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Edited by David A. Lee, MD,
and Peter A. Netland, MD, PhD |
Significant variation in corneal thickness can play an important role in determining the true intraocular pressure. In a cornea thicker than 600 µm, the true IOP may be lower than that measured by applanation, and in one thinner than 500 µm, the IOP measurement may be significantly higher. This article reviews the literature and describes our protocol for measuring pachymetry in the glaucoma service at Duke University.
Variations in Corneal Thickness
The effect of central corneal thickness (CCT) on IOP as measured by the applanation tonometer was first described in 1957.1 Believing that variations in corneal thickness occurred rarely in the absence of corneal disease, these researchers assumed a CCT of 500 µm but acknowledged that at least theoretically, CCT might influence applanation readings. It has since become apparent that CCT is more variable among clinically normal patients than what was originally realized.
A number of studies performed in the 1970s assessed the effect of CCT on IOP.2-4 In a manometric study,4 researchers demonstrated that the average error of tonometry was 0.71 mmHg for a 10-µm deviation from the normal CCT of 520 µm. Other research reported a patient with a CCT of 900 µm with a manometric IOP of 11 mmHg, but when measured by applanation, the IOP had ranged from 30 to 40 mmHg while the patient was receiving maximum medical therapy.5
A manometric study with the Perkins tonometer demonstrated an underestimation of intraocular pressure by as much as 4.9 mmHg in thin corneas, with thick corneas producing an overestimation by as much as 6.8 mmHg.6 This corresponded to a calculated range of 0.18 to 0.49 mmHg of change in IOP for a 10-µm change in CCT from the mean CCT. Goldmann tonometer measures the force required to applanate the eye to 3.06 mm diameter.
The force required is a combination of opposition to IOP plus the force needed to bend the cornea (less a small attraction due to surface tension). Therefore, simply put, the thicker the cornea, the higher the force needed to bend, and the thinner the cornea, the lower the force needed to bend. Hence, deviation from normal CCT results in a potentially incorrect indication of IOP.
A number of studies have looked at the distribution of CCT according to diagnosis in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension. Researchers found a significant difference in the mean CCT of these three groups.
In another study, normal eyes had a mean CCT of 554 µm.7 The POAG eyes had a mean CCT of 550 µm, the NTG eyes had a mean CCT of 514 µm, and the OHT eyes had a mean CCT of 580 µm. If the maximum recorded IOP in these eyes is corrected according to research conducted by Niehls Ehlers’ manometric data,4 44 percent of the NTG eyes would be reclassified as having POAG and 35 percent of the OHT eyes would be reclassified as normal.
| Case Report |
A 64-year-old African-American male was diagnosed with primary open-angle glaucoma 10 years ago when his intraocular pressure was recorded at 28 mmHg OD and 22 mmHg OS. Over the years, he had progression of the glaucomatous atrophy, particularly in the right eye, despite different combinations of glaucoma medications and laser trabeculoplasty. His IOP generally ranged between 18 and 22 mmHg OD and 17 and 21 mmHg OS on therapy over the years.
On initial glaucoma subspecialty evaluation, his glaucoma regimen consisted of brimonidine one drop to both eyes twice daily, dorzolamide/timolol combination one drop to both eyes twice daily, and travoprost one drop to OD nightly. He had a visual acuity of 20/20 OD and 20/15 OS. His IOP was recorded at 19 mmHg OD and 17 mm OS. Slit-lamp evaluation of the anterior segments was unremarkable; gonioscopic exam revealed an angle that was open to ciliary body band for 360 degrees OU with light trabecular meshwork pigmentation. Dilated funduscopic exam revealed a cup-to-disc ratio of 0.85 with inferior notching OD and 0.7 with intact neural rim OS.
Visual fields showed a double arcuate scotoma with split fixation on the right and early partial inferior loss on the left. Pachymetry measurement showed a central corneal thickness average of 457 µm OD and 456 µm OS. |
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Another investigator found that 30 percent of the OHT eyes could be reclassified as normal.8 Our group found this figure to be as high as 65 percent.9 Similarly, other researchers found that patients with OHT had thicker corneas than their control and POAG counterparts; they likewise found that patients classified as having NTG had thinner corneas.10
Until recently, most pachymetry studies were performed on predominately Caucasian populations. One study, however, looked at more than 1,000 Mongolian patients in rural China and found that this population had CCT measurements that were 30 to 40 µm lower than the average CCT in surveys found in Caucasian groups.11
A recent article reports thinner CCT values among African-American male veterans compared with Caucasian counterparts.12 These racial differences in CCT may explain, in part, the more advanced progression of glaucomatous disease at a relatively lower measured IOP among African Americans compared to their Caucasian counterparts.
CCT and Treatment
As far as response to therapy, CCT may have a meaningful impact on the measured efficacy of treatment options.
In the Ocular Hypertension Treatment Study, 82 percent of the patients who were randomized to monotherapy beta-blocker therapy were studied.13 CCT was divided into quartiles, and the response to therapy of the highest and lowest quartiles was compared. Those patients in the lowest quartile of CCT showed a significantly greater measured response to therapy compared to those in the highest quartile of CCT. This study showed that differences in CCT induce a measurement artifact that may explain some of the between-subject variability in response to treatment.
Another study evaluated the efficacy of travoprost in a 12-month multi-center trial.14 The researchers found that black subjects showed a statistically better response to travoprost at each time point measured compared to non-blacks. One wonders if the black patients in the study simply had thinner corneas as shown by Francis LaRosa,12 which would lead to a better measured response to treatment, as shown by another study.13
Unpublished data on file with Alcon Laboratories shows that pachymetry was performed in a 12-month study conducted by Peter Netland, MD. Black subjects had a statistically significantly thinner cornea than did their white counterparts. It is not clear at this time if this difference would have a meaningful effect on the results noted in this study.
Clinical Practice
How do we adjust IOP for corneal thickness? As mentioned, Dr. Ehlers4 determined that a 70-µm change in CCT corresponded to approximately 5 mmHg of IOP difference. More recently, Marc Whitacre, MD, determined that a 100 µm change in CCT corresponded to only a 2 mmHg difference in IOP.6 A recent meta-analysis derived a correction factor of 2.5 mmHg for each 50 µm change in CCT.14 This conversion factor was derived by an exhaustive analysis of the world’s literature in regards to CCT and IOP and falls somewhere between the conversion factors of Dr. Ehlers and Dr. Whitacre.
How do we use this information in daily practice? CCT is measured in every new patient that we evaluate and the true IOP is derived using a nomogram of
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Correction Values |
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Corneal Thickness (µm) |
Correction Value |
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405 |
7 |
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425 |
6 |
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445 |
5 |
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465 |
4 |
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485 |
3 |
|
505 |
2 |
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525 |
1 |
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545 |
0 |
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565 |
-1 |
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585 |
-2 |
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605 |
-3 |
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625 |
-4 |
|
645 |
-5 |
|
665 |
-6 |
|
685 |
-7 |
|
705 |
-8 |
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Correction values according to corneal thickness of 545 µm | |
| These correction values are modified from the work of Doughty and Zamen.15 |
a so-called normal CCT of 545 µm.15 This nomogram is a more conservative estimation of Dr. Ehlers’ original work and probably won’t have a significant effect on the true IOP unless the CCT is greater than 600 µm, or lower than 500 µm. Corneal thickness measurements are made centered over the pupil. We use the DGH Technology 550 model (Pachette 2). It retails at about $4,500.
For the patient presented in the accompanying case report who progressed, despite IOPs in the high teens, one could add about 5 mmHg to his measured applanation IOPs. This would put his true IOPs into the low-to-mid 20s. Therefore, our IOP goal for this patient is to get his measured applanation IOP to lower than 10 mmHg in his right eye. The only way that we will reliably accomplish this goal is with trabeculectomy with Mitomycin-C.
Misclassified?
The implications of the above research are significant. It would appear that large numbers of eyes could have been misclassified based on the measured IOP. Many patients may not be treated as well as they could be. Patients with OHT may be overtreated, which could be avoided with a simple test. Patients with NTG and also POAG could have appropriate target IOPs much lower than what we thought was safe previously. There is adequate information to suggest routine measurement of CCT to help in cases of suspected glaucoma to obtain the correct diagnosis and then to ensure that there is optimum management.
Dr. Herndon is an assistant professor at Duke University Medical Center. He has no financial interest in the products mentioned.
1. Goldmann H, Schmidt T. Uber applanationstonometrie. Ophthalmologica 1957;134:221-42.
2. Ehlers N, Hansen FK, Aasved H. Biometric correlations of corneal thickness. Acta Ophthalmol (Copenh) 1975;53:652-9.
3. Ehlers N, Hansen FK. Central corneal thickness in low-tension glaucoma. Acta Ophthalmol (Copenh) 1974;52:740-6.
4. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh) 1975;53:34-43.
5. Johnson M, Kass MA, Moses RA, et al. Increased corneal thickness simulating elevated intraocular pressure. Arch Ophthalmol 1978;96:664-5.
6. Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on applanation tonometry. Am J Ophthalmol 1993;115:592-6.
7. Shah S, Chatterjee A, Mathai M, et al. Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology 1999;106:2154-60.
8. Argus WA. Ocular hypertension and central corneal thickness. Ophthalmology 1995;102:1810-2.
9. Herndon LW, Choudhri SA, Cox T, et al. Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes. Arch Ophthalmol 1997;115:1137-41.
10. Copt RP, Thomas R, Mermoud A. Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal tension glaucoma. Arch Ophthalmol 1999;117:14-6.
11. Foster PJ, Baasanhu J, Alsbirk PH, et al. Central corneal thickness and intraocular pressure in a Mongolian population. Ophthalmology 1998;105:969-73.
12. LaRosa FA, Gross RL, Orengo-Nania S. Central corneal thickness of Caucasians and African Americans in glaucomatous and nonglaucomatous populations. Arch Ophthalmol 2001;119:23-7.
13. Brandt JD, Beiser JA, Kass MA, et al. The relationship of corneal thickness and IOP response to topical beta-blocker in the ocular hypertension treatment study (OHTS). Invest Ophthalmol Vis Sci 2001;42: S421.
14. Netland PA, Landry T, Sullivan EK, et al and The Travoprost Study Group. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol 2001;132:472-84.
15. Doughty MJ, Zamen ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol 2000;44:367-408.
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