Central corneal thickness determined with opticalcoherence tomography in various types ofglaucoma

Martin Bechmann, Martin J Thiel, Bernhard Roesen, Stephanie Ullrich, Michael W Ulbig,Klaus Ludwig

AbstractAims—To evaluate central corneal thick-ness determined by optical coherencetomography (OCT) in various types ofglaucoma, and its influence on intraocularpressure (IOP) measurement.Methods—Central corneal thickness(CCT) was determined by using OCT in167 subjects (167 eyes). 20 had primaryopen angle glaucoma (POAG), 42 had lowtension glaucoma (LTG), 22 had ocularhypertension (OHT), 10 had primaryangle closure glaucoma (AC), 24 hadpseudoexfoliation glaucoma (PEX), 13had pigmentary glaucoma (PIG), and 36were normal.Results—CCT was significantly higher inocular hypertensive subjects (593 (SD 35)µm, p <0.0001) than in the controls (530 (32)µm), whereas patients with LTG (482 (28)µm, p < 0.0001), PEX (493 (33) µm, p<0.0001), and POAG (512 (30) µm, p <0.05)showed significantly lower readings. Therewas no statistically significant diVerencebetween the controls and patients with PIG(510 (39) µm) and AC (539 (37) µm).Conclusions—Because of thinner CCT inpatients with LTG, PEX, and POAG thismay result in underestimation of IOP,whereas thicker corneas may lead to anoverestimation of IOP in subjects withOH. By determining CCT with OCT, anew and precise technique to measureCCT, this study emphasises the need for acombined measurement of IOP and CCTin order to obtain exact IOP readings.(Br J Ophthalmol 2000;84:1233–1237)

The measurement of intraocular pressure(IOP) using the Goldmann applanation tono-meter is an important factor in the diagnosisand follow up of glaucoma. It has been consid-ered the gold standard for IOP measurements,as it is less likely to be biased by variables suchas scleral rigidity, which can markedly aVectSchiötz tonometer readings.1 The impact ofcentral corneal thickness (CCT) on applana-tion tonometry was first discussed byGoldmann.2 He assumed that the resistance ofthe cornea to indentation was compensated bythe surface tension of the tear film. Thisassumption is only true for a central cornealthickness of 520 µm, otherwise the accuracy ofapplanation tonometry can be considerablyimpaired.

Recent studies have demonstrated an impactof CCT in diagnosing glaucoma. IncreasedCCT measurements were found in patientswith ocular hypertension, which can lead tofalsely elevated IOP readings, and decreasedCCT was found in patients with low tensionglaucoma, resulting in falsely reduced IOPmeasurements.3–8 In line with these results ithas been reported that refractive surgicalprocedures such as excimer photorefractivekeratectomy (PRK) and laser in situ keratomi-leusis (LASIK) tend to lower IOP readingsperformed with applanation tonometry, andthinning of the central cornea is believed to bethe cause.9 10 Apart from one series of eightpatients,3 all studies on CCT used ultrasoundpachymetry,4–9 as the tool of measurement. Inthe present study we used optical coherencetomography (OCT) to measure central cornealthickness in diVerent kinds of glaucoma. Thecapability of OCT to measure CCT has beendemonstrated recently.11 This technique allowsa two dimensional mapping of corneal thick-ness by using non-contact, non-invasive, crosssectional visualisation of the human cornea(Fig 1).

Subjects and methodsIn all, 131 eyes of 131 consecutive patientswith various types of glaucoma and 36 healthyvolunteers were examined at the glaucoma unitat the university eye hospital in Munich,Germany. All patients were given a thoroughophthalmic evaluation including best correctedvisual acuity, slit lamp examination, stereo-scopic disc evaluation using a 78 dioptre lens,Humphrey 30-2 statistic threshold perimetry,CCT measurement using OCT, Goldmannapplanation tonometry, and gonioscopy. Eyes

Figure 1 Cross sectional image of the human cornea gained by optical coherencetomography revealing epithelial layer and corneal stroma, allowing a two dimensionalmapping of corneal thickness.

Br J Ophthalmol 2000;84:1233–1237 1233

Department ofOphthalmology,Ludwig-Maximilians-University, Munich,GermanyM BechmannM J ThielB RoesenS UllrichM W UlbigK Ludwig

Correspondence to:Martin Bechmann,Universitäts Augenklinik,Mathildenstrasse 8, 80336München, Germanymbechman@ak-i.med.uni-muenchen.de

Accepted for publication16 May 2000

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with a history of former incisional surgery, cor-neal disease, diabetic retinopathy, injury, re-cent contact lens wear, or steroid use wereexcluded.

The study included six subgroups with vari-ous types of glaucoma and a control group ofnormals. In the primary open angle glaucomagroup (POAG) 20 patients were included.Inclusion criteria were: glaucomatous opticnerve damage, glaucomatous visual field de-fect, and IOP of 22 mm Hg or beyond and anopen anterior chamber angle in gonioscopy.

Low tension glaucoma (LTG) was definedas glaucomatous optic nerve damage, glauco-matous visual field defect, intraocular pressurewithout treatment of 21 mm Hg or below(recorded on a 24 hour diurnal pressure curveas well as in the total history). Forty twopatients were enrolled in this group.

IOP of 22 mm Hg or more in the presence ofa normal optic nerve head, normal visual field,and normal gonioscopy was classified aspresumed ocular hypertension. Twenty twopatients were included in the ocular hyperten-sive group (OHT).

Angle closure glaucoma (AC) was defined asIOP of 22 mm Hg or more on no treatment,optic nerve head damage, glaucomatous visualfield defect, and an open but narrow chamberangle (<30°) in gonioscopy, or a history ofangle closure glaucoma. Ten patients wereincluded in this group.

In the pseudoexfoliative (PEX) glaucomagroup 24 patients were enrolled on the basis ofthe following criteria: IOP above 21 mm Hgwithout treatment, glaucomatous visual fielddefect, optic nerve head damage, open anteriorchamber angle in gonioscopy, and the observa-tion of the characteristic whitish pseudoexfo-liation material on the surface of the anteriorlens capsule.

In the pigmentary glaucoma group 13patients with the following signs were included:endothelial pigmentation (Krukenberg’s spin-dle), iris transillumination defects, massiveaccumulation of pigment in the trabecularmeshwork, elevated IOP readings (>21 mmHg), and glaucomatous visual field defect andoptic nerve head damage. Measurement ofcentral corneal thickness was performed with acommercially available OCT device (Hum-phrey Instruments, Dublin, CA, USA), whichcan perform high resolution cross sectionalimaging in ocular tissues. Optical coherencetomography is analogous to ultrasonography,except for the use of optical rather than acous-tic waves. A superluminescence diode is usedas low coherence light source, emitting lightwith 20–25 nm band width centred at 830 nm.The time delay of reflected light is determinedusing coherence interferometry. The emittedlight is divided into a probe beam incident tothe ocular tissue and a reference beam incidenton a translating mirror. Both reflected beamsare recombined and distance information ofthe probe beam can be detected.12–14 Whenperforming the measurements, care was takento ensure that the probe beam that passedthrough the cornea bisected the pupil horizon-tally (Fig 2A). An average scan length of 6 mm

was used. Measurements were performed inthe centre of the horizontal section to ensurethe precise central position of the cornea. Thecorneal thickness was determined with thescan profile display of the system. The softwarecontrolled cursors were placed manually at thepeak of the reflectivity signal corresponding tothe anterior and posterior corneal surface (Fig2B). The corneal thickness was calculatedbetween the peaks of the reflectivity spikes.Three consecutive measurements were re-corded. As the OCT technique is a non-contact method, central corneal thicknessmeasurements were performed before appla-nation tonometry and gonioscopy.

Statistical data analysis was performed withSPSS for windows, version 8.0 (SPSS Inc,Chicago, IL, USA) using t tests, Mann-Whitney U tests, ÷2 tests with correction forsmall sample sizes, and unifactorial varianceanalysis (ANOVA). p Values smaller than 0.05were considered significant.

Informed consent was obtained from all par-ticipating patients and volunteers. Only oneeye of each patient or normal subject wasselected for statistical analysis to prevent bias.In bilaterally aVected patients, a randomchoice was made between the right and lefteyes.

ResultsComplete subject characteristics are given inTable 1. There was no statistically significantdiVerence among the seven subgroups for theexamined eye, and, except the pigmentaryglaucoma group with a significant myopic shift,

Figure 2 (A) The positioning of the OCT scan on thecornea is shown. The scan is bisecting the pupil, the scanlength is 6 mm. (B) One dimensional scan profile display ofthe centre of the cornea. Cursors are placed on the peaks ofreflectivity corresponding to the anterior (A) and posterior(P) corneal surface. The corneal thickness was calculatedbetween the peaks of the reflectivity spikes.

A

A

B

P

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for refractive error. There were more femalesubjects in the low tension glaucoma groupthan in the control group (p <0.01). In othergroups, there were also diVerences for distribu-tion of sex, although these diVerences did notreach statistical significance. Patients with pri-mary open angle glaucoma (68.4 (SD 9.6)years) and pseudoexfoliation glaucoma (68.3(7.5) years) were statistically significantly olderthan controls (51.5 (19.7) years), whereaspatients with ocular hypertension (30.3 (12.5)years) and pigmentary glaucoma (29.6 (14.1)years) were significantly younger. For patientswith low tension glaucoma (58.5 (13.1) years)and angle closure glaucoma (59.6 (13.3) years)no statistical significant diVerence from thecontrol group could be found.

CCT results are given in Table 2. MeanCCT of the ocular hypertensive group was sta-tistically significantly higher than in the pri-mary open angle (p <0.0001), or in the controlgroup (p <0.0001). The CCT (mean (SD)) ofthe OHT group was 593 (35 µm, whereasCCT of the POAG group was 512 (30) µm andof the normal controls 530 (32) µm. With amean CCT of 482 (28) µm the readings of thelow tension glaucoma group were statisticallysignificantly lower compared with the primaryopen angle glaucoma group (p <0.001), or thecontrol group (p <0.0001). There was also astatistically significant diVerence between theprimary open angle group and the controlgroup (p <0.05), with a mean CCT of thePOAG group being 18 µm lower comparedwith the control group.

In patients with pseudoexfoliation glaucomamean CCT (493 (33) µm) was statistically sig-nificantly lower than in the POAG (p <0.05)and the control group (p <0.0001). There wasno statistically significant diVerence betweenthe pigmentary glaucoma (510 (39) µm) andthe angle closure glaucoma group (539 (37)µm) and the POAG and the control group,respectively.

ANOVA analysis demonstrated a significantdiVerence between all groups (p <0.001).

DiscussionThe influence of central corneal thickness onthe accuracy of IOP measurements has longbeen recognised.3 15 Goldmann himself first

discussed the influence of CCT on applanationtonometry in his landmark article.2 A tono-meter tip is pressed against the cornea with avariable force until a circular area of 7.35 mm2

is flattened, so that a force of 10 g applied tothe tonometer tip is equal to an intraocularpressure of 10 mm Hg. The rigidity of the cor-nea opposes indentation, and he assumed thatthe surface tension force created by the tearfilm is drawing the tonometer tip to the oppo-site direction and will equal that rigid force.2 Asshown by Ehlers and associates,15 this assump-tion is only true for CCT of 520 µm, but ascorneal thickness varies widely over the popu-lation (from 478 µm to 626 µm in this presentstudy), this can cause an underestimation oroverestimation of intraocular pressure read-ings. By comparing intraocular hydrostaticpressure measured in the anterior chamber(open system) with applanation tonometerreadings in humans with diVerent centralcorneal thickness a positive correlation be-tween CCT and the error of applanationtonometry was found. For a true IOP of 20mm Hg an underestimation of 5.2 mm Hg isgiven by applanation tonometry with a CCT of450 µm, whereas a CCT of 590 µm leads to anoverestimation of IOP of 4.7 mm Hg. Ehlersand coworkers interpolated that deviation fromthe influence of CCT of 520 µm yields anunderestimation of IOP by applanation to-nometry of approximately 0.7 mm Hg per 10µm.15 Other studies confirmed the results pub-lished by Ehlers et al; however, the average cor-rection found was considerably lower.10 16–18

Whitacre et al found a correction of 0.18 to0.23 mm Hg per 10 µm in a direct cannulationstudy,16 and these results were very comparablewith the Rotterdam Study, in which aregression of 0.19 mm Hg per 10 µm could bedemonstrated.17 When comparing the influ-ence of CCT in IOP measurements before andafter LASIK, Emara et al found a correlation of0.32 mm Hg per 10 µm versus 0.27 mm Hgper 10 µm.10

The importance of central corneal thicknessin the discrimination between low tensionglaucoma, primary open angle glaucoma, andocular hypertension has been recognised byother investigators.3–8 In patients with low ten-sion glaucoma, main central corneal thickness

Table 1 Subject characteristics

POAG LTG OHT AC PEX PIG NORM

No of subjects 20 42 22 10 24 13 36Male 13 11 11 2 8 8 17Female 7 31 11 8 16 5 19p Value (÷2) 0.24 <0.01 1 0.11 0.16 0.58 0.87Mean age (SD) years 68.4 (9.6) 58.5 (13.1) 30.3 (12.5) 59.6 (13.3) 68.3 (7.5) 29.3 (14.1) 51.5 (19.7)p Value (Mann–Whitney U) 0.01 0.14 <0.001 0.19 <0.001 <0.01 —Mean (SD) refraction −0.2 (2.64) −0.34 (1.49) −0.33 (1.52) +0.8 (1.47) +0.32 (1.98) −2.75 (1.88) −0.33 (2.01)p Value (Mann–Whitney U) 0.59 0.27 0.583 0.11 0.1 <0.001 —

Table 2 Central corneal thickness (CCT) in various patients and controls

POAG LTG OHT AC PEX PIG NORM

Mean (SD) CCT (µm) 512 (30) 482 (28) 593 (35) 539 (37) 493 (33) 510 (39) 530 (32)p Value (t test, compared with norm) <0.05 <0.0001 <0.0001 0.52 <0.0001 0.10 —p Value (t test, compared with POAG) — <0.001 <0.0001 0.06 <0.05 0.82 <0.05Range CCT (µm) 457–563 423–563 532–653 488–551 449–557 463–583 478–62695% CI (µm) 498–526 473–491 577–609 512–565 479–507 485–533 519–541

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was markedly reduced, leading to an underesti-mation of IOP measurements. By contrast, inpatients with ocular hypertension, highercentral corneal thickness values were obtained,causing an overestimation of IOP readingsgained with a standard Goldmann applanationtonometer. In conclusion, the true IOP in lowtension glaucoma may not be as low aspreviously assumed, whereas the true IOP inocular hypertension may be within the normalrange, after taking central corneal thicknessand its sources of error into account. In 1971Hansen and Ehlers reported on eight patientswith elevated IOP measurements refractive toantiglaucoma treatment. In all eight patients,the central corneal thickness was markedlyincreased.3 Johnson and coworkers published acase of an 17 year old girl who had IOP meas-urements between 30 and 40 mm Hg withoutglaucomatous optic disc changes.19 After show-ing no response to antiglaucomatous therapy,the anterior chamber was cannulated for directIOP measurement. The IOP measured in thisopen system was found to be 11 mm Hg. Thefalsely elevated readings were caused byextremely thick corneas measuring 900 µm inboth eyes without corneal oedema. In a seriesof 129 patients with low tension glaucoma, pri-mary open angle glaucoma, and ocular hyper-tension Herndorn reported on a case with ahistory of laser trabeculoplasty referred for fis-tulating surgery for elevated IOP alone.5 TheCCT of this patient was beyond 600 µm inboth eyes, so the patient was advised to cancelsurgery and discontinue glaucoma medica-tions. A further study including 115 glaucomapatients recently found that after taking centralcorneal thickness into account 31% of thepatients thought to have low tension glaucomaactually met the criteria for primary open angleglaucoma after correcting the applanationtonometer readings.4 In addition, 56% of thepatients with the original diagnosis of ocularhypertension in fact had normal values of cor-rected intraocular pressure. This phenomenoncould explain why only a minority of patientswith OHT develop visual field loss.20

Our findings are in line with these results.The CCT values measured by optical coher-ence tomography reported in this study areconsistent with the findings of earlier studiesusing ultrasonic pachymetry. We have foundthat CCT is increased in eyes with ocularhypertension and decreased in eyes with lowtension glaucoma when compared with normaleyes and eyes with primary open angleglaucoma. When comparing CCT of patientswith primary open angle glaucoma withnormal controls, CCT of the POAG group wassignificantly lower. Although this has beenreported by other investigators,4–8 this diVer-ence did not reach statistical significance. Themean diVerence between the two groups was18 µm, compared with approximately 9 µmdescribed by other investigators.4–8 We alsofound a statistically significant reduction ofCCT in pseudoexfoliation glaucoma, bothwhen compared with POAG patients and withthe control group. To the best of our knowl-edge, this has never been demonstrated before.

Reports in the literature regarding CCT inpseudoexfoliation glaucoma are controversial.A former study found higher CCT values forpseudoexfoliation glaucoma, although this dif-ference did not reach statistical significance.21

Herndon and coworkers reported almost iden-tical values of CCT for pseudoexfoliation glau-coma and POAG, with the PEX glaucomapatients being a subset of the POAG group.5

The reason for the significant reduction ofCCT in PEX glaucoma in this study remainsunclear and requires further investigation. Inpigmentary glaucoma as well as in primaryangle closure glaucoma no statistically signifi-cant diVerence could be found between thePOAG group and the control group, respec-tively.

Except for one study using opticalpachymetry,3 all reports cited in this articlewere performed with ultrasonic pachymetry,4–9

which is believed to be more reliable than opti-cal pachymetry. Although ultrasonic pachy-metry is a widely spread, reliable technique tomeasure corneal thickness, some problemsremain. When performing an examination aprobe tip has to be placed straight on the cen-tre of the cornea. As corneal thicknessincreases peripherally, lateral displacement ofthe probe may cause elevated readings as wellas shift of the probe out of the perpendicular.To avoid this problem, Bron and coworkersperformed 10 measurements in the centre ofthe cornea, but selected only the three lowestreadings.8 Other investigators did not measurein the exact centre of the cornea. The probe tipwas placed 1.5 mm temporal to the cornealight reflex.6 Furthermore, it is diYcult to con-trol the patients gaze during repeated measure-ments, so that the placement of the probe isdiYcult to reproduce. Furthermore, the exactpoints of sound reflection in ultrasonic pa-chymetry are ill defined22 and the applanationforce may disturb the anterior reflectingsurface by pushing away the precorneal tearfilm23 and by the thinning of the epithelium.22

None of these problems exists with thedescribed OCT technique. OCT is a non-invasive, non-contact, monitor controlledmethod of excellent reproducibility, with themonitor based magnification allowing precisepositioning of the probe beam in the centre ofthe cornea. Accordingly, OCT results cannotbe biased by incorrect placement of a probe. Itspossible application for CCT measurementshas recently been demonstrated in a compari-son between ultrasonic and OCT pachymetryin normal and oedematous human corneas.11

By using the OCT technique to measure CCTin diVerent kinds of glaucoma, we demonstratethe influence of corneal thickness on glau-coma, independently from the pachymetrictechnique previously used. We believe thatOCT is an excellent method of measuringCCT, and it is much more independent frombias compared with ultrasonic pachymetry.

In conclusion, although the results of thepresent study are not entirely new, it seemsimportant to confirm the results of previousstudies by using OCT, a new, precise techniqueto measure CCT. As OCT allows an exact

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measurement of CCT without the multiplesources of bias known from ultrasonic pachy-metry, this study confirms the hypothesis thatcorneal thickness plays an important part inthe diagnosis and understanding of varioustypes of glaucoma. It emphasises the need for acombined measurement of IOP and CCT inorder to be able to classify the diVerent types ofglaucoma.

The authors do not have any commercial or proprietary interestin any of the products mentioned in this article.

The authors thank Aljoscha S Neubauer for his statisticaladvice.

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doi: 10.1136/bjo.84.11.1233 2000 84: 1233-1237Br J Ophthalmol

 Martin Bechmann, Martin J Thiel, Bernhard Roesen, et al. types of glaucomaoptical coherence tomography in various Central corneal thickness determined with

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