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Development of Topographic Scoring

System for Identifying Glaucoma in Myopic


Eyes
A Spectral-Domain OCT Study
Sung Uk Baek, MD,1,2,* Ko Eun Kim, MD, PhD,3,* Young Kook Kim, MD,1,2 Ki Ho Park, MD, PhD,1,2
Jin Wook Jeoung, MD, PhD1,2

Purpose: To develop a new scoring system that uses topographic diagnostic signs of spectral-domain (SD)
OCT to enhance glaucoma diagnostic performance for myopic eyes and to validate the system’s diagnostic
ability.
Design: Cross-sectional study.
Participants: A total of 517 patients (517 eyes; spherical equivalent [SE] <e1.0 diopters [D] or axial length
>24.0 mm), including 175 highly myopic eyes (SE <e6.0 D or axial length >26.0 mm), were recruited and divided
into 2, training (241 eyes) and validation (276 eyes) test sets.
Methods: Retinal nerve fiber layer (RNFL) and ganglion celleinner plexiform layer (GCIPL) topographic signs
were selected based on the morphologic patterns of RNFL (size, shape, location, and agreement between
deviation and thickness maps) and GCIPL (size, shape, location, color tone, agreement between maps, and step
sign) abnormalities indicative of higher likelihood of myopic glaucoma on deviation and thickness maps. The
diagnostic score was compiled according to the sensitivity, specificity, and positive likelihood ratio (PLR) of each
diagnostic sign using the training set. The area under the receiver operating characteristic curve (AUC) was
plotted and compared between the OCT-provided parameters and the scoring system in the validation set.
Main Outcome Measures: The diagnostic performance of a new scoring system as validated by AUC.
Results: Among all of the RNFL and GCIPL parameters, the presence of temporal hemifield asymmetry on
the GCIPL thickness map (PLR, 5.98) showed the highest diagnostic ability, followed by location of the RNFL
defect (PLR, 5.79) and color tone of the GCIPL defect (PLR, 5.04). The AUC of the topographic scoring system in
myopic eyes was 0.979, which was significantly higher than those of the inferior (0.895; P < 0.001) and average
(0.894; P < 0.001) RNFL thickness parameters. For highly myopic eyes, the scoring system (AUC, 0.983) also
showed a higher diagnostic performance than that of the RNFL and GCIPL thickness parameters (all P < 0.001).
Conclusions: Our scoring system including OCT topographic parameters demonstrated to be beneficial for
clinicians to differentiate real glaucomatous damage from myopic healthy eyes. Our results support the value of
using multitopographic OCT parameters for detecting glaucoma in myopic eyes. Ophthalmology 2018;-
:1e10 ª 2018 by the American Academy of Ophthalmology

Supplemental material available at www.aaojournal.org.

The approximate worldwide prevalence of myopia has been Previous studies have suggested useful methods for dif-
reported to be 30% for the general population1,2 and 74% to ferentiation of myopic glaucomatous eyes from myopic
84% among people 5 to 18 years of age in East Asia.3,4 healthy eyes using spectral-domain (SD) OCT.11e13
These figures are especially important in light of several Spectral-domain OCT provides various peripapillary
population-based studies’ findings of significant associa- retinal nerve fiber layer (RNFL) and macular ganglion
tions between myopia and glaucoma.5e7 In myopic eyes, celleinner plexiform layer (GCIPL) parameters including
evaluation of glaucomatous structural change in the optic thickness, color-coded diagnostic classification, and patterns
nerve head can be challenging because of considerable of glaucomatous damage, enabling objective and quantita-
differences in morphologic characteristics such as tilted tive evaluation of myopic eyes.14e16 Still, a major impedi-
disc, peripapillary atrophy, larger diameters of optic disc, ment of SD OCT in diagnosing myopic glaucomatous eyes
and larger cup-to-disc ratio.8e10 includes erroneous measurements or high false-positive

ª 2018 by the American Academy of Ophthalmology https://doi.org/10.1016/j.ophtha.2018.05.002 1


Published by Elsevier Inc. ISSN 0161-6420/18
Ophthalmology Volume -, Number -, Month 2018

rates of diagnostic classification.11,17,18 Despite introduction participants with a history of cataract surgery, preoperative SE and
of multiple OCT thickness parameters or diagnostic signs axial length were adopted as the eligibility criteria.
for enhancement of glaucoma diagnostic ability, the sig- Glaucomatous eyes were defined as those showing glaucoma-
nificance and the diagnostic weight of each sign or param- tous optic disc neuropathy (e.g., notching, neuroretinal rim thin-
ning, RNFL defects, or a combination thereof) and corresponding
eter is not understood fully in myopic eyes having
glaucomatous visual field defects, as confirmed by at least 2
distinctive structural characteristics. Therefore, to use these consecutive visual field examinations. The glaucomatous visual
parameters optimally for diagnosis of myopic glaucoma, field defects were defined as a cluster of 3 points or more with
there is a need to understand the diagnostic implication of P < 0.05 on the pattern deviation map in at least 1 hemifield,
each SD OCT parameter. Moreover, as one parameter alone including 1 point or more with P < 0.01; a pattern standard de-
cannot be used in actual clinical settings, the effective viation of P < 0.05; or glaucoma hemifield test results outside the
combination of multiple parameters could provide more normal limits. Only patients with reliable visual field test results,
comprehensive and useful information to clinicians. defined as fixation loss of less than 20%, false-positive errors of
In this regard, in this study, using OCT thickness and less than 15%, and false-negative errors of less than 15%, were
deviation maps for detection of myopic glaucomatous eyes, included. In cases in which both eyes of a patient were eligible for
inclusion, one eye was chosen randomly. The criteria to be eligible
we evaluated the quantitative diagnostic impacts of
for the healthy eyes were a normal anterior segment on slit-lamp
commonly used topographic signs. Based on those param- examination, intraocular pressure between 10 and 21 mmHg, no
eters, we formulated a new scoring system to enhance RNFL defects in red-free RNFL photographs, and no glaucoma-
glaucoma diagnostic performance for myopic eyes and tous visual field defects.
validated the system’s diagnostic ability via comparison
with other OCT parameters. Determination of Training and Validation Sets
We divided the participants into 2 sets, a training set and a vali-
Methods dation set. Using the training set, we designed a new scoring
system based on topographic diagnostic parameters of SD OCT.
This investigation was based on the Macular Ganglion Cell Next, using the validation set, we confirmed the diagnostic ability
Imaging Study, an ongoing prospective study of patients with of the scoring system via comparison with other OCT parameters.
glaucoma and healthy individuals at the Glaucoma Clinic of Seoul Computerized randomization (Statistical Package for the Social
National University Hospital, Seoul, Korea. Eyes were chosen Sciences version 21.0 for Windows; IBM Corp., Armonk, NY)
from a database of glaucoma patients and healthy individuals. This selected 241 eyes (46.6%) of the study population as the training
study adhered to the tenets of the Declaration of Helsinki and was set. The devised topographic scoring system then was applied to
approved by the institutional review board of Seoul National the remaining 276 eyes (53.4%) of the patients in the validation set.
University Hospital. Informed consent to participate was obtained
from all participants. Color Disc Photography and Red-Free Retinal
Nerve Fiber Layer Photography
Participants
Color disc photographs and red-free RNFL photographs were
All participants underwent complete ophthalmologic examinations, evaluated independently by 2 of the authors (K.E.K. and J.W.J.)
including intraocular pressure measurement by Goldmann appla- who were masked to the patients’ clinical information including
nation tonometry, best-corrected visual acuity assessment, refrac- OCT results. The presence of glaucomatous optic disc change was
tive value assessment with an autorefractor (KR-890; Topcon determined by a consensus agreement between the 2 observers. In
Corporation, Tokyo, Japan), central corneal thickness measurement cases where the 2 observers disagreed, those participants were
(Pocket II Pachymeter Echograph; Quantel Medical, Clermont- classified as ambiguous and were excluded from further analysis.
Ferrand, France), axial length measurement (Axis II PR; Quantel
Medical, Inc., Bozeman, MT), slit-lamp examination, gonioscopy, Spectral-Domain OCT Measurements
and dilated fundus examination. After maximum pupil dilation, all
participants underwent red-free RNFL photography (Vx-10; Kowa Macular and optic disc scans were acquired through a dilated pupil.
Optimed, Inc., Tokyo, Japan), stereo optic disc photography, and All of the SD OCT images were obtained by 1 experienced tech-
SD OCT (Cirrus-HD software version 6.0; Carl Zeiss Meditec, nician. Only qualified images with a signal strength of 8 or more
Inc., Dublin, CA). They underwent standard automated perimetry (maximum of 10) without segmentation failure, motion artifacts, or
using the Swedish interactive threshold algorithm with the 30-2 decentration of the measurement circle were included.
standard program (Humphrey Field Analyzer II; Carl Zeiss One macular scan focused on the fovea (200200 cube pro-
Meditec, Inc.). tocol) and 1 peripapillary scan focused on the optic disc (200200
All participants had myopic eyes defined as a spherical equiv- cube protocol) were acquired for every participant. The details of
alent (SE) of less than e1.0 diopter (D) or axial length of more than macular and optic disc cube scan of SD OCT have been reported
24.0 mm. In addition, highly myopic eyes were defined as those previously.19,20 Briefly, an optic disc cube obtained from 3-
with SE of less than e6.0 D or axial length of more than 26.0 mm. dimensional data that cover a 6-mm2 area is centered on the
They had to meet the following criteria for inclusion: optic disc. The ganglion cell analysis algorithm detects and
best-corrected visual acuity of 20/40 or better and a normal anterior measures macular GCIPL thickness within an annulus with inner
chamber and open angle on slit-lamp and gonioscopic examina- vertical and horizontal diameters of 1 and 1.2 mm, respectively,
tions. Patients with a history of ocular surgery other than uncom- and outer vertical and horizontal diameters of 4 and 4.8 mm,
plicated cataract surgery; dense nuclear sclerosis representing respectively. Using these automatically measured thickness data,
myopic shift; any history of retinal pathologic characteristics, SD OCT provides a thickness deviation map of RNFL and
diabetes mellitus, or nonglaucomatous optic neuropathy; or GCIPL. An RNFL thickness deviation map, in comparison with
apparent pathologic myopic changes were excluded. For age-matched normative data, uses yellow and red colors to

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Table 1. Glaucoma Diagnostic Signs on OCT Retinal Nerve Fiber Layer and Ganglion CelleInner Plexiform Layer Maps

Glaucoma Diagnostic Topographic Signs Definition


RNFL defect based on OCT RNFL analysis
Size >20 superpixels (on OCT RNFL deviation map)
Shape Wedge shape (on OCT RNFL deviation map)
Location Superotemporal or inferotemporal area (on OCT RNFL deviation map)
Agreement with RNFL thickness map Decrease in RNFL thickness in the corresponding area of the OCT RNFL defect on OCT RNFL
deviation map
GCIPL defect based on OCT GCIPL analysis
Size >10 superpixels (on OCT GCIPL deviation map)
Shape Arcuate or circular shape (on OCT GCIPL deviation map)
Location Predominantly located in the temporal part (on OCT GCIPL deviation map)
Color tone Yellow or red, dense, monotonous, uniformly color-coded area (on OCT GCIPL deviation map)
Agreement with GCIPL thickness map Decrease in GCIPL thickness in the corresponding area of the OCT GCIPL defect on OCT GCIPL
deviation map
Step sign on GCIPL thickness map Step sign at temporal raphe (hemifield asymmetry)

GCIPL ¼ ganglion celleinner plexiform layer; RNFL ¼ retinal nerve fiber layer.

indicate superpixels in which RNFL thickness falls in less than 5% and GCIPL (size, shape, location, color tone, agreement between
and less than 1% of normal distribution percentiles, respectively. maps, step sign) defects on such maps. The specific characteristics
Uncolored areas demonstrate RNFL thickness within the normal of the topographic glaucoma diagnostic signs for the RNFL and
range. Likewise, the ganglion cell analysis algorithm generates a GCIPL analyses were as follows (Table 1): for the OCT RNFL
GCIPL deviation map, on which areas appear as yellow or red to map, (1) size more than 20 superpixels, (2) wedge shaped, (3)
represent GCIPL thickness less than the lower 5% or 1% of located in the superotemporal or inferotemporal area, and (4)
normative data, respectively, and uncolored areas indicating presence of agreement between RNFL deviation and thickness
normal GCIPL thickness. maps; and for the OCT GCIPL map, (1) size more than 10
superpixels, (2) arcuate to crescent, circular shape, (3) located
predominantly in the temporal area, (4) more dense, monotonous,
Formulation and Evaluation of Topographic uniformly yellow or red color-coded area, (5) presence of agree-
Scoring System Based on Retinal Nerve Fiber ment between GCIPL deviation map and thickness map, and (6)
Layer and Ganglion CelleInner Plexiform Layer step sign on GCIPL thickness map.
Maps Two observers (K.E.K. and J.W.J.) individually evaluated the
patterns of RNFL and GCIPL defects shown on the deviation maps
Previous studies have demonstrated typical glaucomatous patterns in consideration of the aforementioned variables in an independent
of OCT RNFL and GCIPL damage.11,17,18,21e24 We selected and masked manner. The diagnostic score was constructed based
diagnostic signs of OCT from the morphologic patterns of RNFL on the sensitivity, specificity, and positive likelihood ratio (PLR) of
and GCIPL abnormalities on deviation and thickness maps indi- each diagnostic sign using the training set. The diagnostic score
cating glaucomatous damage. We then evaluated the diagnostic then was weighted by the PLR rounded to the nearest integer. The
signs of RNFL (size, shape, location, agreement between maps) total score was calculated for each patient by summing the

Table 2. Baseline Characteristics of Participants

Training Set Validation Set


Myopic Eyes Myopic Glaucomatous Eyes Myopic Eyes Myopic Glaucomatous Eyes
Characteristic (n ¼ 107) (n ¼ 134) P Value (n ¼ 112) (n ¼ 164) P Value
Age (yrs) 48.911.4 51.311.2 0.103* 48.011.9 50.311.4 0.116*
Male 64 (59.8) 76 (56.7) 0.724y 63 (56.3) 92 (56.4) 0.986y
Axial length (mm) 25.81.1 26.11.1 0.074* 25.91.2 26.11.2 0.181*
SE (D) e5.572.45 e6.262.41 0.090* e5.303.25 e6.023.13 0.103*
Average RNFLT (mm) 92.19.9 74.88.9 <0.001* 91.49.9 74.59.3 <0.001*
Average GCIPLT (mm) 77.57.9 68.67.0 <0.001* 75.66.0 68.77.6 <0.001*
Minimum GCIPLT (mm) 72.412.4 59.79.8 <0.001* 72.78.5 59.011.2 <0.001*
SAP C30-2 MD (dB) e0.721.52 e3.863.90 <0.001* e0.671.47 e3.653.73 <0.001*
SAP C30-2 PSD (dB) 1.840.94 6.464.50 <0.001* 2.000.99 5.904.49 <0.001*

D ¼ diopter; GCIPLT ¼ ganglion celleinner plexiform layer thickness; MD ¼ mean deviation; PSD ¼ pattern standard deviation; RNFLT ¼ retinal nerve
fiber layer thickness; SAP ¼ standard automated perimetry; SE ¼ spherical equivalent.
Data are mean  standard deviation or no. (%) unless otherwise indicated.
*Student t test.
y
Chi-square test.

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Table 3. Topographic Scoring System Based on the Positive discrimination. DeLong’s test was used to test for the statistical
Likelihood Ratio of Each Diagnostic Sign Using Training Set significance of the diagnostic performance difference (represented
as AUC) between any 2 parameters.26 The AUCs of different
Positive Likelihood variables were compared using MedCalc software version 12.0
Ratio* Scorey (MedCalc Statistical Software, Marakierke, Belgium). Other
RNFL defect based on OCT RNFL analysis
statistical analyses were performed using the Statistical Package
Size 2.43 2 for the Social Sciences version 21.0 for Windows (IBM Corp.,
Shape 2.76 3 Armonk, NY). Statistical significance was defined as P < 0.05.
Location 5.79 6
Agreement with RNFL thickness map 1.87 2
GCIPL defect based on OCT GCIPL analysis
Size 1.94 2
Results
Shape 1.86 2
This study included 219 myopic healthy eyes and 298 myopic
Location 4.78 5
glaucomatous eyes, including 67 healthy eyes and 108 glaucom-
Color tone 5.04 5
Agreement with GCIPL thickness map 1.99 2
atous eyes with a high degree of myopia. Computerized random-
Step sign on GCIPL thickness map 5.98 6 ization selected a training set (107 myopic healthy eyes and 134
myopic glaucomatous eyes) and a validation set (112 healthy
myopic eyes and 164 myopic glaucomatous eyes).
GCIPL ¼ ganglion celleinner plexiform layer; RNFL ¼ retinal nerve fiber The baseline characteristics are summarized in Table 2.
layer. Moreover, in our validation set, a total of 175 highly myopic
*Positive likelihood ratio ¼ sensitivity / (100 e specificity). eyes were included, with the mean age of 49.111.4 years,
y
Scores were assigned according to the positive likelihood ratio values
rounded off to the nearest whole number for convenience.
mean axial length of 26.80.79 mm, and mean SE of
e7.272.71 D, respectively. There were no significant
differences in mean age between the myopic healthy eyes and
weighted scores of 10 diagnostic signs when topographic findings myopic glaucomatous eyes. Neither gender, nor axial length, nor
were present. It arithmetically ranged from a minimum of 0 to a SE showed any differences between the groups in either the
maximum of 35 points. Of the maximum score of 35 points, 13 training or validation set (all P > 0.05). In a separate analysis of
were allocated to 4 RNFL signs and 22 to 6 GCIPL signs. The highly myopic eyes, no significant difference was found between
scoring system was validated by 2 observers (K.E.K. and S.U.B.) healthy eyes and glaucomatous eyes with regard to age
using the independent validation set. (47.111.2 years vs. 50.211.4 years; P ¼ 0.100), axial length
(26.80.7 mm vs. 26.80.9 mm; P ¼ 0.960), or SE
(e7.272.36 D vs. e7.262.92 D; P ¼ 0.981). However, as
Statistical Analysis expected, the myopic glaucomatous eyes demonstrated thinner
average RNFL and GCIPL thicknesses as well as thinner
The baseline characteristics of the myopic nonglaucomatous and
minimum GCIPL thickness and showed worse visual field
glaucomatous eyes in the training and validation sets were
results than the myopic healthy eyes in both sets (all P < 0.001;
compared using the Student t test and chi-square test for continuous
Table 2).
and categorical variables, respectively. Sensitivity, specificity, and
PLR were evaluated for each of the diagnostic variables using the
training set to determine the scoring system.
To assign different weights of points to each topographic
Diagnostic Ability of Each Retinal Nerve Fiber
sign, the PLR of each sign was derived from the training set. The Layer or Ganglion CelleInner Plexiform Layer
PLR was calculated by the following formula: sensitivity / (100 e Topographic Parameter for Discrimination of
specificity). Ultimately, the PLR of each sign was converted to the Myopic Glaucomatous Eyes from Myopic
topographic scoring system by rounding it off to the nearest whole Healthy Eyes
number. Then, the total score was obtained by summing the con-
verted points of the respective signs. The cutoff points were those To investigate the discriminatory ability of each topographic sign,
with the best balance between sensitivity and specificity. its PLR was evaluated using the training set (Table 3). Among all
The calculated intraobserver reproducibility of the evaluation of of the RNFL and GCIPL parameters, the presence of step sign
topographic diagnostic signs determining glaucomatous defect for (temporal hemifield asymmetry) on a GCIPL thickness map
each rater (S.U.B., K.E.K., J.W.J.) was based on first- and second- (PLR, 5.98) was given the highest value for detection of myopic
round scoring using a scoring system with a 2-week scoring glaucoma on OCT deviation and thickness maps. The location of
interval. A 2-way random effects model was applied to determine RNFL defect, with a PLR of 5.79, was ranked second. Among
reliability based on the intraclass correlation coefficient (ICC) by the RNFL topographic parameters, the shape of the RNFL defect
pooling together the myopic healthy eyes and glaucomatous eyes. received the second highest PLR of 2.76, followed by size of the
An ICC with a 2-way random effects model also was applied to RNFL defect (PLR, 2.43) and agreement between RNFL
determine the interobserver reproducibility for the estimate of deviation and thickness maps (PLR, 1.87). Among the GCIPL
agreement among the 3 raters. An ICC of 0.41 to 0.60 was topographic parameters, color tone of GCIPL defect was
considered fair agreement, an ICC of 0.61 to 0.80 was considered assigned a PLR of 5.04, followed by location (PLR, 4.78),
moderate agreement, and an ICC of more than 0.80 was considered agreement between GCIPL deviation and thickness maps (PLR,
excellent agreement.25 1.99), size (PLR, 1.94), and shape (PLR, 1.86). In the training
The area under the receiver operating characteristic curve set, the cutoff point of our scoring system suggestive of a high
(AUC) with the corresponding 95% confidence interval (CI) was likelihood of myopic glaucoma was 23 (sensitivity, 92.7%;
calculated to determine the diagnostic ability of each parameter to specificity, 97.6%; AUC, 0.977). Figure 1 shows 2 cases of
discriminate glaucomatous eyes from healthy ones: an AUC of 1.0 myopic glaucoma and myopic healthy eyes, respectively, from
represents perfect discrimination, and one of 0.5 represents chance the validation set.

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Assessment of Intraobserver and Interobserver topographic diagnostic signs from RNFL and GCIPL maps
Reproducibility of Evaluation of Topographic whose quantitative diagnostic values were confirmed
Diagnostic Signs for Determination of through the training set of myopic eyes. After confirmation,
Glaucomatous Damage in Myopic Eyes the score was assigned to each topographic sign based on its
degree of significance in detecting glaucomatous damage in
Overall, the intraobserver and interobserver reproducibilities for myopic eyes. In this way, we could determine how impor-
the RNFL (ICC, 0.865e0.986) and GCIPL (ICC, 0.863e0.990) tant a role each diagnostic sign plays in distinguishing
showed excellent agreements (all P < 0.001; Table S1, available at myopic glaucoma. We also confirmed that the topographic
www.aaojournal.org). Despite high intraobserver reproducibility
for the RNFL signs, the size of the RNFL defect (ICC, 0.969)
scoring system, compared with other RNFL and GCIPL
showed the lowest reproducibility, and the location of the RNFL parameters in SD OCT, has a better diagnostic ability for
defect (ICC, 0.986) showed the highest. For the GCIPL signs, discriminating between healthy and glaucomatous eyes in
the color tone of the GCIPL defect (ICC, 0.952) showed the myopia. Further, a classification algorithm based on our
lowest reproducibility, and the step sign (ICC, 0.990) showed the scoring system would be useful to OCT interpretation for
highest. For the interobserver variance, the agreement between glaucoma diagnostic purposes.
the RNFL deviation map and the thickness map (ICC, 0.865) There have been many studies on SD OCT-based diag-
showed the lowest value, and the location of the RNFL defect nosis of glaucoma in myopic eyes. The corresponding re-
(ICC, 0.974) showed the highest for the RNFL signs. For the ports have introduced several diagnostic OCT signsdsuch
GCIPL signs, the shape of the GCIPL defect (ICC, 0.863) as size, shape, location, color tone, and temporal hemifield
presented the lowest interobserver reproducibility, and the step
sign (ICC, 0.968) showed the highest.
asymmetry of OCT RNFL and GCIPL defectsdfor
discrimination of myopic glaucomatous eyes from normal
eyes.11,12,21e23 In clinical settings, however, clinicians
Validation of Diagnostic Performance of diagnose glaucoma based not on a single diagnostic sign on
Topographic Scoring System an OCT printout; rather, they confirm the diagnosis by
To validate the diagnostic performance of the topographic scoring compiling and combining information gathered from mul-
system, its AUC was compared with those of commonly used RNFL tiple OCT results. Accordingly, we created and evaluated
(average and 4 quadrants) and GCIPL (average, minimum, and 6 our new scoring system incorporating topographic diag-
sectors) thickness parameters using the validation set (Table 4). nostic signs found on RNFL and GCIPL deviation and
Among the single OCT parameters, those that were remarkable for thickness maps.
discriminating normal from glaucomatous eyes were inferior In the current study, the presence of temporal hemifield
RNFL thickness (AUC, 0.895; 95% CI, 0.846e0.932), average asymmetry on the OCT GCIPL thickness map was given the
RNFL thickness (AUC, 0.894; 95% CI, 0.846e0.932),
inferotemporal GCIPL thickness (AUC, 0.865; 95% CI,
highest PLR for differentiating myopic glaucoma from
0.794e0.919), minimum GCIPL thickness (AUC, 0.840; 95% CI, myopic healthy eyes. It is well recognized that glaucoma-
0.765e0.898), and inferior GCIPL thickness (AUC, 0.792; 95% tous RNFL defects often occur at the superotemporal or
CI, 0.711e0.858). The topographic scoring system showed an inferotemporal parapapillary region, or both.27,28 Further-
AUC of 0.979 for all myopic eyes, which was significantly higher more, previous studies29e31 have supposed that the retinal
than those of the inferior and average RNFL thickness parameters ganglion cells in the superior or inferior temporal macula
(all P < 0.001) and inferotemporal, minimum, and inferior GCIPL project their axons in an arcuate pattern toward the super-
thickness parameters (all P < 0.001; Fig 2A). Even for highly otemporal or inferotemporal portions of the optic nerve
myopic eyes (67 healthy and 108 glaucomatous eyes), the scoring head. Another study, this one performed by our group,
system (AUC, 0.983; 95% CI, 0.951e0.997) showed a showed that the AUC of a positive step sign (0.938) was
significantly higher diagnostic performance than that of the RNFL
or GCIPL thickness parameters (all P < 0.001; Fig 2B).
greater than that of either inferotemporal GCIPL thickness
(0.814) or minimum GCIPL thickness (0.818).13 By
extension of these spatial and morphologic considerations,
Discussion it is also possible to conclude that characteristic
glaucomatous changes are located predominantly in the
In this study, we formulated a topographic scoring system temporal macular area along the horizontal raphe, which
for typical morphologic changes that determine myopic usually is in the same hemifield as the corresponding
glaucoma. Our scoring system consists of important RNFL defect.

Figure 1. Myopic glaucomatous and healthy eyes from the validation set. A, Myopic glaucomatous eye of a 39-year-old woman with a spherical equivalent of e5.00
diopters (D). An inferior localized retinal nerve fiber layer (RNFL) defect shown by red-free RNFL photograph (arrowhead) was detected on RNFL and ganglion
celleinner plexiform layer (GCIPL) maps of spectral-domain (SD) OCT. In detail, her left eye had a wedge-shaped (3 points) inferotemporal (6 points) RNFL defect of
more than 20 superpixels (2 points) on the OCT RNFL deviation map. The RNFL defect on the deviation map corresponded well with that on the thickness map (2
points). As for the GCIPL maps, an arcuate (2 points) defect of a size of more than 10 superpixels (2 points) on the OCT GCIPL deviation map was located mainly in
the temporal parafoveal area (5 points) showing a dense and monotonous red color (5 points). The GCIPL thickness map showed a defect corresponding to that on the
GCIPL deviation map (2 points) and a temporal step sign respecting the temporal horizontal raphe (6 points). As a result, the patient had a total score of 35 points (13
points from RNFL the analysis and 22 points from the GCIPL analysis), which suggests a high probability of having glaucoma. B, Myopic healthy eye of a 34-year-old
woman with a spherical equivalent of e4.50 D. The red-free RNFL photograph showed no definite structural damage. However, the RNFL and GCIPL deviation maps
with their abnormal color codes could be misinterpreted as indicating glaucomatous damage. The score according to the topographic scoring system was 11 points,
which suggests a low probability of having glaucoma.

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Table 4. Glaucoma Diagnostic Ability of Topographic Scoring System, Retinal Nerve Fiber Layer Thickness, and Ganglion CelleInner
Plexiform Layer Thickness

Area under the Receiver Operating Characteristic Curve (95% Confidence Interval)
All Myopic Eyes (Healthy, n ¼ 112; Highly Myopic Eyes (Healthy, n ¼ 67;
Parameters Glaucomatous, n ¼ 163) P Value* Glaucomatous, n ¼ 108) P Value*
Topographic scoring system 0.979 (0.954e0.993) N/A 0.983 (0.951e0.997) N/A
RNFL thickness
Average 0.894 (0.846e0.932) <0.001 0.895 (0.834e0.940) <0.001
Superior 0.780 (0.719e0.832) <0.001 0.753 (0.675e0.820) <0.001
Nasal 0.611 (0.543e0.676) <0.001 0.589 (0.505e0.669) <0.001
Inferior 0.895 (0.846e0.932) <0.001 0.902 (0.842e0.945) <0.001
Temporal 0.730 (0.666e0.787) <0.001 0.792 (0.718e0.855) <0.001
GCIPL thickness
Average 0.773 (0.691e0.842) <0.001 0.782 (0.693e0.855) <0.001
Minimum 0.840 (0.765e0.898) <0.001 0.850 (0.769e0.911) <0.001
Superotemporal 0.699 (0.612e0.777) <0.001 0.715 (0.621e0.797) <0.001
Superior 0.591 (0.503e0.676) <0.001 0.602 (0.505e0.694) <0.001
Superonasal 0.602 (0.513e0.685) <0.001 0.619 (0.522e0.709) <0.001
Inferonasal 0.676 (0.588e0.756) <0.001 0.693 (0.598e0.778) <0.001
Inferior 0.792 (0.711e0.858) <0.001 0.805 (0.719e0.874) <0.001
Inferotemporal 0.865 (0.794e0.919) <0.001 0.889 (0.815e0.941) <0.001

GCIPL ¼ ganglion celleinner plexiform layer; N/A ¼ not applicable; RNFL ¼ retinal nerve fiber layer.
*Comparison between topographic scoring system and thickness parameters.

Initially, the 10 (4 RNFL and 6 GCIPL) diagnostic signs, thorough analysis, a considerable point of our scoring sys-
which can be recognized easily from the OCT printout tem is that the elements of GCIPL analysis in the total scores
without further manipulation, were determined based on are more predominant than those of RNFL analysis. Spe-
previous investigation of glaucomatous RNFL and GCIPL cifically, 2 additional factors (color tone and step sign on
defect pattern using SD OCT.11,17,18,21e24,31 Then, we GCIPL thickness map) were included in GCIPL signs
evaluated the diagnostic implication of each diagnostic compared with RNFL components. As previously
parameter with our training set of myopic eyes. Despite mentioned, the step sign on the GCIPL thickness map has

Figure 2. Graphs comparing the diagnostic performance between the topographic scoring system and global and sectoral retinal nerve fiber layer (RNFL) and
ganglion celleinner plexiform layer (GCIPL) thickness parameters in (A) all myopia and (B) high myopia using the validation set. The areas under the receiver
operating characteristic curve of the topographic scoring system were 0.979 in the all myopia group and 0.983 in the high myopia group, which were significantly
higher than those of the RNFL and GCIPL thickness parameters (all P < 0.001). Ave_RNFLT ¼ average RNFL thickness; Inf_GCIPLT ¼ inferior GCIPL
thickness; Inf_RNFLT ¼ inferior RNFL thickness; IT_GCIPLT ¼ inferotemporal GCIPL thickness; Min_GCIPLT ¼ minimum GCIPL thickness.

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Ophthalmology Volume -, Number -, Month 2018

shown highly sensitive glaucoma diagnostic power in our disease stages than at more advanced ones. Thus, the
study as well as in previous studies.13,23 At the same time, topographic scoring system might not be as effective for
for the scoring system to have both high sensitivity and high patients with advanced glaucoma. However, we should note
specificity, we should be aware of false-positive signs. that we included patients with early-to-moderate glaucoma
Therefore, for differentiation of true and false-positive because advanced patients can be detected even with basic
diagnostic signs, color tone of GCIPL defect, reported in a clinical examinations. Third, cataract itself can cause a
previous study,18 also was tested with our training set and myopic shift in some patients; therefore, including such
was proven to be highly important (PLR, 5.04). A score cases can be problematic for representing true myopic eyes.
weighted toward GCIPL signs can cause a false-positive Therefore, we rechecked the data of 5 patients from the
diagnostic error in patients with nonglaucomatous macular training set and that of 7 patients from the validation set who
abnormality, but the high diagnostic ability of our scoring had undergone simple cataract surgery. They all showed a
system implied that effective combination of RNFL and moderate degree of myopia by SE and an axial length 25.1
GCIPL signs with different diagnostic capabilities could mm or more before surgery. Still, participants with acquired
overcome this limit. myopic shift resulting from cataract could have been
Previous studies have shown the SD OCT device’s included in the study, regardless of cataract surgery. Fourth,
RNFL thickness parameter AUC ranges from 0.60 to 0.98, the most reasonable comparison of glaucoma diagnostic
depending on the specific parameters and patient charac- ability would be that between the scoring system and the
teristics.21,32e37 In those reports, inferior RNFL thickness thickness parameters of certain RNFL or GCIPL defect
often demonstrated the best accuracy for discriminating areas. Unfortunately, no system determining RNFL or
normal eyes from eyes with glaucoma.21,32,33 In the present GCIPL thickness within a specific area by Cirrus OCT is
study, the AUC of our topographic scoring system was available. Thus, we compared the topographic scoring sys-
0.979, which was significantly higher than that of inferior tem with the currently available global and sectoral thick-
RNFL thickness parameters (AUC, 0.895; P < 0.001; ness parameters that can be identified easily from OCT
Table 4; Fig 2A). Moreover, the results of the present study printouts. Finally, our scoring system presented merely
correspond well with those of an earlier study reporting on a validates OCT results; it offers neither any consideration of
scoring system (0e5) developed to analyze the RNFL other structural measurements (e.g., red-free RNFL photo-
thickness deviation map by taking into consideration graphs and optic nerve head photographs) nor functional
defect size, shape, depth, location, and distance from the assessment. That is, our topographic scoring system is a
disc margin (a map score of 5 points attained a supplemental method that can be used in combination with
significantly higher sensitivity compared with clock-hour other clinical parameters.
or average RNFL thickness categorical classification by In conclusion, our scoring system incorporating OCT
SD OCT).21 topographic parameters was demonstrated to be beneficial
The initial purpose of this study was to create a scoring for clinicians’ differentiation of real glaucomatous damage
system to facilitate glaucoma diagnosis in myopic eyes. from myopic healthy eyes. Our results suggest that the OCT
However, after confirming from additional analyses topographic scoring system can be an effective adjunctive
(Table S2, available at www.aaojournal.org) the high diagnostic tool for detection of myopic glaucoma.
diagnostic ability of the scoring system even for nonmyopic
eyes, the authors realized that a new scoring system could
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Footnotes and Financial Disclosures


2
Originally received: January 11, 2018. Department of Ophthalmology, Seoul National University Hospital,
Final revision: April 27, 2018. Seoul, Korea.
Accepted: May 1, 2018. 3
Department of Ophthalmology, Nowon Eulji Medical Center, Eulji Uni-
Available online: ---. Manuscript no. 2018-97. versity, Seoul, Korea.
1
Department of Ophthalmology, Seoul National University College of *Both authors contributed equally as first authors.
Medicine, Seoul, Korea.

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Ophthalmology Volume -, Number -, Month 2018
Financial Disclosure(s): Overall responsibility: Baek, K.E.Kim, Jeoung
The author(s) have no proprietary or commercial interest in any materials Abbreviations and Acronyms:
discussed in this article.
AUC ¼ area under the receiver operating characteristic curve;
HUMAN SUBJECTS: This study included human subjects or tissues. No CI ¼ confidence interval; D ¼ diopter; GCIPL ¼ ganglion celleinner
animals were used in this study. Study protocol was approved by the plexiform layer; ICC ¼ intraclass correlation coefficient; PLR ¼ positive
institutional review board of the Seoul National University Hospital. likelihood ratio; SD ¼ spectral-domain; RNFL ¼ retinal nerve fiber layer;
Informed consent was obtained from all human subjects. This research SE ¼ spherical equivalent.
adhered to the tenets of the Declaration of Helsinki.
Correspondence:
Author Contributions: Jin Wook Jeoung, MD, PhD, Department of Ophthalmology, Seoul Na-
Conception and design: Baek, K.E.Kim, Y.K.Kim, Park, Jeoung tional University Hospital, Seoul National University College of Medicine,
Analysis and interpretation: Baek, K.E.Kim, Y.K.Kim, Park, Jeoung 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. E-mail: neuroprotect@
Data collection: Baek, K.E.Kim, Y.K.Kim, Park, Jeoung gmail.com.
Obtained funding: none

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