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Page 1: Corneal Thickness in Ocular Hypertension, Primary … · Corneal Thickness in Ocular Hypertension, Primary Open-angle Glaucoma, and ... (Dr Thomas). ARCH OPHTHALMOL/VOL ... Corneal

Corneal Thickness in Ocular Hypertension,Primary Open-angle Glaucoma, andNormal Tension GlaucomaRene-Pierre Copt, MD; Ravi Thomas, MD; Andre Mermoud, MD

Objectives: To determine the effect of central cornealthickness (CCT) on the measurement of intraocular pres-sure (IOP) and on the resultant reclassification of patientsas having primary open-angle glaucoma (POAG), normaltension glaucoma (NTG), or ocular hypertension (OHT).

Methods: Intraocular pressure (Goldmann applana-tion tonomety) and CCT (ultrasound pachymetry) weremeasured in 22 patients with NTG, 49 with POAG, 44with OHT and in 18 control subjects. The CCT was usedto obtain a corrected value for the IOP and to reclassifythe type of glaucoma.

Results: There was no significant difference in CCT be-tween controls (552 ± 35 µm) and patients with POAG(543 ± 35 µm), but the CCT in the group with NTG

(521 ± 31 µm) was significantly lower than that in the con-trol group or the group with POAG (P,.001), and theCCT in the group with OHT (583 ± 34 µm) was signifi-cantly higher than in controls or patients with POAG(P,.001). Correcting IOP for corneal thickness, 31% ofthe patients with NTG could be reclassified as havingPOAG, and 56% of the patients with OHT as normal.

Conclusions: Patients with NTG have a thinner CCTthan do patients with POAG or controls. Underestima-tion of the IOP in patients with POAG who have thin cor-neas may lead to a misdiagnosis of NTG, while overes-timation of the IOP in normal subjects who have thickcorneas may lead to a misdiagnosis of OHT.

Arch Ophthalmol. 1999;117:14-16

I NTRAOCULAR PRESSURE (IOP) isan important parameter in the di-agnosis and follow-up of glau-coma. While Goldmann appla-nation tonometry is the preferred

method of measurement of IOP, severalfactors, including corneal thickness, mayinfluence its accuracy.1 A positive linearcorrelation between central corneal thick-ness (CCT) and IOP has been reported byKruse Hansen and Ehlers.2,3 Intraocularpressure measured by applanation may beoverestimated or underestimated in thickor thin corneas, respectively.

Patients with ocular hypertension(OHT) have thicker central corneas thando control subjects .4-6 It has recently beenshown that thinning of the cornea follow-ing excimer laser photorefractive keratec-tomy may lead to an underestimation ofthe IOP as determined by applanation to-nometry.7 We hypothesized that the IOPin some patients with primary open-angle glaucoma (POAG) and thin cor-

neas may thus be underestimated, therebyleading to a misdiagnosis of normal ten-sion glaucoma (NTG). We undertook thisstudy to determine the potential numberof patients with glaucoma misdiagnosedas having NTG and/or OHT due to varia-tions in corneal thickness.

RESULTS

The study included 64 women (10 con-trols; 16 with NTG; 18 with OHT; and20 with POAG) and 69 men (8 controls; 6with NTG; 26 with OHT; and 29 withPOAG). Controls and patients with OHTwere younger than patients with POAG andNTG (58.7 ± 25.9 and 60.3 ± 12.6 vs68.8 ± 15.3 and 75.3 ± 10.1 years, respec-tively [mean ± SD]) (P,.001). The meanfollow-up before the study was 8.5 ± 4.2years for the patients with NTG, 9.6 ± 4.5years for those with OHT, and 7.6 ± 5.7years for those with POAG. The CCT, IOP,spherical equivalent, and number of glau-coma medications used in each group aregiven in Table 1. The mean SD for CCTreadings was 5 µm. Patients with POAG andcontrols had equivalent mean corneal thick-

For editorial commentsee page 104

CLINICAL SCIENCES

From the Hopital OphtalmiqueJules Gonin, University ofLausanne, Lausanne,Switzerland (Drs Copt andMermoud); and Schell EyeHospital, CMC Vellore, India(Dr Thomas).

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ness measurements. The mean corneal thickness in thegroup with NTG was significantly lower than in patientswith POAG or controls (P,.001). Central cornealthickness was significantly greater in groups with OHTthan in groups with POAG or in controls (P,.001).

Therefractionwasnotnotablydifferentbetweengroups.Using the reported correction for corneal thickness,8 IOPin patients with NTG was underestimated by a mean of 2.2mm Hg (Table 2); IOP in patients with OHT was over-estimated by a mean of 2.3 mm Hg. When the IOP was cor-rected for corneal thickness, 7patients (31%)whoweredi-agnosed initially as having NTG had IOPs of 21 mm Hg orgreater, and25patients (56%)whowerediagnosed initiallyas having OHT had IOPs of 21 mm Hg or lower.

In this study, corneal thickness ranged from 484 to700 µm. As Goldmann applanation tonometry is accu-rate for a corneal thickness of 520 µm,8 the maximumunderestimation of IOP was 4.8 mm Hg, and the maxi-mum overestimation was 10.5 mm Hg.

COMMENT

Goldmann and Schmidt9 first discussed the influence ofvariations in corneal thickness and scleral rigidity on ap-

planation tonometry. Ehlers et al8 reported that the Gold-mann tonometer provided accurate readings only whenthe CCT was 0.52 mm; they calculated that applanationtonometry overestimated or underestimated IOP by ap-proximately 5 mm Hg for every 0.070 mm of deviationin corneal thickness.8 More recently Whitacre et al5 re-ported that thin corneas may result in a 4- to 9-mm Hgunderestimation of IOP, and thick corneas may result inoverestimation of the IOP by 6.8 mm Hg.

Our patients with NTG had considerably thinnerCCT than did the group with POAG or the controls, whilethe group with OHT had notably thicker CCT than didpatients with POAG or controls. We have shown that un-derestimation of IOP may result in some patients withPOAG receiving a misdiagnosis and being treated forNTG. Indeed, when corneal thickness was taken into ac-count, 7 (31%) of our patients thought to have NTG ac-tually met the criteria for a diagnosis of POAG. Simi-larly, many patients diagnosed as having OHT (25 [56%]in our study) actually have normal IOP. In other words,7 patients (31%) of the patients diagnosed as having NTGactually had POAG, and 25 (56%) of the patients diag-nosed as having OHT really had an IOP that was withinnormal limits. Half of the patients diagnosed as having

Table 1. Values for Central Corneal Thickness, IOP, Spherical Equivalent, and Number of Glaucoma Medicationsfor the Different Groups of Patients*

Controls NTG OHT POAG

Central corneal thickness, µm 552 ± 35 521 ± 31 583 ± 34 543 ± 35IOP, mm Hg 15.83 ± 2.82 17.25 ± 1.93 27.13 ± 3.84 23.33 ± 7.10Spherical equivalent, diopters 0.53 ± 2.02 −0.37 ± 2.03 −0.12 ± 2.02 −0.63 ± 2.50No. of glaucoma medications 0 1.54 ± 1.20 1.01 ± 0.93 1.63 ± 1.08

*NTG indicates normal tension glaucoma; OHT, ocular hypertension; POAG, primary open-angle glaucoma; and IOP, intraocular pressure. All values are given asmean ± SD.

PATIENTS, MATERIALS,AND METHODS

One hundred fifteen white patients (49 with POAG, 22 withNTG, and 44 with OHT) seen in the glaucoma depart-ment of the Jules Gonin Eye Hospital, Lausanne, Switzer-land, from June 1997 to January 1998 were included in thestudy; 18 control subjects were also recruited. All patientswere informed concerning the study and gave their oral con-sent to undergo corneal thickness measurements.

Primary open-angle glaucoma was defined as an IOPof 22 mm Hg or higher in the presence of a typical glau-comatous disc and field changes and an open angle on go-nioscopy. Normal tension glaucoma was defined as a typi-cal glaucomatous disc and field changes with an IOP of 21mm Hg or lower on diurnal measurement and an open angleon gonioscopy. Ocular hypertension was defined as an IOPof 22 mm Hg or higher with normal discs and visual fieldsand open angles on gonioscopy.

Patients with ocular disease other than glaucoma orOHT were excluded, as were those with myopia or hyper-metropia of more than 3 diopters (D) or an astigmatism ofmore than 1 D.

The type of glaucoma, IOP measurement, refraction,corneal thickness, and number of glaucoma medicationsused were recorded. Intraocular pressure was measured ina standard manner with a calibrated Goldmann applana-tion tonometer. The average of 3 consecutive readings be-fore initiation of glaucoma medication was recorded.

Central corneal thickness was measured with an ul-trasonic pachymeter (DGH-1000, DGH Technology Inc,Frazer, Pa). All of the measurements were performed bythe same examiner (A.M.). Each patient was asked to blinkbefore CCT measurement to avoid any bias because of cor-neal drying. Ten measurements were made at the centerof the cornea of each eye. The lowest CCT reading was usedfor analysis as it was thought to most likely reflect a per-pendicular placement of the pachymeter probe and, there-fore, to be the most accurate measurement.

A cycloplegic refraction was performed using an au-torefractometer (Nidek AR-1100, Nidek, LTD, Tokyo, Ja-pan). In each subject the mean spherical equivalent wasconsidered for analysis. All measurements were carried outby an observer (R.-P.C.) masked to the diagnosis, and only1 eye (randomly selected) of each patient was used for analy-sis. Comparison of means was performed using the Stu-dent t test.

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OHT, but ultimately found to have normal IOP, had beenundergoing treatment with one or more medications.

A high incidence of NTG has been reported in a na-tionwide survey conducted in Japan.10 It would be inter-esting to see if central corneal pachymetry performed ona sample of that population showed that the high inci-dence of NTG is more actually associated with thinnercorneas.

It is recognized that only a minority of patients withOHT develop visual field loss.11,12 This may be becausemany of of these individuals actually only have a thickercornea, which leads to an overestimation of the IOP. Thereis also a potential bias in phase 3 pharmacologic stud-ies, in which the effects of new compounds are often testedon patients with OHT, many of whom may actually benormal.

The correct diagnosis and management of patientswith glaucoma is dependent on an accurate determina-tion of IOP. Our study has shown that there is a poten-tial for patients with POAG who have thin corneas to begiven a misdiagnosis and treated inappropriately for NTG;

similarly, normal individuals with thick corneas may begiven a misdiagnosis and treated for OHT. We have shownthat central corneal pachymetry is important to ensureaccurate diagnosis and management of patients sus-pected of having some form of glaucoma. We suggest thatmeasurement of CCT should be part of the routineworkup of patients with glaucoma and those suspectedof having glaucoma.

Accepted for publication June 17, 1998.Reprints: Rene-Pierre Copt, MD, Jules Gonin Hospi-

tal, 15, ave de France, 1004 Lausanne, Switzerland(e-mail: [email protected]).

REFERENCES

1. Whitacre MM, Stein R. Sources of error with the Goldmann-type tonometers.Surv Ophthalmol. 1993;38:1-30.

2. Kruse Hansen F. A clinical study of the normal human central corneal thickness.Acta Ophthalmol (Copenh). 1971;49:82-89.

3. Kruse Hansen F, Ehlers N. Elevated tonometer readings caused by a thick cor-nea. Acta Ophthalmol (Copenh). 1971;49:775-778.

4. Johnson M, Kass MA, Moses R, Grodzki W. Increased corneal thickness simu-lating elevated intraocular pressure. Arch Ophthalmol. 1978;96:664-665.

5. Whitacre MM, Stein RA, Hassanein K. The effect of corneal thickness on appla-nation tonometry. Am J Ophthalmol. 1993;115:592-596.

6. Argus WA. Ocular hypertension and central corneal thickness. Ophthalmology.1995;102:1810-1812.

7. Chatterjee A, Shah S, Bessant DA, Naroo SA, Doyle SJ. Reduction in intraocularpressure after excimer laser photorefractive keratectomy. Ophthalmology. 1997;104:355-359.

8. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thick-ness. Acta Ophthalmol (Copenh). 1975;53:34-43.

9. Goldmann H, Schmidt T. Uber Applanationstonometrie. Ophthalmologica. 1957;134:221-242.

10. Shiose Y, Kitazawa Y, Tsukahara S. Epidemiology of glaucoma in Japan: a na-tionwide glaucoma survey. Jpn J Ophthalmol. 1991;35:133-155.

11. Pohjanpelto PEJ, Palva J. Ocular hypertension and glaucomatous optic nerve dam-age. Acta Ophthalmol (Copenh). 1962;69:1-5.

12. Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressureand primary open-angle glaucoma among white and black Americans. Arch Oph-thalmol. 1991;109:1090-1095.

Table 2. Comparison of IOP ReadingsWith and Without Treatment and TheirRespective Correction for Corneal Thickness*

NTG OHT POAG

IOP reading withoutglaucoma treatment

17.25 ± 1.93 27.13 ± 3.84 23.33 ± 7.10

Corrected IOP withoutglaucoma treatment

19.45 ± 2.42 24.83 ± 2.53 23.97 ± 6.90

IOP reading withglaucoma treatment

13.13 ± 3.32 22.22 ± 4.16 18.59 ± 8.90

Corrected IOP withglaucoma treatment

15.33 ± 2.01 19.92 ± 4.22 19.23 ± 7.54

*NTG indicates normal tension glaucoma; OHT, ocular hypertension;POAG, primary open-angle glaucoma; and IOP, intraocular pressure.Comparisons were made using the formula of Ehlers.8 Values are given asmean ± SD and measured in millimeters of mercury.

ARCHIVES Web Quiz

B e sure to visit the Archives of Ophthalmology’s World Wide Web site (http://www.ama-assn.org/ophth) and try yourhand at our new Clinical Challenge interactive quiz. We invite visitors to make a diagnosis based on selectedinformation from a case report or other feature scheduled to be published in the following month’s print edition of

the ARCHIVES. The first visitor to e-mail our Web editors with the first correct answer wins an Archives of OphthalmologyCD-ROM and will be recognized in the print journal and on our Web site. A full discussion of the case featured in the quizcan be found in the following month’s print edition of the journal.

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