Researchers are developing much-needed improved forms of tonometry

Murray Fingeret

Several years ago, one of our students had a habit of recording her Goldmann applanation tonometry (GAT) readings to the tenths of millimeters of mercury. For example, she would record 19.5 mm Hg as her tonometry reading. She was under the impression that this was the proper recording method. My question to her was, “Do you think GAT is that precise?”

We now realize that GAT is a relatively imprecise measure with a host of artifacts. Corneal thickness, hydration and rigidity all may lead to erroneous readings. A further question now being explored is, “Can we measure IOP accurately?”

GAT is a variable-force tonometer that obtains a static measurement of the force required to flatten a fixed area of the cornea. Dr. Goldmann recognized that inter- and intra-individual variations in corneal resistance and thickness may affect the readings. Still, it is doubtful that Dr. Goldmann realized how often corneas varied from his original model. A great deal of information becoming available on IOP and tonometry is changing our perspective of how we should both measure and use IOP clinically.

Circadian measurements

If you ask optometrists when IOP is the highest, most would answer in the morning hours. Interestingly, this is often not the case, as a series of studies done by John Liu and colleagues have shown. Their work at the University of California San Diego investigates the question of diurnal variability and 24-hour circadian measurements.

We previously made assumptions about what the IOP is at night, in large part because previous studies that evaluated nocturnal IOP measured it in a clinical, not bedtime, setting. Nighttime measures were taken just after waking the individual and seating him or her at a slit lamp. The most obvious artifact with this approach is that individuals do not sleep in the vertical position, but rather in a supine position.

Liu and colleagues used a sleep laboratory in which volunteers were placed in a 16-hour light and 8-hour dark environment with sleep occurring during the dark hours. IOP was measured every 2 hours using a pneumatonometer. The advantage with using a pneumatonometer is that the probe could be held in different positions without affecting the accuracy of the readings. Every precaution was taken to measure the IOP while the patient was in the sleeping, supine position, such as using night goggles and minimizing the amount of light entering the room.

Liu’s work has shown that IOP increases at the onset of the dark cycle and starts to reduce at the beginning of the light cycle. It may peak early in the dark cycle and stay elevated throughout or increase steadily during the dark hours. Either way, the IOP declines by the time the early light cycle begins.

An approximately 4-mm Hg IOP elevation occurs when going from the sitting to supine position, but the IOP rises during nocturnal hours even when the measurements are taken in a sitting position. Thus, while the IOP elevation at night is due in part to the difference between the sitting and supine position, other factors are involved. Interestingly, aqueous humor production declines during the nighttime hours, but this decline does not offset other factors such that the IOP still elevates regardless of posture.

A comparison of 24-hour patterns of IOPs in aging and young volunteers: Solid symbols represent a group of 50- to 69-year-old volunteers (n=21). Intraocular pressure was measured by a pneumatonometer 30 minutes after the odd hours in both the sitting (dark circle) and supine (dark triangle) positions during the light/wake period (7 a.m.-11 p.m.) and only in the supine position during the dark period (11 p.m.-7 a.m.). Error bars represent SEM. Previously published results from two separate groups of 18- to 25-year-old volunteers were included for comparison. In one group (n=12), IOP was measured in the sitting position (open circle) during the light/wake period and in the other group (n=21) in the supine position (open triangle). During the dark period, all measurements of IOP were performed with subjects supine. Participants started 24-hour experiments at different times evenly distributed during the light/wake period. Reprinted with permission from Liu JHK, et al. Twenty-four hour pattern of intraocular pressure in the aging population. IOVS. 1999;40(12):2912-2917.

Therapeutic lessons

The clinician should bear several points in mind with this information. Timolol does not appear to effectively blunt this nighttime IOP spike as well as prostaglandins, which is one reason why prostaglandins deserve to be first-line glaucoma agents.

Certain individuals with glaucoma whose IOP appears to be low may have significant nighttime IOP spikes that may not be measured. This may explain why some individuals progress when they appear to be controlled. Also, some medications may do a better job of reducing the nocturnal IOP spikes than others. This explains the difficulty in predicting which patient will be controlled based upon a single IOP measurement. It also points out that diurnal IOP is a significant risk factor in regard to the development and progression of glaucoma.

Recent work has illustrated that diurnal variability is a significant risk factor, regardless of IOP levels. The most important measurement (diurnal IOP range, mean IOP or peak IOP) is still debatable.

Central corneal thickness

The Ocular Hypertension Treatment Study (OHTS) showed that central corneal thickness varied among the ocular hypertensive population and that thick corneas were associated with elevated IOP readings. This brought home the point that GAT is far less accurate than previously thought.

Different algorithms have been circulated to correct IOP based upon central corneal thickness. They vary from Ehlers work, with a 5-mm Hg change associated with 70 µm to Doughty’s meta-analysis showing 2.5 mm Hg correlated with a 50 µm change, to Whitacre’s and the Rotterdam Eye Study’s formula of 2 mm Hg per 100 µm.

Which is the one to use? And even if we knew what the “true” correction was, Meideros has shown that a thin cornea is an independent risk factor for the development of glaucoma. Correcting the IOP does not remove a thin cornea from risk in the OHTS multivariable risk model.

Corneal biomechanics and IOP

The newest area of investigation relates to corneal biomechanics and how it influences IOP measurements. These properties include corneal curvature, thickness and rigidity.

In regard to curvature, the steeper the cornea, the higher the IOP measurement, but even with a very steep cornea, this effect is low.

In regard to corneal thickness, the thicker the cornea, the higher the measurement. A thick cornea can have a moderate impact on IOP, but the most important biomechanical factor is rigidity. A stiff cornea can elevate the IOP significantly. More importantly, thin, stiff corneas and thick, soft corneas exist, which further confuse this area.

Ocular Response Analyzer

Reichert’s Ocular Response Analyzer uses a noncontact-type tonometer reading to evaluate corneal biomechanics. The applanation reading is compared when the pulse is going into and out of the eye. The difference is termed “hysteresis” and is felt to be a measure of the cornea’s viscoelastic properties.

There is a correlation between hysteresis and the development of glaucoma, though how this measurement is used is still being evaluated. Hysteresis represents another important factor and emphasizes that the measurement of IOP is far more complex than we once thought.

Pascal DCT

The Pascal Dynamic Contour Tonometer (DCT) (Ziemer Ophthalmic Systems) is another new instrument that aims to reduce the impact of corneal thickness and relative corneal viscoelasticity on IOP measurement. The instrument, while appearing like a Goldmann tonometer, is actually quite different.

Unlike the Goldmann, the Pascal is not a variable force tonometer, but rather uses a small piezoelectric pressure sensor embedded within the tonometer tip. The external and internal forces are equalized when the central cornea has taken the shape of the tip, at which point measurements are taken. Recent studies have shown that DCT is an accurate, reproducible measure that correlates well with true IOP, though it tends to be approximately 1.7 mm Hg higher than GAT. It has been shown to be uninfluenced by the corneal changes resulting from LASIK surgery.

Many questions arise as this information is digested. Most clinicians have now gotten accustomed to taking GAT and corneal thickness measurements. Can one forget about pachymetry if he or she has a DCT? Probably not, as central corneal thickness is a risk factor regardless of correcting the IOP.

How would one use the DCT, because the readings differ from GAT? In this situation, the clinician needs to learn a new set of values that allow for the Pascal’s higher normative curve. Using the Pascal, the range of so-called normal IOP values changes from the traditional values of about 12 to 21 mm Hg to 14 to 23 mm Hg.

Also, should one adjust the Goldmann IOP for central corneal thickness? I recommend not correcting IOPs for a host of reasons, primarily because we do not know what correcting factor to use. In addition to corneal thickness, other factors that affect IOP measurements include technique, corneal viscoelasticity, diurnal variability and regression to the mean.

In addition, Goldmann tonometers are frequently out of calibration. In a recent paper, 51% of Goldmann tonometers were found to be miscalibrated. We are dealing with an imprecise measurement that we would like to be exacting.

IOP measurements evolving

The science of measuring IOP is evolving. As more information becomes available, further questions arise before answers become apparent. The Goldmann tonometer is a mechanical device that dates back to the 1950s. We need a better instrument to measure IOP.

Luckily, researchers are working to develop new forms of tonometry such as some capable of 24-hour continuous monitoring that may take readings independent of thickness or other biomechanical factors. Other glaucoma instruments such as confocal scanning laser ophthalmoscopy and polarimetry have brought new abilities to measure areas that we used to grossly measure. It is hoped that during the next decade, technological advances will occur with tonometry such that similar clinical advances occur.

For Your Information:

• Murray Fingeret, OD, is chief of the optometry section at the Department of Veterans’ Affairs Medical Center in Brooklyn and Saint Albans, N.Y., and a professor at SUNY College of Optometry. He is also a member of the Primary Care Optometry News Editorial Board. He may be contacted at St. Albans VA Hospital, Linden Blvd. and 179th St., St. Albans, NY 11425; (718) 526-1000; fax: (516) 569-3566; e-mail: murrayf@optonline.com. Dr. Fingeret has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned. Ziemer has loaned Dr. Fingeret a Pascal Dynamic Contour Tonometer.

• The Ocular Response Analyzer is available from Reichert Ophthalmic Instruments, 3374 Walden Ave., Depew, NJ 14043; (716) 686-4500; fax: (716) 686-4545; Web site: www.reichertoi.com.
• The Pascal Dynamic Contour Tonometer is available from Ziemer Ophthalmic Systems, AG, 1603 Watermark Circle NE, St. Petersburg, FL 33702; (727) 525-2881; fax: (727) 526-9401; Web site: ziemer-ophthalmics.com.

Suggested Reading

• Liu JHK, Kripke DF, Twa MD, et al. Twenty-four hour pattern of intraocular pressure in the aging population. IOVS. 1999;40:2912-2917.
• Liu JHK, Zhang X, Kripke DF, Weinreb RN. Twenty-four hour intraocular pressure pattern associated with early glaucomatous changes. IOVS. 2003;44:1586-1590.
• Orzalesi N, Rosetti L, Invernizzi T, et al. Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension. IOVS. 2000;41:2566-2573.
• Hansen F, Ehlers N. Elevated tonometer readings caused by a thick cornea. Acta Ophthalmol (Copenh). 1971;9:775-778.
• Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh). 1975;53:34-43.
• Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on applanation tonometry. Am J Ophthalmol. 1993;115:592-596.
• Shah S. Accurate intraocular pressure measurement—the myth of modern ophthalmology? Ophthalmology. 2000;107:1805-1807.
• Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: A review and meta-analysis approach. Surv Ophthalmol. 2000;44:367-408.
• Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study. Arch Ophthalmol. 2002;120:701-703.
• Kniestedt C, Nee M, Stamper RL. Dynamic contour tonometry: A comparative study on human cadaver eyes. Arch Ophthalmol. 2004;122:1287-1293.
• Kaufmann C, Bachmann LM, Thiel MA. Comparison of dynamic contour tonometry and Goldmann applanation tonometry. IOVS. 2004;45:3118-3121.
• Wolfs RC, Klaver CC, Vingerling JR, et al. Distribution of central corneal thickness and its association with intraocular pressure: The Rotterdam Study. Am J Ophthalmol. 1997;123(6):767-772.
• Nouri-Mahdavi K, Hoffman D, Coleman AL, et al. Advanced Glaucoma INtervention Study: Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004;111(9):1627-1635.
• Asrani S, Zeimer R, Wilensky J, Gieser D, Vitale S, Lindenmuth K. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9(2):134-142.
• 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(5):805-813.
• Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108(10):1779-1788.
• Sandhu SS, Chattopadhyay S, Birch MK, Ray-Chaudhuri N. Frequency of Goldmann applanation tonometer calibration error checks. J Glaucoma. 2005;14(3):215-218.