ARTICLE

Evaluation of bilater

al minimum thicknessof normal corneas based on Fourier-domain

optical coherence tomographyGaurav Prakash, MD, Dhivya Ashok Kumar, MD, Amar Agarwal, MS, FRCS, RCOphth,

Yoga Sarvanan, ME, Soosan Jacob, MS, DNB, FRCS, Athiya Agarwal, MD, DO

Q 2010 A

Published

SCRS an

by Elsev

PURPOSE: To determine the normative ranges and various aspects of the relationship between theminimum corneal thicknesses (MCT) in fellow eyes and the location of the MCT in relation to thecentral cornea using Fourier-domain optical coherence tomography (OCT).

SETTING: Tertiary care ophthalmic hospital, Chennai, India.

METHODS: In this cross-sectional observational trial, both eyes of consecutive healthy youngsubjects with a low refractive error and no clinical or topographic evidence of corneal disordershad bilateral pachymetric assessment with a Fourier-domain OCT platform (RTVue). The MCT,central corneal thickness (CCT), and x–y coordinates of the MCT location were noted.

RESULTS: The CCT and MCT followed a normal distribution with a good correlation. The differencebetween CCT and MCT was approximately 5 mm in right eyes and left eyes (P<.05 for both). Thedifference in CCT was the best predictor of the difference in MCT. The mean distance from the center(0.63 mm G 0.13 [SD], right eyes; 0.66 G 0.17 mm, left eyes) was well correlated. The MCT pointsin fellow eyes tended to be symmetrical along the vertical midline. The mean angular distance be-tween mirror-superimposed MCT points was 20.54 G 17.6 degrees and the mean linear distance,0.25 G 0.17 mm.

CONCLUSIONS: The findings establish normative MCT pachymetry data and location using Fourier-domain OCT. The MCT and CCT points, although symmetrical, differed significantly in location andmagnitude and should be evaluated separately in normal eyes and eyes with disease.

Financial Disclosure: No author has a financial or proprietary interest in any material or methodmentioned. Additional financial disclosures are found in the footnotes.

J Cataract Refract Surg 2010; 36:1365–1372 Q 2010 ASCRS and ESCRS

A tendency toward structural symmetry has been ob-served in fellow eyes of humans. The retinal nerve fi-ber layer, retinal capillary perfusion, astigmatic axis,higher-order aberrations (HOAs), and overall cornealthickness, as well as the epithelial thickness, have sim-ilar patterns, mirror-symmetric patterns, or both.1–11

Minimum corneal thickness (MCT) is an importantparameter in surgical planning and in the detectionof pathology in certain corneal and refractive surgeryprocedures, in which accurate assessment of MCTand its location is crucial.12–16 Errors in pachymetricmeasurement are factors in poor surgical outcomes, in-cluding ectasia after laser in situ keratomileusis.17–19

Corneal topographic assessment can be inaccuratein the presence of motion artifacts. Fourier-domain

d ESCRS

ier Inc.

optical coherence tomography (OCT), also known asfrequency-domain tomography, overcomes this prob-lem to a large extent because of its high acquisitionspeed.21,22,A In Fourier-domain OCT, the light fromthe reference arm interferes with the reflected light,generating spectral interference fringes that are even-tually analyzed using Fourier transformation.20–22

Therefore, information in an entire A-scan area canbe acquired by a charge-coupled device camera simul-taneously. This increases the acquisition rate manytimes without physical movement.20–22

Recently, we found that Fourier-domain OCT hasbetter repeatability than time-domain OCT (Visante,Carl Zeiss) for minimum, central, and paracentral cor-neal thickness measurements.23 A previous study24

0886-3350/$dsee front matter 1365doi:10.1016/j.jcrs.2010.02.023

1366 MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

found that time-domain OCT pachymetry correlatesbetter with the gold standard (ultrasound pachyme-try) than with Orbscan pachymetry (Bausch & Lomb).

The aim of the current study was to determine thenormative ranges and various aspects of the relation-ship between the minimum corneal thicknesses(MCT) in fellow eyes and the location of theMCT in re-lation to the central cornea using Fourier-domain opti-cal coherence tomography (OCT). To our knowledge,no similar study using the Fourier-domain OCT plat-form has been published.

SUBJECTS AND METHODS

This trial was performed at a tertiary care ophthalmic hospi-tal and approved by the institutional review board. The re-search followed the tenets of the Declaration of Helsinki.After receiving an explanation of the nature of the study,all subjects provided informed consent.

The participants in the study were normal young volun-teers with no previously documented ocular morbidity otherthan a myopic error less than or equal to �3.00 diopters (D).Slitlamp evaluation was performed to rule out corneal disor-ders, including ectatic disorders, scarring, or thinning. Orbs-can IIz topographic evaluation was also performed in allcases. The KISA% index25 and the Melki and Azar Massa-chusetts Eye and Ear Infirmary index26 were used to ruleout cases of keratoconus and cases suspected of keratoconus.Fellow eyes with unilateral forme fruste or more severe ker-atoconus were excluded from the study. No subject worecontact lenses.

To minimize the effect of diurnal variation in cornealthickness,27,28 all tests were performed between 2 PM and5 PM by the same experienced examiner. The sequence of ex-amination (right, left–left, right) was randomized by a com-puter-generated sequence of 100 randomly selected optionsusing the numbers 1 and 2 (1 Z right eye examined first;2 Z left eye examined first).

Corneal assessment was performed using the RTVue OCTsystemA (Optovue, Inc.), which takes 26 000 A-scans per sec-ond, a much higher acquisition speed than with most otheravailable anterior segment assessment devices. The optionalcornea anterior module was used for anterior segment imag-ing. The scan beam wavelength is 840 nm G 10 (SD) and theexposure power at the pupil, 750 mW.A The L lens of themodule can acquire 6.0 mm � 6.0 mm scans of the corneafor pachymetric analysis. The frame rate is 256 to 4096 Ascans/frame. The resolution depth is 5.0 mm and the

Submitted: August 20, 2009.Final revision submitted: January 15, 2010.Accepted: February 13, 2010.

From Dr. Agarwal’s Group of Eye Hospitals, Chennai, India.

Additional financial disclosures: Dr. Amar Agarwal is a consultant toAbbott Medical Optics Inc., Staar Surgical Co., and Bausch & Lomb.

Corresponding author: Amar Agarwal, MS, FRCS, FRCOphth, Dr.Agarwal’s Eye Hospital and Eye Research Centre, 19, CathedralRoad, Chennai-600 086, India. E-mail: dragarwal@vsnl.com.

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transverse resolution, 15.0 mm. The scan beam wavelengthis 840 G 10 nm and the exposure power at the pupil, 750 W.

The subject’s head was positioned on the headrest. Theexaminer observed the infrared (IR) image of the corneaon the examination screen. All scans were performed withthe subject’s eye wide open by his or her own effort. Scan-ning was performed on visualization of a centered bright IRimage of the central cornea. No topical anesthesia or lubri-cating drops were used. The scan was repeated if the firstwas decentered or had a poor corneal apex reflection. Theoutput screen of the OCT system shows an IR image ofthe cornea in the upper right followed by, in clockwisedirection, keratoconus analysis data, an axial scan ofthe cornea, a color-coded corneal pachymetry map, anda numerical data map divided into zones (Figure 1). The2.0 mm central zone is surrounded by a 2.0 to 5.0 mmzone and a 5.0 to 6.0 mm zone divided into 45-degree sub-tending angles. The mean pachymetry in the respectivezones is included in the output. The MCT and its relationto the center of the cornea are shown in the keratoconusanalysis box. The location is also marked on the color-coded pachymetric map.

Mathematical Calculations and Transformations

The distance of the MCT from the center of the cornea wascalculated as

D Z�x2 þ y2

�0:5

To assess symmetry, the left-eye coordinates were trans-formed along possible axes to match the right eye data andevaluated for patterns and symmetry. A direct symmetrymodel was evaluated with the original values of R(x, y)and L(x, y). Then, reflections were performed along the y-axis (vertical midline, x Z 0), along the x-axis (horizontalmidline, y Z 0), and across the equivalence diagonal (y Z x).

The distance between the right-eye coordinates R(x, y) andthe transformed left-eye coordinates (x0, y0) was calculated as

S ZhðRx � Lx0Þ2 þ ðRy � Ry0Þ2

i0:5

To determine the angular distance, the angle q between Rand L0 was calculated as

q Z cos�1fðR � L0Þ=ðjRj� jL0jÞgwhere

R�L0Z ðRx� Lx0 þ Ry�LyÞand the cross product of R is L0

jRj � jL0j Zh�Rx2 þ Ry2

�0:5i �h�Lx2 þ Ly2

�0:5i

The angle was then converted from radians to degrees.

Statistical Analysis

The data were analyzed using SPSS software (version16.0, SPSS, Inc.). Paired t tests were used to analyze the dif-ferences in mean values, which are reported with the stan-dard deviation. Correlation coefficients and best-fit linearequations were computed to assess the correlation betweenmeasurements in right eyes and measurements in left eyes.Bland-Altman plots were drawn to show the effect of cornealthickness on the difference in measurements between the 2

VOL 36, AUGUST 2010

Figure 1. Pachymetric output of theFourier-domain OCT device. Clockwisefrom top left: Infrared image capture,keratoconus analysis box, color-codedpachymetric map, and the zone thick-ness map.

1367MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

eyes and the 95% limits of agreement (95% LoA). To preventconfusion from the x and y coordinates at the thinnest point,the regression fit-related linear equations in the study arepresented as b Z ma C c rather than in the conventional

Figure 2. Frequency distribution of CCT and MCT in right eyes andleft eyes (CCT Z central corneal thickness; LE Z left eye; MCT Zminimum corneal thickness; RE Z right eye).

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y Z mx C c form, where a and b are the x and y coordinates,respectively, of the regression fit line;m is the gradient of thestraight-line graph; and c is the y intercept of the straight-linegraph.

RESULTS

Demographics

The study evaluated 200 eyes of 100 subjects (52men, 48 women) with a mean age of 25.4 G 1.8 years(range 23 to 32 years). The mean spherical equivalentwas �1.02 G 0.7 D (range �3.0 to 0.0 D) in righteyes and �1.04 G 0.6 D (range �3.0 to 0.0 D) in lefteyes.

Corneal Pachymetry

Central Corneal Thickness Both right-eye and left-eyepachymetric values followed a normal distributioncurve (P Z .5 and P Z .3, respectively; Kolmogorov-Smirnov test for normality) (Figure 2). The mean cen-tral corneal thickness (CCT) was 517.3 G 35.4 mm(range 440 to 624 mm) in right eyes and 516.6 G36.0 mm (range 450 to 636 mm) in left eyes. The meandifference between the CCT in right eyes and lefteyes was 0.68 G 5.9 mm (P Z .25, paired t test). Therewas a statistically significant correlation between theCCT in right eyes and the CCT in left eyes (r Z 0.98,(P!.001). Figure 3, A, shows the best-fit line, suggest-ing an excellent linear fit (r2 Z 0.97).

VOL 36, AUGUST 2010

Figure 3. Linear best-fit plots between pachymetric values. A: Cen-tral corneal thickness in right eye (CCTR) and left eye (CCTL). B:Minimum corneal thickness in right eye (MCTR) and left eye(MCTL).

Figure 4. Overlay Bland-Altman plot showing the difference infellow-eye pachymetry as a function of the mean pachymetry inright eyes and in left eyes.

1368 MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

Minimum Corneal Thickness Both right-eye and left-eye values followed a normal distribution curve(P Z .5 and P Z .7, respectively; Kolmogorov-Smirnov Z test) (Figure 2).The mean MCT was 511.9G 35.2 mm (range 435 to 624 mm) in right eyes and

Table 1. Symmetry analysis of the right and left eye coordinates.

Original Coordinates (M

Right Eye

Transform Group Rx Ry

I �0.51 G 0.20 �0.28 G 0.43 �II �0.51 G 0.20 �0.28 G 0.43 �III �0.51 G 0.20 �0.28 G 0.43 �IV �0.51 G 0.20 �0.28 G 0.43 �

Transform Z transformation*Analysis of variance, Tukey HSD

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511.7 G 35.7 mm (range 440 to 633 mm) in left eyes.The mean difference in the MCT between right eyesand left eyes was 0.29 G 5.86 mm (P Z .6, pairedt test).There was a statistically significant correlationbetween the 2 MCT values (r Z 0.98, P!.001).Figure 3, B, shows the best-fit line, suggesting an excel-lent linear fit (r2 Z 0.97).

Difference Between Central and MinimumPachymetry

The mean pachymetric difference between the CCTand theMCTwas 5.34G 4.48 mm in right eyes and 4.95G 3.6 mm in left eyes (both P!.001, paired t test).

Relationship Between Thicknesses in Thinnerand Thicker Corneas

An overlay Bland-Altman plot to determinewhether the difference in fellow-eye MCT or CCT

ean G SD)

Left Eye

Lx Ly Transform Along Line

0.51 G 0.28 �0.21 G 0.33 None0.51 G 0.28 �0.21 G 0.33 x Z 00.51 G 0.28 �0.21 G 0.33 y Z 00.51 G 0.28 �0.21 G 0.33 x Z y

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1369MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

was more or less in thinner or thicker corneas (differ-ence in pachymetry as a function of mean pachymetryfor MCT and CCT separately) showed a 95% LoArange of 23.5 mm and 25.8 mm for MCT and CCT, re-spectively. Both measures showed a poor statisticallynonsignificant linear fit (Figure 4).

Location of Minimum Corneal Thickness

The Cartesian location of the point of MCT wasgiven in the output screen as x and y coordinates (inmillimeters), with the center of the cornea being 0.0.Therefore, the right-eye and left-eye coordinateswere denoted as R(x,y) and L(x,y). The mean value ofthe x coordinate was �0.51 G 0.21 mm (range �0.91to �0.06 mm) in right eyes (Rx) and 0.46 G 0.32 mm(range �0.30 to 1.09 mm) in left eyes (Lx). The meanvalue of the y coordinate was �0.24 G 0.23 mm(range �0.82 to 0.40 mm) in right eyes (Ry) and�0.30 G 0.28 mm (�1.06 to 0.74 mm) in left eyes(Ly). Therefore, the position of the thinnest point(r2 Z 0.68 and r2 Z 0.47 for x coordinate and y coordi-nate, respectively) was not as highly correlated be-tween eyes as the pachymetric value (r2 Z 0.97).

The location (x and y coordinates) of the thinnestpoints in right eyes and in left eyeswas statistically sig-nificantly different from the location of the center ofthe cornea (0, 0) (P!.001; 1-sample t test with testvalue of zero).

Distance of Minimum Corneal Thicknessfrom Center

The mean distance between the MCT and the centerof the cornea was 0.63 G 0.13 mm (range 0.46 to0.98 mm) in right eyes and 0.66 G 0.17 mm (range0.38 to 1.11 mm) in left eyes. The mean difference inthe distance between right eyes and left eyes was�0.03 G 0.08 mm (P!.001, paired t test). There wasa good linear correlation between the 2 eyes(r Z 0.87, P!.001).

Change inCoordinates of L Mean Lx0 G (SD) Mean Ly0 G (SD)

MeaBetwee

L(x,y) / L(x, y) 0.51 G 0.28 �0.21 G 0.33L(x,y) / L(�x, y) �0.51 G 0.28 �0.21 G 0.33L(x,y) / L(x, �y) 0.51 G 0.28 0.21 G 0.33L(x,y) /L(�x, �y) �0.51 G 0.28 0.21 G 0.33

Table 1. (continued)

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Symmetry

Table 1 shows the transformations along the directsymmetry model (Figure 5, A), the vertical midline(Figure 5, B), the horizontal midline (Figure 5, C),and the across-the-equivalence diagonal (y Z x)(Figure 5, D).

The distance between the right-eye coordinates andthe transformed left-eye coordinates was significantlylower for the reflection along the y-axis (vertical mirrorsymmetry) than the original position (direct symme-try) and the other 2 transformations along the x-axisand along the y Z x (analysis of variance with TukeyHSD, Table 1). Therefore, the location of the thinnestpoints in right eyes and in left eyes tended to havesymmetry along the vertical midline.

Normal Range of Symmetry of Linear and AngularDistances

The finding that there was symmetry along x Z0 helped establish the normal range of the minimumlinear and angular distances between the locations’ 2corresponding MCT points. This analysis used theoriginal right-eye coordinates (Rx, Ry) and trans-formed left-eye coordinates (Lx0, Ly), where Lx0 ZLx � (�1). The mean scalar (linear) distance was 0.25G 0.17 mm (range 0.1 to 0.79 mm) (Figure 6). Themean angular distance between the points of MCTwas 20.54 G 17.6 degrees (range 0.06 to 74.2 degrees).

DISCUSSION

Accurate noncontact analysis of corneal structure hasbeen difficult. Previous studies have evaluatedscanning-slit, rotating Scheimpflug imaging, andtime-domain OCT platforms for such analysis. In a re-cent study,23 we found that repeated Fourier-domainOCT corneal pachymetry measurements were highlyconsistent and, in contrast to time-domain OCT, didnot seem to underestimate normal corneal thickness.

The variability in MCT and CCT measurements hasbeen a recent area of interest. Rufer et al.29 used

n Distance (mm)n R(x,y) and L(x0,y0)

Difference fromSmallest Distance (II) (mm) P Value*

1.07 G 0.44 0.81 .0010.25 G 0.17 0.00 d

1.32 G 0.30 1.06 .0010.65 G 0.39 0.40 .001

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Figure 5.Assessment of symmetry inMCT location between right eyes and left eyes. The points aremapped on aCartesian gridwith the center ofthe cornea being origin (0,0). The original coordinates on Fourier-domain OCT output are R(x, y) for right eyes and L(x, y) for left eyes. Thesepoints are assessed for symmetry by reflecting points along the axis by inverting the sign of Lx, Ly, or both; Lx0 Z�1� Lx and Ly0 Z�1� Ly.A:Direct symmetry, no transformation. B: Vertical midline, Lx / Lx0. C: Horizontal midline, Ly / Ly0.D: Along diagonal y Z x, Lx, y / Lx0, Ly0.

1370 MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

scanning-slit measurements and found that the MCTand the CCT were significantly different in right eyesand in left eyes. The mean location of the thinnest pointin their study was 0.56 G 0.4 mm in right eyes and 0.69G 0.4 mm in left eyes. The location was slightly morecentral than previously reported by Liu et al.30 (0.90 G0.51 mm) using scanning-slit measurements of normalcornea.Ashwin et al.31 used rotating Scheimpflug imag-ing tomap the thinnest point. They found theMCTwas5.57 mm thinner than the CCT. Themean distance of thethinnest point from the corneal apex was 0.62 mm inright eyes and 0.79 mm in left eyes. In a study usingvery-high-frequency digital ultrasound, themean abso-lute stromal thickness progression from the thinnestpointwas governedbyaquadratic equation andwas in-dependent of stromal thickness at the thinnest point.32

Our finding of a difference of approximately 5 mm inCCT and MCT tends to corroborate better with theScheimpflug findings of Ashwin et al.31 than with

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the scanning-slit studies. In addition, the location ofthe MCT point was more similar to that of Ashwinet al.31 and of Liu et al.30 There are many likely reasonsfor the differences in observations between OCT,scanning-slit, and Scheimpflug imaging platforms;they include variations in algorithms, imaging resolu-tion, scan center, optical axis, and acquisition speedbetween platforms. Therefore, we recommend againstextrapolating the results of one platform to another, es-pecially during a serial follow-up of a patient.

In this study, we have also evaluated the relation-ship between the difference in CCT and the differenceinMCT and detailed themapping of the thinnest pointin terms of the scalar distance of the point from the cen-ter and the distance between the geometrically trans-formed thinnest points (linear and angular). Thestrongest predictor of a difference inMCTwas a differ-ence in CCT between 2 eyes, suggesting that normaleyes have a similarly governed architecture that

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Figure 6.Diagramof a superimposed image of fellow-eye pachymet-ric output showing different entities used to map the thinnest point.Terms: R(x, y) and L(x, y) Z original locations; L(x0,y) Z reflection ofL along vertical midline; q Z angle between the 2 points with thecenter of the cornea as the vertex; S Z scalar distance between the2 points; DR and DL Z the distance of the locations of the points ofMCT from the central cornea for right eyes and left eyes. The differ-ence is seen as an annular zone denoted by the circles drawn withdashed lines.

1371MINIMUM CORNEAL THICKNESS ASSESSMENT BY FOURIER-DOMAIN OCT

determines CCT and MCT. It will be interesting to de-termine whether such a relationship is disturbed incorneas with pathology. Using time-domain OCT, Liet al.14 found that a pachymetry-based diagnostic cri-teria of keratoconus may be as sensitive and specificas the topography-based KISA% index.

Mirror symmetry that is not superimposable hasbeen reported in refractive entities such as astigmatismaxis and HOAs.1–5 We found that the location of thin-nest cornea had best symmetry along the vertical mid-line. The relationship between the angle k, HOAs, thethinnest point, and the center of the corneal domeshould be studied further. As of now, OCT platformsdo not measure the angle k, and a similar study shouldbe performed with a single, fast instrument operatingat high acquisition speeds to compensate for move-ment errors.

The current study provides normative data forMCTas well as its location in relation to the central cornealarea with Fourier-domain OCT, a high-speed acquisi-tion system. The use of Fourier-domain OCT ensuredthat the motion artifact was reduced to a minimum.The study confirmed that the CCT andMCT are not in-terchangeable and that both should be considered sep-arately when evaluating eyes for corneal disease andsurgical planning. The ranges in the normal variationsin the thinnest point of the cornea in normal eyes canserve as useful parameters for ruling out pathology.

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A study with a population that includes eyes with ker-atoconus, forme fruste keratoconus, high myopia, andhyperopia is underway and should provide further in-formation in this area.

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VOL

36, AUGUST 2010

First author:Gaurav Prakash, MD

Tertiary care ophthalmic hospital,Chennai, India