corneal thickness measurements in normal and keratoconic eyes: pentacam comprehensive eye scanner...

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Corneal thickness measurements in normal and keratoconic eyes: Pentacam comprehensive eye scanner versus noncontact specular microscopy and ultrasound pachymetry O ¨ mu ¨rO ¨ zlenen Uc ¸akhan, MD, Muhip O ¨ zkan, PhD, Ayfer Kanpolat, MD PURPOSE: To compare central corneal thickness (CCT) measurements taken with the Pentacam com- prehensive eye scanner (CES), noncontact specular microscopy (SM), and ultrasound pachymetry (UP) in normal and keratoconic corneas. SETTING: Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey. METHODS: In a prospective study, 3 CCT measurements were taken with the Pentacam CES, SM, and UP in that sequence from 1 eye of 45 consecutive patients with myopia (group A) and 62 consecutive patients with keratoconus (group B). Eyes with keratoconus were further divided into 3 subgroups, mild, moderate, and severe, according to the mean keratometry readings. RESULTS: Pentacam CES (r Z 0.994) and UP (r Z 0.993) demonstrated very high and comparable re- producibility in group A. In group B, Pentacam CES displayed better reproducibility (r Z 0.988) than UP (r Z 0.969) and SM (r Z 0.901). The mean CCT measurements of Pentacam CES and UP were not sig- nificantly different in group A (P Z .37) and in eyes with mild keratoconus (P Z .29), whereas signif- icant differences between all instrument pairs were evident in group B and in moderate and severely keratoconic eyes (P<.05). Noncontact SM measurements were significantly smaller than those of Pen- tacam CES and UP in all groups (P<.05) when a measurement could be obtained. There were significant linear correlations between CCT measurements of Pentacam CES, UP, and noncontact SM in groups A, B, and mildly keratoconic eyes (P<.001). CONCLUSIONS: Results suggest that whereas Pentacam CES and UP may be used interchangeably in normal eyes in the clinical setting for the measurement of CCT, one should be cautious interpreting corneal thickness data from Pentacam CES, UP, and particularly SM in eyes with keratoconus. Whereas, in normal and mildly keratoconic eyes, Pentacam CES and UP demonstrated very high and comparable reproducibility, in moderately keratoconic eyes, Pentacam CES readings showed better reproducibility than UP. J Cataract Refract Surg 2006; 32:970–977 Q 2006 ASCRS and ESCRS Accurate measurement of the corneal thickness is of paramount importance for monitoring ectatic dystrophies such as keratoconus, contact-lens-related complications, accurate determination of intraocular pressure, and preoperative assessment and planning and follow-up of all corneal refractive procedures both in normal and in kerato- conic eyes. The various techniques to measure central corneal thickness (CCT) include optical pachymetry, 1 contact and noncontact specular microscopy (SM), 2,3 dual-beam partial coherence interferometry (PCI), 4,5 optical coherence tomography (OCT), 6 slit-scanning corneal topography (Orbscan, Orbtek, Inc.), 7–12 confocal microscopy, 13 ultrasound biomicroscopy (UBM), 14,15 and ultrasound pachymetry (UP). 1–3,5–9,11,12,16 Among these, the most commonly used methods in clinical practice are the UP and noncontact SM. Ultrasound pachymetry is an efficient and accurate way to measure cor- neal thickness with the advantages of ease of use, portabil- ity, and low cost. However, limitations of this system include measurements requiring corneal contact and there- fore topical anesthesia, possible incorrect and unrepeatable probe placement, lack of a fixation light for gaze control, ill-defined points of reflection of ultrasound within the cor- nea, and the variability of sound speed in wet and dry Q 2006 ASCRS and ESCRS Published by Elsevier Inc. 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.02.037 970 J CATARACT REFRACT SURG - VOL 32, JUNE 2006

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J CATARACT REFRACT SURG - VOL 32, JUNE 2006

Corneal thickness measurements in normal

and keratoconic eyes: Pentacam comprehensive

eye scanner versus noncontact specular

microscopy and ultrasound pachymetry

Omur Ozlenen Ucakhan, MD, Muhip Ozkan, PhD, Ayfer Kanpolat, MD

PURPOSE: To compare central corneal thickness (CCT) measurements taken with the Pentacam com-prehensive eye scanner (CES), noncontact specular microscopy (SM), and ultrasound pachymetry (UP)in normal and keratoconic corneas.

SETTING: Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey.

METHODS: In a prospective study, 3 CCT measurements were taken with the Pentacam CES, SM,and UP in that sequence from 1 eye of 45 consecutive patients with myopia (group A) and 62consecutive patients with keratoconus (group B). Eyes with keratoconus were further divided into3 subgroups, mild, moderate, and severe, according to the mean keratometry readings.

RESULTS: Pentacam CES (r Z 0.994) and UP (r Z 0.993) demonstrated very high and comparable re-producibility in group A. In group B, Pentacam CES displayed better reproducibility (r Z 0.988) than UP(r Z 0.969) and SM (r Z 0.901). The mean CCT measurements of Pentacam CES and UP were not sig-nificantly different in group A (P Z .37) and in eyes with mild keratoconus (P Z .29), whereas signif-icant differences between all instrument pairs were evident in group B and in moderate and severelykeratoconic eyes (P<.05). Noncontact SM measurements were significantly smaller than those of Pen-tacam CES and UP in all groups (P<.05) when a measurement could be obtained. There were significantlinear correlations between CCT measurements of Pentacam CES, UP, and noncontact SM in groups A, B,and mildly keratoconic eyes (P<.001).

CONCLUSIONS: Results suggest that whereas Pentacam CES and UP may be used interchangeably innormal eyes in the clinical setting for the measurement of CCT, one should be cautious interpretingcorneal thickness data from Pentacam CES, UP, and particularly SM in eyes with keratoconus. Whereas,in normal and mildly keratoconic eyes, Pentacam CES and UP demonstrated very high and comparablereproducibility, in moderately keratoconic eyes, Pentacam CES readings showed better reproducibilitythan UP.

J Cataract Refract Surg 2006; 32:970–977 Q 2006 ASCRS and ESCRS

Accurate measurement of the corneal thickness is of

paramount importance for monitoring ectatic dystrophies

such as keratoconus, contact-lens-related complications,

accurate determination of intraocular pressure, and

preoperative assessment and planning and follow-up of all

corneal refractive procedures both in normal and in kerato-

conic eyes. The various techniques to measure centralcorneal thickness (CCT) include optical pachymetry,1

contact and noncontact specular microscopy (SM),2,3

dual-beam partial coherence interferometry (PCI),4,5

optical coherence tomography (OCT),6 slit-scanning

corneal topography (Orbscan, Orbtek, Inc.),7–12 confocal

Q 2006 ASCRS and ESCRS

Published by Elsevier Inc.

970

microscopy,13 ultrasound biomicroscopy (UBM),14,15 and

ultrasound pachymetry (UP).1–3,5–9,11,12,16

Among these, the most commonly used methods in

clinical practice are the UP and noncontact SM. Ultrasound

pachymetry is an efficient and accurate way to measure cor-

neal thickness with the advantages of ease of use, portabil-

ity, and low cost. However, limitations of this systeminclude measurements requiring corneal contact and there-

fore topical anesthesia, possible incorrect and unrepeatable

probe placement, lack of a fixation light for gaze control,

ill-defined points of reflection of ultrasound within the cor-

nea, and the variability of sound speed in wet and dry

0886-3350/06/$-see front matterdoi:10.1016/j.jcrs.2006.02.037

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

tissues.6,12,16 As such, reproducibility of the UP measure-

ments are subject to observer bias from probe placement,

which therefore may require some degree of experience,

and the measurements may be adversely influenced by

changes in tissue hydration.5,11,16,17

Whereas UP measurements depend on the reflection ofsound, SM measurements depend on the reflection of light

waves from the anterior and posterior corneal surfaces.

Contact or noncontact specular microscopes are optical in-

struments that provide pachymetric measurements and SM

simultaneously.2,3,8 The advantages of this method include

operator independency and noninvasiveness.2,3,8 However,

because of its operating principle, SM requires clear reflec-

tions of the epithelial and endothelial surfaces to obtainreliable thickness measurements. As such, its clinical use

is limited to corneas that are free of edema, scarring,

deposits, or opacities that may distort light transmission.

However, the advantages include operator independency

and noninvasiveness.15

The Pentacam CES (Oculus, Inc.) instrument uses a

rotating Scheimpflug camera system that provides

3-dimensional scanning of the whole anterior segment ofthe eye. From the images acquired, information regarding

the anterior and posterior corneal topography, corneal

pachymetry, anterior chamber depth, and angle and lens

density can be measured quickly and noninvasively.

This prospective study was performed to compare CCT

measurements obtained using the new Pentacam CES with

measurements obtained using noncontact SM and UP in

normal and keratoconic corneas.

PATIENTS AND METHODS

Forty-five consecutive healthy patients with mild myopia(manifest refraction spherical equivalent of at most �6.00 diop-ters [D], with a cylinder of at most 1.00 D) and 62 consecutivepatients previously diagnosed keratoconus were included in thisprospective study. After a routine eye examination includingvisual acuity, manifest refraction, slitlamp examination, andophthalmoscopy, informed consent was obtained from all patientsbefore entry into the study.

Accepted for publication September 16, 2005.

From the Department of Ophthalmology (Ucakhan, Kanpolat) An-kara University School of Medicine, and the Department of Biom-etry and Genetic Animal Husbandry (Ozkan), University of Ankara,Ankara, Turkey.

Presented in part as a poster at the XXIInd Congress of theEuropean Society Cataract & Refractive Surgeons, Paris, France,September 2004.

No author has a financial or proprietary interest in any material ormethod mentioned.

Reprint requests to Omur O. Ucakhan, MD, Cinnah Caddesi 9/7,Cankaya 06680, Ankara, Turkey. E-mail: [email protected].

J CATARACT REFRACT SURG

An eye was diagnosed as having keratoconus if there werescissoring reflex on retinoscopy and central or paracentral steep-ening of the cornea on computerized topography with at least 1 ofthe following slitlamp findings of keratoconus: central or paracen-tral thinning, anterior bulging or conicity, hemosiderin deposition(Fleischer’s ring), stromal striae (Vogt’s striae), Descemet’s breaks,apical scars, and subepithelial fibrosis. According to the meankeratometry (K) readings obtained from computerized topogra-phy, eyes with keratoconus were subgrouped as mild (K!47 D),moderate (47!K!55), or severe (KO55).

Any eye with other ocular pathology or patients who had everused contact lenses were excluded from the study, as were kerato-conic eyes with extensive scarring.

Central corneal thickness measurements were performedusing Pentacam CES noncontact SP-2000P specular microscope(Topcon Corp.) and Micropach 200P ultrasound pachymetry (So-nomed, Inc.) by the same experienced investigator (O.O.U.) ineach eye in that order. All examinations took place on the sameday with a 5-minute to 10-minute interval between the measure-ments of successive instruments.

For Pentacam CES examination, the patient sat on a chair,placing the chin on the chin rest and slightly pressing the foreheadinto the headband. The patients were asked to open both eyes andlook into the black spot in the middle of the blue fixation beam ofthe instrument. Meanwhile, the investigator observed the image ofthe eye on the monitor and brought the image into focus and cen-tralized it within the aiming circle on the monitor. When in focus,the instrument took the measurement automatically. The Penta-cam CES system is based on a 180-degree rotating computer-aidedScheimpflug camera that generates reconstructions of the anteriorsegment from 12 to 50 single captures, depending on the investi-gator’s preference. In this study, 25 single captures were chosen foreach eye. Each measurement took about half a minute, and withthe patient asked to relax and blink for a few minutes betweenthe examinations, 3 successive measurements of each eye of allpatients were obtained.

With the SM, the patient was seated with the chin on the chinrest and slightly pressing the forehead into the headband andwas asked to look into the built-in fixation target. The head posi-tion was adjusted so that the image of the pupil on the monitorwas in clear focus and within the aiming circle visible on the mon-itor. In this study, measurements were taken in the automaticmode of the instrument. At proper alignment and focus, the in-strument took both SM and corneal thickness measurements. Be-tween successive measurements, the patient was asked to relaxand blink a few times. Three measurements that could be obtainedwhile the double corneal light reflections were central on themonitor, providing clear endothelial images, were obtained fromeach eye.

Ultrasound pachymetry was used last since it is a contactmethod. Before the measurement, each cornea was anesthetizedwith 1 drop of proparacaine hydrochloride 0.5%. The patientwas seated and asked to look at a distant fixation target straightahead while the ultrasound probe was aligned perpendicular tothe center of the cornea. Three successive measurements sepa-rated by few blinks were obtained from each eye of all patients.

Statistical Analysis

For statistical analysis, 1 eye of each patient in each groupwas chosen according to a randomization table.

To determine the intraobserver reproducibility of measure-ments for the 3 instruments, intraclass correlation coefficients

- VOL 32, JUNE 2006 971

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

with 95% confidence intervals (CIs) for the 3 repeated measure-ments obtained using each instrument were calculated in eachgroup. The difference between the repeatability of 2 instrumentswas regarded to be significant whenever the 95% CI limits ofthe 2 sets of measurements were not coinciding.

Comparison of the mean CCT values for the 3 instrumentswas conducted by repeated-measures analysis of variance(ANOVA). Pairwise differences were determined using the posthoc test of Duncan. Linear regression was used to quantify thecorrelation between 2 methods and to extract a valid equationfor deriving accurate values of CCT from the Pentacam CES.

RESULTS

The mean age was 26.6 years G 9.9 (SD) (range 13 to

58 years) in normal patients (group A) and 26.2 G 9.0years (range 13 to 52 years) in patients with keratoconus

(group B). There were no statistically significant differences

in age between the study groups (Student t test, PO.05). In

group A, the mean manifest refraction spherical equivalent

(MRSE) was �3.3 G 1.6 diopters (D) (range �0.25 to

�6.00 D) (Figure 1). In this group, no correlations could

be detected between the MRSE and the CCT measurements

taken by the Pentacam CES (r Z �0.065, P Z .670), UP(r Z �0.05, P Z .749), or SM (r Z �0.047, P Z .761).

In the keratoconus group, 19 eyes (19 patients, 30%) had

mild, 28 eyes (28 patients, 45%) had moderate, and 15

eyes (15 patients, 25%) had severe keratoconus.

The mean keratometry measurement obtained using

the Pentacam CES was 43.2 G 1.4 D in group A and 52.4

G 8.8 D in group B, and these measurements were statisti-

cally significantly different (P!.001, 2-sample t test).Whereas, CCT measurements could be obtained by

Pentacam CES and UP in all eyes enrolled in the study,

SM failed to make any measurements in 12 eyes (12 of

Histogram

-07 -06 -05 -04 -03 -02 -01 00Manifest Refraction

0

1

2

3

4

5

6

7

8

9

Freq

uenc

ies

Figure 1. Histogram showing the manifest refraction spherical equivalent

of patient eyes in group A (n Z 45).

J CATARACT REFRACT SURG972

18, 42.9%) with moderate and all eyes (15 of 15, 100%)

with severe keratoconus, making a total of 43.5% of the

eyes with keratoconus.

Reproducibility of Measurements

Reproducibility of test results in groups A and B are

summarized in Table 1. Accordingly, Pentacam CES andUP demonstrated very high and comparable reproducibil-

ity in normal eyes (group A). Although within acceptable

limits, reproducibility of SM was lower than Pentacam

CES and UP in these eyes.

In group B and in eyes with moderate keratoconus,

Pentacam CES displayed better reproducibility than UP

and SM (SM failed to take any measurements in 42.9% of

eyes with moderate keratoconus). In eyes with mild andsevere keratoconus, reproducibility of Pentacam CES and

UP was very high and comparable (SM failed to take any

measurements in 100% of patient eyes with severe

keratoconus).

Comparisons of the Mean CCT Measurements

The mean CCT measurements obtained by the 3

methods in all groups and subgroups are shown in Table 2

and plotted in Figure 2. There were significant variations

in the CCT measurements obtained using the 3 methodsin both normal and keratoconic eyes (P!.001, repeated-

measures ANOVA in both groups).

Table 3 shows the statistical differences (P values) be-

tween the mean CCT values measured with the 3 instru-

ments. The CCT measurements obtained using the

Pentacam CES and UP were not statistically significantly

different in normal eyes (P Z .37, Duncan test) and in

eyes with mild keratoconus (P Z .29, Duncan test). How-ever, statistically significant differences between the CCT

measurements taken with the 2 instruments were evident

in group B as a whole and when moderate and severely ker-

atoconic eyes were evaluated separately.

The measurements of noncontact SM were statistically

significantly smaller than those of Pentacam CES and UP in

both groups A and B and in the mild keratoconus subgroup.

No comparisons could be made for the severe keratoconussubgroup because no SM measurements could be obtained

in these eyes. In eyes with moderate keratoconus, although

SM seemed to measure the CCT significantly smaller than

the other 2 instruments, SM measurements could not be

obtained in 42.9% of the eyes.

Table 4 summarizes the differences in the CCT

measurements among the 3 instruments in each group.

The mean difference between the Pentacam CES and UPwas 2.7 mm (95% CI, �3.4 to 8.9) in normal eyes and

�11.2 mm (95% CI, �18.4 to �4.0) in keratoconic eyes.

Therefore, whereas in normal eyes, Pentacam CES tended

- VOL 32, JUNE 2006

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

Table 1. Correlation coefficients for reproducibility of measurements of Pentacam CES, UP, and SM in the study groups.

Intraclass correlation coefficient (95% CI)

Group Pentacam CES UP SM

Normal 0.994 (0.991-0.997) 0.993 (0.989-0.996) 0.968 (0.936-0.985)Keratoconus 0.988 (0.981-0.992) 0.969 (0.953-0.981) 0.901 (0.835-0.944)Mild KC 0.989 (0.982-0.991) 0.982 (0.962-0.993) 0.969 (0.933-0.987)Moderate KC 0.998 (0.978-0.994) 0.908 (0.837-0.953) 0.798 (0.618-0.911)Severe KC 0.982 (0.945-0.996) 0.988 (0.970-0.996) Not available

CI Z confidence interval; KC Z keratoconus

to measure CCT thicker than UP, in eyes with keratoconus,

particularly in eyes with moderate and severe keratoconus,

it measured CCT thinner than UP.

In normal eyes, the greatest mean difference was found

between SM and Pentacam CES measurements, 21.9 mm

(95% CI, 15.9 to 27.9). The mean difference between UP

and SM was 19.4 mm (95% CI, 12.7 to 29.1). In keratoconic

eyes, the greatest mean difference was found between SMand UP, 18.8 mm (95% CI, 14.3 to 23.2). In this group

and in eyes with mild to moderate keratoconus, the mean

differences between CCT measurements of Pentacam CES

and SM were lower than those between UP and SM because

in these eyes, the mean CCT measurements obtained by

Pentacam CES were thinner than those obtained by UP.

A 2-tailed paired sample test confirmed that of all

instrument pairs, only the differences between PentacamCES and UP measurements in normal and mildly kera-

toconic eyes were statistically not significantly different

(P Z .360 and P Z .337, respectively).

Agreements Between the Pachymetry Methods

Table 5 shows the correlation coefficients (r values)

representing the agreements between CCT measurements

of Pentacam CES, UP, and SM in the study groups. In nor-

mal eyes and in keratoconus groups, there were significantlinear correlations among Pentacam CES, UP, and noncon-

tact SM whenever a comparison could be made (for all in-

strument pairs, P!.001) (Figures 3 to 5).

Table 2. The mean CCT measurements obtained by the 3 instruments in

all groups and subgroups.

Mean G SD (mm)

Group Pentacam CES UP SM

Normal 557.6 G 6.5 554.9 G 7.4 535.5 G 6.5Keratoconus 456.3 G 8.7 462.5 G 8.0 444.5 G 8.0Mild KC 478.6 G 10.5 481.9 G 10.3 464.8 G 10.2Moderate KC 433.7 G 14.7 444.2 G 11.4 426.9 G 11.4Severe KC 358.2 G 19.2 385.2 G 14.7 NA

KC Z keratoconus; NA Z not available

J CATARACT REFRACT SURG

In normal eyes (group A), particularly Pentacam CES

and UP measurements showed highly significant correla-

tions with a standardized regression coefficient (r) of

0.949 (P!.001). Linear regression analysis yielded the

following correlation: CCTPentacam Z 45.8 C 0.921 �CCTUltrasound.

In normal eyes, regression correlations for Pentacam

CES and SM measurements (r Z 0.891, P!.001) were:CCTPentacam Z 79.4 C 0.893 � CCTSM, and for UP and

SM measurements (r Z 0.901, P!.001) were: CCTUP Z2.7 C 1.03 � CCTSM.

In group B, again, there was very good correlation

between the CCT measurements taken by the Pentacam

CES and UP (r Z 0.923, P!.001), and linear regression

analysis yielded the following correlation: CCTPentacam Z�69.3 C 1.13 � CCTUltrasound. In the keratoconussubgroups, the correlation between the CCT measurements

taken by the Pentacam CES and UP was again highly

10152422 1321153921 1321153922N =

Severe

KC

Modera

te KC

Mild KC

Keratoc

onus

Normal

580560540520500480460440420400380360340320300

Pentacam CES

UP

SM

Figure 2. The mean and standard deviations of CCT measurements taken

using the Pentacam CES, UP, or SM in normal eyes, keratoconic eyes, and

eyes with mild, moderate, and severe keratoconus.

- VOL 32, JUNE 2006 973

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

significant (r Z 0.945, P!.001) in mildly keratoconic eyes

(CCTPentacam Z 18.1 C 0.955 � CCTUltrasound). Although

the correlation between the instruments somewhat

decreased as the severity of keratoconus increased, itremained considerably good such that the correlation

coefficient (r) was 0.886 (P!.001, CCTPentacam Z �57.7

C 1.11 � CCTUltrasound) in moderately keratoconic eyes

and was 0.828 (P!.001, CCTPentacam Z �57.9 C 1.08 �CCTUltrasound) in severely keratoconic eyes.

In group B, SM could take measurements from all eyes

only in the mild keratoconus subgroup. In this subgroup,

regression correlations for Pentacam CES and SMmeasurements (r Z 0.948, P!.001) were CCTPentacam Z27.2 C 0.971 � CCTSM, and for UP and SM measure-

ments (r Z 0.967, P!.001) were: CCTUP Z 26.6 C0.980 � CCTSM. In this subgroup, SM measurements

were strongly correlated to Pentacam CES and UP

measurements.

The study sought to determine whether the CCT mea-

surements obtained using the 3 instruments were influ-enced by the keratometry measurements taken by the

Pentacam CES. No significant correlation was found

between flat, steep, or mean K-readings and the CCT mea-

surements taken with the Pentacam CES or UP in normal

eyes (PO.05, ANOVA). However, in keratoconic eyes, there

were significant correlations between the CCT measure-

ments obtained using the Pentacam CES and UP and the

flat, steep, and mean K measurements. Accordingly, the

Table 3. Statistical differences (P values, Duncan test) between mean CCT

measured by Pentacam CES, UP, and SM in the study groups.

GroupPentacam

vs UPPentacam

vs SM UP vs SM

Normal .37 !.001* !.001*Keratoconus .047* !.001* !.001*Mild KC .29 !.001* !.001*Moderate KC .049* !.001* !.001*Severe KC .025* NA NA

KC Z keratoconus; NA Z not available

*Difference is statistically significant (P!.05)

J CATARACT REFRACT SURG974

CCT tended to decrease as the flat, steep, and mean

K-readings increased (P!.001 for all correlations, ANOVA).

While this is an expected finding for keratoconic eyes,

such correlation could not be demonstrated for the

astigmatism measurements and the CCT measurements

of any instrument (PO.05).

DISCUSSION

In this study, we compared CCT measurements ob-

tained using Pentacam CES, UP, and SM. Of special concern

was to show how Pentacam CES measurements taken from

normal and keratoconic eyes compared to those from the 2

most commonly used pachymetry methods in clinical prac-tice, UP and SM. Although numerous studies have been

performed to compare different pachymetry methods, to

our knowledge, this is the first study evaluating the pachy-

metry measurements of Pentacam CES in either normal or

keratoconic eyes.

Since a single investigator made all the measurements,

the variability of values in repeated measurements of the

same eye represented intraobserver reproducibility. Inthis study, in normal eyes, reproducibility of all 3 instru-

ments was quite high. Particularly, Pentacam CES and UP

demonstrated very high and comparable reproducibility.

Although within acceptable limits, reproducibility of SM

was lower than both Pentacam CES and UP in these eyes.

Although always considered to be within acceptable

limits, in previous studies, the reproducibility data of UP

have been reported to be worse than PCI5; comparableto,10,12 worse,5,18,19 or better7 than Orbscan; and compara-

ble to that of OCT6 and UBM.15 There have been highly

variable previous reports of intraobserver variability

comparing UP to SM as well, apparently depending on

the criteria of different investigators for accepting a particu-

lar measurement and on the model of the instrument

used.2,5,6,12,15

In eyes with keratoconus, we are not aware of any re-port of reproducibility of CCT measurements using any pa-

chymetry method in the literature. In our study, Pentacam

CES and UP displayed fairly good reproducibility in all

Table 4. Mean differences between CCT measurements obtained by the instruments in the study groups.

Mean G SD (mm) (95% CI)

Group Pentacam vs UP Pentacam vs SM UP vs SM

Normal 2.7 G 13.5 (�3.4 to 8.9) 21.9 G 13.6 (15.9 to 27.9) 19.4 G 14.7 (12.7 to 2.1)Keratoconus �11.2 G 28.4 (�18.4 to 4.0) 12.7 G 20.1 (6.1 to 19.3) 18.8 G 13.6 (14.3 to 23.2)Mild KC �3.4 G 15.1 (�10.7 to 3.9) 13.8 G 14.6 (6.8 to 20.9) 17.2 G 11.6 (11.6 to 22.8)Moderate KC �8.1 G 23.7 (�17.3 to 1.1) 6.8 G 23.2 (�5.5 to 19.2) 17.4 G 14.4 (9.7 to 25.0)Severe KC �27.0 G 41.9 (�50.3 to 3.8) NA NA

CI Z confidence interval; KC Z keratoconus; NA Z not available

- VOL 32, JUNE 2006

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

keratoconus subgroups, including eyes with severe kerato-

conus. Particularly, in group B as a whole and in eyes with

moderate keratoconus, Pentacam CES displayed better re-producibility than UP and SM. Once again, SM failed to

take any measurements in 42.9% of eyes with moderate

and 100% of eyes with severe keratoconus.

In normal eyes (group A), Pentacam CES and UP mea-

surements particularly showed highly significant correla-

tions with a standardized regression coefficient (r) of 0.

(P!.001). In these eyes, the Pentacam CES system pro-

vided a mean CCT value (557.6 G 6.5 mm) that was notsignificantly different from the value obtained by UP

(554.9 G 7.4 mm). Overall, in these eyes, Pentacam CES

tended to measure CCT mildly thicker than UP (2.7 G13.5 mm [95% CI, �3.4 to 8.9 ml]). Linear regression anal-

ysis yielded the following correlation: CCTPentacam Z 45.8

C 0.921 � CCTUltrasound.

While Pentacam CES is a noncontact instrument with

an optical operating principle, UP is a contact instrumentthat depends on propogation of sound waves through

Pentacam700600500400300200100

UP

700

600

500

400

300

Keratoconus

Normal

Figure 3. Scatterplot of CCT measurements in normal and keratoconic

eyes taken using the Pentacam CES and UP.

Table 5. Correlation coefficients (r values) representing the agreement

among CCT measurements of Pentacam CES, UP, and SM in the study

groups (for all instrument pairs, P!.001).

GroupPentacam

vs UPPentacam

vs SM UP vs SM

Normal 0.949 0.891 0.901Keratoconus 0.923 0.932 0.958Mild KC 0.945 0.948 0.967Moderate KC 0.886 0.932 0.950Severe KC 0.828 NA NA

KC Z keratoconus; NA Z not available

J CATARACT REFRACT SUR

corneal tissue. As such, minor differences may be expected

between the measurements taken with these 2 instruments.In UP, the exact posterior corneal reflection point of sound

waves is unknown but is supposed to be located between

Descemet’s membrane and the anterior chamber. It has

also been proven that the ultrasound probe can displace

the 7 to 40 mm thick tear film and compression may thin

the epithelium,15,20 thus resulting in slightly thinner CCT

measurements. In our study, although UP measurements

were slightly thinner as proposed, the difference was notsignificant and Pentacam CES and UP measurements

were found to be in strong agreement with each other.

In this study, in normal eyes, although significant lin-

ear correlations existed between SM and Pentacam CES

Pentacam700600500400300

SM

700

600

500

400

300

Keratoconus

Normal

Figure 4. Scatterplot of CCT measurements in normal and keratoconic

eyes taken using the Pentacam CES and SM.

UP700600500400

SM

700

600

500

400

300

Keratoconus

Normal

Figure 5. Scatterplot of CCT measurements in normal and keratoconic

eyes taken using the UP and SM.

G - VOL 32, JUNE 2006 975

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

(0.891, P!.001) and SM and UP measurements (0.901,

P!.001), the mean CCT measurement taken with SM

(535.5 G 6.5 mm) was significantly thinner than the mea-

surements of the other 2 instruments (P!.001). Previous

studies have reported inconsistent variability of data from

UP and SM. However, similar to our data, most studies re-ported that noncontact SM provided thinner CCT measure-

ments than UP in normal eyes.2,3,8,12 Although such

differences are probably attributable to the different operat-

ing principles of each system, the exact mechanisms under-

lying the discrepancies in corneal thickness readings are yet

unknown.

Although the operating principle of Pentacam CES is

different from that of Orbscan II, both instruments are ca-pable of providing corneal topography and pachymetry

data simultaneously. Studies evaluating pachymetry mea-

surements of Orbscan II system have reported variable re-

sults in normal eyes. Since this system was proposed to

measure the hydrated mucous component of the tear film

over the cornea, its readings tended to be higher than those

of UP, and the use of the linear acoustic correction factor

(LACF) had been suggested. When this factor was used,some studies reported that the CCT measurements ob-

tained using UP were higher than those obtained using

Orbscan II,5,21 whereas others reported them to be compa-

rable9,10,12 in normal eyes. Studies evaluating CCT mea-

surements of Pentacam CES and Orbscan are required to

determine how measurements of these 2 instruments com-

pare to each other.

In this study, our other concern was to evaluate andcompare the pachymetry readings obtained with all 3 in-

struments in eyes with keratoconus. Similar to normal

eyes, the CCT measurements obtained using the Pentacam

CES and UP were not statistically significantly different in

eyes with mild keratoconus (P Z .29). However, statisti-

cally significant differences between the CCT measure-

ments taken with the 2 instruments were evident in

group B as a whole and when moderate and severely kera-toconic eyes were evaluated separately (P!.05). Therefore,

we suggest that one should be cautious when interpreting

corneal thickness data from Pentacam CES and UP in

eyes with keratoconus, and although specific regression

equations might be used, data from the 2 instruments

should not be used interchangeably.

The mean difference between the Pentacam CES and

UP was �11.2 mm (95% CI, �18.4 to �4.0) in keratoconiceyes. Therefore, despite normal eyes, in eyes with keratoco-

nus, particularly in eyes with moderate and severe kerato-

conus, Pentacam CES measured CCT significantly thinner

than UP. Because of this, in eyes with mild to moderate ker-

atoconus, and in group B as a whole, the mean differences

between CCT measurements of Pentacam CES and SM

were lower than those between UP and SM.

J CATARACT REFRACT SUR976

The measurements of noncontact SM were again statis-

tically significantly thinner than those of Pentacam CES

and UP in group B and in mildly and possibly moderately

keratoconic eyes. No comparisons could be made in the

severe keratoconus subgroup because no SM measure-

ments could be obtained in these eyes. Overall, since noCCT measurements could be obtained in 43.5% of the

eyes in group B, we suggest that SM is of limited value in

measurement of the CCT in keratoconic eyes. Whereas

regression equations might be used for mildly keratoconic

eyes when available, data from this instrument should be

evaluated with caution, particularly in eyes with moderate

and severe keratoconus.

The literature on the comparison of corneal thicknessmeasurements from different instruments in keratoconus

is scarce; nevertheless, data point that UP tends to measure

CCT thicker than Orbscan in these eyes. Gherghel et al.21

recently compared corneal thickness measurements ob-

tained using Orbscan II and UP in 72 normal and 36 kera-

toconic eyes with unreported severity. The authors

reported that when the default LACF was applied, the 2 in-

struments provided similar CCT readings in normal pa-tients, whereas Orbscan II provided significantly lower

measurements in keratoconic eyes such that the authors

recommended omittance of the LACF in eyes with kerato-

conus. Kawana et al. reported that in 21 keratoconic eyes

with unknown severity, CCT measurements obtained using

UP and noncontact SM were comparable, and were higher

than those obtained using Orbscan II (K. Kawana et al.

IOVS 2004; ARVO E-Abstract #B527). Haque et al. also re-ported that in 20 keratoconic eyes, UP readings were higher

than Orbscan II and optical coherence tomography read-

ings (S. Haque et al. IOVS 2004; ARVO E-Abstract #B526).

It has been suggested that because altered organization

of collagen fibers,22 presence of anterior clear stromal

spaces,23 uneven hydration of different parts of the

stroma,24 and irregularities of the corneal endothelium or

epithelium may modify the refractive index and the veloc-ity of sound or light waves through the cornea of kerato-

conic eyes, the accuracy of UP and SM measurements in

these eyes is questionable.21 Indeed, in our study, despite

the fact that we excluded any patient eye with extensive

corneal scarring, using SM, we were unable to take any

measurements in about 43% of eyes and in none of the

eyes with severe keratoconus.

Although Pentacam CES is capable of measuring thepachymetry of the cornea from limbus to limbus, in this

study, due to comparative purposes, we used only CCT

measurements. With UP, no matter what approach is

used, we believe that locations of the peripheral pachyme-

try measurements are never precise. One of the major ad-

vantages of Pentacam CES is the opportunity to measure

2 very important corneal parametersdtopography and

G - VOL 32, JUNE 2006

CORNEAL PACHYMETRY IN NORMAL AND KERATOCONIC EYES

pachymetrydwith 1 instrument. This saves time of both

the patient and the practitioner, whether the instrument

is being used for diagnostic purposes or for refractive surgi-

cal planning. Furthermore, the measurement is quick, non-

invasive and comfortable and does not require topical

anesthesia. Due to video monitor control, precise position-ing of the instrument’s camera system is assisted by magni-

fication, thus avoiding measurements to be biased by

incorrect centration. Since the measurements of the instru-

ment do not depend on reflection of light or sound waves

from the corneal surfaces, they are not supposed to be influ-

enced by scarring or edema, which have been shown to

effect both UP6,20 and SM15 measurements.

In summary, in normal eyes and in eyes with mild ker-atoconus, CCT measurements of Pentacam CES showed

excellent correlation to those obtained by UP, giving com-

parable readings, whereas in these eyes, SM tended to mea-

sure the CCT significantly thinner than the other 2

instruments. In these eyes, the CCT measurements of all

3 instruments showed significant linear correlations with

each other and all provided comparable repeatability of

measurements. In moderate or severely keratoconic eyes,fairly significant correlations still existed between Penta-

cam CES and UP measurements. We propose that Pentacam

CES and UP can be used interchangeably in normal eyes. In

keratoconic eyes, these instruments should not be used in-

terchangeably; instead, conversion equations may be used

for the clinical comparison of CCT readings. While SM

should never be used interchangeably with the other 2 in-

struments in normal eyes, this instrument may even failto take measurements in moderate or severely keratoconic

eyes. Therefore, if required, in keratoconus, the use of SM

for pachymetry purposes should be limited to mildly kera-

toconic eyes and conversion equations should be used for

clinical comparison of its readings in these eyes. Informa-

tion derived from this study is of particular value for plan-

ning of refractive surgery in normal and keratoconic eyes,

where both accuracy and precision of measurements areconstantly required. Further studies are needed to evaluate

the accuracy of Pentacam CES in corneas that have had re-

fractive surgery or in other corneal pathologies.

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