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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.
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
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
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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
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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.
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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.
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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.
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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.
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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
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of group age differences on sensitivity are difficult to 622–5.
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all decrease with age, and this age effect could influence our significant visual field defects in highly myopic eyes. Am J
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on disc morphology, and so the outcomes may be biased 11. Chon B, Qiu M, Lin SC. Myopia and glaucoma in the South
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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:
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