assessment of central corneal thickness in normal, keratoconus, and post-laser in situ...

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Assessment of central corneal thickness in normal, keratoconus, and post-laser in situ keratomileusis eyes using Scheimpflug imaging, spectral domain optical coherence tomography, and ultrasound pachymetry Dilraj S. Grewal, MD, Gagandeep S. Brar, MD, Satinder P.S. Grewal, MD PURPOSE: To compare the central corneal thickness (CCT) in normal eyes, eyes with keratoconus, and eyes after laser in situ keratomileusis (LASIK) using 3 methods. SETTING: Cornea Clinic, Grewal Eye Institute, Chandigarh, India. METHODS: In this study, CCT was measured by sequential Scheimpflug imaging, spectral-domain anterior segment optical coherence tomography (AS-OCT), and ultrasound (US) pachymetry. RESULTS: Each of the 3 groups comprised 50 eyes. There were no differences between the 3 groups in age, sex, or intraocular pressure. In normal eyes, CCT was statistically significantly higher by US pachymetry (mean 525.8 mm G 41.4) [SD] than by Scheimpflug imaging (mean 519.4 G 40.9 mm) and AS-OCT (mean 517.9 G 41.5 mm) (both P<.001). In keratoconus eyes, CCT by US pachymetry (mean 446.4 G 57.9 mm) was statistically significantly higher than by Scheimpflug imaging (mean 439.6 G 62.1 mm) (P Z .002) and AS-OCT (mean 441.8 G 58.4 mm) (P Z .007). In post-LASIK eyes CCT by US pachymetry (mean 462.4 G 44.7 mm) was significantly higher than by Scheimpflug imaging (mean 457.9 G 33.6 mm) (P Z .012) and AS-OCT (mean 455.4 G 43.2 mm) (P<.001). In all groups, CCT measured by Scheimpflug imaging and AS-OCT was similar. CONCLUSIONS: There was a statistically significant difference between Scheimpflug imaging and US pachymetry and AS-OCT, with US pachymetry measurements being consistently thicker. Thus, CCT should be interpreted in the context of the instrument used. Financial disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:954–964 Q 2010 ASCRS and ESCRS Central corneal thickness (CCT) measurements are important for monitoring the health of the corneal endothelial function, assessing the cornea before and after keratorefractive surgery, obtaining accurate in- traocular pressure (IOP) measurements, and assisting in the detection of endothelial disease and graft failure after penetrating keratoplasty. Studies show that a 10% difference in CCT would result in a 3.4 mm Hg difference in IOP. 1 In the Ocular Hypertension Treatment Study, 2 each 40 mm reduction in CCT was associated with a relative risk of 1.71 for development of primary open-angle glaucoma. In refractive surgery, overestimation or underestimation of corneal thickness could lead to serious complications. Several instruments are available to measure the corneal thickness with varying degrees of accuracy. Ultrasound (US) pachymetry is commonly used to measure CCT because it is easy to use and relatively inexpensive and has been considered the gold stan- dard for CCT measurement. Disadvantages of US pa- chymetry include the need to anesthetize the cornea, cornea–probe contact, corneal indentation and the possible compression effect during measurement, and corneal surface disturbance, which can interfere with other evaluations such as topography and wave- front acquisition. There is also the risk for corneal epithelial damage and transmission of infections. 3 In addition, measurements can vary as a result of probe Q 2010 ASCRS and ESCRS 0886-3350/$dsee front matter Published by Elsevier Inc. doi:10.1016/j.jcrs.2009.12.033 954 ARTICLE

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ARTICLE

Assessment of central co

rneal thickness in normal,keratoconus, and post-laser in situ keratomileusiseyes using Scheimpflug imaging, spectral domainoptical coherence tomography, and ultrasound

pachymetryDilraj S. Grewal, MD, Gagandeep S. Brar, MD, Satinder P.S. Grewal, MD

Q

P

954

2010 A

ublished

PURPOSE: To compare the central corneal thickness (CCT) in normal eyes, eyes with keratoconus,and eyes after laser in situ keratomileusis (LASIK) using 3 methods.

SETTING: Cornea Clinic, Grewal Eye Institute, Chandigarh, India.

METHODS: In this study, CCT was measured by sequential Scheimpflug imaging, spectral-domainanterior segment optical coherence tomography (AS-OCT), and ultrasound (US) pachymetry.

RESULTS: Each of the 3 groups comprised 50 eyes. There were no differences between the 3groups in age, sex, or intraocular pressure. In normal eyes, CCT was statistically significantly higherby US pachymetry (mean 525.8 mm G 41.4) [SD] than by Scheimpflug imaging (mean519.4 G 40.9 mm) and AS-OCT (mean 517.9 G 41.5 mm) (both P<.001). In keratoconus eyes,CCT by US pachymetry (mean 446.4 G 57.9 mm) was statistically significantly higher than byScheimpflug imaging (mean 439.6 G 62.1 mm) (P Z .002) and AS-OCT (mean 441.8 G 58.4mm) (P Z .007). In post-LASIK eyes CCT by US pachymetry (mean 462.4 G 44.7 mm) wassignificantly higher than by Scheimpflug imaging (mean 457.9 G 33.6 mm) (P Z .012) andAS-OCT (mean 455.4 G 43.2 mm) (P<.001). In all groups, CCT measured by Scheimpflugimaging and AS-OCT was similar.

CONCLUSIONS: There was a statistically significant difference between Scheimpflug imaging andUS pachymetry and AS-OCT, with US pachymetry measurements being consistently thicker.Thus, CCT should be interpreted in the context of the instrument used.

Financial disclosure: No author has a financial or proprietary interest in any material or methodmentioned.

J Cataract Refract Surg 2010; 36:954–964 Q 2010 ASCRS and ESCRS

Central corneal thickness (CCT) measurements areimportant for monitoring the health of the cornealendothelial function, assessing the cornea before andafter keratorefractive surgery, obtaining accurate in-traocular pressure (IOP) measurements, and assistingin the detection of endothelial disease and graft failureafter penetrating keratoplasty. Studies show thata 10% difference in CCT would result in a 3.4 mm Hgdifference in IOP.1 In the Ocular HypertensionTreatment Study,2 each 40 mm reduction in CCT wasassociated with a relative risk of 1.71 for developmentof primary open-angle glaucoma. In refractive surgery,overestimation or underestimation of corneal thicknesscould lead to serious complications.

SCRS and ESCRS

by Elsevier Inc.

Several instruments are available to measure thecorneal thickness with varying degrees of accuracy.Ultrasound (US) pachymetry is commonly used tomeasure CCT because it is easy to use and relativelyinexpensive and has been considered the gold stan-dard for CCT measurement. Disadvantages of US pa-chymetry include the need to anesthetize the cornea,cornea–probe contact, corneal indentation and thepossible compression effect during measurement,and corneal surface disturbance, which can interferewith other evaluations such as topography and wave-front acquisition. There is also the risk for cornealepithelial damage and transmission of infections.3 Inaddition, measurements can vary as a result of probe

0886-3350/$dsee front matter

doi:10.1016/j.jcrs.2009.12.033

955CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

misalignment or decentering and the probemay not beperpendicularly aligned or may be inaccurately posi-tioned because of a lack of fixation and gaze control.Otherdisadvantages include theestimationof the thick-ness of a single point with each contact and changes inthe speed of sound in corneal tissues with differentdegrees of hydration.4 No correlation has been shownbetween compression and applied force.5–7 Therefore,the reproducibility of US pachymetry measurementsis largely dependent on examiner experience and inter-examiner reproducibility is lower than intraexaminerrepeatability, even when measurements are performedin normal corneas by expert examiners.8

Keratoconus is an ectatic corneal dystrophy char-acterized by progressive noninflammatory cornealthinning.9 Measurement of CCT is used for diagno-sis,10 staging,11 and follow-up and for planning surgi-cal procedures in cases of keratoconus.11–13 Thesemeasurements also help detect and manage cornealpathology associated with corneal thinning and dis-criminate between keratoconus and contact lens–induced corneal thinning.14 Measuring CCT is crucialfor evaluating patient eligibility for refractive surgery.Overestimation of thickness preoperatively can in-crease the risk for keratectasia, whereas underestima-tion can result in exclusion of patients who may begood candidates for refractive surgery.3 In addition,systematic errors tend to bias postoperative estimatesof CCT and the contribution of CCT to IOP measure-ment as well as to affect intraocular lens powercalculation after laser in situ keratomileusis (LASIK).Random errors can also artificially alter CCTmeasure-ments, leading the clinician to err about retreatment ormisdiagnose early iatrogenic keratectasia in eyes thathave had LASIK.

Currently available technologies allow a morecomplete picture of the distribution of thicknessthroughout the cornea. These noncontact instrumentscreate a pachymetrymap that provides thickness read-ings across the cornea as opposed to providing a set of

Submitted: May 7, 2009.Final revision submitted: November 2, 2009.Accepted: December 7, 2009.

From Grewal Eye Institute (D.S. Grewal, Brar, S.P.S. Grewal),Chandigarh, India, and Bascom Palmer Eye Institute (D.S. Grewal),Palm Beach Gardens, Florida, USA.

Presented at the ASCRS Symposium on Cataract, IOL and Refrac-tive Surgery, San Francisco, California, USA, April 2009.

Corresponding author: Dilraj S. Grewal, MD, Bascom Palmer EyeInstitute, Department of Ophthalmology, University of Miami MillerSchool of Medicine, 7101 Fairway Drive, Palm Beach Gardens,Florida 33418, USA. E-mail: [email protected].

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single readings, as in US pachymetry. Slit-scanningoptical pachymetry, rotating Scheimpflug imaging,high-speed anterior segment optical coherence tomog-raphy (AS-OCT), and very-high-frequency ultrasoundimaging all allow pachymetric mapping of the cornea.However, replacing conventional pachymetry and to-pography devices with a single noncontact system,such as Scheimpflug imaging or AS-OCT, requiresthat the validity of measurements by the noncontactsystems be assessed and compared with those by USpachymetry.

In this study, we evaluated the agreement of 3methods of CCT measurement in normal eyes, eyeswith keratoconus, and eyes after LASIK.

SUBJECTS AND METHODS

This observational cross-sectional study comprised normaleyes, eyes with keratoconus, and eyes that had previousLASIK. The study adhered to the tenets of the Declarationof Helsinki and was approved by an institutional reviewboard. After receiving an explanation of the nature of thestudy, all participants provided written informed consent.If both eyes of a participant satisfied the inclusion criteria,1 eye was randomly selected for enrollment.

All normal eyes had a corrected distance visual acuity of20/30 or better and no ocular abnormality other thancataract or refractive error. Exclusion criteria were a historyof ocular surgery, contact lens use in the preceding week, in-ability to cooperate for examination, and evidence of cornealpathology such as keratoconus.

In keratoconus eyes, the initial diagnosis of keratoconuswas based on the presence of characteristic elevation on cor-neal topography (ie, central or paracentral steepening) and 1or more of the following slitlamp findings: central or para-central thinning, anterior bulging or conicity, hemosiderindeposition (Fleischer ring), stromal striae (Vogt striae), De-scemet breaks, apical scars, and subepithelial fibrosis. Eyeswith previous acute corneal hydrops or a history of cornealsurgery were excluded from the study.

The LASIK group comprised consecutive patients havinga 1-year follow-up examination. The same surgeon (S.P.S.G.)performed all LASIK procedures using a Visx Star S4 exci-mer laser (Abbott Medical Optics, Inc.). Flaps were createdwith an Amadeus keratome (Abbott Medical Optics, Inc.);the intended flap thickness was 120 mm. All patients hadhealthy corneas, and none had dry eye before or after LASIK.

Patients in all groups had complete topographic analysisof the cornea. The thinnest-point calculations were per-formed by Scheimpflug imaging or AS-OCT; therefore, toavoid a bias, CCT values were evaluated instead of thethinnest-point corneal thickness. All subjects had a completeophthalmic examination that included visual acuity, refrac-tion, dilated fundus evaluation, and indirect ophthalmos-copy. To avoid the effects of diurnal variation on CCT,15

subjects were examined between 10 AM and 12 PM and afterthey had been awake for at least 3 hours.

The Scheimpflug imaging was performed using a Penta-cam scanning-slit topographer (Oculus); the technique andacquisition protocol for CCT assessment have been describedin detail.3–5,7 Similar to previous studies, the ‘‘25 images perscan’’ optionwas used.3,4 To reduce operator-dependent var-iables, the automatic release mode was used. Images of eyes

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Table 1. Characteristics of the study population by group.

ParameterNormal(n Z 50)

Keratoconus(n Z 50)

Post-LASIK(n Z 50)

PValue

Age (y) .8*Mean G SD 32.6 G 4.4 30.6 G 3.1 29.2 G 5.6Range (25-60) 18–54 (18-49)

Sex .8†

Male 24 26 23Female 26 24 27

Mean IOP(mm Hg) G SD

14 G 3.3 14.9 G 4.2 15.2 G 3.4 .8*

IOP Z intraocular pressure; LASIK Z laser in situ keratomileusis*One-way analysis of variance†Chi-square test

956 CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

that were flagged as a ‘‘blink’’ or that contained anotherartifact were taken again. Scans with a quality score greaterthan 95 were included.

Anterior segment OCT was performed using RTVue100spectral-domain OCT (Optovue) with a corneal adaptormodule. This module is an auxiliary lens adapter that isadded in front of the existing ocular lens; it is used for invivo imaging and measurement of the cornea and otheranterior segment structures. This spectral-domain AS-OCTunit uses an 830 nmwavelength light source with a scanningspeed of 26 000 A-scans per second; the depth resolution is 5mm. The images have a high axial resolution that defines thecorneal boundaries using signal peaks without interferencefrom stromal reflections. The spectral domain OCT detectssignals from the entire depth range in parallel rather than se-rially, which results in higher speed without loss of thesignal-to-noise ratio. During AS-OCT measurements, pa-tients were asked to fixate on the optical target in the system.The center of measurement was aligned with the cornealapex. The pachymetry scan protocol was used for the assess-ment. The scan pattern consists of 6.0 mm radial lines on 8meridians centered on the vertex reflection; this generatesa map of the pachymetry values. The average readingdisplayed in the center represents the central 2.0 mm andwas used for analysis in this study.

The noncontact assessments (Scheimpflug imaging andspectral-domain AS-OCT) were performed first with noorder of preference. Next, after the cornea was anesthetizedwith topical proparacaine hydrochloride 0.5%, CCT wascalculated using a Micropach US pachymeter (model 200P,Sonomed, Inc.). The calibrated US probe (US velocity1640m/s) was placedmanually as perpendicular as possibleon the center of the corneawhile the patientwas instructed tofixate on a distant target. Five measurements of the centralcornea were obtained; the mean of the measurements wasused for analysis. Each measurement in turn consisted of256 individual recordings. Calibration of the instrumentwas checked using its test block. The Scheimpflug andspectral domain AS-OCT CCT readings were not read untilafter US pachymetry calculations were performed.

Statistical Analysis

Statistical analysis was performed using Statistical Pack-age for Social Sciences software (version 16.0, SPSS, Inc.).

J CATARACT REFRACT SURG

Measurements obtained with the 3 methods were comparedusing repeated-measures analysis of variance (ANOVA).The assumption of sphericity was checked using theMauchly test. The Bonferroni method was used to performpairwise comparisons when a significant overall test resultwas determined. The Pearson correlation (r) and Bland-Altman plots were used to assess the difference betweenindividual measurements in each eye. A P value less than0.05 was considered statistically significant.

RESULTS

One hundred fifty eyes of 150 subjects were enrolled.Table 1 shows the clinical characteristics of the studypopulation by group. The 3 groups were matched inage, sex distribution, and IOP. In the LASIK group,the mean time from surgery to CCT measurementwas 12.9 months.

Table 2 compares the mean CCT measurements byUS pachymetry, AS-OCT, and Scheimpflug imagingin the 3 study groups. The Mauchly test found theassumption of sphericity to be plausible (P Z .47).The overall test for differences in means in therepeated-measured ANOVA was statistically signifi-cant (P!.001). In the normal group, CCT measuredby US pachymetry was statistically significantly high-er than by Scheimpflug imaging and AS-OCT (bothP!.001). In the keratoconus group, CCT measuredby US pachymetry was statistically significantly high-er than by Scheimpflug imaging (P Z .002) andAS-OCT (P Z .007). In the post-LASIK group, CCTmeasured by US pachymetry was statistically signifi-cantly higher than by Scheimpflug imaging (P Z.012) and AS-OCT (P!.001). In all 3 groups, CCTvalues measured by Scheimpflug imaging and spec-tral domain AS-OCT were similar.

Figures 1 to 3 show Bland-Altman plots of thebetween-instrument differences in CCT measure-ments against their means and the 95% limits of agree-ment (LoA) (mean difference G 1.96 SD). In thenormal group, the 95% limits of agreement (LoA)were �16.32 to 13.34 mm between Scheimpflug imag-ing and AS-OCT,�21.62 to 8.76 mmbetween Scheimp-flug imaging and US pachymetry, and �20.98 to5.14 mm between AS-OCT and US pachymetry. Inthe keratoconus group, the 95% LoA were �19.08 to23.53 mm between Scheimpflug imaging and AS-OCT, �34.71 to 21.07 mm between Scheimpflug imag-ing and US pachymetry, and �17.81 to 26.99 mmbetween AS-OCT and US pachymetry. In the post-LASIK group, the 95% LoA were �21.31 to 16.37 mmbetween Scheimpflug imaging and AS-OCT, �28.08to 19.09 mm between Scheimpflug imaging and USpachymetry, and �11.89 to 25.81 mm betweenAS-OCT and US pachymetry.

Table 3 shows the Pearson coefficients for the correla-tion in CCT measurements between the 3 instruments.

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Table 2. Mean CCT by group and comparison by measurement method.

Mean CCT (mm) G SD P Value*

Group Pachymetry Scheimpflug AS-OCTUS Pachymetry Vs

ScheimpflugUS PachymetryVs AS-OCT

ScheimpflugVs AS-OCT

Normal !.001 !.001 .17Mean G SD 525.8 G 41.4 519.4 G 40.9 517.9 G 41.5Range 412–594 414–594 399–584

Keratoconus .002 .007 .16Mean G SD 446.4 G 57.9 439.6 G 62.1 441.8 G 58.4Range 384–550 325–543 353–540

Post-LASIK .012 !.001 .078Mean G SD 462.4 G 44.7 457.9 G 33.6 455.4 G 43.2Range 390–564 391–552 387–551

AS-OCTZ spectraldomainanterior segmentoptical coherence tomography;CCTZ central corneal thickness; LASIKZ laser in situ keratomileusis;USZultrasound*Pairwise comparisons by Bonferroni method

957CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

The scatterplot of CCTmeasurements by instrument isshown for the normal group in Figure 4, the keratoco-nus group in Figure 5, and the post-LASIK group inFigure 6. In all 3 groups, there was a significant posi-tive correlation in CCTmeasurements between US pa-chymetry and Scheimpflug imaging, US pachymetryand AS-OCT, and AS-OCT and Scheimpflug imaging.Figure 7 shows the distribution of CCT measurementsby the 3 instruments.

DISCUSSION

Accurate assessment of corneal thickness is importantto minimize the risk for serious post-LASIK complica-tions, such as keratectasia. Knowing the corneal thick-ness allows the surgeon to compute the depth ofresidual corneal tissue and determine the safety limitof a procedure.16 Given the amount of uncertainty indetermining CCT, considerably more tissue wouldhave to be left unablated to ensure safety. This is espe-cially important when treating eyes with higher myo-pic refractive errors with proportionally largerablation depths.7 Furthermore, highly accurate cornealthickness measurements are critical in ensuring theaccuracy and safety of enhancement procedures.17,18

Although US pachymetry has been the standard forCCT measurement because of its established reliabil-ity, the high speed and noncontact approach ofScheimpflug imaging and spectral domain AS-OCTmake these methods promising alternatives. In ourstudy, CCT measurements by Scheimpflug imaging,spectral domain AS-OCT, and US pachymetry weresignificantly correlated in normal, keratoconus, andpost-LASIK eyes. However, US pachymetry measure-ments differed significantly from those of Scheimpflugimaging and AS-OCT in all 3 groups, with US

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pachymetrymeasurements being systematically thick-er. The AS-OCT and Scheimpflug imaging measure-ments were similar. Previous studies show thatScheimpflug CCT measurements are more reproduc-ible and repeatable than those obtained with US pa-chymetry, suggesting that the Scheimpflug camera issuitable for disease staging and follow-up. Table 4compares the results in previous studies of CCT mea-surement3–5,7,19–27 using 2 of the 3 techniques in differ-ent study populations.

There is no satisfactory explanation for the system-atic measurement differences between US and opticalmethods. They are likely the result of different loca-tions of the respective reflective interfaces in the cor-nea. The AS-OCT measurement includes the tearfilm, whereas the US contact probe displaces the tearfilm, which could slightly bias AS-OCTmeasurementstoward higher values. On the other hand, AS-OCTprovides better measurement centration and per-pendicularity than US pachymetry, which couldbias AS-OCT measurements slightly toward lowervalues.28 Several studies23,28,29 report that CCTmeasurements in normal eyes were thinner by AS-OCT than by US pachymetry.

Another possible reason for the difference is theprinciple on which the instruments are based. Ultra-sound pachymetry, developed by Kremer, works onthe time-of-flight principle and calculates cornealthickness as follows: transit time� propagation veloc-ity/2.30 With US pachymetry, accurately measuringthe propagation velocity of sound in the cornea cancomplicate the calculation of corneal thickness. Thestandard velocity used is 1640 m/sec. However, thevalue varies with hydration of the corneal tissue andmay differ in diseased corneas.4 These changes will,in turn, influence CCT measurements. The speed of

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Figure 1. Bland-Altman plots of the differences in CCT measure-ments in normal eyes between 2 methods plotted against the meanvalue obtained with the 2 methods (AS-OCT Z spectral domain an-terior segment optical coherence tomography; CCT Z central cor-neal thickness; US Z ultrasound).

Figure 2. Bland-Altman plots of the differences in CCT measure-ments in the keratoconus group between 2 methods plotted againstthe mean value obtained with the 2 methods (AS-OCT Z spectraldomain anterior segment optical coherence tomography; CCT Zcentral corneal thickness; US Z ultrasound).

958 CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

J CATARACT REFRACT SURG - VOL 36, JUNE 2010

Figure 3. Bland-Altman plots of the differences in CCT measure-ments in the post-LASIK group between 2 methods plotted againstthe mean value obtained with the 2 methods (AS-OCT Z spectraldomain anterior segment optical coherence tomography; CCT Zcentral corneal thickness; US Z ultrasound).

Table 3. Correlation between CCT measurements of the 3 in-struments by study group.

Group/Parameter

PachymetryVs Scheimpflug

PachymetryVs AS-OCT

ScheimpflugVs AS-OCT

Normalr value* 0.97 0.98 0.99D mean

(mm) G SD�6.8 G 14.2 �4.6 G 11.4 �2.2 G 10.9

95% CI �5.4 to .9 �7.9 to �1.3 �10.9 to �2.8P value !.001 !.001 !.001

Keratoconusr value* 0.964 0.977 0.977D mean

(mm) G SD�3.4 G 7.1 �2.3 G 5.7 1.1 G 5.4

95% CI �10.9 to �2.73 �7.9 to 1.3 �5.4 to 10.9P value !.001 !.001 !.001

Post�LASIKr value* 0.964 0.977 0.977D mean

(mm) G SD�4.5 G 12.1 �6.9 G 9.6 2.5 G 9.6

95% CI �7.9 to �1.0 �9.7 to �4.2 �.3 to 5.2P value !.001 !.001 !.001

D Z interdevice difference; AS-OCT Z spectral domain anterior segmentoptical coherence tomography; CCT Z central corneal thickness; CI Zconfidence interval; LASIK Z laser in situ keratomileusis; US Zultrasound*Pearson correlation coefficient

959CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

J CATARACT REFRACT SURG

sound in the cornea and diseased tissue is not as wellknown as the estimates of group velocity of lightfrom the refractive index of the cornea. This may bethe cause for the discrepancy in measurements. Select-ing a faster velocity would produce a thicker cornealreading and vice versa. Another possible explanationfor the thicker measurements of US pachymetry isthat the exact location within the corneal bordersthat generates the major echo is not clear.31

Optical coherence tomography also works on thetime-of-flight principle; that is, of the delay of light as ittravels through ocular tissue.32 In time-domain OCT,a moving reference mirror measures the return time ofthe light from the cornea or retina. Reflections from var-ious tissue layers are detected 1 depth layer at a time byscanning theposition of the referencemirror. In contrast,in spectral-domain OCT, the reference mirror remainsstationary and the interference between the sampleand reference beams is detected as a spectrum. SpectraldomainOCT is faster andmoreefficientbecause it simul-taneouslydetects reflections from the entire depth range.

In the Bland-Altman plots for normal eyes in ourstudy, the values for the difference from the mean arepositively skewed in the plot comparing US pachyme-try and spectral-domain AS-OCT measurements. Theyare not as randomly distributed as the plots comparingScheimpflug imaging measurements with US

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Figure 4. Scatterplots of CCTmeasurements in normal eyes. The dot-ted lines represent the fit and the solid lines, the 45-degree angle (AS-OCT Z spectral domain anterior segment optical coherence tomog-raphy; CCT Z central corneal thickness; US Z ultrasound).

Figure 5. Scatterplots ofCCTmeasurements in thekeratoconusgroup.The dotted lines represent the fit and the solid lines, the 45-degreeangle (AS-OCTZ spectral domain anterior segment optical coherencetomography; CCT Z central corneal thickness; US Z ultrasound).

960 CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

pachymetry and AS-OCT measurements. These plotssuggest a relationship between CCT measurements bythe 2 time-of-flight methods (ie, US pachymetry andspectral-domain AS-OCT) in normal eyes that does

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not existwith the Scheimpflug imaging.A similar distri-bution was observed for the spectral-domain AS-OCTand US pachymetry plots in eyes with keratoconusand post-LASIK eyes, although the relationship was

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Figure 6. Scatterplots of CCT measurements in the post-LASIKgroup. The dotted lines represent the fit and the solid lines, the45-degree angle (AS-OCT Z spectral domain anterior segmentoptical coherence tomography; CCT Z central corneal thickness;US Z ultrasound).

Figure 7. Distribution of CCT measurements (AS-OCT Z spectraldomain anterior segment optical coherence tomography; US Zultrasound).

961CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

not as prominent as in normal eyes. This may offer anexplanation for the differences in CCT measurements.

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The discrepancy between rotating Scheimpflugimaging and US pachymetry in CCT measurementsmay be greater when histopathologic features affectthe optical properties and hydration of corneal tissue

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Table 4. Comparison of CCT measurements in previous studies.

Mean CCT (mm) G SD P Value

Study*/Date Population Scheimpflug US Pachymetry AS-OCTScheimpflug

Vs US PachymetryAS-OCT Vs

US Pacymetry

Ucakhan19/2006 Normal eyes 557.6 G 6.5 554.9 G 7.4 d .37 d

Barkana20/2005 Normal eyes 511.38 G 32.28 517.47 G 28.69 d !.05Amano5/2006 Normal eyes 538 G 31.3 545 G 31.3 d .57 d

Lackner7/2005 Normal eyes 542 G 29.3 552 G 31.7 d d

O’Donnell21/2005 Normal eyes 528 G 45 534 G 47 d .006 d

Li22/2008 Normal eyes d 550.3 G 31.1 535.7 G 30.2 d !.001Wong23/2002 Normal eyes d 555.11 G 35.3 523.21 G 33.54 d

Hashemi24/2007 Pre-LASIK eyes 548 G 32 555 G 30 d d

Kim25/2007 Pre-PRK eyes 561 G 32 550 G 33.7 d .53 d

Ho3/2007 Post-LASIK eyes 431 G 40 438 G 41 427 G 42 !.01 !.01Hashemi24/2007 Post-LASIK eyes 468 G 48 478 G 51 d d

Ciolono26/2008 Post-LASIK eyes 506 G 22 505 G 32 d d

Kim25/2007 Post-PRK eyes 494 G 33.1 481 G 33.1 d .589 d

Ucakhan19/2006 Keratoconus eyes 456.3 G 8.7 462.5 G 8 d .047 d

de Sanctis4/2007 Keratoconus eyes 478.9 G 34.6 486.6 G 30 d d

Fujioka27/2007 POAG, PACG, OHT, controls 559 G 38 553 G 39 d .26 d

AS-OCT Z spectral domain anterior segment optical coherence tomography; CCT Z central corneal thickness; LASIK Z laser in situ keratomileusis;OHT Z ocular hypertension; PACG Z primary angle-closure glaucoma; POAG Z primary open-angle glaucoma; PRK Z photorefractive keratectomy;US Z ultrasound*First author

962 CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

in keratoconic corneas. Irregular and elongated epithe-lial cells, altered organization of collagen fibers, clearstromal spaces, and endothelium irregularity havebeen observed in these corneas.4,33–35 These alterationsmay influence the path of light rays and the velocityof US, leading to an inaccuratemeasurement.4 Interexa-miner reproducibility and intraexaminer repeatabilityof US pachymetry in keratoconic corneas are lowerthan in normal corneas, and even lower than in cornealgrafts.8,36 Typically, the thickness values in keratoconiccorneas are more irregular and variable than those innormal corneas. Thus, slight, but systematic differencesbetween examiners in centering and aligning the probemay cause wider interexaminer variability than in nor-mal corneas. In addition, the distorted corneal shape ineyeswith keratoconus canmake it difficult to determinethe real position of the pupil center. Caution should beexercisedwhen interpreting CCTmeasurements by dif-ferent AS-OCT imaging systems, even though theyhave similar designs and working principles.22 Thesedifferences are relevant given the increasing numberof AS-OCT and Scheimpflug instruments available.37

The instruments we evaluated use differentmethods to generate corneal thickness data, and de-tailed information on the algorithms that the Scheimp-flug rotating camera uses to generate the data is notavailable.4 The exact image-processing algorithmsused in AS-OCT and Scheimpflug imaging are propri-etary, and internal processing algorithms might be

J CATARACT REFRACT SURG

based on different (ie, higher resolution or contrast)data sets. The accuracy of automatic algorithms in de-lineating the anterior and posterior corneal surfacescould also explain the discrepancy in CCT measure-ments. Manually identifying the central anterior andposterior corneal boundaries rather than using the au-tomatic algorithms might result in varying measure-ments. Central corneal epithelial thickening38,39 andshifts in stromal hydration after LASIK for myopia40,41

might alter the corneal index and acoustic velocity,which in turn would affect AS-OCT and US pachyme-try measurements.

The Scheimpflug camera is also an optical device; assuch, a correction factor may be required to correlateits measurements with US pachymetrymeasurements.Scheimpflug imaging has been shown to be reliableand repeatable as well as highly agreeable with US pa-chymetry in normal corneas,6,7,21 post-LASIK eyes,26

and eyes with keratoconus.4 However, a correctionfactor for the Scheimpflug imaging system and the re-liability of the device’s corneal thickness measurementin postoperative eyes have not been addressed. InScheimpflug imaging, the center of the cornea is de-tected automatically and measurement alignment isnot examiner dependent; however, the reproducibilityand repeatability of the method depend on the patientmaintaining correct gaze.4 Ultrasound pachymetry isamanual technique; therefore, its accuracy is examinerdependent because it relies on corneal touch

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963CENTRAL CORNEAL THICKNESS MEASUREMENTS IN NORMAL, KERATOCONIC, AND POST-LASIK EYES

technique, correct centering, and perpendicular align-ment of the probe. In addition, the measurement accu-racy of Scheimpflug imaging and AS-OCT may beaffected by changes in the optical quality or by a lossof transparency in the cornea, similar to what hasbeen reported for Orbscan optical pachymetry.42

In conclusion, despite the statistically significant dif-ference between Scheimpflug imaging and US pachy-metry measurements and between AS-OCT and USpachymetry measurements, there was a close correla-tion between the 3 modalities. However, correlationcoefficients are not relevant when comparing 2methods. Clinicians should be aware of the differencesbetween Scheimpflug imaging, AS-OCT, and US pa-chymetry and always interpret CCT in the context ofthe instrument used to measure it.

Further work is required to assess the accuracy andrepeatability of measurement instruments when thecornea is unusually thick, thin, scarred, or distorted.The comparable range of LoAbetween the instrumentsmay allow development of appropriate conversionequations (correction factors) so that measurementsfrom Scheimpflug imaging and AS-OCT devices areinterchangeable with each other and with USpachymetry. This could be useful in preoperativeplanning and postoperative assessment for refractiveprocedures, especially if the patient is being followedby several ophthalmologists or in different offices.

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First authorDilraj S. Grewal, MD

Bascom Palmer Eye Institute, PalmBeach Gardens, Florida, USA