**5. Corneal biomechanics**

Ocular biomechanics is an increasingly important field. Overt corneal biomechanical prob‐ lems have long been seen in keratoconus and corneal ectasia after corneal refractive sur‐ gery [32].

In keratoconus, there are clear changes in the corneal collagen, and the cornea loses rigidity over time and becomes ectatic; in corneal ectasia, the ablation of some corneal stroma can weaken the cornea and result in progressive corneal deformation [33]. In refractive surgical practice, patients with preexisting ectasia usually are excluded from treatment. However, in‐ dividual variations in biomechanical integrity and postoperative wound healing preclude preoperative identification of all potentially vulnerable patients. There is considerable but mostly indirect evidence suggesting that the biomechanical corneal properties vary with age. Quantifying the biomechanical corneal properties is difficult, but the available evidence supports corneal stiffening with age; in other words, there is an increment in Young's mod‐ ulus [34], the ocular rigidity coefficient, that expresses the elastic properties of the globe [35,36], the cohesive tensile strength, and the breaking force of a tissue [37].

Young's modulus, also known as the tensile modulus, is a measure of the stiffness of an elastic material and is a parameter used to characterize elastic materials. Perhaps the single best descriptor of a given material's biomechanical properties at low strain is its Young's modulus (E), which is defined as the ratio of stress to strain or

#### *Young* '*smodulus*(*E*)=*stress* /*strain*

Medeiros and Weinreb [26] argued that other factors besides corneal thickness such as cor‐ neal elasticity and viscoelasticity might affect tonometric readings and the formulas to cor‐ rect the GAT IOP [19] do not fully consider these factors [19, 27, 28]. The DCT measurements have been proposed and agree closely with the manometric measurements [20]. Therefore, the inclusion of DCT measurements along with corneal thickness in a model predictive of glaucoma might better assess the true independent value of IOP. A biologic link might exist between some corneal parameters such as the thickness or the viscoelastic properties and the structure/deformability/physiology of the lamina cribosa and peripapillary sclera.

It is noteworthy that in the Early Manifest Glaucoma Trial (EMGT) the IOP was not used to determine patient eligibility or treatment decisions, and thus the possible effect of the CCT on GAT measurements was less likely to affect the incidence of glaucoma progression. In the EMGT, the CCT was an independent factor predictive of POAG progression [29]. In the population-based, longitudinal Barbados Eye Studies, the CCT (measured 9 years after the recruitment) was an independent risk factor for development of glaucoma [30]. In the popu‐ lation-based Los Angeles Latino Eye Study (LALES), the prevalence of glaucoma was higher among individuals with thin CCTs than among individuals with normal or thick CCTs across all IOP levels [31]. The LALES, which investigated whether adjusting each IOP indi‐ vidually for CCT using the Doughty and Zaman algorithm [16] changed this relationship, reported almost no change in the association between a thin CCT and a higher prevalence of glaucoma. This algorithm showed that 2.5 mmHg was correlated with a 50-µm difference from the baseline CCT. Each of these corrective factors had proponents, and the use of algo‐ rithms to correct for the IOP based on the CCT became popular. The LALES concluded that the CCT is an independent factor itself [31]. The findings of the EMGT, Barbados Eye Stud‐ ies, and LALES suggest that the effect of CCT on the glaucoma development risk is caused

Ocular biomechanics is an increasingly important field. Overt corneal biomechanical prob‐ lems have long been seen in keratoconus and corneal ectasia after corneal refractive sur‐

In keratoconus, there are clear changes in the corneal collagen, and the cornea loses rigidity over time and becomes ectatic; in corneal ectasia, the ablation of some corneal stroma can weaken the cornea and result in progressive corneal deformation [33]. In refractive surgical practice, patients with preexisting ectasia usually are excluded from treatment. However, in‐ dividual variations in biomechanical integrity and postoperative wound healing preclude preoperative identification of all potentially vulnerable patients. There is considerable but mostly indirect evidence suggesting that the biomechanical corneal properties vary with age. Quantifying the biomechanical corneal properties is difficult, but the available evidence supports corneal stiffening with age; in other words, there is an increment in Young's mod‐ ulus [34], the ocular rigidity coefficient, that expresses the elastic properties of the globe

[35,36], the cohesive tensile strength, and the breaking force of a tissue [37].

by more than just a tonometry artifact.

**5. Corneal biomechanics**

234 Glaucoma - Basic and Clinical Aspects

gery [32].

where stress is an applied force (load/unit area), and strain is the deformation of the materi‐ al to which stress has been applied (displacement/unit length). This parameter depends on the material's physical properties and dimensions. Importantly, when stress is applied and removed, elastic materials follow the same path during deformation and relaxation and ulti‐ mately recover the original shape. Viscoelastic materials, such as the cornea, also can recover the original shape after stress is removed, but the relaxation path differs from the deforma‐ tion path; therefore, the relationship between stress and strain is nonlinear, and stiffening occurs as strain increases [38-40] (Figure 4). This behavior, referred to as corneal hysteresis (CH), results from dissipation of energy as heat in the material.

**Figure 4.** Here, it can be seen the relationship between stress and strain is linear in an elastic behaviour and nonlinear in a viscoelastic behaviour.

The GAT IOP measurement, obtained from the force needed to applanate the cornea, is based on a number of assumptions about corneal deformability. The corneal mix of collagen types, corneal hydration, collagen fibril density, ECM, and other factors vary among indi‐ viduals. In some patients, these factors dwarf the effect of the CCT on the accuracy of the GAT IOP value. In fact, the effect of the corneal thickness on GAT measurements may be less important than the effect of variations in corneal elasticity [41].

and the air pressure applied to the eye decreases in an inverse-time symmetric fashion. However, before that decrease, the cornea is indented substantially as the air pressure peaks about 3 ms after applanation. As the pressure decreases from its peak, the cornea passes through a second applanated state while returning to the normal convex curvature. This al‐ lows detection of a second applanation point. Using the first applanation pressure point (P1) and the second applanation pressure point (P2) [42,43] (Figure 7), the ORA generates two separate IOP output parameters, and the difference between the two pressures is CH.

Cornea and Glaucoma

237

http://dx.doi.org/10.5772/53017

The Goldmann-correlated IOP (IOPg) is the average of the inward (P1) and outward (P2) ap‐

The CH measurement also provides a basis for two additional new parameters: the cornealcompensated IOP (IOPcc), an IOP measurement that is less affected by corneal properties than other tonometric methods, such as GAT, and CRF, an index of corneal resistance to de‐ formation derived from the formula P1 x kP2, where k is the constant determined from em‐ pirical analysis of the relationship between both P1 and P2 and CCT to develop a corneal

The CH in patients with glaucoma and in those with acquired optic nerve head (ONH) pits is lower than in normal controls [43, 45]. Other authors also have found that the CH predicts visual field damage progression. However, other studies using the ORA have reported that the CRF and CH did not change significantly when the IOP was lowered using topical anti‐ glaucoma drugs and that the relationship between the GAT IOP and CRF or CH is weak and

The changes in the GAT IOP after corneal refractive surgery have been studied because of the large number of patients who undergo laser refractive procedures. In corneal laser exci‐ mer refractive surgery, the cornea becomes thinner and, therefore, the IOP measurement is affected [47,48]. Because most patients undergoing laser refractive surgery are myopic and

planation pressures. This parameter is closely correlated with the GAT IOP.

**Figure 7.** This picture shows de P1 and P2 points. Hysteresis is also showed.

parameter more strongly associated with CCT than CH [44].

unchanged by ocular hypotensive drugs [46].

**6. Corneal and refractive surgeries**

CH is a measure of the viscoelastic properties of the corneal tissue together with the corneal resistance factor (CRF), i.e., the "energy absorption capability" of the cornea, and indicates the biomechanical integrity. The Ocular Response Analyzer (ORA) (Reichert Ophthalmic In‐ struments, Inc., Buffalo, NY) provides both parameters (Figure 5).

**Figure 5.** Ocular response analyzer.

The ORA, which measures some of the corneal biomechanical properties in vivo, uses a 25 millisencond (ms) air pulse to apply pressure to the cornea. The air pulse causes the cornea to move inward, past applanation and into a slight concavity, before returning to the normal curvature. Corneal deformation is recorded via an electro-optical infrared detection system similar to classic air-puff tonometry. The ORA acquires corneal biomechanical data by quan‐ tifying this differential inward and outward corneal response to the air pulse over about 20 ms (Figure 6).

**Figure 6.** This picture shows the measurements done by ORA.

Because of the dynamic nature of the measurement process, viscous damping in the cornea causes delays in the inward and outward applanation events (energy absorption). Millisec‐ onds after the first applanation, the air pump that generated the air pulse also shuts down, and the air pressure applied to the eye decreases in an inverse-time symmetric fashion. However, before that decrease, the cornea is indented substantially as the air pressure peaks about 3 ms after applanation. As the pressure decreases from its peak, the cornea passes through a second applanated state while returning to the normal convex curvature. This al‐ lows detection of a second applanation point. Using the first applanation pressure point (P1) and the second applanation pressure point (P2) [42,43] (Figure 7), the ORA generates two separate IOP output parameters, and the difference between the two pressures is CH.

**Figure 7.** This picture shows de P1 and P2 points. Hysteresis is also showed.

types, corneal hydration, collagen fibril density, ECM, and other factors vary among indi‐ viduals. In some patients, these factors dwarf the effect of the CCT on the accuracy of the GAT IOP value. In fact, the effect of the corneal thickness on GAT measurements may be

CH is a measure of the viscoelastic properties of the corneal tissue together with the corneal resistance factor (CRF), i.e., the "energy absorption capability" of the cornea, and indicates the biomechanical integrity. The Ocular Response Analyzer (ORA) (Reichert Ophthalmic In‐

The ORA, which measures some of the corneal biomechanical properties in vivo, uses a 25 millisencond (ms) air pulse to apply pressure to the cornea. The air pulse causes the cornea to move inward, past applanation and into a slight concavity, before returning to the normal curvature. Corneal deformation is recorded via an electro-optical infrared detection system similar to classic air-puff tonometry. The ORA acquires corneal biomechanical data by quan‐ tifying this differential inward and outward corneal response to the air pulse over about 20

Because of the dynamic nature of the measurement process, viscous damping in the cornea causes delays in the inward and outward applanation events (energy absorption). Millisec‐ onds after the first applanation, the air pump that generated the air pulse also shuts down,

less important than the effect of variations in corneal elasticity [41].

struments, Inc., Buffalo, NY) provides both parameters (Figure 5).

**Figure 5.** Ocular response analyzer.

236 Glaucoma - Basic and Clinical Aspects

**Figure 6.** This picture shows the measurements done by ORA.

ms (Figure 6).

The Goldmann-correlated IOP (IOPg) is the average of the inward (P1) and outward (P2) ap‐ planation pressures. This parameter is closely correlated with the GAT IOP.

The CH measurement also provides a basis for two additional new parameters: the cornealcompensated IOP (IOPcc), an IOP measurement that is less affected by corneal properties than other tonometric methods, such as GAT, and CRF, an index of corneal resistance to de‐ formation derived from the formula P1 x kP2, where k is the constant determined from em‐ pirical analysis of the relationship between both P1 and P2 and CCT to develop a corneal parameter more strongly associated with CCT than CH [44].

The CH in patients with glaucoma and in those with acquired optic nerve head (ONH) pits is lower than in normal controls [43, 45]. Other authors also have found that the CH predicts visual field damage progression. However, other studies using the ORA have reported that the CRF and CH did not change significantly when the IOP was lowered using topical anti‐ glaucoma drugs and that the relationship between the GAT IOP and CRF or CH is weak and unchanged by ocular hypotensive drugs [46].
