Corneal Biomechanics

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Article initiated by:
Majid Moshirfar, M.D., Jason Edmonds MD
All contributors:
Eric Weinlander, MD, Maria A. Woodward, MD, Joobin Khadamy, MD, FEBO, Colleen Halfpenny, M.D., Erica Bernfeld M.D., Vandana Reddy, MD, Majid Moshirfar, M.D., Dylan Griffiths, Amy Lin, MD
Assigned editor:
Eric Weinlander, MD, Mary Daly, MD
Review:
Assigned status Update Pending
 by Eric Weinlander, MD on February 15, 2024.


Introduction

The biomechanics of the cornea affect its functional responses and greatly impact vision. The physical composition of the cornea gives it viscoelastic properties, meaning it exhibits elements of both elasticity and viscosity. While various methods have been devised to study the biomechanics of the cornea, only the Ocular Response Analyzer allows direct analysis of corneal biomechanical properties in the clinic. An understanding of corneal biomechanics is important in describing disease states such as keratoconus and ectasia. In addition, successful corneal treatments depend on interactions between biological and biomechanical factors and their impact on surrounding ocular tissues.

Properties of the Cornea

The material properties of the cornea are responsible for its functionality. Freidenwald first described the viscoelastic properties of the cornea in 1937, followed, in subsequent decades, by Nyquist and Woo.[1][2]

The cornea exhibits elastic and viscoelastic properties, which give it the quality of hysteresis. Elasticity refers to the ability of a substance to deform reversibly under stress. Viscous materials, on the other hand, flow when an external shear force is applied and do not regain their original shape when the force is removed. Viscoelastic materials exhibit characteristics of both viscosity and elasticity, resulting in energy dissipation when stress is applied. The energy lost in this dissipation process is called hysteresis.

Measurement of Mechanical Properties

Several techniques have been developed for testing corneal tissue in an attempt to measure the mechanical properties of the cornea. These techniques have been divided into ex vivo destructive tests and in vivo nondestructive tests.[3][4]

Ex Vivo Destructive Tests

This type of evaluation involves testing either complete corneas or strips of cornea that have been removed from the eye. Biomechanical properties are measured by exposing corneal tissue to stress under controlled conditions with constant humidity. Ex-vivo destructive testing techniques include strip extensiometry and pressure inflation of intact corneas.[5][6][7][8][9][10][11][12][13][14][15][16] While this type of investigation allows for extensive testing, including multiple loading patterns and measurement of various properties, the nature of testing ex vivo introduces the potential for error. These error risks include altering fibril orientation (especially if corneal strips are used) and poor replication of in-vivo humidity conditions.

Principles Confirmed with Ex Vivo Testing

Despite its weaknesses, ex-vivo destructive testing has successfully confirmed the following biomechanical principles:

  1. The cornea exhibits a non-linear stress versus strain response with progressive stiffening at high strains.[10][11]
  2. The cornea exhibits a non-linear viscoelastic response with varying amounts of hysteresis on different loading cycles.[5]
  3. The cornea shows regional in-plane variation in strain and deformation, meaning the paracentral and peripheral cornea is stiffer than the central cornea due to differing orientation and number of collagen fibrils.[7]
  4. Corneal elastic strength is a function of depth, with decreasing strength from the anterior to the posterior stroma.[15][16]
  5. Corneal mechanical properties are dependent on age, with corneal stiffness increasing with the age of the patient.[14]

In vivo Nondestructive Testing

Several methods have been developed and investigated for measuring corneal biomechanics in vivo. The clinical application of these devices is variable. In vivo methods avoid the potential for error inherent with removing the cornea from its native environment, but they are also limited in their scope of investigation.

Ocular Response Analyzer

The Ocular Response Analyzer (ORA) (Reichert Inc., Depew, New York), described by Luce et al, is the only commercially available medical device capable of measuring corneal biomechanics in vivo.[17] The ORA uses a puff of air to deflect the cornea while an infrared beam tracks changes in the shape of the anterior cornea during inward and outward deviation. Analysis of the parameters produced by the infrared waveform signal allows the calculation of several useful values. Corneal hysteresis (CH) is calculated as the difference in air pressures between force-in applanation (P1) and force-out applanation (P2), or (P1 – P2). Studies have shown that CH is altered in various disease states.[17][18][19][20] Measurement of CH also provides a more complete characterization of the contribution of corneal resistance to intraocular pressure measurements than central corneal thickness (CCT) alone.[17] However, corneal hysteresis values can be produced by various combinations of corneal thickness, rigidity, intraocular pressure, and hydration. Corneal resistance factor (CRF) is another measurement provided by ORA and is derived using the formula (P1 – kP2), where k is a constant. The constant, k, was developed through empirical evaluation of the relationship between P1 and P2 and CCT, such that the value of k is more strongly associated with CCT than CH. Thus, CRF is a measurement of corneal resistance that is relatively independent of IOP. Analysis of the infrared signal waveform parameters produced by the ORA has proven useful in diagnosis and prognosis after refractive surgery.[21][22] Ongoing research seeks to understand the biomechanical correlation of the waveform parameters reported by ORA as well as their clinical significance.[21][23]

Brillouin Microscopy in Corneal Biomechanics

Brillouin microscopy is an advanced, non-invasive imaging technique that measures the biomechanical properties of the cornea by analyzing the interaction between light (photons) and acoustic phonons, which are vibrations of atoms or molecules within the tissue. When a near-infrared laser light is directed onto the cornea, it interacts with these phonons, causing a small shift in the frequency of the scattered light. These frequency shifts, measured in gigahertz (GHz), can be converted into gigapascals (GPa) to estimate the tissue's stiffness or elasticity. The resulting data is used to create a color-coded Brillouin map, which provides a visual representation of the cornea's mechanical properties.

Although experimental prototypes of Brillouin microscopy devices are available, current models face challenges such as lengthy measurement times and inconsistent results, often influenced by environmental factors like temperature and patient cooperation. Future advancements, including artificial intelligence (AI) integration, could improve the precision and efficiency of these devices, potentially making them more suitable for clinical use. AI could help by filtering out erroneous measurements and selecting the most accurate data, thereby enhancing the reliability of the Brillouin map.

This technology holds promise for management of patients with corneal ectasia, identifying patients at risk of corneal complications before refractive surgery, monitoring myopia progression and scleral properties in glaucoma, evaluating treatment efficacy after corneal cross-linking (CXL), and assessing lens properties related to accommodation. Additionally, Brillouin microscopy could provide more accurate intraocular pressure (IOP) measurements by accounting for individual variations in corneal biomechanics.

One key advantage of Brillouin microscopy over other technologies is its ability to measure the cornea's longitudinal viscoelastic modulus (LVM), which reflects the tissue's ability to resist deformation over time. This differs from other methods like the Ocular Response Analyzer (ORA) or Corvis ST, which measure corneal hysteresis or deformation response but do not provide a full three-dimensional map of the cornea's biomechanical properties. By offering a more comprehensive view of the cornea's mechanical behavior, Brillouin microscopy could play a crucial role in advancing our understanding of various ocular conditions.[24]

Other in vivo Methods

Shear wave propagation velocity has been used as a means of measuring biomechanical properties including estimation of elastic modulus and Poisson’s ratio from linear elastic model approximation.[25][26][27] However, clinical applications of this technology have not proven successful. One emerging technique utilizes placido disk imaging to measure corneal curvature changes while the cornea is deformed with an indenter. Imaging results are compared with those of normal and abnormal corneas to identify patterns in bending resistance.[28] Another emerging technique employs optical coherence elastography (OCE) to measure the deviation in interior stroma during indentation with a concave lens. OCE measures strain in the middle and posterior cornea and allows measurement of variations in corneal mechanical properties in these areas.[29] High resolution ultrasound strain imaging of the cross-sectional cornea is another emerging technique which may be capable of tracking deformation of interior layers of the cornea.[30]

Intraocular Pressure Measurement

It is well documented that true intraocular pressure (IOP) is overestimated by thick or steep corneas and underestimated in thin or flat corneas.[31] This is due to limitations in Goldmann applanation tonometry, the gold standard of IOP measurement. Developed in 1957 by Goldmann and Schmidt, this technique relies on the Imbert-Fick principle which states that the pressure inside a fluid-filled sphere surrounded by an infinitely thin membrane can be measured using the pressure required to just flatten a fixed external portion of the membrane.[32] The law assumes that the membrane is infinitely thin, completely spherical, perfectly dry, and perfectly elastic. Goldmann and Schmidt intended to correct for the finite thickness, asphericity, and rigidity of the cornea by assuming a constant cornea thickness of about 500 µm and that the surface tension of the tear meniscus drawing the applanation instrument to the cornea would compensate for corneal rigidity. Studies have since proven that these assumptions are not accurate. While studies agree that an increase in CCT results in increased IOP, the exact relationship between CCT and IOP is complex and non-linear.[31][33][34] The ORA allows for several IOP measurements, including Goldmann-correlated IOP (IOPG) and corneal compensated IOP (IOPCC). The IOPCC value is a more accurate indicator of true IOP than IOPG because it is less affected by corneal properties such as CCT and CH.

Biomechanical Pathology

Disruption of the corneal fiber network by disease or surgery can result in decreased structural integrity of the cornea, degeneration, surface irregularities, and distorted vision. Understanding the specific processes of corneal degeneration allows for targeted treatments to be developed and administered to affected patients.

Iatrogenic Corneal Ectasia

Iatrogenic corneal ectasia is a rare complication of refractive surgery thought to be the result of inadequate residual stromal bed left after surgery (most commonly, LASIK) or surgery performed on a cornea with unidentified keratoconus.[35] Iatrogenic ectasia is characterized by biomechanical degeneration with progressive steepening of the cornea and a very thin stromal bed (<300 µm). The result is progressive, asymmetric corneal steepening which leads to myopic shift, irregular astigmatism, and reduced visual acuity.[36][37] Evaluation of ectatic corneas reveals a normal thickness laser-assisted in situ keratomileusis (LASIK) flap, Bowman’s layer breaks, thin residual stromal beds, reduced number and thickness of lamellae, and larger than normal interlamellar clefts in the elastic region.[38] The main risk factor for iatrogenic ectasia is irregular topography preoperatively, including asymmetric inferior corneal steepening or asymmetric bowtie patterns with skewed steep radial axes above and below the horizontal meridian.[39][40] In addition, thin residual stromal beds (225-250 µm), high myopia, young age at operation, and deep ablations have been identified as risk factors.[39][40] Combined screening programs which include tomographic and topographic evaluation are suggested preoperatively to prevent iatrogenic ectasia, but detection of at-risk corneas remains a challenge.[41][42]

Keratoconus

Keratoconus is a progressive ectatic disorder of the cornea characterized by bilateral, asymmetric, non-inflammatory degeneration which results in central and paracentral thinning and protrusion. Progression of the disease is thought to begin with focal degeneration of material properties, followed by a cycle of thinning, increased strain, and redistribution of stress.[43] While collagen composition, distribution, and packing appear normal in keratoconus, the native collagen network is mostly unorganized.[44] Irregularities in the collagen network result in distortion of refractive function which can lead to high myopia and irregular astigmatism. Keratoconus corneas also exhibit increased levels of collagenolysis, loss of keratocytes, reduced collagen cross-links, and significantly weakened stress-versus-strain responses.[45][46][47] Factors potentially contributing to the biomechanical degeneration of diseased corneas include genetics, contact lens microtrauma, eye rubbing, and atopy.[48][49] Forme fruste keratoconus is a latent biomechanical instability that is a major cause of iatrogenic ectasia. While ORA, placido-disk imaging, and Scheimpflug imaging have all shown promise in detecting some aspects keratoconus, a combination of these techniques is usually required to maximize the specificity and sensitivity of diagnosing subclinical disease.[50][51][52]

Conclusion

An understanding of corneal biomechanics is fundamental to the diagnosis and treatment of corneal disease. A combination of investigative techniques has expanded our knowledge of the mechanical properties of the cornea and their impact on disease states. As the only device capable of measuring corneal biomechanics in the clinical setting, the ORA is useful in diagnosis and prognosis after refractive surgery. However, many of the ORA’s parameters are poorly understood. Future studies to define the correlations between ORA parameters and biomechanical properties will likely provide insight into the pathogenesis of disease states such as keratoconus and iatrogenic ectasia. Understanding the interactions between biomechanics and functionality will allow better screening and more effective treatment of these diseases.

Additional Resources

References

  1. ↑ Nyquist GW: Rheology of the cornea: experimental techniques and results. Experimental eye research 1968, 7(2):183-188.
  2. ↑ Woo SL, Kobayashi AS, Lawrence C, Schlegel WA: Mathematical model of the corneo-scleral shell as applied to intraocular pressure-volume relations and applanation tonometry. Annals of biomedical engineering 1972, 1(1):87-98.
  3. ↑ Nyquist GW: Rheology of the cornea: experimental techniques and results. Experimental eye research 1968, 7(2):183-188.
  4. ↑ Kotecha A: What biomechanical properties of the cornea are relevant for the clinician? Survey of ophthalmology 2007, 52 Suppl 2:S109-114.
  5. ↑ 5.0 5.1 Boyce BL, Jones RE, Nguyen TD, Grazier JM: Stress-controlled viscoelastic tensile response of bovine cornea. Journal of biomechanics 2007, 40(11):2367-2376.
  6. ↑ Bryant MR, McDonnell PJ: Constitutive laws for biomechanical modeling of refractive surgery. Journal of biomechanical engineering 1996, 118(4):473-481.
  7. ↑ 7.0 7.1 Hjortdal JO: Regional elastic performance of the human cornea. Journal of biomechanics 1996, 29(7):931-942.
  8. ↑ Hoeltzel DA, Altman P, Buzard K, Choe K: Strip extensiometry for comparison of the mechanical response of bovine, rabbit, and human corneas. Journal of biomechanical engineering 1992, 114(2):202-215.
  9. ↑ Jue B, Maurice DM: The mechanical properties of the rabbit and human cornea. Journal of biomechanics 1986, 19(10):847-853.
  10. ↑ 10.0 10.1 Shin TJ, Vito RP, Johnson LW, McCarey BE: The distribution of strain in the human cornea. Journal of biomechanics 1997, 30(5):497-503.
  11. ↑ 11.0 11.1 Wollensak G, Spoerl E, Seiler T: Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. Journal of cataract and refractive surgery 2003, 29(9):1780-1785.
  12. ↑ Boyce BL, Grazier JM, Jones RE, Nguyen TD: Full-field deformation of bovine cornea under constrained inflation conditions. Biomaterials 2008, 29(28):3896-3904.
  13. ↑ Elsheikh A, Alhasso D, Rama P: Biomechanical properties of human and porcine corneas. Experimental eye research 2008, 86(5):783-790.
  14. ↑ 14.0 14.1 Elsheikh A, Wang D, Brown M, Rama P, Campanelli M, Pye D: Assessment of corneal biomechanical properties and their variation with age. Current eye research 2007, 32(1):11-19.
  15. ↑ 15.0 15.1 Randleman JB, Dawson DG, Grossniklaus HE, McCarey BE, Edelhauser HF: Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery. Journal of refractive surgery 2008, 24(1):S85-89.
  16. ↑ 16.0 16.1 Smolek MK: Interlamellar cohesive strength in the vertical meridian of human eye bank corneas. Investigative ophthalmology &amp;amp;amp;amp;amp;amp;amp;amp;amp; visual science 1993, 34(10):2962-2969.
  17. ↑ 17.0 17.1 17.2 Luce DA: Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. Journal of cataract and refractive surgery 2005, 31(1):156-162.
  18. ↑ Ortiz D, Pinero D, Shabayek MH, Arnalich-Montiel F, Alio JL: Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. Journal of cataract and refractive surgery 2007, 33(8):1371-1375.
  19. ↑ Touboul D, Roberts C, Kerautret J, Garra C, Maurice-Tison S, Saubusse E, Colin J: Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry. Journal of cataract and refractive surgery 2008, 34(4):616-622.
  20. ↑ Shah S, Laiquzzaman M, Bhojwani R, Mantry S, Cunliffe I: Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Investigative ophthalmology &amp;amp;amp;amp;amp;amp; visual science 2007, 48(7):3026-3031.
  21. ↑ 21.0 21.1 Kerautret J, Colin J, Touboul D, Roberts C: Biomechanical characteristics of the ectatic cornea. Journal of cataract and refractive surgery 2008, 34(3):510-513.
  22. ↑ Glass DH, Roberts CJ, Litsky AS, Weber PA: A viscoelastic biomechanical model of the cornea describing the effect of viscosity and elasticity on hysteresis. Investigative ophthalmology &amp;amp;amp;amp;amp;amp; visual science 2008, 49(9):3919-3926.
  23. ↑ Lam AK, Chen D, Tse J: The Usefulness of Waveform Score from the Ocular Response Analyzer. Optometry and vision science : official publication of the American Academy of Optometry 2010.
  24. ↑ Loveless B A, Moin K A, Hoopes P C, et al. (July 30, 2024) The Utilization of Brillouin Microscopy in Corneal Diagnostics: A Systematic Review. Cureus 16(7): e65769. doi:10.7759/cureus.65769
  25. ↑ Dupps WJ, Jr., Netto MV, Herekar S, Krueger RR: Surface wave elastometry of the cornea in porcine and human donor eyes. Journal of refractive surgery 2007, 23(1):66-75.
  26. ↑ Liu J, He X, Pan X, Roberts CJ: Ultrasonic model and system for measurement of corneal biomechanical properties and validation on phantoms. Journal of biomechanics 2007, 40(5):1177-1182.
  27. ↑ Tanter M, Touboul D, Gennisson JL, Bercoff J, Fink M: High-resolution quantitative imaging of cornea elasticity using supersonic shear imaging. IEEE transactions on medical imaging 2009, 28(12):1881-1893.
  28. ↑ Grabner G, Eilmsteiner R, Steindl C, Ruckhofer J, Mattioli R, Husinsky W: Dynamic corneal imaging. Journal of cataract and refractive surgery 2005, 31(1):163-174.
  29. ↑ Ford MR, Dupps WJ, Jr., Rollins AM, Roy AS, Hu Z: Method for optical coherence elastography of the cornea. Journal of biomedical optics 2011, 16(1):016005.
  30. ↑ Hollman KW, Emelianov SY, Neiss JH, Jotyan G, Spooner GJ, Juhasz T, Kurtz RM, O'Donnell M: Strain imaging of corneal tissue with an ultrasound elasticity microscope. Cornea 2002, 21(1):68-73.
  31. ↑ 31.0 31.1 Doughty MJ, Zaman ML: Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Survey of ophthalmology 2000, 44(5):367-408.
  32. ↑ Goldmann H, Schmidt T: [Applanation tonometry]. Ophthalmologica Journal international d'ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde 1957, 134(4):221-242.
  33. ↑ Liu J, Roberts CJ: Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. Journal of cataract and refractive surgery 2005, 31(1):146-155.
  34. ↑ Ehlers N, Hansen FK, Aasved H: Biometric correlations of corneal thickness. Acta Ophthalmol (Copenh) 1975, 53(4):652-659.
  35. ↑ O'Keefe M, Kirwan C: Laser epithelial keratomileusis in 2010 - a review. Clinical &amp;amp;amp; experimental ophthalmology 2010, 38(2):183-191.
  36. ↑ Rad AS, Jabbarvand M, Saifi N: Progressive keratectasia after laser in situ keratomileusis. Journal of refractive surgery 2004, 20(5 Suppl):S718-722.
  37. ↑ Pallikaris IG, Kymionis GD, Astyrakakis NI: Corneal ectasia induced by laser in situ keratomileusis. Journal of cataract and refractive surgery 2001, 27(11):1796-1802.
  38. ↑ Dawson DG, Randleman JB, Grossniklaus HE, O'Brien TP, Dubovy SR, Schmack I, Stulting RD, Edelhauser HF: Corneal ectasia after excimer laser keratorefractive surgery: histopathology, ultrastructure, and pathophysiology. Ophthalmology 2008, 115(12):2181-2191 e2181.
  39. ↑ 39.0 39.1 Winkler von Mohrenfels C, Salgado JP, Khoramnia R: [Keratectasia after refractive surgery]. Klinische Monatsblatter fur Augenheilkunde 2011, 228(8):704-711.
  40. ↑ 40.0 40.1 Randleman JB: Post-laser in-situ keratomileusis ectasia: current understanding and future directions. Current opinion in ophthalmology 2006, 17(4):406-412.
  41. ↑ Belin MW, Ambrosio R, Jr.: Corneal ectasia risk score: statistical validity and clinical relevance. Journal of refractive surgery 2010, 26(4):238-240.
  42. ↑ Randleman JB: Evaluating risk factors for ectasia: what is the goal of assessing risk? Journal of refractive surgery 2010, 26(4):236-237.
  43. ↑ Dauwe C, Touboul D, Roberts CJ, Mahmoud AM, Kerautret J, Fournier P, Malecaze F, Colin J: Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus. Journal of cataract and refractive surgery 2009, 35(10):1761-1767.
  44. ↑ Meek KM, Tuft SJ, Huang Y, Gill PS, Hayes S, Newton RH, Bron AJ: Changes in collagen orientation and distribution in keratoconus corneas. Investigative ophthalmology &amp;amp;amp; visual science 2005, 46(6):1948-1956.
  45. ↑ Bron AJ: Keratoconus. Cornea 1988, 7(3):163-169.
  46. ↑ Zimmermann DR, Fischer RW, Winterhalter KH, Witmer R, Vaughan L: Comparative studies of collagens in normal and keratoconus corneas. Experimental eye research 1988, 46(3):431-442.
  47. ↑ Andreassen TT, Simonsen AH, Oxlund H: Biomechanical properties of keratoconus and normal corneas. Experimental eye research 1980, 31(4):435-441.
  48. ↑ McMonnies CW: The evidentiary significance of case reports: eye rubbing and keratoconus. Optometry and vision science : official publication of the American Academy of Optometry 2008, 85(4):262-269.
  49. ↑ Wang Y, Rabinowitz YS, Rotter JI, Yang H: Genetic epidemiological study of keratoconus: evidence for major gene determination. American journal of medical genetics 2000, 93(5):403-409.
  50. ↑ Auffarth GU, Wang L, Volcker HE: Keratoconus evaluation using the Orbscan Topography System. Journal of cataract and refractive surgery 2000, 26(2):222-228.
  51. ↑ Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS: Keratoconus: a review. Contact lens &amp;amp;amp; anterior eye : the journal of the British Contact Lens Association 2010, 33(4):157-166; quiz 205.
  52. ↑ Arntz A, Duran JA, Pijoan JI: [Subclinical keratoconus diagnosis by elevation topography]. Archivos de la Sociedad Espanola de Oftalmologia 2003, 78(12):659-664.
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