How Corneal Biomechanics Affect IOP Measurements

Measuring these biomechanical parameters provides intriguing diagnostic clues.

BY LEON W. HERNDON, MD

Elevated intraocular pressure is the major modifiable risk factor for the development¹ and progression² of glaucoma. The Goldmann applanation tonometer is currently the gold standard for measuring IOP. In first describing their applanation tonometer, Goldmann and Schmidt discussed the effect of central corneal thickness (CCT) on IOP as measured by the new device.³ They felt that variations in corneal thickness occurred rarely in the absence of corneal disease and assumed a CCT of 520 μm but acknowledged that, at least theoretically, CCT might influence applanation readings.

This article will discuss efforts to examine the role of corneal biomechanics in influencing applanation IOP measurements and the prediction of disease progression.

Goldmann and Schmidt started from the hypothesis that the cornea might be considered as a sheath covered by two membranes between which almost non-shifting water is located. It has since become apparent that CCT is more variable among clinically normal patients than Goldmann and Schmidt ever realized. Von Bahr^4,5 showed that there were large variations in CCT within a normal population and Ehlers and co-workers² demonstrated that this variation in CCT had an effect on applanation-measured IOP. Many studies have since looked at the influence of CCT on IOP measurement, with most agreeing there is an increase in measured IOP with increasing CCT.⁶ However, CCT alone accounts for only a small proportion of the inter-individual variation in measured IOP.

The Role of the ORA

Goldmann applanation tonometry measures IOP by flattening the cornea, which is not neutral in this measurement. Liu and Roberts7 have shown that factors affecting corneal resistance include structural considerations such as the amount of rigidity produced by the way the collagen beams in the tissue line up.

The “bendability” of corneal tissue can also be affected by short-term factors such the presence of corneal edema. Reichert's Ocular Response Analyzer (ORA) (Figure 1) measures the corneal response to indentation by a rapid air pulse. (Figure 2) The principles of the ORA are based on those of non-contact tonometry, in which the IOP is determined by the air pressure required to applanate the central cornea.

Figure 1. The ORA is used to make biomechanical measurements of the cornea.

Figure 2. The air-pulse test to determine corneal hysteresis is very simple.

The ORA makes two measurements of the corneal response to the pulse of air — the force required to flatten the cornea as the air pressure rises (force-in applanation, P1) and the force at which the cornea becomes flat again as the air pressure falls (force-out applanation, P2). The difference between the two is termed corneal hysteresis (CH).

Corneal Hysteresis and Corneal Resistance

Corneal hysteresis is a direct measure of the cornea's biomechanical properties and may more completely describe the contribution of corneal resistance to IOP measurements than CCT alone.⁸ The corneal resistance factor (CRF) is another measurement of corneal biomechanics produced by the ORA and is derived from the formula P1-kP2, where k is a constant. The CRF offers a measurement of corneal resistance and is a parameter that is relatively unaffected by changes in IOP.

A feature of the ORA is that the maximum air pressure applied is not constant and is dependent on P1, a value determined by both the true IOP and the structural resistance of each individual eye. Kotecha et al⁹ recently assessed what effect this feature might have on CH values by measuring eyes before and after pharmacological reduction of IOP. The study found a weak, but significant, negative correlation between changes in CH and changes in IOP, such that higher values of CH were found at lower levels of IOP. Variations in maximum air pressure applied to the cornea may cause differing amounts of corneal indentation. Further work is needed to determine whether these variations alter the CH measurement.

The same study also assessed the relationship between changes in P1 and P2 following the medical lowering of IOP and found that for every unit change in P1 there was a corresponding, proportional change in P2. This relationship was used to determine k for the equation P1-kP2 to derive a parameter termed the corneal constant factor (CCF). Both the CCF and CRF are corneal parameters that are relatively unaffected by IOP, unlike CH. In this study, CH, CCF and CRF were positively associated with CCT, suggesting that thicker corneas exhibit greater viscoelastic properties. There was a negative association between both CCF and CRF and advancing age, possibly due to an age-related increase in cross-linking of collagen fibrils within the cornea leading to a stiffer structure.

Some Diseases/Procedures Reduce CH

Corneal hysteresis has been shown to be reduced in patients with keratoconus and Fuchs' endothelial dystrophy, conditions that cause a progressive decrease and increase in CCT, respectively. This finding may be an indication of the bio-mechanical similarities of such corneas in which alterations of stromal lamellar organization are known to occur.^10,11 CH has also been shown to be markedly reduced in children with congenital glaucoma, especially in those with marked Haab's striae and larger corneal diameters.¹² Pepose et al.¹³ have shown that CH and CRF show a marked reduction following LASIK. This change in corneal biomechanical properties may be a result of the creation of the LASIK flap altering anterior stromal lamellar organization.

The effect of diabetes mellitus on the cornea may have clinical significance.¹⁴ Stromal changes include structural alterations produced by collagen cross-linking.¹⁵ In vitro studies show that collagen cross-linking causes increased stiffness of the cornea,^16,17 which in turn may affect the measurement of IOP, causing overestimation of the true IOP.¹⁸ Goldich et al.¹⁹ compared parameters of biomechanical response of the human cornea measured with the ORA in patients with diabetes mellitus and healthy control subjects. The results of their study showed that the CCT, CH and corneal resistance factor in diabetic eyes were significantly higher than in nondiabetic eyes. The results of the Ocular Hypertension Treatment Study²⁰ suggest that there may be some protective effect of diabetes on the progression to POAG. Although this finding has been widely debated, the results of the Goldich study support it.

Implications for Future Research

Researchers have investigated the possibility that a thick or thin cornea may tell us something about the back of the eye. It's been noted, for instance, that African-Americans have thinner corneas than Caucasians and often have more advanced glaucoma,^21-23 so it's possible that a thinner cornea may indicate a thinner or more susceptible lamina cribrosa or optic nerve. Other research has found that ocular hypertensive patients with thinner corneas have thinner nerve fiber layers than ocular hypertensive patients with thicker corneas and healthy control subjects.²⁴

It is also possible that differences in corneal biomechanics may indicate more generalized structural differences between eyes. Wells et al.²⁵ investigated the relationship between acute IOP-induced optic nerve head deformation and CH and CCT in normal and glaucomatous eyes. They found that in glaucoma patients CH, but not CCT, was associated with increased deformation of the optic nerve surface during transient elevations of IOP.

This finding did not hold true in control patients, suggesting that glaucoma may modify the biomechanical properties of tissues supporting the optic nerve head. Quigley and colleagues²⁶ and Hernandez²⁷ have reported that there are alterations in the elastin of the optic nerve head in both human and experimental glaucoma and have suggested that differences in elastin function may have a part to play in susceptibility to glaucomatous injury. Congdon et al.²⁸ found that a lower CH was more associated with progression of visual field loss in their study than was a lower CCT.

It has only recently become possible to measure the biomechanical properties of the cornea in vivo, and the importance of these properties rests primarily with its effects on IOP measurement. It is possible, however, that corneal biomechanics may give an indication of the struc tural integrity of the optic nerve head. Further work is required to determine precisely how we might be able to risk-stratify glaucoma patients based on their bio me chan ical properties. OM

References

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Leon W. Herndon MD, is associate professor of ophthalmology/glaucoma service at the Duke University Eye Center in Durham, NC. He can be reached via e-mail at hernd012@mc.duke.edu.