Data do not support adjusting tonometry for central corneal thickness

Patient care may be adversely affected if clinicians focus only on IOP.

ByJames D. Brandt, MD

James D. Brandt

A number of studies indicate that central corneal thickness is an important predictor of increased risk for developing glaucoma.^1-4 In the 1970s, Ehlers and colleagues reported a relationship between Goldmann applanation tonometry and central corneal thickness.⁵ Because central corneal thickness can affect the precision of Goldmann applanation tonometry, many ophthalmologists attempt to adjust tonometry to account for this factor when assessing IOP in patients.

Although Ehlers’ work is often cited and many clinicians base correction nomograms on his finding, it is important to note that Ehlers’ study was based on a small cohort (29 patients undergoing cataract surgery) consisting entirely of Scandinavian patients with a limited range of central corneal thickness. More recent studies improved on the design of the Ehlers analysis and used larger sample sizes and more modern techniques for intracameral measurements of “true” IOP.

Other factors influence tonometry

Despite these updated manometry studies, the utility of such data to adjust IOP in an individual patient is still limited by variables that hamper the descriptive capabilities of linear regression models. In a linear regression model, half of the data points rest above the regression line and half rest below the line. Consider whether a surgeon should adjust Goldmann applanation tonometry downward for a patient with corneal thickness of 610 µm. The surgeon does not know the cornea is thick and soft (as in sub clinical edema) or thick and stiff. In the former, correcting IOP downward is likely wrong. Clearly, central corneal thickness is an important component of error in Goldmann applanation tonometry, but it is almost certain that other factors, such as the viscoelastic properties of the cornea, minimize the influence of central corneal thickness on tonometry. Engineering models demonstrate that compared with central corneal thickness, Young’s modulus (a measure of corneal “stiffness”) has a more significant effect on Goldmann applanation tonometry.⁶ Tonometry cannot be accurately adjusted based on only one component of the error.

A good analogy can be made with serum cholesterol. Scientists have known for decades that elevated serum cholesterol is a risk factor for cardiovascular disease, but the data fit was poor. After understanding the role of high-density lipoproteins and low-density lipoproteins and their ratio, lipid profiles became more accurate in predicting cardiovascular risk. Similarly, a definite risk relationship between IOP and glaucoma exists, but there are many confounders. Central corneal thickness is just one factor influencing the disease, and ophthalmologists do not fully understand how all these factors fit together and how to use them to treat glaucoma.

A recent British study showed that perhaps half of Goldmann applanation tonometers in use are off calibration by more than 2.5 mm Hg;⁷ add to this the fact that the repeatability of Goldmann applanation tonometry measurements under ideal clinical conditions is usually about ±2 mm Hg, and it is obvious that ophthalmologists who slightly adjust IOP measurements by a few mm Hg using an algorithm are misled if they believe they could be achieving more accurate IOP measurements.

Central corneal thickness as a predictive tool

The Ocular Hypertension Treatment Study confirmed earlier reports that patients with ocular hypertension often have thicker corneas,¹ and showed that black Ocular Hypertension Treatment Study subjects had thinner corneas compared with white subjects. The Ocular Hypertension Treatment Study risk model, the first to include central corneal thickness as a parameter, provided strong evidence that central corneal thickness is an independent risk factor for the development of glaucoma.⁴ These findings were recently validated by the European Glaucoma Prevention Trial.⁸

It is unclear if the impact of central corneal thickness in the Ocular Hypertension Treatment Study risk model is related to tonometry or biology. For example, are aspects of the front of the eye that can be measured, such as central corneal thickness and viscoelasticity, linked to the structure/deformability/physiology of the lamina cribrosa? Attempts by statisticians to correct IOP using various published algorithms indicate that such adjustments do not eliminate central corneal thickness from the Ocular Hypertension Treatment Study multivariate predictive model. These findings suggest several possible explanations: the algorithms could be incorrect; not enough data exist to properly adjust IOP; or a biological basis exists that links central corneal thickness to glaucoma risk.

Underlying physiology

...Ophthalmologists should use a techinque similar to that used for sizing optic discs when assessing central corneal thickness.

—James D. Brandt, MD

Understanding past advances in diabetes management helps place the role of tonometry in context. Would glaucoma management greatly advance if tonometers that could provide more accurate and precise IOP measurements were developed? The history of diabetes management suggests the answer is likely “no.” With diabetes, lab testing evolved during the last century from random, crude measurements of blood and urine glucose to targeted measurements (fasting blood sugar), provocative tests (glucose tolerance tests), measures of recent glycemic control (Hgb A1c), and patients now have accurate portable glucose meters to monitor themselves and adjust therapy in real time. Today, clinicians would not diagnose or manage diabetes based solely on random blood sugar measurements. Yet, this is what we are doing in glaucoma management. Clinicians manage the disease with IOP measurements taken randomly just a few times a year for most patients. Better measures of underlying physiology, such as provocative tests and tonography, and 24-hour monitoring of IOP are sorely needed. A 24-hour IOP monitor, even one whose which precision was only ± 5 mm Hg, would represent a more important advance in glaucoma management than would a more precise and accurate tonometer.

Instead of using central corneal thickness Goldmann applanation tonometry measurements, ophthalmologists should instead use a technique similar to that advocated for evaluating cup to disc ratio, in which the size of the optic disc is important for understanding the context of the C/D ratio; ophthalmologists should characterize CCT as thin, average, and thick and incorporate that information into the global assessment of the individual patient. Attempting to be more precise than this is not supported by the data and can adversely affect patient care if the clinician focuses solely on IOP.

References

Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108:1779-1788.

Medeiros FA, Sample PA, Zangwill LM, Bowd C, Aihara M, Weinreb RN. Corneal thickness as a risk factor for visual field loss in patients with preperimetric glaucomatous optic neuropathy. Am J Ophthalmol. 2003;136:805-813.

Herndon LW, Weizer JS, Stinnett SS. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol. 2004;122:17-21.

Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK 2nd, Wilson MR, Kass MA. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714-720.

Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta ophthalmol (copenh). 1975;53:34-43.

Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg. 2005;31:146-155.

Sandhu SS, Chattopadhyay S, Birch MK, Ray-Chaudhuri N.. Frequency of goldmann applanation tonometer calibration error checks. J Glaucoma. 2005;14:215-218.

Ocular Hypertension Treatment Study Group, European Glaucoma Prevention Study Group. Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007;114:10-19.

James D. Brandt, MD is the professor of ophthalmology & vision science and director of the Glaucoma Service at the University of California, Davis.