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Comparison of Retinal Nerve Fiber LayerThickness and Optic Disk Algorithms withOptical Coherence Tomography to Detect

Glaucoma

ANITA MANASSAKORN, MD, KOUROS NOURI-MAHDAVI, MD,

AND JOSEPH CAPRIOLI, MD

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PURPOSE: To compare the performance of the retinalerve fiber layer (RNFL) thickness and optic disk algo-ithms as determined by optical coherence tomography toetect glaucoma.DESIGN: Observational cross-sectional study.METHODS: SETTING: Academic tertiary-care center.

TUDY POPULATION: One eye from 42 control subjects and5 patients with open-angle glaucoma with visual acuityf >20/40, and no other ocular pathologic condition.BSERVATION PROCEDURES: Two optical coherence tomog-aphy algorithms were used: “fast RNFL thickness” andfast optic disk.” MAIN OUTCOME MEASURES: Area underhe receiver operating characteristic curves and sensitiv-ties at fixed specificities were used. Discriminating abil-ty of the average RNFL thickness and RNFL thicknessn clock-hour sectors and quadrants was compared withhe parameters that were derived from the fast optic disklgorithm. Classification and regression trees were usedo determine the best combination of parameters for theetection of glaucoma.RESULTS: The average visual field mean deviation

�SD) was 0.0 � 1.3 and �5.3 � 5.0 dB in the controlnd glaucoma groups, respectively. The RNFL thicknesst the 7 o’clock sector, inferior quadrant, and the vertical/D ratio had the highest area under the receiver oper-

ting characteristic curves (0.93 � 0.02, 0.92 � 0.03,nd 0.90 � 0.03, respectively). At 90% specificity, theest sensitivities (�SE) from each algorithm were 86%

3% for RNFL thickness at the 7 o’clock sector and9% � 4% for horizontal integrated rim width (esti-ated rim area). The combination of inferior quadrantNFL thickness and vertical C/D ratio achieved the best

lassification (misclassification rate, 6.2%).CONCLUSION: The fast optic disk algorithm performs

s well as the fast RNFL thickness algorithm for discrim-nation of glaucoma from normal eyes. A combination of

he two algorithms may provide enhanced diagnostic

Ie

© 2006 BY ELSEVIER INC. A002-9394/06/$32.00oi:10.1016/j.ajo.2005.08.023

erformance. (Am J Ophthalmol 2006;141:105–115.2006 by Elsevier Inc. All rights reserved.)

UBJECTIVE EVALUATION OF THE OPTIC DISK AND

retinal nerve fiber layer (RNFL) is the currentstandard for detection of early and internal structural

amage in glaucoma. However, this subjective approach isssociated with high intra- and interobserver variability.1

n recent years, new imaging techniques for detection oftructural damage in glaucoma have been introduced.ptical coherence tomography (OCT), one of the prom-

sing technologies, uses near-infrared light to produceigh-resolution cross-sectional images of the retina androvides quantitative measurements. Various OCT algo-ithms have been used for evaluation of the optic nerve andetina.2–4 For detection of glaucoma, the fast RNFL thick-ess5–15 and the fast optic disk algorithms of StratusOCT14–17

ave been explored recently. Both algorithms generateuantitative data that are amenable to statistical andraphic analyses. However, there is limited informationvailable regarding the comparative performance of thewo algorithms to detect glaucoma.14,15 The purpose of thistudy was to compare the performance of the fast RNFLhickness and the fast optic disk algorithms of the OCTmodel 3000, StratusOCT; software version 3.0; Carl Zeisseditec Inc, Dublin, California) for the detection of early

o moderate glaucoma.

ccepted for publication Aug 5, 2005.From the Glaucoma Division, Jules Stein Eye Institute, University of

alifornia Los Angeles, Los Angeles, California.Presented as a poster at the annual meeting of ARVO, May 1–5, 2005,

ort Lauderdale, Florida.Supported by a grant from “Research to Prevent Blindness” and from

he National Institutes of Health R01 EY12738.Inquiries to Joseph Caprioli, MD, Glaucoma Division, Jules Stein Eye

nstitute, 100 Stein Plaza, Los Angeles, CA 90095; fax: 310-206-7773;-mail: caprioli@jsei.ucla.edu

LL RIGHTS RESERVED. 105

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MATERIAL AND METHODS

HIS OBSERVATIONAL CROSS-SECTIONAL STUDY WAS CON-

ucted at the Glaucoma Division, Jules Stein Eye Institute,niversity of California at Los Angeles. The University’s

nstitutional review board approved this investigation, andll participants gave their approval and signed an informedonsent form to participate in the study. Eligible partici-ants were recruited from a clinical database or werenrolled prospectively. Patients with glaucoma and theontrol group met the following criteria: age �40 years,isual acuity �20/40, spheric refractive error between �6nd �6 diopters (D), astigmatism �3 diopters, and in-raocular pressure �8 mm Hg at the time of the OCTxamination. Eligible eyes had a SITA-standard 24 to 2umphrey visual field available within 6 months of theCT measurement. Patients who had other intraocular oreurologic diseases that affected the RNFL, optic disk orisual field, secondary causes for increased intraocularressure, and nonglaucomatous disk abnormalities werexcluded.

The control group was recruited from university staff,atient spouses, and volunteers. They had no history ofcular symptoms or diseases and no previous incisional oraser surgery. All participants had normal anterior seg-ents on slit-lamp biomicroscopy, open angles on gonios-

opy, normal posterior segments by indirectphthalmoscopy at the slit-lamp, and reliable normalITA-standard 24 to 2 Humphrey visual fields. A reliableisual field was defined as one with �30% fixation loss,alse-positive, and false-negative responses. A normal visualeld was defined as a visual field with a glaucoma hemifieldest result within normal limits and a pattern standardeviation with a probability value of �5%. All glaucomaases had open-angle glaucoma (primary high- or low-ension glaucoma, exfoliative or pigmentary glaucoma)nd had reliable abnormal Humphrey visual fields con-rmed at least once. A glaucomatous visual field defect wasefined as a visual field with a glaucoma hemifield testesult outside normal limit and a pattern standard devia-ion with probability value of �5% confirmed on at leastne visual field.OCT was used to image the RNFL and the optic nerve

ead (ONH). Imaging with the two algorithms was per-ormed at the same session by an experienced ophthalmichotographer. For the fast RNFL thickness protocol, three.4-mm diameter circular scans were acquired over 1.92econds. A good quality image was defined as an image witheneralized signal distribution, a reflectance signal fromither RNFL or retinal pigment epithelium strong enougho identify either layer, and no missing parts caused by eyeovement. The segmentation line that defines the upper

nd lower border of the RNFL must be on the internalimiting membrane and lower border of the RNFL. The-scan value and signal-to-noise ratio are provided on the

nalysis printout. Images with �90% satisfactory A-scan d

AMERICAN JOURNAL OF06

r a signal-to-noise ratio of �25 dB were excluded.18

omparison to an age-matched normative database iserformed automatically by the OCT and provides quan-itative, color-coded data. The OCT RNFL thickness dataere exported to a personal computer. Left eye data areonverted automatically into right eye format during thexport procedure. The following parameters were calcu-ated: average RNFL thickness, RNFL thickness in theuperior and inferior hemifields, RNFL thickness in fouruadrants (superior: 46 to 135 degrees; nasal: 136 to 225

IGURE 1. The fast optic disk algorithm orientation andraphic output display. A, Orientation of the six linear scans ofhe individual radial scan analyses from the fast optic disklgorithm of optical coherence tomography. B, An example ofhe graphic output display of the fast optic disk algorithm. Fivearameters are derived from each of the six individual radialcan analyses: rim area (area above the line dividing theeuroretinal rim and the cup to the anterior surface of the opticisk: red-hashed area, [A]); average nerve width at disk (theeight of the nerve fiber bundle: straight yellow line [B]); diskiameter (the distance between the inner edges of the retinaligment epithelium: straight blue line [C]); cup diameter (theength of the line that connects the outermost borders of theup at the level of 150 �m above the disk reference line:ashed, straight red line [D]); and rim length (disk diameterinus the cup diameter [E]).

egrees; inferior: 226 to 315 degrees, and temporal: 316 to

OPHTHALMOLOGY JANUARY 2006

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5 degrees), and RNFL thickness in twelve 30-degreelock hour sectors.

The fast optic disk algorithm performs six 4-mm radialinear scans in 1.92 seconds (Figure 1A). For each scan,he A-scan detects the anterior surface of the RNFL andhe retinal pigment epithelium (retinal pigment epithe-ium). Then, the boundary of the optic disk (disk referenceine) is defined as the inner edge of the retinal pigmentpithelium and used as the reference to calculate all theast optic disk parameters. A line located 150 �m abovehe level of the retinal pigment epithelium and runningarallel to the line that connects the edge of the retinaligment epithelium on the two sides of the disk isefined as the dividing line between the neuroretinalim and the cup. There are two output displays, thendividual radial scan analysis and the ONH analysis.rom the individual radial scan analysis, the followingve parameters are evaluated (Figure 1B): rim area,verage nerve width at disk, disk diameter, cup diame-er, and rim length. The OCT uses the aforementioned

TABLE 1. Demographic Characteristics of the Study SampleDisc Algorithms With Optical Cohere

Control

Total no. of eyes

Right 21 (50%)

Left 21 (50%)

Age (y)

Mean 57.9

SD 8.6

Range 40–78

Race (n)

White 25 (60%)

Black 1 (2%)

Hispanic 8 (19%)

Asian 8 (19%)

Sex (n)

Male 16 (38%)

Female 26 (62%)

Spheric equivalent (D)

Mean –0.3

SD 1.8

Range –5.4–2.5

Mean deviation (dB)

Mean 0.0

SD 1.3

Range �2.5 to 3.9 �2

Pattern standard deviation (dB)

Mean 1.5

SD 0.3

Range 1.1 to 2.1 1

*Chi-square test.†Unpaired t-test.‡Mann-Whitney Test.

easurements to calculate the eight parameters of the t

COMPARISON OF DIFFERENTOL. 141, NO. 1

NH analysis printout: vertical integrated rim areaVIRA), horizontal integrated rim width (HIRW), diskrea, cup area, rim area, cup/disk (C/D) area ratio,orizontal C/D ratio, and vertical C/D ratio. VIRA is anstimation of the total volume of the neuroretinal rim,nd HIRW is the estimated total neuroretinal rim area.utomated data are generated from the ONH analysis of

he OCT without any correction for misidentification ofhe retinal pigment epithelium edge. Manual correctionf the retinal pigment epithelium edge location is alsoossible. For manual correction, the scans were assessedndividually; in cases in which the innermost border ofhe retinal pigment epithelium was misidentified, theine was moved manually to fit the edge of the retinaligment epithelium. The ONH analyses were repeatedfter manual correction. We evaluated the performancef automated individual radial scan analyses and theight parameters that were derived from automated andanually corrected ONH analysis and compared themith parameters that were calculated by the RNFL

to Compare Retinal Nerve Fiber Layer Thickness and Opticomography in Detecting Glaucoma

oma P Value Early glaucoma P Value

%) .816* 23 (52%) .833*

%) 21 (48%)

.4 .098‡ 61.2 .092†

.4 9.5

77 42–77

%) .063* 32 (76%) 134*

%) 4 (9%)

%) 5 (11%)

) 3 (7%)

%) .258* 24 (55%) 126*

%) 20 (45%)

.5 .062‡ –0.5 .042‡

.6 1.7

5.8 –4.4–5.8

.3 �.001‡ –2.5 �.001†

.0 1.6

o 0.85 �5.4 to 0.9

.8 �.001‡ 3.8 �.001‡

.0 2.4

15.1 1.5 to 15.1

Usednce T

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hickness algorithm. All of the analyses were repeated

ALGORITHMS OF OCT 107

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or a subset of glaucomatous eyes with early glaucomamean deviation, ��6.0 dB).

Unpaired Student t test, chi–square, or Mann-Whitneyests were used to compare the glaucoma and normalroups. Receiver operating characteristic curves and sen-itivities and specificities were used to compare the perfor-

TABLE 2. Comparison of Results of the Fast Retinal NerveBetween Normal Patients

Variable Control (mean

Average RNFL thickness (microns) 98.2 (� 1

RNFL thickness at clock hour sectors (microns)

1 112.5 (� 4

2 87.2 (� 3

3 56.3 (� 2

4 66.8 (� 2

5 102.0 (� 3

6 135.6 (� 3

7 143.7 (� 2

8 78.5 (� 2

9 55.6 (� 1

10 84.4 (� 2

11 130.3 (� 3

12 125.4 (� 4

RNFL thickness in hemifields (microns)

Superior 99.7 (� 1

Inferior 96.5 (� 1

RNFL thickness in quadrants (microns)

Superior 122.8 (� 2

Inferior 127.4 (� 2

Temporal 69.4 (� 2

Nasal 73.6 (� 2

Fast optic disc (automated)

VIRA (mm3)* 0.43 (� 0

HIRW (mm2)† 1.68 (� 0

Disc area (mm2) 2.27 (� 0

Cup area (mm2) 0.67 (� 0

Rim area (mm2) 1.60 (� 0

C/D area ratio 0.29 (� 0

Horizontal C/D ratio 0.55 (� 0

Vertical C/D ratio 0.48 (� 0

Fast optic disc (manual)

VIRA (mm3) 0.41 (� 0

HIRW (mm2) 1.65 (� 0

Disc area (mm2) 2.00 (� 0

Cup area (mm2) 0.59 (� 0

Rim area (mm2) 1.40 (� 0

C/D area ratio 0.28 (� 0

Horizontal C/D ratio 0.54 (� 0

Vertical C/D ratio 0.49 (� 0

HIRW � Horizontal integrated rim width (an estimation of the total

of the total volume of the RNFL tissue in the rim).

*Unpaired t-test.†Mann-Whitney test.

ance of the two algorithms and to assess the multivariate a

AMERICAN JOURNAL OF08

odels. We used classification and regression treesCART) methods (software version 3.1; SPSS Inc, Chi-ago, Illinois) for determining the optimal parsimoniousombination of parameters from both algorithms that havehe highest performance for discrimination of glaucoma-ous from normal eyes. Logistic regression or discriminant

r Layer (RNFL) Thickness and Fast Optic Disc AlgorithmsPatients With Glaucoma

Glaucoma Early Glaucoma

Mean (� SE) P Value Mean (� SE) P Value

73.0 (� 2.1) �.001* 76.6 (� 2.3) �.001*

82.8 (� 3.4) �.001* 82.4 (� 4.3) �.001*

72.5 (� 2.9) .002* 73.8 (� 3.7) .011*

53.4 (� 1.8) .281† 53.7 (� 2.2) .360†

59.5 (� 2.1) .047† 60.9 (� 2.6) .131†

74.7 (� 3.0) �.001* 77.2 (� 3.1) �.001*

87.9 (� 3.7) �.001† 95.6 (� 4.3) �.001*

88.7 (� 3.9) �.001† 99.9 (� 4.2) �.001*

56.9 (� 2.3) �.001* 61.9 (� 2.9) �.001*

48.5 (� 1.8) �.001† 49.7 (� 2.1) .029*

65.1 (� 3.2) �.001* 69.1 (� 3.3) .001*

91.0 (� 4.3) �.001† 98.1 (� 4.9) �.001*

94.5 (� 4.1) �.001* 96.6 (� 5.2) �.001*

76.6 (� 2.6) �.001* 79.1 (� 3.0) �.001*

69.2 (� 2.0) �.001* 73.9 (� 2.1) �.001*

89.5 (� 3.4) �.001† 92.4 (� 4.2) �.001*

84.0 (� 3.1) �.001* 91.3 (� 3.2) �.001*

61.7 (� 2.0) .022† 62.6 (� 2.6) .070*

56.7 (� 2.2) �.001† 60.1 (� 2.4) �.001*

0.15 (� 0.02) �.001† 0.16 (� 0.02) �.001†

1.23 (� 0.04) �.001* 1.27 (� 0.04) �.001*

2.38 (� 0.06) .243* 2.32 (� 0.07) .620*

1.37 (� 0.07) �.001† 1.29 (� 0.08) �.001†

1.01 (� 0.05) �.001† 1.03 (� 0.06) �.001*

0.57 (� 0.02) �.001† 0.55 (� 0.03) �.001*

0.77 (� 0.02) �.001† 0.76 (� 0.02) �.001†

0.72 (� 0.02) �.001† 0.70 (� 0.02) �.001*

0.14 (� 0.02) �.001† 0.15 (� 0.02) �.001†

1.16 (� 0.04) �.001† 1.22 (� 0.04) �.001*

2.03 (� 0.05) .674† 2.04 (� 0.06) .610†

1.19 (� 0.07) �.001† 1.15 (� 0.07) �.001†

0.81 (� 0.05) �.001† 0.86 (� 0.06) �.001*

0.58 (� 0.02) �.001† 0.56 (� 0.03) �.001†

0.76 (� 0.02) �.001† 0.76 (� 0.02) �.001†

0.74 (� 0.02) �.001† 0.72 (� 0.02) �.001*

oretinal rim area); VIRA � vertical integrated rim area (an estimation

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OPHTHALMOLOGY JANUARY 2006

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umber of correctly classified cases is so high and becauseoth models would lead to inflated odds ratios. The CARTpproach is particularly well suited for this kind of high-imensional data with relatively few cases. CART softwareakes no previous assumptions regarding the distribution

f the data or the relationship of each variable with the

TABLE 3. The Area Under the Receiver OFast Retinal Nerve Fiber Layer (RNFL) T

Entire G

Variable

Average RNFL thickness (microns)

RNFL thickness at clock hour sectors (micron

1

2

3

4

5

6

7

8

9

10

11

12

RNFL thickness in hemifields (microns)

Superior

Inferior

RNFL thickness in quadrants (microns)

Superior

Inferior

Temporal

Nasal

Fast optic disc (automated)

VIRA (mm3)*

HIRW (mm2)†

Disc area (mm2)

Cup area (mm2)

Rim area (mm2)

C/D area ratio

Horizontal C/D ratio

Vertical C/D ratio

Fast optic disc (manual)

VIRA (mm3)

HIRW (mm2)

Disc area (mm2)

Cup area (mm2)

Rim area (mm2)

C/D area ratio

Horizontal C/D ratio

Vertical C/D ratio

HIRW � Horizontal integrated rim width (an

vertical integrated rim area (an estimation of t

utcome (glaucoma or normal status in this case). CART p

COMPARISON OF DIFFERENTOL. 141, NO. 1

oftware explores each variable for the best cutoff pointnd orders the variables according to the probability valuehat is derived from the Pearson’s chi–square or theikelihood ratio, with a Bonferroni adjustment. The vari-bles are used successively to extract the best classificationith the smallest number of variables. The following

ing Curve (AUC) for All Parameters From theess and Fast Optic Disc Algorithms in thema Group

AUC � SE

Sensitivity at Fixed

Specificity (% � SE)

80% 90%

0.89 � 0.03 83 � 4 76 � 4

0.79 � 0.04 66 � 5 51 � 5

0.67 � 0.05 42 � 5 29 � 4

0.56 � 0.06 25 � 4 11 � 3

0.61 � 0.06 40 � 5 25 � 4

0.81 � 0.04 69 � 4 57 � 5

0.90 � 0.03 85 � 3 75 � 4

0.93 � 0.02 89 � 3 86 � 3

0.81 � 0.04 68 � 5 57 � 5

0.71 � 0.05 54 � 5 42 � 5

0.77 � 0.05 65 � 5 54 � 5

0.82 � 0.04 75 � 4 65 � 5

0.77 � 0.05 59 � 5 49 � 5

0.82 � 0.04 72 � 4 68 � 5

0.92 � 0.03 89 � 3 82 � 4

0.82 � 0.04 68 � 5 66 � 5

0.92 � 0.03 86 � 3 79 � 4

0.63 � 0.06 29 � 4 22 � 4

0.80 � 0.05 72 � 4 63 � 5

0.89 � 0.03 82 � 4 72 � 4

0.89 � 0.03 82 � 4 79 � 4

0.59 � 0.06 40 � 5 19 � 4

0.84 � 0.04 77 � 4 62 � 5

0.86 � 0.04 77 � 4 74 � 4

0.88 � 0.03 82 � 4 71 � 4

0.83 � 0.04 71 � 4 52 � 5

0.90 � 0.03 88 � 3 77 � 4

0.89 � 0.03 79 � 4 75 � 4

0.90 � 0.03 85 � 3 82 � 4

0.52 � 0.06 32 � 5 9 � 3

0.83 � 0.04 71 � 4 59 � 5

0.86 � 0.04 79 � 4 77 � 4

0.88 � 0.03 79 � 4 69 � 4

0.84 � 0.04 68 � 5 65 � 5

0.90 � 0.03 85 � 3 79 � 4

ation of the total neuroretinal rim area); VIRA �

tal volume of the RNFL tissue in the rim).

perathicknlauco

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estim

arameters from both algorithms were entered simulta-

ALGORITHMS OF OCT 109

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eously into the model for CART analysis: average RNFLhickness, RNFL thickness at 12 clock hour sectors andour quadrants, and the eight parameters that were derivedrom the fast optic disk algorithm. An � value of .01 forplitting and merging and an equal misclassification cost

TABLE 4. The Area Under the Receiver OFast Retinal Nerve Fiber Layer (RNFL) Thic

Glau

Variable

Average RNFL thickness (microns)

RNFL thickness at clock hour sectors (micron

1

2

3

4

5

6

7

8

9

10

11

12

RNFL thickness in hemifields (microns)

Superior

Inferior

RNFL thickness in quadrants (microns)

Superior

Inferior

Temporal

Nasal

Fast optic disc (automated)

VIRA (mm3)*

HIRW (mm2)†

Disc area (mm2)

Cup area (mm2)

Rim area (mm2)

C/D area ratio

Horizontal C/D ratio

Vertical C/D ratio

Fast optic disc (manual)

VIRA (mm3)*

HIRW (mm2)†

Disc area (mm2)

Cup area (mm2)

Rim area (mm2)

C/D area ratio

Horizontal C/D ratio

Vertical C/D ratio

HIRW � Horizontal integrated rim width (an

vertical integrated rim area (an estimation of t

ere used. Also, a 25-fold cross-validation was performed. a

AMERICAN JOURNAL OF10

To help validate our tree analysis, we did a 25-foldross-validation that omitted a different one-25th of theata (roughly two control subjects, three patients withlaucoma) for each replication. Thus, each replicationsed 42 control subjects and 65 patients with glaucoma,

ing Curve (AUC) for All Parameters From thes and Fast Optic Disc Algorithms in the EarlyGroup

AUC � SE

Sensitivity at Fixed

Specificity (% � SE)

80% 90%

0.88 � 0.04 82 � 4 73 � 4

0.79 � 0.05 66 � 5 50 � 5

0.66 � 0.06 41 � 5 30 � 5

0.56 � 0.06 23 � 4 9 � 3

0.60 � 0.06 39 � 5 21 � 4

0.80 � 0.05 71 � 5 52 � 5

0.86 � 0.04 80 � 4 68 � 5

0.91 � 0.03 86 � 3 82 � 4

0.74 � 0.05 59 � 5 43 � 5

0.69 � 0.06 50 � 5 36 � 5

0.73 � 0.06 59 � 5 46 � 5

0.80 � 0.05 71 � 5 59 � 5

0.74 � 0.05 57 � 5 50 � 5

0.80 � 0.05 68 � 5 61 � 5

0.90 � 0.03 86 � 3 77 � 4

0.80 � 0.05 64 � 5 61 � 5

0.90 � 0.03 82 � 4 73 � 4

0.62 � 0.06 30 � 5 18 � 4

0.76 � 0.05 66 � 5 52 � 5

0.88 � 0.04 82 � 4 66 � 5

0.88 � 0.04 77 � 4 75 � 4

0.55 � 0.06 36 � 5 14 � 3

0.83 � 0.05 75 � 4 52 � 5

0.85 � 0.04 73 � 4 71 � 5

0.88 � 0.04 80 � 4 66 � 5

0.83 � 0.04 68 � 5 50 � 5

0.90 � 0.03 89 � 3 74 � 4

0.88 � 0.04 75 � 4 71 � 5

0.88 � 0.04 82 � 4 77 � 4

0.53 � 0.06 34 � 5 9 � 3

0.83 � 0.04 68 � 5 55 � 5

0.84 � 0.04 75 � 4 73 � 4

0.87 � 0.04 77 � 4 64 � 5

0.83 � 0.04 64 � 5 61 � 5

0.89 � 0.03 84 � 4 75 � 4

ation of the total neuroretinal rim area); VIRA �

tal volume of the RNFL tissue in the rim).

peratknescoma

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estim

nd the rules that were obtained were applied subsequently

OPHTHALMOLOGY JANUARY 2006

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o the remaining one-25th of eyes that were not used inach replication. Splits that were present in all 25 treesere retained for the final model, and the sensitivity and

pecificity was based on the average value across the 25rees.

RESULTS

NE EYE EACH FROM 42 NORMAL CONTROL SUBJECTS AND

5 patients with glaucoma were recruited. The demo-raphic characteristics of the study sample are shown inable 1. The mean age of the control group was not

ignificantly different from that of the glaucoma groupP � .098 and 0.092 for the entire glaucoma and earlylaucoma groups, respectively). Average mean deviation�SD) was 0.0 � 1.3 dB for normal eyes, �5.3 � 5.0 dBor all patients with glaucoma, and �2.5 � 1.6 dB for earlylaucomatous eyes. The mean (�SE) RNFL thickness inhe entire glaucoma group was 73.0 � 17.1 �m andignificantly lower than the control group98.2 � 10.8 �m; P � .001; Table 2). In the entirelaucoma group, the RNFL thickness was significantlyifferent from the control group (P � .001) in superior (1,0, 11, and 12), inferior (5, 6, 7, and 8), and 9 o’clockectors along with the superior, inferior, and nasal quad-ants. Among the 12 clock hour sectors, RNFL thickness athe 7 o’clock sector had the highest area-under-the-eceiver operating characteristic curve (AUC; �SE), fol-owed by the 6 and 11 o’clock sectors (0.93 � 0.02, 0.90 �.03, and 0.82 � 0.04, respectively). Among the fouruadrants, the inferior quadrant had the highest AUC

IGURE 2. Receiver operating characteristic curves for theest parameters of the retinal nerve fiber layer thicknessretinal nerve fiber layer [RNFL] thickness in the 7 o’clockector and the inferior quadrant) and fast optic disk algorithmsvertical C/D ratio) and the average retinal nerve fiber layerhickness in the entire glaucoma group.

0.92 � 0.02; Table 3). The sensitivities for the RNFL s

COMPARISON OF DIFFERENTOL. 141, NO. 1

hickness parameters at 80% and 90% specificities arerovided in Table 3. The highest sensitivity at 90%pecificity belonged to the 7 o’clock (inferotemporal)ector (86% � 3%). In the early glaucoma group, the threeighest AUCs (�SE) belonged to the RNFL thickness athe 7, 6, and 11 o’clock sectors (0.91 � 0.03, 0.86 � 0.04,nd 0.80 � 0.05, respectively). The same locations alsoad the highest sensitivities at fixed specificities (Table 4).All fast optic disk parameters, except disk area, demon-

trated a significant difference between the control andlaucoma groups (P � .001; Table 2). In the entirelaucoma group, the three highest AUCs (�SE) from theutomated analysis belonged to the vertical C/D ratio,IRW, and VIRA (0.90 � 0.03, 0.89 � 0.03, and 0.89 �

.03), respectively (Table 3; Figure 2). The same parame-ers also had the best performance in the following orderfter manual correction: HIRW, vertical C/D ratio, andIRA (AUCs: 0.90 � 0.03, 0.90 � 0.03, and 0.89 � 0.03,

espectively). The AUCs for all parameters, except theisk area, were not significantly different between auto-ated and manually corrected analyses. The HIRW

howed the best sensitivity at 90% specificity with both theutomated method (79% � 4%) and after manual correc-ion (82% � 4%). When only eyes with early glaucomaere evaluated, the three highest AUCs from the auto-ated method were the same (Table 4; Figure 3).The AUCs for the rim area and average nerve width at

isk from the individual radial scan analyses for bothlaucoma groups are described in Table 5. The averageerve width at disk belonging to scan number 1 (1 to 7’clock axis) had the highest AUC of 0.93 � 0.02, with a

IGURE 3. Receiver operating characteristic curves for theest parameters of the retinal nerve fiber layer thicknessretinal nerve fiber layer [RNFL] thickness at the 7 o’clockector and the inferior quadrant) and fast optic disk algorithmsvertical C/D ratio) and the average retinal nerve fiber layerhickness in the early glaucoma group.

ensitivity of 80% � 4% at 90% specificity.

ALGORITHMS OF OCT 111

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We simultaneously evaluated variables from both theast RNFL thickness and the fast optic disk algorithms withART to determine whether an optimal parsimoniousodel could be found (Figure 4). We found that a

ombination of RNFL thickness in the inferior quadrantnd the vertical C/D ratio provided the best accuracy of4% � 2% after cross validation. The nominal sensitivitynd specificity of this multivariate model was 92% (60/65)nd 95% (40/42), respectively.

DISCUSSION

HE CURRENT INVESTIGATION WAS CARRIED OUT TO

valuate and compare the performance of the fast RNFLhickness and fast optic disk algorithms of the OCT. TheNFL thickness in the 7 o’clock sector and in the inferioruadrant had the highest AUC for discrimination betweenormal eyes and eyes with glaucoma. The RNFL thickness

n the 7 o’clock sector was also the most sensitive (86% at0% specificity) among the RNFL thickness parameters.he vertical C/D ratio, HIRW, and VIRA from theutomated ONH analysis had the highest AUC for dis-riminating glaucomatous from normal eyes among the fastptic disk parameters; the highest sensitivities at the 90%pecificity belonged to HIRW and the vertical C/D ratio.mong the parameters for the individual radial scan

nalyses, the average nerve width at disk at scan number 11 to 7 o’clock axis) had the highest AUC.

The performance of the OCT RNFL thickness algo-

TABLE 5. The Area Under the Receiver Operating Characteristhe Rim Area and Average Nerve Width From the Indiv

Individual Radial Scan Parameters

At Scan

Number

Enti

AUC � SE

Rim Area* (mm2)

1 0.88 � 0.03

2 0.86 � 0.04

3 0.83 � 0.04

4 0.87 � 0.04

5 0.88 � 0.03

6 0.87 � 0.04

Average nerve width at disc

(mm)†1 0.93 � 0.02

2 0.88 � 0.03

3 0.86 � 0.04

4 0.87 � 0.03

5 0.91 � 0.03

6 0.88 � 0.03

*The average area above the cup line to the anterior surface of t†The average nerve width from each disc reference point to the n

ithm with different versions of the OCT has been evalu- S

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ted previously. The AUC for the average RNFL thicknessas ranged from 0.73 to 1.00 for the OCT prototype andCT 2000,12,13,19–21 and 0.90 to 0.97 for OCT 3.14,15,22–24

n this study, we found that the AUC of the average RNFLhickness was 0.89 for the entire group and 0.88 for thearly glaucoma group (average mean deviation, �2.5 �.6 dB). The unusually high AUC of 1.00 for the OCTrototype and the OCT 2000 was reported in a sample ofatients with glaucoma with an average mean deviation of12.0 dB,21 which represents advanced visual field loss.he performance of optic nerve and RNFL imaging de-ices depends on how advanced the glaucoma is in theample that is under study. Our findings are consistent withradual improvement of the performance of consecutiveersions of the OCT.An interesting finding of this study was that both

lgorithms performed equally well when only eyes witharly glaucoma were considered. The AUCs and sensitiv-ties were very similar to, but slightly lower than, those forhe entire glaucoma group. The best parameters from theast RNFL thickness and fast optic disk algorithms were theame. These results are consistent with those of Nouri-

ahdavi and associates,13 in which the performance ofCT 2000 in a group of early perimetric patients with

laucoma was reported. Our study also confirms the find-ngs of previous studies that the RNFL thickness in thenferior quadrant has the best discriminating ability foretection of glaucoma.12,14,15,19–25 Similarly, the sensitivityor the best parameters from the fast RNFL thicknesslgorithm was consistent with published studies with

urve (AUC) and the Sensitivity at 80% and 90% Specificity ofRadial Scan Analysis of the Fast Optic Disc Algorithm

coma Group Early Glaucoma Group

Sensitivity at Fixed

Specificity (% � SE)

AUC � SE

Sensitivity at Fixed

Specificity (% � SE)

80% 90% 80% 90%

80 � 4 65 � 5 0.88 � 0.04 80 � 4 57 � 5

61 � 5 52 � 5 0.87 � 0.04 55 � 5 50 � 5

66 � 5 49 � 5 0.85 � 0.04 68 � 5 48 � 5

72 � 4 66 � 5 0.88 � 0.04 73 � 4 64 � 5

83 � 4 71 � 4 0.87 � 0.04 82 � 4 64 � 5

75 � 4 69 � 4 0.87 � 0.04 75 � 4 66 � 5

87 � 3 80 � 4 0.92 � 0.03 85 � 4 75 � 4

77 � 4 58 � 5 0.87 � 0.04 73 � 4 59 � 5

74 � 4 66 � 5 0.86 � 0.04 71 � 5 56 � 5

77 � 4 67 � 5 0.86 � 0.04 72 � 4 60 � 5

87 � 3 74 � 4 0.90 � 0.03 87 � 3 69 � 5

81 � 4 69 � 4 0.87 � 0.04 76 � 4 61 � 5

tic disc from both sides of each scan in vertically.

st point on the anterior surface of the retinal nerve fiber layer.

tic Cidual

re Glau

he op

tratusOCT.14,15,22–24 Despite the advances in OCT tech-

OPHTHALMOLOGY JANUARY 2006

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ology, the sensitivity of both algorithms remains fairlyow at high levels of specificity.

Although measuring the RNFL thickness can providehe clinician with invaluable information regarding thextent of glaucomatous damage, clinical evaluation of theptic nerve is still a mainstay of glaucoma evaluation. Theast optic disk algorithm of the OCT has been introducedo provide the clinician with objective, quantitative ONHeasurements. Wollstein and associates14 and Medeiros

nd associates15 found that the fast optic disk algorithm ofhe StratusOCT performs as well as the fast RNFL thick-ess algorithm. The various ONH parameters, except diskrea, performed equally well in the aforementioned two

IGURE 4. The diagram shows the results of the classificationrom the fast retinal nerve fiber layer thickness and fast opticyes. Vertical C/D ratio p value was determined by Pearson’s

tudies and in the current investigation. The presence of m

COMPARISON OF DIFFERENTOL. 141, NO. 1

eripapillary atrophy can cause the misidentification of theisk margin when the automated ONH analysis of the fastptic disk algorithm is used.16 In these cases, the innerdge of the retinal pigment epithelium or choriocapillarisannot be identified in some scans, and manual correctionhould be used to locate the correct position of the retinaligment epithelium edge. Lai and associates16 investigatedhe influence of peripapillary atrophy on the results of theast optic disk algorithm in 31 subjects. They found thathe findings of the automated fast optic disk are reasonablyccurate and can be used in most cases. The correlationetween automated and manually corrected methods wasigh.17 We found the performance of the automated and

regression trees analysis for the best combination of parameteralgorithms for the discrimination of glaucomatous and normalquare.

anddiskchi–s

anual methods to be similar. Correcting the location of

ALGORITHMS OF OCT 113

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he retinal pigment epithelium border is a time-consumingrocedure and, considering our findings, may need to beerformed only in selected eyes.No previous study has evaluated the individual radial

can analysis. We found that the rim area and the averageerve width at disk performed as well as other disk orNFL parameters. A single radial scan of the optic disk

the scan number 1 at 1 to 7 o’clock axis) had an AUChat was similar to that of the RNFL thickness at the 7’clock sector. This finding can be applied clinicallyecause the use of only a single scan for glaucomacreening may be a useful time- and cost-efficientpproach.

We used the CART analysis to find the optimal parsi-onious combination of parameters for detecting glau-

oma. As shown in Figure 4, the first parameter to be usedor classification by CART was the RNFL thickness in thenferior quadrant followed by the vertical C/D ratio of theast optic disk algorithm. The combination of these twoarameters resulted in a low misclassification rate (6.2%).owever, we must emphasize that, given the high corre-

ation and good discriminating ability of many of theNFL and ONH parameters, there are potentially otherairwise combinations of different variables that couldork nearly as well. The CART analyses are helpfulotentially for defining clinically useful cutoff points thatave immediate application for the clinician (Figure 4).onfirmation of our findings in other groups of patientsith glaucoma is required before the results can beeneralized.

One limitation of our study is that there is no generallyccepted criteria for the definition of a good quality scanith the fast optic disk algorithm. To avoid bias in the

election of fast optic disk images, we included all the fastptic disk images of patients whose RNFL images wereonsidered eligible on the basis of the criteria describedarlier. This may have led to the inclusion of poor images.owever, any such bias would have led to a worse

erformance of the fast optic disk algorithm compared withhe fast RNFL thickness algorithm.

In conclusion, the performance of the fast RNFL thick-ess and fast optic disk algorithms for the detection of earlylaucoma are similar, and both can be used clinically toetect early glaucomatous damage. A combination of theesults from both algorithms leads to a better diagnosticrecision. The use of only one scan from the individualadial scan analysis may be a useful and practical tool forlaucoma screening.

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Biosketch

nita Manassakorn, MD, is Visiting Assistant Professor, Glaucoma Division, at Jules Stein Eye Institute, UCLA, Losngeles, CA and Instructor in Ophthalmology, at Chiang Mai University, Chiang Mai, Thailand. Her research interests

nclude imaging in glaucoma, visual field progression, and glaucoma management.

AMERICAN JOURNAL OF OPHTHALMOLOGY15.e1 JANUARY 2006