**4. Corneal thickness and glaucoma**

Most of the knowledge regarding the impact of corneal thickness in glaucoma is referred to CCT; however, Jordan et al. [24] found differences between the OHT and normal tension glaucoma (NTG) groups in central and paracentral corneal thicknesses measured by optical slip scan pachymetry. The study corroborated differences in CCT between OHT and NTG but also found that the corresponding paracentral quadrants differed significantly between groups. Patients with NTG had overall thinner corneas and those with OHT had overall thicker corneas. Is the corneal thickness an independent risk factor for glaucoma?

Goldmann first suggested in 1957 that the IOP measured by applanation tonometry might be affected by the CCT [25]. He found that IOP measurements in patients with thin corneas tended to be underestimated but overestimated in those with thick corneas.

In the OHTS, the GAT IOP was used to determine participant eligibility, guide treatment de‐ cisions, and construct a model predictive of POAG development. Had the OHTS been car‐ ried out with a perfectly accurate, cornea-independent tonometer, which does not exist, the IOP might have been a more powerful predictor of POAG development and the CCT might have been a less powerful predictor. Some investigators interpreted the OHTS results to in‐ dicate that the CCT is an independent risk factor for glaucoma development. Because the GAT measurements ultimately depend on the CCT, Medeiros and Weinreb [26] stated that it is impossible, based on the original model, to disassociate the effects of both. Some groups have evaluated [19,27,28] whether the OHTS prediction model could be improved using CCT-corrected IOP using previously published formulas (Table 1), evaluated using the c sta‐ tistics (a measure of concordance), and calibration chi-squares. The c statistic is the fraction of patients with an outcome among pairs of patients, in which one has the outcome and one does not; the patient with the higher predictive value is classified as the one with the out‐ come. The c statistic varies between 0.5 when a model provides no information and 1.0 in sensible models. The CCT also remained a significant predictor of glaucoma development in a multivariable model that included the CCT-corrected IOP.


**Table 1.** Correction values for IOPs based on CCT [ 8,17].

Because the IOP is an important risk factor for glaucoma, accurate measurement is important, and it can be achieved by intraocular manometry; however, this is an invasive method that obvi‐

The only way to fully evaluate the possible independent role of CCT as a prognostic factor for glaucoma development is to include in the predictive model the IOP measurements obtained by a CCT-independent tonometer. The Pascal dynamic contour tonometer (DCT), is a slit-lampmounted, nonapplanation, digital contact tonometer that provides continuous tonometry re‐ cordings that measure the IOP and the ocular pulse amplitude, which is the difference between the minimal and maximal values of the pulsatile IOP wave contour, and does not require cor‐ neal applanation and the DCT IOP measurements seem to agree closely with manometric meas‐ urements [23]. Therefore, including DCT measurements with the CCT in a predictive model for glaucoma might better assess the true independent value of CCT compared with use of only the CCT-corrected GAT values. This has been investigated in patients undergoing phacoemulsifi‐ cation, that had the anterior chamber cannulated in a closed system and the IOP was set to 15, 20, and 35 mmHg by a water column. The IOP measurements then were taken by DCT. The results showed that the DCT agree well with the intracameral IOP. Interestingly, the CCT had a low but

The DCT measurement principle is based on contour matching, which assumes that if the eye were enclosed by a contoured, tight-fitting shell, the forces generated by IOP would act on the shell wall. Replacing part of the shell wall with a pressure sensor would enable measurement of these forces and therefore the IOP. The DCT has a central gauge surrounded by a contoured plastic tip that is in contact with the cornea and creates a tight-fitting shell. The DCT compen‐ sates for all forces exerted on the cornea and an electronic sensor measures IOP independent of

Most of the knowledge regarding the impact of corneal thickness in glaucoma is referred to CCT; however, Jordan et al. [24] found differences between the OHT and normal tension glaucoma (NTG) groups in central and paracentral corneal thicknesses measured by optical slip scan pachymetry. The study corroborated differences in CCT between OHT and NTG but also found that the corresponding paracentral quadrants differed significantly between groups. Patients with NTG had overall thinner corneas and those with OHT had overall

Goldmann first suggested in 1957 that the IOP measured by applanation tonometry might be affected by the CCT [25]. He found that IOP measurements in patients with thin corneas

In the OHTS, the GAT IOP was used to determine participant eligibility, guide treatment de‐ cisions, and construct a model predictive of POAG development. Had the OHTS been car‐ ried out with a perfectly accurate, cornea-independent tonometer, which does not exist, the IOP might have been a more powerful predictor of POAG development and the CCT might

thicker corneas. Is the corneal thickness an independent risk factor for glaucoma?

tended to be underestimated but overestimated in those with thick corneas.

ously cannot be used in a clinical setting,

232 Glaucoma - Basic and Clinical Aspects

significant effect on the DCT measurements [23].

**4. Corneal thickness and glaucoma**

the corneal properties.

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.

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

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235

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

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

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

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

modulus (E), which is defined as the ratio of stress to strain or

(CH), results from dissipation of energy as heat in the material.

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

in a viscoelastic behaviour.

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 by more than just a tonometry artifact.
