Sie sind auf Seite 1von 9

Diagnostic Accuracy of Optical Coherence

Tomography and Scanning Laser


Tomography for Identifying Glaucoma in
Myopic Eyes
Rizwan Malik, MD, PhD,1,2 Anne C. Belliveau, BSc,1 Glen P. Sharpe, BSc,1 Lesya M. Shuba, MD, PhD,1
Balwantray C. Chauhan, PhD,1 Marcelo T. Nicolela, MD1

Purpose: Ruling out glaucoma in myopic eyes often poses a diagnostic challenge because of atypical optic disc
morphology and visual field defects that can mimic glaucoma. We determined whether neuroretinal rim assessment
based on Bruch’s membrane opening (BMO), rather than conventional optic disc margin (DM)-based assessment or
retinal nerve fiber layer (RNFL) thickness, yielded higher diagnostic accuracy in myopic patients with glaucoma.
Design: Case-control, cross-sectional study.
Participants: Myopic patients with glaucoma (n ¼ 56) and myopic normal controls (n ¼ 74).
Methods: Myopic subjects with refraction error greater than 2 diopters (D) (spherical equivalent) and typical
myopic optic disc morphology, with and without glaucoma, were recruited from a glaucoma clinic and a local
optometry practice. The final classification of myopic glaucoma or myopic control was based on consensus
assessment by 3 clinicians of visual fields and optic disc photographs. Participants underwent imaging with
confocal scanning laser tomography for measurement of DM rim area (DM-RA) and with spectral domain optical
coherence tomography (SD OCT) for quantification of a BMO-based neuroretinal rim parameter, minimum rim
width (BMO-MRW), and RNFL thickness.
Main Outcome Measures: Sensitivity of DM-RA, BMO-MRW, and RNFL thickness at a fixed specificity of
90% and partial area under the curves (pAUCs) for global and sectoral parameters for specificities 90%.
Results: Sensitivities at 90% specificity were 30% for DM-RA and 71% for both BMO-MRW and RNFL
thickness. The pAUC was higher for the BMO-MRW compared with DM-RA (P < 0.001), but similar to RNFL
thickness (P > 0.5). Sectoral values of BMO-MRW tended to have a higher, but nonsignificant, pAUC across all
sectors compared with RNFL thickness.
Conclusions: Bruch’s membrane opening MRW is more sensitive than DM-RA and similar to RNFL thickness
for the identification of glaucoma in myopic eyes and offers a valuable diagnostic tool for patients with glaucoma
with myopic optic discs. Ophthalmology 2016;123:1181-1189 ª 2016 by the American Academy of Ophthal-
mology.

Supplemental material is available at www.aaojournal.org.

The diagnosis of primary open-angle glaucoma relies on the with the challenge of diagnosing glaucoma in myopic eyes,
clinician’s ability to identify structural abnormality of the requiring more sensitive and specific methods for diagnosis.
optic disc.1 In myopia, identification of glaucomatous optic Automated imaging devices, such as confocal scanning
disc changes often poses a diagnostic challenge2 because laser tomography (CSLT) and optical coherence tomogra-
atypical optic disc morphology, including substantial phy, give an objective and reproducible measure of optic
peripapillary atrophy,3 varying degrees of disc tilt,4e6 and nerve head or retinal nerve fiber layer (RNFL) structure.16
abnormally large7,8 or small optic disc size, often is pre- However, the utility of these devices has been limited in
sent.5 Furthermore, individuals with myopia can have visual myopic eyes because of low diagnostic accuracy.17e19 At
field defects that mimic glaucomatous loss.6,9,10 90% specificity, CSLT has been reported to have a sensi-
Myopia is a significant risk factor for the development of tivity of approximately 50% in these eyes.18
primary open-angle glaucoma,11e13 and there is strong In clinical settings, CSLT has been used widely for neu-
supporting evidence for an increase in the prevalence of roretinal rim measurement for quantifying the likelihood of
myopia, particularly in urban areas.14,15 As these myopic glaucoma20 and its progression.21 Neuroretinal rim
individuals age, clinicians likely are to be increasingly faced measurements from CSLT are based on the clinically

 2016 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2016.01.052 1181


Published by Elsevier Inc. ISSN 0161-6420/16
Ophthalmology Volume 123, Number 6, June 2016

Figure 1. Optic disc photographs of eyes in the control group, selected at random. A, Right eye of 72-year-old man with spherical equivalent (SE) of 3.25
diopters (D). B, Left eye of 53-year-old man with SE of 9.38 D. C, Left eye of 70-year-old man with SE of 6.25 D. D, Right eye of 59-year-old woman
with SE of 7.11 D. E, Right eye of 67-year-old woman with SE of 4.50 D. F, Right eye of 37-year-old man with SE of 7.50 D. G, Left eye of 78-year-old
man with SE of 7.25 D. H, Left eye of 37-year-old man with SE 7.12 D. I, Right eye of 62-year-old woman with SE of 9.00 D. J, Left eye of 63-year-old
man with SE of 3.50 D.

identifiable optic disc margin (DM). However, recent findings could also be present circumferentially around the optic disc.
with optical coherence tomography have challenged the Optic disc tilt also is part of the typical myopic optic disc
validity and accuracy of conventional DM-based mea- morphology, but its presence was not necessary for inclusion in
sures.22 Alternative anatomically and geometrically accurate this study.
For both groups, additional inclusion criteria were best-
rim parameters,23,24 based on the Bruch’s membrane open-
corrected visual acuity of 20/40, myopia greater than 2 di-
ing (BMO), have been proposed. A new parameter measuring opters (D) (spherical equivalent refraction), cylinder correction
the minimum distance between the BMO and the internal within 4 D, absence of retinal disease (including degenerative
limiting membrane, termed “BMO-minimum rim width” myopia) or optic nerve disease other than glaucoma, and willing-
(BMO-MRW), seems to provide a better representation of the ness to participate in the study. If both eyes were eligible, 1 eye
amount of neuroretinal rim tissue than conventional DM- was randomly selected for analysis.
based parameters. Previous studies have demonstrated better The study was approved by the Ethics Review Board of Capital
diagnostic accuracy24 and greater correlation with other Health and followed the tenants of the Declaration of Helsinki. All
structural and functional parameters25,26 of BMO-MRW subjects provided written informed consent.
than conventional DM-based rim measures.
The primary aim of this study was to compare the Study Definition of Patients with Glaucoma and
diagnostic accuracy of BMO-MRW with DM-based rim Myopic Controls
assessment from CSLT and RNFL thickness measurements The diagnosis of myopic glaucoma or myopic control was defined
to separate individuals with myopic optic disc morphology by consensus among 3 fellowship-trained glaucoma subspecialists
with glaucoma (myopic glaucoma) from those without who evaluated the visual fields and optic disc photographs from all
glaucoma (myopic controls). Secondarily, we also explored participants independently and were masked from all other de-
the sensitivity of these measures on a sectoral basis. mographic and clinical information. To minimize bias and maintain
an independent reference standard for evaluating the diagnostic
accuracy of structural tests, visual field appearance was primarily
Methods used for deciding the diagnostic group of the participants. In-
dividuals were included in the myopic control group if their visual
Participants field was graded as normal or with abnormalities consistent with
myopia, but not glaucoma, independently by all 3 clinicians,
Study participants included myopic patients with glaucoma and regardless of the grading given to their optic disc. If all 3 clinicians
healthy controls with myopic optic disc morphology (defined graded the visual field as having glaucomatous abnormalities, the
later). Patients with glaucoma and myopia were recruited pro- participant was included in the myopic glaucoma group. In cases of
spectively from the glaucoma clinic at the Eye Care Centre, Queen disagreement in visual field grading, the clinicians used the optic
Elizabeth II Health Sciences Centre, Halifax, Canada. Myopic disc evaluation to obtain a consensus decision to place the partic-
participants without glaucoma were recruited consecutively from a ipant in the glaucoma or control group (examples given in
local optometry practice. Typical myopic optic disc morphology “Results”).
(Fig 1) was defined as the presence of significant beta type
of peripapillary atrophy, characterized by complete loss of Study Procedures
retinal pigment epithelium, adjacent to the optic disc.27 Beta
peripapillary atrophy usually was present sectorally, mostly Study subjects had a variety of diagnostic tests (described later)
temporally, associated with the direction of the optic disc tilt, but performed in 1 study visit. For individuals who were perimetrically

1182
Malik et al 
Diagnosis of Glaucoma in Myopia

Figure 2. A, Infrared image showing the position of the radial section; B, Corresponding SD OCT image for this radial scan. Optical coherence tomography
landmarks and Bruch’s membrane opening minimum rim width (BMO-MRW) (blue arrow) for one of the images in the study. Red dots indicate the BMO.
The disc margin rim area (DM-RA), BMO-MRW, and retinal nerve fiber layer (RNFL) thickness profile for this patient is shown in Figure 8. ILM ¼ internal
limiting membrane.

naïve, a training visual field test was obtained initially, with the internal limiting membrane.30 The segmentation was checked by
second test used for the study. During the study visit, best- an experienced observer (GPS) and corrected when necessary.
corrected distance visual acuity, ocular biometry (IOLMaster, The automated segmentation has been shown to be highly
Zeiss, Carl Zeiss Meditec, Dublin, CA), Goldmann applanation comparable to manual segmentation in nonmyopic eyes.30
tonometry, and a complete slit-lamp and fundus examination were Second, a 12 circular scan centered on BMO center was used to
performed. Standard automated perimetry was performed with the measure the circumpapillary RNFL thickness. The scan was
Humphrey Field Analyzer (Carl Zeiss Meditec) and the 24-2 SITA composed of 768 A-scans and data were averaged from 100
strategy, with the appropriate near refractive correction. Only individual B-scans. For each SD OCT scan, the operator checked
reliable (15% false-positives, 30% fixation losses, and 30% the image quality, automated segmentation of RNFL, which was
false-negatives) visual fields were included. All participants had corrected manually when necessary, and quality score (>20).
fundus imaging with stereo disc photography (Zeiss Visucam Pro
NM fundus nonmydriatic camera, Carl Zeiss Meditec Inc., Jena, Neuroretinal Rim Parameters
Germany), CSLT (Heidelberg Retina Tomograph, Heidelberg
Engineering GmbH, Heidelberg, Germany), and spectral domain For CSLT, the internal software (Heidelberg Eye Explorer) was
optical coherence tomography (SD OCT) (Spectralis, Heidelberg used to generate the DM-RA as well as the results of the Moor-
Engineering GmbH). fields Regression Analysis (MRA).20 The MRA uses the
For CSLT, mean topography and reflectance images were relationship between the optic disc area and the DM-RA and the
automatically computed by the software from 3 individual 15 age of the subject in a normal population to derive the normal
images centered on the optic disc. Only images with a mean prediction limits of neuroretinal RA. For a given optic disc, a
standard deviation mean pixel height <40 mm and without obvious classification of within normal limits is made if the RA is within
motion artifacts were accepted. The optic disc contour line was the 95% prediction interval for the given disc area; borderline, if
drawn by an experienced technician and subsequently checked by a the RA is within the 95% and 99.9% prediction intervals; or
clinician (RM). Rim area (RA) was computed using the standard outside normal limits if the RA is outside the 99.9% prediction
reference plane.28 interval.28
Two scanning patterns were used with SD OCT. First, a radial The BMO-MRW parameter has been detailed by Reis et al.23
pattern comprising 24 angularly equidistant high-resolution 15 B- Briefly, 48 BMO points are yielded from the 24 radial scans
scans was used to compute the neuroretinal rim parameters. Both with 3-dimensional coordinates through which the software
scan patterns were centered on the BMO center, which was aligned automatically fitted a spline to derive a closed curve representing
with the fovea, because previous studies showed significant vari- the BMO around the ONH. From this, the BMO area was
ation on the position of the fovea relative to the center of BMO, computed and a best-fit plane representing the BMO reference
which could have consequences in sectorial neuroretinal rim plane was computed. The BMO-MRW was defined as the mini-
analysis.29 Before scan acquisition, the operator manually marked mum distance between the BMO and the internal limiting mem-
4 BMO points on 2 separate perpendicular radial scan lines. These brane (Fig 2) and determined automatically by the software. The
2 radial scans were selected on the basis of the clarity of the BMO. BMO-MRW was computed at the 48 equally spaced angular po-
The image acquisition was then completed, with the scan pattern sitions around the BMO center.23,31
aligned with the center of the 4 points. After image acquisition,
the true BMO center was determined on the basis of all 48 BMO Sample Size
points (24 radial scans). The true center (based on 48 points)
was then compared with the initial scan center (based on 4 It was estimated that for a power of 0.8, with type I error a set to
points). If the discrepancy between these 2 central points was 0.05, at least 55 participants would be needed in each group
greater than 100 mm, the whole process of image acquisition was (myopic control/myopic glaucoma) to detect a difference of 0.20
repeated. Data for each B-scan were averaged from 20 to 30 (taken to be clinically significant difference) between the area of
individual B-scans, with 1536 A-scans per B-scan. An automated receiver operating characteristic (ROC) curves for DM-RA and
segmentation algorithm (Heidelberg Eye Explorer 1.7.1.0; BMO-MRW, assuming an area under the curve (AUC) ROC of
Heidelberg Engineering GmbH) was used to segment BMO and 0.70 for DM-RA.32

1183
Ophthalmology Volume 123, Number 6, June 2016

Data Analysis Table 1. Mean (Standard Deviation) of Descriptive Parameters in


Myopic Controls and Myopic Patients with Glaucoma
The primary analysis involved the comparison of sensitivity of
global measures for identifying glaucoma in myopic eyes: BMO- Myopic Controls Myopic Glaucoma
MRW with DM-RA and BMO-MRW with RNFL thickness. In a n [ 74 n [ 56 P Value
secondary analysis, we also explored trends of sensitivity of these
parameters across 6 sectors. Age (yrs) 56.4 (11.3) 62.5 (9.46) 0.001
All rim parameters were computed globally and sectorally. For Sex (M:F) 33:41 34:22 0.08
SE (D) 5.81 (2.24) 6.06 (3.04) 0.61
CSLO, the sectors were 90 nasally and temporally and 45 for
Axial length (mm) 26.0 (1.26) 26.4 (1.61) 0.13
each of the other 4 sectors (superotemporal, superonasal, infer-
Disc size (mm2) 1.90 (0.64) 2.08 (0.98) 0.24
onasal, inferotemporal), with the temporal sector centered on the BMO area (mm2) 2.11 (0.66) 2.07 (0.76) 0.80
horizontal meridian. For SD OCT, there were four 40 sectors Mean deviation (dB) 0.52 (1.47) 7.08 (4.92) <0.001
(superior-temporal, inferior-temporal, superior-nasal, and inferior-
nasal), one 90 temporal sector, and one 110 nasal sector, with
the center of the temporal sector centered on the fovea. Raw values BMO ¼ Bruch’s membrane opening; D ¼ diopters; dB ¼ decibels; SE ¼
of both global and sectoral DM-RA were extracted from the CSLT spherical equivalent.
software, and raw values of global BMO-MRW and the circum-
papillary RNFL were extracted from the SD OCT software. The
AUC and partial AUC (pAUC) ROC curve for specificity 90% automated segmentation. The circular scans were all adequately
were computed and compared for these parameters. Partial areas centered, and none of these required manual adjustment.
were standardized by the method described by McClish.33 The The baseline characteristics of the study participants are shown
sensitivity of these parameters at fixed specificities of 90% and in Table 1. The spherical refractive error and axial length were
95% were reported. similar in the 2 groups (P > 0.12), as was the proportion of men
In addition to the DM-RA raw values, we also evaluated the (P ¼ 0.08, chi-square test). The patients with glaucoma were, on
diagnostic performance of the MRA. Because the MRA yields a average, 6 years older than the controls (P ¼ 0.001). Optic disc
borderline classification, 2 different MRA criteria were used: (1) size, as measured by CSLT, and the area enclosed by the Bruch’s
liberal, MRA1, where the borderline cases were classified as membrane (BMO area) were similar in the 2 groups (P > 0.23).
abnormal; and (2) conservative, MRA2, where borderline cases Visual field mean deviation, in decibels, was significantly lower
were classified as normal. Thus, there were 2 discrete points for the in the myopic glaucoma group compared with myopic controls
MRA analysis on the ROC curve corresponding to MRA1 and 2, (P < 0.001). The DM-RA, BMO-MRW, and RNFL thickness were
whereas DM-RA, MRW, and RNFL thickness were continuous all significantly lower in myopic patients with glaucoma compared
curves. with myopic controls (Table 2).
Categoric variables were compared using a chi-square test, and The AUC was higher (P < 0.01) for the BMO-MRW than the
continuous variables were compared using a t test. Receiver DM-RA (Fig 5 and Table 3). The pAUC for specificities 90%
operating characteristic analysis was performed with the pROC also was higher for the BMO-MRW compared with DM-RA
package34 in the open platform R software.35 Confidence intervals (P < 0.01) (Table 3). Both the AUC and pAUC for BMO-MRW
for AUC and pAUC were computed with a bootstrap method with were similar to RNFL thickness (P > 0.25). Sensitivities at a
2000 iterations. The AUCs were compared using function ROCtest fixed specificity of 90% were 30.0% for DM-RA and 71.4% for
in the package pROC, which uses a Wald statistic, dividing the both BMO-MRW and RNFL thickness. Respective sensitivity
observed difference by its standard error compared with the values for specificity of 95% are shown in Table 3. MRA1 yielded
standard normal distribution to report a P value.36 sensitivity of 64.3% and specificity of 71.6%, whereas the
respective values of MRA2 were 41.1% and 90.5% (not shown
in Table 3).
The ROC curves for 6 sectors are shown in Figure 6 (available
Results at www.aaojournal.org). The pAUCs for the specificity 90% for
the 6 sectors are shown in Table 4 (available at
A total of 131 eyes of 131 participants were included in this study. www.aaojournal.org). In general, the same trends were observed
Figure 3 (available at www.aaojournal.org) shows examples of with sectoral analysis as found with global parameters. The
visual fields that were classified as myopic normal and pAUC for BMO-MRW was higher than for DM-RA for each
glaucoma. Masked independent agreement for classifying visual sector (P  0.01). The pAUC for BMO-MRW tended to be higher
fields for the 3 observers is shown in Figure 4 (available at
www.aaojournal.org). All 3 clinicians agreed that 42 subjects
(32%) were glaucomatous and 72 subjects (55%) were
nonglaucomatous (i.e., complete agreement observed in 114 Table 2. Mean (Standard Deviation) of Diagnostic Parameters
subjects [88%]). Kappa agreement (L) ranged from 0.71 to 0.73 Evaluated in Myopic Controls and Myopic Patients with
among the 3 possible pairs of clinicians (good agreement). There Glaucoma
was incomplete initial agreement in visual field classification for
17 subjects (13%). From these, agreement among the 3 observers Myopic Controls Myopic Glaucoma
was reached by consensus in 16 subjects after reviewing their n [ 74 n [ 56 P Value
optic disc photographs; agreement could not be reached for 1 DM-RA (mm2) 1.38 (0.52) 1.09 (0.43) 0.0008
subject, who was excluded from the study. Therefore, the final BMO-MRW (mm) 295 (74.0) 182 (50.9) <0.0001
study sample consisted of 56 eyes from 56 subjects in the RNFL thickness (mm) 84.8 (10.8) 64.8 (10.9) <0.0001
myopic glaucoma group and 74 eyes from 74 subjects in the
myopic control group.
For the radial SD OCT images, the BMO had to be manually BMO ¼ Bruch’s membrane opening; DM-RA ¼ rim area (from CSLT);
MRW ¼ minimum rim width; RNFL ¼ retinal nerve fiber layer.
adjusted in at least 1 radial scan in 91 eyes (70%) after the

1184
Malik et al 
Diagnosis of Glaucoma in Myopia

landmark that is accurately identified by the automated


delineation software.30 In addition to that, the axons
composing the optic nerve have to exit the eye by going
through the BMO, making it the logical choice as a plane
from which to measure neuroretinal rim.24 By measuring
the minimal distance between the BMO and the internal
limiting membrane (BMO-MRW), we can theoretically
have a better assessment of the amount of neuroretinal rim
in tilted optic nerves with an oblique insertion, commonly
seen in myopic individuals, as opposed to measuring
tissue on the plane of the BMO.
Our study showed that both global and sectoral BMO-
MRW had significantly better diagnostic performance in
identifying glaucoma in patients with myopia than the
conventional DM-RA measures, similar to what has been
reported in a study that limited the degree of myopia to
6 D.24 Likewise, the diagnostic performance of BMO-
MRW was comparable to that of RNFL thickness.24
However, the sensitivity of both BMO-MRW and RNFL
thickness was lower in myopic eyes (71% at 90% speci-
ficity). As a comparison, these parameters had higher
Figure 5. Receiver operating characteristic (ROC) curve for global mea-
sures. See text for explanation of Moorfields regression analysis (MRA)1
sensitivity at 90% sensitivity (85% and 81%, respectively)
and 2. The grey shaded box shows the maximum partial area under the curve in a previous study that excluded subjects with myopia
(pAUC) for specificities between 90% and 100%. BMO ¼ Bruch’s mem- exceeding 6 D,24 although in the previous study patients
brane opening; MRW ¼ minimum rim width; RA ¼ (disc margin-based) had an earlier stage of disease compared with the current
rim area (confocal scanning laser tomography [CSLT]); RNFL ¼ retinal one (mean deviation of 4.0 and 7.1 decibels,
nerve fiber layer. respectively). This finding is not surprising considering the
significant structural abnormalities in myopic eyes, which
adversely affect the diagnostic performance of imaging
than for RNFL thickness, although statistical significance was devices in this population.
observed only in the inferonasal sector (P < 0.01). Across the 6
sectors, the sensitivity of MRA1 ranged from 40% to 60% and of Several investigators have evaluated the diagnostic per-
MRA2 ranged from 50% to 70% for MRA2. formance of SD OCT in myopic eyes. The AUC for RNFL
Figures 7 and 8 show representative examples of a myopic thickness reported in myopic eyes ranged from 0.84 to
control and a myopic patient with glaucoma, respectively. In 0.98,19,37,38 which was similar to what we observed in the
both examples, the BMO-MRW and RNFL thickness results current study (0.90). However, it is difficult to compare
seem to be more consistent with the status of the visual field than diagnostic performance across studies, because the inclu-
the DM-RA results. sion/exclusion criteria and the stage of disease vary. In the
current study, we selected only eyes with myopic optic disc
morphology in the control group, which is likely to reduce
sensitivity estimates.
Discussion Likewise, previous studies have found poor diagnostic
performance of DM-RA in myopic eyes.18,32 Mayama
Spectral domain OCT permits a better visualization of the et al18 found that the AUC was significantly lower for
deep optic nerve and its exit through the scleral canal. The myopic eyes compared with emmetropic eyes. The poor
termination of Bruch’s membrane, which delineates the diagnostic performance of DM-RA in these eyes can be
BMO, is, in most cases, an easily identifiable anatomic explained by a number of factors. First, the oblique insertion

Table 3. Areas and Partial Areas Under the Receiving Operator Characteristic Curve and Sensitivities at Fixed Specificities of 90% and
95%, with Corresponding 95% Confidence Intervals

Sensitivity
AUC pAUC 90% Specificity 95% Specificity
DM-RA 66.7 (57.7e76.2) 55.6 (50.5e63.5) 30.0 (8.94e48.2) 14.3 (3.63e36.6)
BMO-MRW 90.0 (84.4e94.4) 80.5 (73.8e87.8) 71.4 (55.48e85.7) 62.5 (48.2e78.6)
RNFL thickness 89.7 (83.9e94.7) 77.5 (67.8e87.1) 71.4 (57.1e84.6) 64.9 (28.8e78.8)

AUC ¼ total area under ROC curve; BMO ¼ Bruch’s membrane opening; DM-RA ¼ disc-margin rim area from CSLT; MRW ¼ minimum rim width;
pAUC¼ partial area under ROC curve for specificity range 90%e100%; RNFL ¼ retinal nerve fiber layer.

1185
Ophthalmology Volume 123, Number 6, June 2016

Figure 7. Data for the right eye of a myopic control subject in the study: A, Visual field exam. B, Confocal scanning laser tomography (CSLT) image.
C, Bruch’s membrane opening minimum rim width (BMO-MRW) profile with corresponding infrared image D (red dots show BMO opening). E, Retinal
nerve fiber layer (RNFL) thickness profile with corresponding infrared image F. In this example, the Moorfields regression analysis (MRA) for CSLT was
“outside normal limits,” although both BMO-MRW and RNFL thickness, in addition to the visual field, showed normal results. BMO ¼ Bruch’s membrane
opening; INF ¼ inferior; NAS ¼ nasal; NS ¼ nasal superior; SUP ¼ superior; TMP ¼ temporal; TS ¼ temporal superior.

of the optic nerve fibers into the scleral canal is not taken determine in these eyes. Fourth, myopic optic discs can be
into consideration in conventional DM-RA estimates, where abnormally small or abnormally large, and the diagnostic
measurements are made in the plane of the optic disc. performance of DM-RA has been shown to be negatively
Second, the cup in these eyes often is shallow and sloping, affected by optic disc size, both small and large.39
and the margin between cup and rim is difficult to identify. In the sectoral analysis, BMO-MRW performed better
Third, myopic discs often have a large amount of peri- than RNFL thickness for all 6 sectors, although statistical
papillary atrophy, and the clinical DM can be difficult to significance was observed only for the inferonasal sector.

1186
Malik et al 
Diagnosis of Glaucoma in Myopia

Figure 8. Data from the left eye of a myopic subject with glaucoma in the study (same patient shown in Figure 2). A, Visual field exam. B, confocal scanning
laser tomography (CSLT) image. C, Minimum rim width (MRW) profile with Bruch’s membrane opening (BMO) opening with corresponding infrared
image (D). E, Retinal nerve fiber layer (RNFL) thickness profile with corresponding infrared image F. This patient had a superotemporal visual field
defect (Fig 7A). Dashed arrow in C shows a dip in the BMO-MRW, with thin RNFL in the same region (E). An RNFL defect is visible on the CSLT
image (B, blue arrow) and infrared optical coherence tomography (OCT) image (F, yellow arrow). Although the Moorfields regression analysis (MRA)
classification was only borderline inferonasally, the BMO-MRW was markedly thin in the same region (Fig 7C). INF ¼ inferior; NAS ¼ nasal; NS ¼ nasal
superior; SUP ¼ superior; TMP ¼ temporal; TS ¼ temporal superior.

Another interesting finding was that the inferotemporal Study Limitations


sector best differentiated between myopic controls and
myopic glaucomatous eyes. Further studies should better There are a number of possible limitations of this study.
evaluate the utility of sectoral analysis in myopic eyes, but First, classification of glaucoma was primarily based on
our results suggest that it might provide useful diagnostic visual field appearance with clinical judgment of the optic
information. disc in ambiguous cases. This approach permitted the

1187
Ophthalmology Volume 123, Number 6, June 2016

inclusion of a range of both normal and glaucomatous 6. Tay E, Seah SK, Chan SP, et al. Optic disk ovality as an index
myopic optic disc appearances and was designed to reduce of tilt and its relationship to myopia and perimetry. Am J
potential spectrum bias (the selection of individuals without Ophthalmol 2005;139:247–52.
diagnostic uncertainty), which could artificially increase 7. Nagaoka N, Ohno-Matsui K, Saka N, et al. Clinical charac-
diagnostic accuracy.40,41 It is possible that some individuals teristics of patients with congenital high myopia. Jpn J Oph-
thalmol 2011;55:7–10.
were misclassified; however, it is unlikely that this would 8. Jonas JB, Gusek GC, Naumann GO. Optic disk morphometry
affect our overall conclusions because the relative, rather in high myopia. Graefes Arch Clin Exp Ophthalmol 1988;226:
than absolute, diagnostic capabilities of the studied param- 587–90.
eters were being compared. Second, the control group was 9. Vuori ML, Mantyjarvi M. Tilted disc syndrome may mimic
younger than the patient group. Although the precise effect false visual field deterioration. Acta Ophthalmol 2008;86:
of group age differences on sensitivity are difficult to 622–5.
quantify, DM-RA,20 BMO-MRW,24 and RNFL thickness42 10. Hwang YH, Yoo C, Kim YY. Long-term development of
all decrease with age, and this age effect could influence our significant visual field defects in highly myopic eyes. Am J
results. Last, the inclusion in the study was partially based Ophthalmol 2011;152:878–9. author reply 9e80.
on disc morphology, and so the outcomes may be biased 11. Chon B, Qiu M, Lin SC. Myopia and glaucoma in the South
Korean population. Invest Ophthalmol Vis Sci 2013;54:
in terms of favoring rim, rather than RNFL thickness, for 6570–7.
identifying glaucoma. The diagnostic performance of 12. Vijaya L, Rashima A, Panday M, et al. Predictors for incidence
RNFL thickness may have been higher if the population of primary open-angle glaucoma in a South Indian population:
had been selected on the basis of established RNFL loss the Chennai eye disease incidence study. Ophthalmology
rather than rim loss, although in the majority of subjects 2014;121:1370–6.
inclusion was based on visual field assessment, and disc 13. Marcus MW, de Vries MM, Junoy Montolio FG,
morphology was used for inclusion only in 17 patients in Jansonius NM. Myopia as a risk factor for open-angle glau-
whom there was disagreement on the visual field coma: a systematic review and meta-analysis. Ophthalmology
classification. 2011;118:1989–1994 e2.
In conclusion, BMO-MRW and RNFL thickness yield a 14. Lin LL, Shih YF, Hsiao CK, Chen CJ. Prevalence of myopia
in Taiwanese schoolchildren: 1983 to 2000. Ann Acad Med
higher diagnostic accuracy in myopic discs than DM-RA, Singapore 2004;33:27–33.
with all parameters performing less well compared with 15. Vitale S, Sperduto RD, Ferris FL 3rd. Increased prevalence of
nonmyopic eyes. It is possible that combining information myopia in the United States between 1971-1972 and 1999-
from BMO-MRW and RNFL thickness, as well as incor- 2004. Arch Ophthalmol 2009;127:1632–9.
porating sectoral analysis and other structural information, 16. Greenfield DS, Weinreb RN. Role of optic nerve imaging in
such as extent and type of peripapillary atrophy, may glaucoma clinical practice and clinical trials. Am J Ophthalmol
yield to increased diagnostic performance in myopic eyes, 2008;145:598–603.
which is a subject of future study. We propose that 17. Melo GB, Libera RD, Barbosa AS, et al. Comparison of optic
BMO-MRW should be incorporated into routine clinical disk and retinal nerve fiber layer thickness in nonglaucomatous
practice to assist clinicians in detecting glaucoma in myopic and glaucomatous patients with high myopia. Am J Oph-
thalmol 2006;142:858–60.
patients. 18. Mayama C, Tsutsumi T, Saito H, et al. Glaucoma-induced
Acknowledgments. The authors thank David Dobbelsteyn, optic disc morphometric changes and glaucoma diagnostic
OD, Paul Gray, OD, Carl Davis, OD, Jeff Sangster, OD, Leah ability of Heidelberg Retina Tomograph II in highly myopic
Gallie, OD, and the staff at the Insight Optometry Group, Halifax, eyes. PLoS One 2014;9:e86417.
Nova Scotia, for assistance with recruiting healthy volunteers for 19. Shoji T, Nagaoka Y, Sato H, Chihara E. Impact of high
this study. myopia on the performance of SD-OCT parameters to detect
glaucoma. Graefes Arch Clin Exp Ophthalmol 2012;250:
1843–9.
References 20. Wollstein G, Garway-Heath DF, Hitchings RA. Identification
of early glaucoma cases with the scanning laser ophthalmo-
scope. Ophthalmology 1998;105:1557–63.
1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet 21. Bowd C, Balasubramanian M, Weinreb RN, et al. Performance
2004;363:1711–20. of confocal scanning laser tomograph Topographic Change
2. Chang RT, Singh K. Myopia and glaucoma: diagnostic and Analysis (TCA) for assessing glaucomatous progression.
therapeutic challenges. Curr Opin Ophthalmol 2013;24: Invest Ophthalmol Vis Sci 2009;50:691–701.
96–101. 22. Chauhan BC, Burgoyne CF. From clinical examination of the
3. Chang L, Pan CW, Ohno-Matsui K, et al. Myopia-related optic disc to clinical assessment of the optic nerve head: a
fundus changes in Singapore adults with high myopia. Am J paradigm change. Am J Ophthalmol 2013;156:218–227.e2.
Ophthalmol 2013;155:991–999 e1. 23. Reis AS, O’Leary N, Yang H, et al. Influence of clinically
4. How AC, Tan GS, Chan YH, et al. Population prevalence of invisible, but optical coherence tomography detected, optic
tilted and torted optic discs among an adult Chinese population disc margin anatomy on neuroretinal rim evaluation. Invest
in Singapore: the Tanjong Pagar Study. Arch Ophthalmol Ophthalmol Vis Sci 2012;53:1852–60.
2009;127:894–9. 24. Chauhan BC, O’Leary N, Almobarak FA, et al. Enhanced
5. Samarawickrama C, Mitchell P, Tong L, et al. Myopia-related detection of open-angle glaucoma with an anatomically ac-
optic disc and retinal changes in adolescent children from curate optical coherence tomography-derived neuroretinal rim
Singapore. Ophthalmology 2011;118:2050–7. parameter. Ophthalmology 2013;120:535–43.

1188
Malik et al 
Diagnosis of Glaucoma in Myopia

25. Gardiner SK, Ren R, Yang H, et al. A method to estimate the 34. Robin X, Turck N, Hainard A, et al. pROC: an open-source
amount of neuroretinal rim tissue in glaucoma: comparison package for R and Sþ to analyze and compare ROC curves.
with current methods for measuring rim area. Am J Oph- BMC Bioinformatics 2011;12:77.
thalmol 2014;157:540–549.e1e2. 35. R Development Core Team (2014). R: A language and
26. Pollet-Villard F, Chiquet C, Romanet JP, et al. Structure- environment for statistical computing. Vienna, Austria: R
function relationships with spectral-domain optical coherence Foundation for Statistical Computing. Available at: https://
tomography retinal nerve fiber layer and optic nerve head www.r-project.org/. Accessed June 1, 2013.
measurements. Invest Ophthalmol Vis Sci 2014;55:2953–62. 36. Pepe M, Longton G, Janes H. Estimation and comparison of
27. Jonas JB, Nguyen XN, Gusek GC, Naumann GO. Para- receiver operating characteristic curves. Stata J 2009;9:1.
papillary chorioretinal atrophy in normal and glaucoma eyes. I. 37. Akashi A, Kanamori A, Nakamura M, et al. The ability of
Morphometric data. Invest Ophthalmol Vis Sci 1989;30: macular parameters and circumpapillary retinal nerve fiber
908–18. layer by three SD-OCT instruments to diagnose highly myopic
28. Heidelberg-Engineering. Heidelberg Retinal Tomograph II glaucoma. Invest Ophthalmol Vis Sci 2013;54:6025–32.
(manual). Dossenheim, Germany: Heidelberg Engineering 38. Shoji T, Sato H, Ishida M, et al. Assessment of glaucomatous
GmbH; 2001. changes in subjects with high myopia using spectral domain
29. Danthurebandara VM, Sharpe GP, Hutchison DM, et al. optical coherence tomography. Invest Ophthalmol Vis Sci
Enhanced structure-function relationship in glaucoma with 2011;52:1098–102.
an anatomically and geometrically accurate neuroretinal 39. Hawker MJ, Vernon SA, Ainsworth G. Specificity of the
rim measurement. Invest Ophthalmol Vis Sci 2015;56: Heidelberg Retina Tomograph’s diagnostic algorithms in a
98–105. normal elderly population: the Bridlington Eye Assessment
30. Almobarak FA, O’Leary N, Reis AS, et al. Automated seg- Project. Ophthalmology 2006;113:778–85.
mentation of optic nerve head structures with optical coher- 40. Rao HL, Kumbar T, Addepalli UK, et al. Effect of spectrum
ence tomography. Invest Ophthalmol Vis Sci 2014;55: bias on the diagnostic accuracy of spectral-domain optical
1161–8. coherence tomography in glaucoma. Invest Ophthalmol Vis
31. Reis AS, Sharpe GP, Yang H, et al. Optic disc margin anatomy Sci 2012;53:1058–65.
in patients with glaucoma and normal controls with spectral 41. Medeiros FA, Ng D, Zangwill LM, et al. The effects of study
domain optical coherence tomography. Ophthalmology design and spectrum bias on the evaluation of diagnostic ac-
2012;119:738–47. curacy of confocal scanning laser ophthalmoscopy in glau-
32. Lee NY, Park HL, Park CK. Glaucoma detection in high coma. Invest Ophthalmol Vis Sci 2007;48:214–22.
myopia with the Heidelberg Retina Tomograph 3. Semin 42. Alasil T, Wang K, Keane PA, et al. Analysis of normal retinal
Ophthalmol 2015;1–6. nerve fiber layer thickness by age, sex, and race using spectral
33. McClish DK. Analyzing a portion of the ROC curve. Med domain optical coherence tomography. J Glaucoma 2013;22:
Decis Making 1989;9:190–5. 532–41.

Footnotes and Financial Disclosures


Originally received: November 18, 2015. Supported by a Canadian Glaucoma Clinical Research Council Grant.
Final revision: January 19, 2016. Author Contributions:
Accepted: January 29, 2016. Conception and design: Malik, Chauhan, Nicolela
Available online: March 16, 2016. Manuscript no. 2015-2039.
1 Data collection: Malik, Belliveau, Sharpe, Shuba, Nicolela
Department of Ophthalmology and Visual Sciences, Dalhousie Univer-
sity, Halifax, Nova Scotia, Canada. Analysis and interpretation: Malik, Shuba, Chauhan, Nicolela
2
NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Obtained funding: Nicolela
Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, Overall responsibility: Malik, Chauhan, Nicolela
London, United Kingdom. Abbreviations and Acronyms:
Presented at the Association for Research in Vision and Ophthalmology, AUC ¼ area under the curve; BMO ¼ Bruch’s membrane opening;
May 4e8, 2014, Orlando, Florida. CSLT ¼ confocal scanning laser tomography; D ¼ diopters; DM ¼ disc
Financial Disclosure(s): margin; MRA ¼ Moorfields Regression Analysis; MRW ¼ minimum rim
The author(s) have made the following disclosure(s): R.M.: A part of the width; pAUC ¼ partial area under the curve; RA ¼ rim area;
author’s salary was paid by the National Institute for Health Research (UK) RNFL ¼ retinal nerve fiber layer; ROC ¼ receiver operating characteristic;
during research fellowship. SD OCT ¼ spectral domain optical coherence tomography; SE ¼ spherical
B.C.C.: Unrestricted funding support  Heidelberg Engineering; equivalent.
Consultant Allergan. Correspondence:
M.T.N.: Consultant  Alcon and Allergan. Marcelo T. Nicolela, MD, Department of Ophthalmology and Visual Sci-
R.M.: Supported by a Research Award from the Special Trustees of ences, Dalhousie University, 1276 South Park Street, 2W Victoria, Room
Moorfields Eye Hospital (ST12 07E). 2035, Halifax, NS B3H 2Y9, Canada. E-mail: nicolela@dal.ca.

1189

Das könnte Ihnen auch gefallen