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.
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.
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. 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:
- The cornea exhibits a non-linear stress versus strain response with progressive stiffening at high strains.
- The cornea exhibits a non-linear viscoelastic response with varying amounts of hysteresis on different loading cycles.
- 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.
- Corneal elastic strength is a function of depth, with decreasing strength from the anterior to the posterior stroma.
- Corneal mechanical properties are dependent on age, with corneal stiffness increasing with the age of the patient.
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. 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. 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. 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. Ongoing research seeks to understand the biomechanical correlation of the waveform parameters reported by ORA as well as their clinical significance.
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. 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. 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. 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.
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. 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. 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. 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.
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. 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. 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. 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. In addition, thin residual stromal beds (225-250 µm), high myopia, young age at operation, and deep ablations have been identified as risk factors. 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.
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. While collagen composition, distribution, and packing appear normal in keratoconus, the native collagen network is mostly unorganized. 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. Factors potentially contributing to the biomechanical degeneration of diseased corneas include genetics, contact lens microtrauma, eye rubbing, and atopy. 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.
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.
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