Hyun Yun
    • 1
  • Theo Seiler
    • 3
  1. 1.Wellman Center for Photomedicine - Massachusetts General Hospital, Harvard Medical SchoolHarvard UniversityBostonUSA
  2. 2.Universitätsklinik für AugenheilkundeInselspitalBernSwitzerland
  3. 3.Institut für Refraktive und Ophthalmo-Chirurgie (IROC), Stockerstrasse 37, 8002 Zürich, Switzerland

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