Glaucoma Probability Score vs Moorfields Classification in Normal, Ocular Hypertensive, and...

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Glaucoma Probability Score vs MoorfieldsClassification in Normal, Ocular Hypertensive,

and Glaucomatous Eyes

JAVIER MORENO-MONTAÑÉS, ALFONSO ANTÓN, NOELIA GARCÍA, LORETO MENDILUCE,
ELEONORA AYALA, AND ANGELES SEBASTIÁN
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PURPOSE: To evaluate the Heidelberg Retina TomographII (HRT III) glaucoma probability score in differenti-ting normal from pathologic eyes and to compare thelaucoma probability score with Moorfields regressionnalysis (MRA). DESIGN: Prospective cross-sectional study. METHODS: Fifty-nine normal, 40 hypertensive, and 83laucomatous eyes were examined with Swedish interac-ive threshold algorithm standard 24-2 visual fields andRT III. Sensitivity and specificity were evaluated using

lobal and sectorial glaucoma probability score and MRAompared with damage in visual fields. Areas undereceiver operating characteristic (ROC) curves werevaluated. Agreement between MRA and glaucoma prob-bility score was calculated using the � coefficient.laucoma probability score was considered to be displacedhen a symbol was outside and the opposite symbol was

nside the optic disk. RESULTS: MRA sensitivity and specificity were 39.8%nd 93.2% (most specific criteria) and 68.7% and 83.1%least specific criteria), respectively. Glaucoma probabil-ty score sensitivity and specificity were 71.1% and9.5% (most specific criteria) and 85.5% and 54.2%least specific criteria), respectively. Visual field param-ters were related to the global (P � .001) and sectorialP < .05) glaucoma probability score. A displaced glau-oma probability score was found in 35 eyes, but withnchanged glaucoma probability score sensitivity andpecificity. Areas under the ROC curves of glaucomarobability score was 0.77. The � coefficient was 0.34. CONCLUSIONS: Glaucoma probability score analysisends to be more sensitive but less specific than MRA.laucoma probability score did not differentiate normal

nd hypertensives eyes. When displaced, glaucoma prob-bility score sensitivity and specificity were unchanged.

ccepted for publication Sep 11, 2007.From the Department of Ophthalmology, Clínica Universitaria, Uni-

ersidad de Navarra, Pamplona, Spain (J.M.-M., N.G., L.M.); thelaucoma Department, Institut Catalá de la Retina, Barcelona, Spain

A.A., E.A.); the Glaucoma Unit, Hospital de la Esperanza y el MarIMAS), Universidad Autónoma de Barcelona, Barcelona, Spain (A.A.,.A.); and Instituto Universitario de Oftalmobiología Aplicada (IOBA),niversidad de Valladolid, Valladolid, Spain (A.S.).Inquiries to Javier Moreno-Montañés, Department of Ophthalmology,

slínica Universitaria, Universidad de Navarra, Apartado 4209, 31080amplona, Spain; e-mail: [email protected]

© 2008 BY ELSEVIER INC. A60

RA and glaucoma probability score agreement was low.laucoma probability score is advantageous over MRA in

arly-stage glaucoma. (Am J Ophthalmol 2008;145:60 –368. © 2008 by Elsevier Inc. All rights reserved.)

laucoma is an important cause of blindness worldwide.1

he evaluation of morphologic parameters of the optic nerves changes in the optic disk is crucial for early detection oflaucoma and often precedes visual field loss.2–5 Some com-onents of the optic disk (the cup, neuroretinal rim, or theize of the disk) are major determinants of glaucomatousamage.6–8

The Heidelberg Retinal Tomograph (HRT; Heidelbergngineering GmBH, Dossenheim, Germany) is a confocalcanning laser ophthalmoscope that acquires 3-dimen-ional topographic images of the optic disk and surround-ng retina. The HRT was developed to provide objectivend reproducible analysis of optic disk morphologic param-ters,9,10 allowing optic disk analysis and its topographiceasurements to detect structural damage up to eight years

arlier than expert assessment of stereo disk photographyr visual field loss.11 One algorithm of the HRT is theoorfields regression analysis (MRA), which was devel-

ped to improve the diagnostic ability of HRT by consid-ring the differences in the area of the optic disk in theuantitative evaluation of the rim area.7,12 The advantagef the MRA is that it uses global and sectorial rim sectorrea estimates adjusted for optic disk size and age tomprove specificity. The MRA technique discriminatesetween glaucomatous and normal eyes with high sensi-ivity and specificity.7,12 However, the MRA diagnosticnalysis depends on the position of a manually placedontour line to outline the area of the optic disk, and theontour lines drawn by different examiners vary consider-bly.13

The new generation of the HRT, HRT III (software.3.0.), provides the well-known MRA algorithm and aew one that does not rely on a manually drawn contour

ine. This algorithm, the glaucoma probability scoreGPS), based on the technique of Swindale and associates,ses two measurements of the peripapillary retinal nerveber layer (RNFL) shape (horizontal and vertical RNFLurvature) and three measurements of the optic nerve head
hape (cup size, cup depth, and rim steepness) for input
LL RIGHTS RESERVED. 0002-9394/08/$34.00doi:10.1016/j.ajo.2007.09.006

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nto a vector machine-learning classifier that estimates therobability of having damage consistent with glaucoma.14

his new HRT III software version also includes a largernd ethnicity-specific normative database that improveshe discrimination of glaucoma compared with the previ-us generation of the HRT.The aim of this study was to evaluate the GPS in healthy,

cular hypertensives, and glaucomatous eyes and to comparehe GPS with the MRA algorithm in the same groups ofatients. We also analyzed if the displacement in the GPSlgorithm can modify the classification of patients.

METHODS

PATIENTS: A prospective study of consecutive patientsas performed in the Departments of Ophthalmology,línica Universitaria de Navarra, Pamplona, Spain, and

IGURE 1. Four cases of displaced glaucoma probability score.oth cases result from a large optic disk. (Bottom) Two cases wases are in an optic disk without a cup. Green check mark �ed cross � outside normal limits.

he Institut Catalá de la Retina, Barcelona, Spain. All g

HRT III IN NORMAL, OCULAR HYPERTEOL. 145, NO. 2

articipants were White and underwent a complete oph-halmic examination, including medical and family histo-ies, visual acuity measurement, Goldmann applanationonometry, anterior and posterior segment slit-lamp exam-nations, white-white visual field using the Swedish inter-ctive threshold algorithm standard 24-2 of the Humphreyield Analyzer (Carl Zeiss Meditec, Dublin, California,SA), and optic disk imaging using the HRT III. All

atients had a spherical equivalent within 5.0 diopters orewer and astigmatism of 3.00 diopters or fewer, a best-orrected visual acuity (BCVA) of 20/40 or better, noorneal or retinal pathologic features, and no substantialedia opacity that obscured the fundus.The glaucoma group included patients with a clinical

iagnosis of open-angle glaucoma and visual field defects.he open-angle glaucoma was defined by gonioscopy.

nclusion in the glaucoma group was defined by visual fieldharacteristics alone. The visual field was classified as

) Two cases with glaucoma probability score slightly displaced.more extensive glaucoma probability score displacement. Bothin normal limits; Yellow exclamation mark � borderline; and

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laucomatous when at least three contiguous locations

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ere outside the 95% normal limits of the pattern devia-ion plot and one was outside the 99% normal limitsglaucoma definition). This damage was reproducible in ateast three reliable and consecutive visual fields. A sub-roup of patients with early glaucoma was defined by aean deviation (MD) of �5 decibels (dB) or fewer.The ocular hypertensives group included patients with

hree consecutive normal visual fields and Goldmannntraocular pressure (IOP) exceeding 21 mm Hg on threeifferent days. The normal group included patients withOP of 21 mm Hg or lower, normal visual fields, and noamilial glaucoma.

A total of 182 eyes (96 right, 86 left eyes) of 182atients were enrolled (median age, 65 years; 75% inter-uartile range [IR], 54 to 72 years). Eighty-seven were menmedian age, 62 years; IR, 49 to 71 years) and 95 wereoman (median age, 65 years; IR, 57 to 72 years; P � .06).ifty-nine eyes were normal, 40 eyes had ocular hyperten-ion, and 83 eyes were glaucomatous.

OBSERVATION PROCEDURES: Before HRT III imaging,upils were dilated with 1% tropicamide. The HRT IIIvaluation, carried out according to the manufacturer’snstructions, was performed the same day and after theisual field study. A reliable visual field was defined as oneith less than 30% fixation losses and false-positive and

alse-negative responses. All HRT III images obtainedere good quality, defined as having a topographic stan-ard deviation (SD) of 30 �m or fewer and no floaters orpaque areas. Contour lines, needed to perform the MRAlgorithm, were placed in the margin of the optic disk byxperienced users and were reviewed by two authorsJ.M.M., A.A.) using the 3-dimensional optic disk view. Ifetermining the disk margin was impossible, the case was

TABLE 1. Demographic Data and Classification of MoorfieldsHypertensive, and

Normal (59 Cases)

Men/women 26/33

Median age (IR), yrs 56 (47 to 67)

Optic disk size (IR), �m 2.1 (1.78 to 2.46)

MD of visual field (IR), dB �0.63 (�1.81 to �0.18)

PSD of visual field (IR), dB 1.45 (1.28 to 1.68)

Moorfields regression analysis

Within normal limits 49 (83.1%)

Borderline 6 (10.2%)

Outside normal limits 4 (6.8%)

Glaucoma probability score

Within normal limits 32 (54.2%)

Borderline 9 (15.3%)

Outside normal limits 18 (30.0%)

Displaced glaucoma probability score 5 (8.5%)

dB � decibels; IR � interquartile range; MD � mean deviation; P

xcluded. c

AMERICAN JOURNAL OF62

The MRA automatically classified the optic disk withinormal limits (WNL), borderline (BL), or outside normal

imits (ONL). Analysis output was provided as a GPSanging from 0% to 100%. Scores from 0% to 27% wereategorized by the software as WNL (green check mark),8% to 64% as BL (yellow exclamation mark), and 65% to00% as ONL (red cross). The overall GPS diagnosis wasrovided as an ordinal output. If a GPS diagnosis wasbtained in the global area but not in each sector, the caseas counted and excluded. The GPS classification symbolas determined by one author (J.M.M.) to be centered ifvery sector classification symbol was surrounding theptic disk and was displaced if the GPS classificationymbols were distributed asymmetrically on or around theisk. Specifically, a displaced GPS was characterized by theresence of one GPS symbol outside the optic disk mar-ins, being the opposite symbol inside the optic diskargins (Figure 1).In all patient groups, the MRA and GPS classifications

WNL, BL, and ONL) were compared with the definitionsf the groups (normal, ocular hypertensives, and glau-oma). The MRA and GPS classifications also wereompared with the glaucoma hemifield test results of theisual field (glaucoma hemifield test classification, normal,nd ONL). The effect of other parameters (HRT topo-raphic SD, HRT optic disk size, and ametropia as spher-cal equivalent) on the MRA and GPS results wasvaluated.

Comparisons between MRA and glaucoma diagnosisnd GPS and glaucoma diagnosis with respect to sensitiv-ty and specificity evaluations were performed by consid-ring BL cases as test negatives (most specific criteria) andy considering BL cases as test positives (least specific

ression Analysis and Glaucoma Probability Score in Normal,ucomatous Eyes

Hypertensives (40 Cases) Glaucoma (83 Cases) P value

16/24 45/38 .55

63.5 (57 to 70.5) 68 (60 to 73) .001

1.89 (1.72 to 2.35) 2.11 (1.82 to 2.37) .43

�0.99 (�2.52 to �0.29) �4.94 (�12.58 to �2.67) .001

1.5 (1.40 to 1.87) 4.29 (2.15 to 8.34) .001

29 (72.5%) 26 (31.3%) .001

7 (17.5%) 24 (28.9)

4 (10%) 33 (39.8%)

17 (42.5%) 12 (14.5%) .001

11 (27.5%) 12 (14.5%)

12 (30%) 59 (71.1%)

9 (22.5%) 21 (25.3%) .04

pattern standard deviation.

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OPHTHALMOLOGY FEBRUARY 2008

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Agreement between MRA and GPS also was assessed,ith complete agreement (same classification group), par-

ial agreement (classified by one analysis as BL and by thether as either WNL or ONL), and no agreementonsidered.

STATISTICAL STUDY: Data were evaluated using SPSSoftware version 13.1 (SPSS, Inc, Chicago, Illinois, USA).he Kolmogorov–Smirnov test was used to check for aormal distribution of quantitative variables. The Mann–hitney U test, Kruskal–Wallis test, and Chi-square

onparametric test provided the nonparametric data dis-ribution. Values were expressed as medians and 25% and5% IRs. The level of significance for each contrast was� .05. The GPS and visual field parameters were correlatedith the use of the Spearman test. Sensitivities and specific-

ties were calculated for MRA and GPS algorithms globallynd in every sector compared with visual field classifica-ions and glaucoma hemifield test results. Receiver oper-ting characteristic (ROC) curves were used to determinehe discriminatory capabilities between healthy and glau-omatous eyes. Areas under the ROC curves were com-ared using the method of DeLong and DeLong.15 Optimalut-off levels were determined using the Youden indexg � sensitivity � specificity � 1).16 This index providessingle numerical value that intends to gather the infor-ation of sensitivity and specificity. The cut-off point that

ffers the maximal value is named maximal Youden index,nd it is the estimated optimal cut-off point. Agreementetween MRA and GPS was calculated using the un-

IGURE 2. Scatterplot demonstrating the mean deviationMD) of the visual field vs glaucoma probability score (GPS) ofhe Heidelberg Retina Tomograph III [HRT III] (linear regres-ion and 95% confidence interval). Open squares, normalroup; closed squares, glaucoma group; triangles, hypertensivesyes (ro, �0.37; P � .001; n � 182).

eighted � coefficient.17 P


RESULTS

DEMOGRAPHICS AND GLAUCOMA PROBABILITY

CORE RESULTS: Demographic data, MRA distribution,nd the GPS in normal, ocular hypertensive, and glauco-atous eyes are shown in Table 1. The median global GPS

alues were 0.24 (IR, 0.10 to 0.70) in the normal group,.37 (IR, 0.12 to 0.76) in the ocular hypertensive group,nd 0.84 (IR, 0.48 to 0.91) in the glaucoma group (P �001). The sectorial GPS values also differed among theroups (P � .001). No significant differences were found inhe global GPS value (P � .27) or in sectorial GPS valuesP � .05) between normal and ocular hypertensive eyes.he median and IRs of the global GPS value were 0.26

IR, 0.11 to 0.69) in cases with normal glaucoma hemifieldest results and 0.85 (IR, 0.50 to 0.91) in cases with ONLlaucoma hemifield test results (P � .001). The differenceslso were significant in every GPS sector compared withhe glaucoma hemifield test classification (P � .001). Inhree normal eyes, one ocular hypertensive eye, and threelaucomatous eyes, the GPS failed to provide a sectoriallassification; these cases were excluded from the enrolledroup.

GLAUCOMA PROBABILITY SCORE AND VISUAL FIELD

ARAMETERS: A significant relationship was found be-ween the MD of the Humphrey visual field and the global

RA value (ro, �0.37; P � .001; Figure 2) and betweenhe MD and sectorial GPS values (P � .001). A significantorrelation was found between the pattern standard devi-tion (PSD) of the Humphrey visual field and the globalPS value (ro, 0.40; P � .001; Figure 3) and between the

IGURE 3. Scatterplot demonstrating the pattern standardeviation (PSD) of visual field vs GPS of the HRT III (linearegression and 95% confidence interval). Open squares, normalroup; closed squares, glaucoma group; triangles, hypertensivesyes (ro, 0.40; P � .001; n � 182).

SD and sectorial GPS values (P � .001), with the


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earson correlation ranging between 0.42 in the temporalPS sector and 0.40 in the temporal inferior GPS sector.

GLAUCOMA PROBABILITY SCORE AND MOORFIELDS

EGRESSION ANALYSIS COMPARISON: In relation to thelaucoma definition, the sensitivity and specificity usingRA were 39.8% (95% confidence interval [CI], 29.35 to

1.11) and 93.2% (95% CI, 82.72 to 97.80; most specificriteria) and 68.7% (95% CI, 57.43 to 78.16) and 83.1%95% CI, 70.57 to 91.14, least specific criteria), respec-ively. The MRA sensitivity and specificity in relation to

IGURE 4. Receiver operating characteristic (ROC) curve foriscriminating between healthy and glaucomatous eyes usingoorfields regression analysis (MRA) classification (dotted

ine) and GPS classification (solid line). The area under theOC curve is 0.76 in the MRA and 0.73 in the glaucomarobability score.

TABLE 2. Sensitivity and Specificity of Moorfields

Most Specific Criteria*

Moorfields Regression Analysis Glaucoma Proba

Sensitivity (%) Specificity (%) Sensitivity (%)

Temporal 20.5 100 69.9

Temporal superior 32.5 100 60.2

Temporal inferior 47 93.2 69.9

Nasal 34.9 89.8 69.9

Nasal superior 37.3 91.5 67.5

Nasal inferior 55.4 93.2 68.7

Global 39.8 93.2 71.1

*With borderline considered negative.†With borderline considered positive.

he glaucoma hemifield test definition were 43.3% (95% 0


I, 31.14 to 55.91) and 88.5% (95% CI, 77.17 to 94.87;ost specific criteria), and 67.2% (95% CI, 54.49 to

7.85) and 77% (95% CI, 64.19 to 86.45; least specificriteria), respectively. When the GPS was compared withhe glaucoma definition, the sensitivity and specificityere 71.1% (95% CI, 59.94 to 80.25) and 69.5% (95% CI,5.97 to 80.45; most specific criteria) and 85.5% (95% CI,5.71 to 91.98) and 54.2% (95% CI, 40.84 to 67.07; leastpecific criteria). The GPS sensitivity and specificity inelation to the glaucoma hemifield test definition were6.1% (95% CI, 66.87 to 85.33) and 67.3% (95% CI,3.88 to 78.36; most specific criteria) and 89.6% (95% CI,9.06 to 95.34) and 50.8% (95% CI, 37.83 to 63.70; leastpecific criteria).

Table 2 shows the sensitivity and specificity in eachector using most and least specific criteria. The sensitivitynd specificity of the MRA and GPS were similar in eyesith high-quality images (topographic SD � 15 �m) and

n eyes with a topographic SD between 15 and 30 �m (P �05). In the early glaucoma group (42 eyes, MD � �5 dB),he global MRA sensitivity was 35.7% and the global GPSensitivity was 61.9% (most specific criteria; difference notignificant compared with all eyes; P � .05), and theensitivity of MRA and GPS were 66.7% and 83.3%,espectively (least specific criteria; not significant com-ared with all eyes; P � .05). When the global GPS andlobal MRA were evaluated together, when one or bothere altered, the sensitivity was 74.7% (95% CI, 63.75 to3.32), the specificity was 69.5% (95% CI, 55.97 to0.45), and the area under the ROC curve 0.73.The ROC curve of the GPS and the MRA global

lassification are shown in Figure 4. The cut-off value forhe global GPS in the ROC curve that best discriminatedetween glaucomatous and normal eyes was 0.70 (sensitiv-ty, 66.26%; specificity, 77.96%; Youden index, 0.44). Thereas under the ROC, evaluated in the global GPS andach sector, varied from 0.76 in the nasal GPS sector to

ression Analysis and Glaucoma Probability Score

Least Specific Criteria†

core Moorfields Regression Analysis Glaucoma Probability Score

city (%) Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%)

.2 38.6 96.6 81.9 55.9

56.1 88.1 77.1 71.2

.6 61.4 84.7 80.7 59.3

.9 53 84.7 83.1 59.3

.2 60.2 86.4 83.1 59.3

.6 68.7 86.4 81.9 55.9

.5 68.7 83.1 85.5 54.2

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GLAUCOMA PROBABILITY SCORE DISPLACEMENT:

he GPS was displaced in 35 eyes (19.2%), always in theorizontal axis. The number of cases with a displaced GPSas higher in glaucomatous than normal cases (P � .04;able 1). A displaced GPS was unrelated to topographicD (P � .09), optic disk size (P � .46), or patient age (P �

09). No relationship was observed between GPS sensitiv-ty and specificity in all eyes and eyes without a displacedPS (P � .05).

GLAUCOMA PROBABILITY SCORE AND MOORFIELDS

EGRESSION ANALYSIS AGREEMENT: Table 4 shows thegreement between the global MRA and global GPS.omplete agreement was seen in 103 eyes (56.6%), with acoefficient of 0.34 (95% CI, 0.23 to 0.45). Complete

greement was found in the 49% of glaucomatous eyes,2.5% of ocular hypertensives eyes, and 62.7% of healthyyes (P � .43). If the displaced GPS cases were excluded,he � coefficient was 0.37 (95% CI, 0.25 to 0.49; P � .34ompared with agreement in all eyes). The agreement also

TABLE 3. Area under the Receiver Operatingand Youden Index for Differentiating bet

Glaucoma Probability Score of t

Area Under the

ROC Curve

95% C

In

Temporal 0.775 0.69

Temporal superior 0.792 0.71

Temporal inferior 0.782 0.70

Nasal 0.768 0.69

Nasal superior 0.776 0.70

Nasal inferior 0.782 0.70

Global 0.771 0.69

ROC � receiver operating characteristic.

*Statistical significance of the area under the†Cut-off point between sensitivity and specifi

eyes, according to the maximal Youden index.‡Maximal Youden index (� � sensitivity � sp

TABLE 4. Agreement between Moorfields RegressionAnalysis and Glaucoma Probability Score (No. Cases)

Moorfields Regression Analysis

WNL BL ONL Total

Glaucoma probability score

WNL 56 4 1 61

BL 21 9 2 32

ONL 27 24 38 89

Total 104 47 41 182

BL � borderline; ONL � outside of normal limits; WNL �

within normal limits.

as unrelated to spherical equivalent (P � .34), quality of s


he HRT III measurement (defined as topographic SD; P �79), or optic disk size (P � .93). Agreement betweenectorial MRA and sectorial GPS classifications variedetween � values of 0.12 (minimum � in the temporalector) and 0.35 (maximum � in the nasal inferior sector).

DISCUSSION

HE MRA, DEVELOPED TO IMPROVE HRT DIAGNOSTIC ABIL-

ty, considers variability in the area of the optic disk in theuantitative evaluation of the rim area. The MRA tech-ique uses linear regression of the rim area by disk area to

mprove the HRT diagnostic capacity.7,18 In early glau-oma, sensitivity of 84.6% and specificity of 95.8% wereeported.18 Subsequently, different sensitivity and specific-ty have been reported for a number of reasons.19–24 First,ptic disk shapes and cup sizes vary widely in normal andpen-angle glaucoma populations.24–26 Second, the sensi-ivities and specificities depend on the severity or stage oflaucoma.21 There also are differences in the diagnosis oflaucoma depending on the techniques compared, such asisual field, stereophotographs, and other.18,20 There areifferent visual field criteria to define glaucomatous dam-ge.22 Other studies also have shown the importance of opticisk size and race in the classification of glaucomatous orealthy eyes using the MRA.24,27,28 However, despite differ-nt criteria and fair sensitivity, MRA has a high specificity,hich limits the number of false-positive test results.22

The new HRT III offers changes that attempt toncrease diagnostic precision, including a normative data-ase of 733 healthy white eyes and a new GPS algorithm.29

ntil now, few reports have been published regardingncreased MRA sensitivity using the HRT III and thesefulness of GPS in glaucoma detection.30–32 In the current

racteristic Curve, 95% Confidence Interval,Normal and Glaucomatous Eyes Using

eidelberg Retina Tomograph III

nce

P value* Cut-off (�, %)†Youden

Index‡

52 .001 0.68 0.44

65 .001 0.73 0.48

57 .001 0.77 0.44

47 .001 0.70 0.43

54 .001 0.60 0.43

57 .001 0.72 0.46

49 .001 0.70 0.44

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sing HRT III, which is slightly inferior to 71.4% or 78%ublished previously.31,32 The discrepancy might have re-ulted from the fact that 50% of our patients had earlylaucoma—higher than the 30% reported previously.32 TheRA specificity was similar to that of previous studies.31,32

Regarding the GPS algorithm, we obtained sensitivityimilar to other studies and the specificity was lower.31,32

hus, the GPS has a tendency for higher sensitivity andower specificity compared with MRA, but the area underhe ROC curve is similar in the MRA and GPS, suggestinghat the relation between sensitivity and specificity isimilar in both. However, our best results were obtainedhen considering BL GPS values as negative results andL MRA values as positive results.We also analyzed the MRA and GPS together, evaluat-

ng the results if one or both were altered. We obtained aensitivity of 74.7% and a specificity of 69.5%. As reportedreviously,31 combining MRA with GPS did not increaseiagnostic performance significantly because the area un-er the ROC curve was similar to the MRA or GPSeparately. The cut-off in the GPS value according to theaximal Youden index was 0.70. Although the HRT III

atabase provides a classification of ONL with scoresxceeding 65%, our results suggest that the best limit maye 70%. Sectorial analysis also obtained values exceeding5% in all sectors except the nasal superior sector.The correlation between visual fields indices and mor-

hologic optic disk parameters is important for earlyetection of glaucomatous field loss. Different reports haveuggested a correlation between different visual field tech-iques and HRT parameters.33–37 Iester and associateseported a correlation between HRT parameters and the

D or PSD of white-white visual field.33 Teesalu andssociates reported a strong correlation between cup shapend the MD of the blue-on-yellow visual fields.35,36 Inddition, in early-stage glaucoma, most HRT variablesorrelated better with the blue-on-yellow MD than withhe white-white MD visual fields.36 Iester and associates,ho evaluated the association between HRT parametersnd frequency doubling technology (FDT), found that cuphape was the most significant factor correlating FDT

D.34 González de la Rosa and associates, using Octopusisual fields, also found that HRT indices correlated wellith some Octopus parameters.37 Finally, Jampel andssociates reported that changes in structural HRT param-ters predict visual field damage progression.38 In theurrent study, we compared MD and PSD with the GPSalue and found a significant but weak correlation betweenhe global GPS value and these visual field parameters.his correlation also was found between MD or PSD andll sectorial GPS values. To our knowledge, no previoustudies have reported this relationship. This weak correla-ion may be because the GPS is not a measure of theeverity of optic disk damage as much as optic nerveamage probability, although GPS score should increase
ith optic nerve damage. d

Complete agreement between MRA and GPS was foundn 56.6% of cases with a � coefficient of 0.34. Burgansky-liash and associates30 reported agreement of 78.5% (�,.56), and Coops and associates reported agreement of1% (�, 0.52).31 The reason for this discrepancy in theurrent study also might have been the number of eyesith early glaucoma. Various studies have reported that

he sensitivity of both algorithms decreases, especially forRA, in eyes with early glaucoma.31,32 Thus, agreementas lower in our cases because the sensitivity was higher inPS than in MRA in early glaucoma.In the current study, GPS displacement was evaluated to

etermine if the results in cases should be excluded. ThePS software provides automated analysis of the optic disk

hape without manual definition of the optic disk margin.fter the GPS was performed in our patients, we observed

hat in a group of patients, the GPS symbols were displacedn relation to the optic disk center. To our knowledge, norevious reports have been published on GPS displace-ent or regarding whether the GPS displaced should be

onsidered invalid values. Displaced GPS was defined inhis study when a symbol was outside the optic disk and thepposite symbol was inside the optic disk. We found 35yes with GPS displaced according to our classification,nd the frequency was higher in glaucomatous eyes than inormal eyes. When we evaluated the optic disk with GPSisplacement, we found that with a normal disk, displace-ent was an effect of the optic disk with no cup or a

hallow cup. In glaucomatous eyes, the cause was anncentered cup or a big cup. However, the sensitivity andpecificity did not change if these eyes were excluded,ecause most cases were glaucomatous and the GPS resultsndicate glaucoma. In addition, MRA and GPS agreementid not improve if these cases were excluded. GPS is basedn optic nerve head and RNFL shapes in the topographiceripapillary area, and symbol displacement does notecessarily produce an error in the GPS algorithm. Inddition, in the original description of the GPS algo-ithm,14 the best parameter of the model was horizontalmage curvature; all displaced cases in the current studyad horizontal displacement. Thus, the effect on theesults could be low. Although GPS displacement did notodify GPS evaluation, our results must be considered

autiously because our GPS displacement classification isubjective. Further studies should determine more abouthe importance of the GPS displacement.

This report had some limitations. First, the number ofatients is low, because some patients with glaucoma hadataract or macular diseases that produced high topo-raphic SD or fixation movements. In addition, only eyesith a topographic SD of 30 �m or fewer, and in other

tudies were included cases with a topographic SD of 40m or less.32,38 However, the number of patients was

imilar to that of other studies using HRT III.30,32 Second,he definition of glaucoma included only visual field
amage without including an optic disk evaluation that

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ight have affected the low sensitivity of the MRAlassification. This might have resulted in including eyesith high IOP and no functional damage but initial

tructural damage in the ocular hypertensives group thatid not affect the sensitivity and specificity curves. How-ver, we used two different definitions of glaucoma dam-ge, that is, a cluster of three contiguous locations alteredn the visual field and a glaucoma hemifield test classifica-ion of normal or ONL. In addition, we compared bothunctional and structural damage. If we had included anptic nerve evaluation in the glaucoma classification, weould have introduced bias into the HRT III results. Inddition, despite the fact that different technicians placedhe contour line, which may have affected the results, thislso reflects the clinical situation, and the contour lines inll cases later were revised by two authors. Despite theimitations, our results have contributed to the knowledgebout HRT III optic disk study, particularly when compar-
ng MRA and GPS. l
moscope. Ophthalmology 1998;105:1557–1563.

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In conclusion, this study compared GPS and MRA inRT III and found that GPS has more sensitivity and

ess specificity than MRA in detecting glaucoma. Theest relation between sensitivity and specificity wasbtained when considering BL as a negative test resultor GPS and a positive test for MRA. The GPS did notiscriminate between normal and ocular hypertensivesyes. GPS displacement was seen in 19% of cases andas seen more frequently in patients with glaucoma.hen the GPS was displaced, GPS sensitivity and

pecificity were unchanged. The GPS cut-off betweenormal and glaucomatous eyes was 0.70. The agreementetween GPS and MRA was low, with a � coefficient of.34. Our results suggest that GPS could be a valuablelgorithm for glaucoma detection and screening withoutperator-dependent contour line placement. GPS has aonsiderable advantage over MRA in early-stage glau-oma. Further studies are needed to determine the
imitations of this new GPS algorithm.
HE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN CONCEPT ANDesign (J.M.-M., A.A.); analysis and interpretation (J.M.-M., A.A.); data collection (N.G., L.M., E.A.); writing the article (J.M.-M., N.G.); criticalevision (A.A.); statistical expertise (N.G., M.A.S.); literature search (E.A., M.A.S.); and final approval (J.M.-M.). This study and data accumulationre in conformity with all Spanish laws, that informed consent has been obtained from each patient and the study is in adherence to the tenets ofeclaration of Helsinki.

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Biosketch

avier Moreno-Montañes, MD, PhD, is a medical consultant of the Department of Ophthalmology, Clínica Universitariae Navarra, Universidad de Navarra, Pamplona, Spain. He is the Chairman and full Professor of Ophthalmology in theedical School since 1992. Dr Moreno-Montañes obtained his MD and PhD from the Universidad Autónoma de

arcelona and Universidad de Sevilla. He is a reviewer of different international journals of ophthalmology. His researchnterest are glaucoma tools, diagnosis tools, cataract surgery, combined surgery of glaucoma, and corneal procedures.

HRT III IN NORMAL, OCULAR HYPERTENSIVE, AND GLAUCOMATOUS EYESOL. 145, NO. 2 368.e1

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