**Purpose**:
The intraocular pressure (IOP) measured using Goldmann Applanation Tonometry (GAT) is confounded by individual corneal properties. We investigated a modified method that removes the confoundment by incorporating corneal properties into the Imbert-Fick's law is investigated.

**Method**:
Porcine eyes were pressurized between 10 and 40 mm Hg using a manometer. The eyes were indented using a flat cylindrical indenter. A modified corneal indentation device (CID) procedure was used to obtain the corneal moduli *E _{qs}*. The calculated IOP

_{NC}from the Imbert-Fick's Law using the corneal moduli

*E*was compared to the natural IOP

_{qs}_{N}, measured using pressure sensor inserted into the eye.

**Results**:
Test results showed that IOP-dependent corneal modulus *E _{qs}* is a primary confounding factor in IOP calculation. The average elastic modulus

*E*is 0.173 ± 0.018 MPa at 20 mm Hg, and increases with IOP at a linear rate of 0.0066 MPa per mm Hg (

_{qs}*r*= 0.997,

*P*< 0.001). Incorporation of individual

*E*into IOP

_{qs}_{NC}calculation showed that IOP

_{NC}are in good agreement with reference IOP

_{N}(slope = 0.999,

*r*= 0.939,

*P*< 0.001).

**Conclusions**:
The IOP-dependent corneal modulus *E _{qs}* is a primary confounding factor in IOP calculation. A modified CID-GAT procedure to obtain natural cornea-independent IOP

_{NC}is developed and verified in this study. The CID-GAT IOP modification may be used in place of conventional GAT when the confounding effects in eyes with atypical cornea (e.g., laser-assisted in situ keratomileusis [LASIK] thinned) are significant.

**Translational Relevance**:
Confoundment from corneal properties results in IOP measurement errors. The study showed that the CID-GAT method can significantly reduce the confounding corneal errors.

^{1–9}Confoundment by these parameters leads to >3 mm Hg error in the measurement.

^{9–13}The majority of the geometric parameters, including CCT and curvature, can be measured in vivo, and methodologies to account for these geometric parameters in GAT intraocular pressure (IOP) have been developed.

^{9}Despite these advances, a gap between the GAT and natural (IOP

_{N}) IOP in the eye remains because of the inability to account for individual biomechanical properties in the GAT IOP.

*A*and calculates the IOP using the Imbert-Fick's law.

^{14}During applanation, the applanation force

*F*is opposed by the surface tension

*s*from the tear film, upward corneal resistance

*b*, and outward IOP. The force balance is given as Equation 1.

*b*cancels out the corneal surface tension

*s*. Mechanics analysis

^{15,16}showed that the individual corneal resistance

*b*is not a constant, but is a function of the corneal thickness

*,*indentation depth

*v*, and Goldmann quasistatic elastic modulus

^{14}examined the corneal applanation behavior on a group of patients. The study determined that the population-averaged

*b*is counterbalanced by

*s*at the GAT applanation contact area

^{4}The error has been theoretically examined by Liu et al.

^{8}They showed that when the elastic modulus is halved or doubled, up to 5 mm Hg of error may occur (Fig. 1). In further work by others,

^{16–18}the corneal behavior is shown to be nonlinear viscoelastic, such that the effective elastic modulus is dependent on the IOP and loading rate (Fig. 2). In Goldmann applanation, the load is measured after the applanation is stabilized. Under this quasistatic condition, the

^{4}in GAT.

_{N}are developed and tested using porcine eyes.

^{16–18}The instrumented corneal indentation was used to characterize load-displacement data at high speed for eyes pressurized between 20 mm Hg and 40 mm Hg. The procedure was tested on porcine eyes ex vivo and rabbit eyes in vivo. The corneal indentation device (CID, Fig. 3) was developed from these earlier studies and was designed to indent the cornea using a flat punch indenter; the loads and displacements are recorded during corneal indentation. The CID was deployed successfully in clinical trials to characterize the in vivo corneal tangent modulus

^{16–18}in humans. In CID tests on porcine eyes, the indentation load becomes stable at fixed displacement after the displacement is held for 2 or more seconds (Fig. 4). The stabilized CID quasistatic load is fully relaxed, and the load measured under this condition corresponds directly with the quasistatic load in GAT. The quasistatic stiffness of the eye then is the change in quasistatic load per unit indent depth. The procedure to characterize the quasistatic stiffness as a function of IOP under the quasistatic Goldmann condition is detailed below.

*P*was adjusted between 10 and 40 mm Hg by adjusting the liquid level in the manometer and calculated using,

_{m}*g*is the gravitational acceleration, and

*h*is the height difference between the hypodermic needle and liquid level in the manometer. A needle pressure sensor was inserted into the anterior chamber to monitor the reference IOP

_{N}in the chamber synchronously as feedback.

*K*is,

_{g}*t*is the central corneal thickness,

*v*is the Poisson's ratio of the cornea (

*v*∼ 0.5

^{19}), and

*a*is the empirical geometry coefficient, determined from indentation geometry constant

^{15}

*s*can be determined by the diameter of the contact area between the indenter and the cornea,

^{2,8}),

*D*is the diameter of the indenter, and

_{NC}is computed using the Imbert-Fick's law in Equation 1 while the GAT IOP was determined by Equation 3 where the applanation area was set to

_{NC}with the reference IOP

_{N}.

^{3,8}The Figures show the

*r*= 0.997,

*P*< 0.001). The quasistatic corneal modulus

^{8}(Fig. 8). Comparison of IOP

_{NC}, calculated using individual E

_{qs}, with reference IOP

_{N}is plotted in Figure 9. Analysis showed that IOP

_{NC}is in good agreement with IOP

_{N}(

*n*= 15,

*r*= 0.94,

*P*< 0.001). This shows that the CID-GAT procedure and the modified calculation method successfully removed the confounding effect from the cornea from IOP

_{NC}.

_{NC}and reference IOP

_{N}is dependent on the ability of the CID to characterize the quasistatic

*E*of the cornea. Asejczyk-Widlicka et al.

_{qs}^{20}reported a corneal elastic modulus of 0.05 to 0.24 MPa in the IOP range from 12 to 25 mm Hg on porcine eyes ex vivo.

^{20}Inflation tests were conducted in their study, but the rates were not specified. Elsheikh et al.

^{3}performed inflation tests on human and porcine eyes. In their tests, the eyes were quasistatically loaded to set pressure and with similar loading conditions to our study. The corneal quasistatic tangent moduli determined in their inflation tests of porcine eyes (dashed line) are in the same range of results as the present study shown in Figure 7.

^{8}They investigated the IOP elevation in porcine eyes after glutaraldehyde treatment and found that the corneal modulus increased 1 MPa for every 5 mm Hg change in IOP.

^{21}Our results are in line with their model over the tested range of pressure (Fig. 8).

*E*on IOP are shown in Figures 10 to 13, respectively. The variation between the IOP

_{qs}_{N}and IOP

_{GAT}indicates the dependencies of GAT measurement on these corneal properties. Comparison (Fig. 14) showed that the standard deviation (SD = 0.11) of IOP

_{NC}from IOP

_{N}was significantly smaller than that (SD = 0.32) of the IOP

_{GAT}from IOP

_{N}. More than 80% of IOP

_{NC}were within 10% error of IOP

_{N}while IOP

_{GAT}generally deviated from IOP

_{N}by 50%.

_{N}by accounting for the effects of individual-specific corneal biomechanical properties and corneal geometries on IOP

_{N}. Changes in corneal curvature (

*R*), thickness (

_{c}*t*), and corneal elastic properties (

*E*) were accounted for in Equation 6. The corneal elastic properties (i.e., the elastic modulus of the tissue) are known to increase with aging and IOP.

_{qs}^{22–25}The curvature and corneal modulus may change in subjects with keratoconus, and the corneal thickness may increase in subjects with edematous corneas. These confounding effects from aging or illnesses are readily accounted for by the CID-GAT method in Equation 6.

_{NC}using corneal modulus obtained from the CID showed good agreement with IOP

_{N}, the natural IOP of the eye. The CID-GAT method to calculate IOP

_{N}may be of particular relevance and use for subjects with corneas having abnormal biomechanical properties (e.g., aging effects, refractive surgeries, swelling, keratoconus, and so forth).

**S.-H. Lu**, None;

**I.T. Chong**, None;

**S.Y.Y. Leung**, None;

**D.C.C. Lam**, None

*Surv Ophthalmol*. 2008; 53: 203–218.

*J Glaucoma*. 2003; 12: 69–80.

*Exp Eye Res*. 2008; 86: 783–790.

*Optom Vis Sci*. 2008; 85: 445–450.

*J Refract Surg*. 2007; 23: 85–88.

*J Biomech*. 2008; 41: 1707–1713.

*Med Eng Phys*. 2012; 34: 129–139.

*J Cataract Refract Surg*. 2005; 31: 146–155.

*Bull Math Biol*. 1999; 61: 551–572.

*Acta Ophthalmol*. 1975; 53: 34–43.

*Am J Ophthalmol*. 1993; 115: 592–596.

*Surv Ophthalmol*. 2000; 44: 367–408.

*Arch Ophthalmol*. 2006; 124: 471–476.

*Ophthalmologica*. 1957; 134: 221–242.

*Roark's Formulas for Stress*&

*Strain*. 7th ed. New York: McGraw-Hill; 2002: 1–852.

*Acta Ophthalmol*. 2013; 91: e263–e269.

*Mol Cell Biomech*. 2012; 9: 251–268.

*Med Eng Phys*. 2014; 36: 96–101.

*Cornea*. 2000; 19: 355–363.

*Br J Ophthalmol*. 2008; 92: 1415–1418.

*Invest Ophthalmol Vis Sci*. 2009; 50: 2224–2229.

*Mol Cell Biomech*. 2012; 9: 157–173.

*Am J Ophthalmol*. 2007; 143: 39–47.

*J Cataract Refract Surg*. 2007; 33: 1371–1375.

*Exp Eye Res*. 2013; 116: 47–54.