Multiple Temporal Lamina Cribrosa Defects in

Myopic Eyes with Glaucoma and Their

Association with Visual Field Defects
Yu Sawada, MD, PhD,1 Makoto Araie, MD, PhD,2 Makoto Ishikawa, MD, PhD,1 Takeshi Yoshitomi, MD, PhD1

Purpose: To investigate characteristics of lamina cribrosa (LC) defects in myopic eyes with open-angle
glaucoma (OAG) using spectral-domain (SD) optical coherence tomography (OCT).
Design: Cross-sectional study.
Participants: One hundred thirty-three eyes with OAG and 83 eyes without OAG, with axial length of 24 mm
or more.
Methods: Serial enhanced depth imaging SD OCT B-scans of the optic disc were acquired and reviewed for
LC defects (diameter,
100 mm) and large pores (diameter, 60e100 mm). The numbers and locations of LC
defects and large pores in each eye were assessed. In eyes with OAG, factors related to the number of LC defects
were evaluated, as well as the association between the locations of LC defects and visual field (VF) defects
(e.g., paracentral scotoma [PCS] and superior or inferior hemifield defects).
Main Outcome Measures: Numbers and locations of LC defects and large pores.
Results: In myopic eyes with and without OAG, the average numbers of LC defects were 3.8 and 0.8 and
numbers of large pores were 1.9 and 1.6, respectively. In both groups, LC defects and large pores were located
predominantly at the temporal periphery. Among eyes with OAG, the number of LC defects was relatively high in
the eyes with greater optic disc tilt angle and worse mean deviation of the VF (both P < 0.001). The number of
temporal LC defects and tilt angle were associated with presence of PCS, whereas the number of inferior and
superior LC defects and torsion direction were associated with presence of superior and inferior VF defects.
Conclusions: Myopic eyes with OAG exhibited LC defects and large pores at similar locations as those
without OAG, but in greater numbers, suggesting that these focal alternations of the LC in myopic eyes may
evolve into larger defects when glaucoma develops in the eye. The number of LC defects, which was related to
the optic disc tilt angle, was associated significantly with glaucomatous VF defects in both severity and location.
This suggests that myopia may influence glaucomatous VF defects through optic disc tilt by way of an increased
number of LC defects at the temporal periphery. Ophthalmology 2017;124:1600-1611 ª 2017 by the American
Academy of Ophthalmology

Supplemental material available at www.aaojournal.org.

The lamina cribrosa (LC) is considered to be the principle
site of axonal injury in glaucoma.1,2 Deformation of the LC
promotes glaucomatous optic neuropathy by blocking
axoplasmic flow within the optic nerve head.3 The
configuration of LC in glaucomatous eyes has been studied
using histologic methods1e7 and more recently with optical
coherence tomography (OCT),8,9 and deformations such as
posterior displacement,4,8,9 posterior migration of the inser-
tion,5,6 initial thickening and subsequent thinning,2,6,7 and
localized defect10e14 have been described. These de-
formations are considered to be induced by intraocular
pressure (IOP)erelated stress and strain or biometric
remodeling of the laminar tissue.15
Myopia is accepted as one of the risk factors for the
development of glaucoma.15e17 The association between
myopia and glaucoma has been studied intensively, and it
gradually becomes clear that myopia influences glaucoma-
tous damage not through refractive error itself, but through
deformation of the parapapillary region.18,19 Myopic eyes
present characteristic deformations of the parapapillary
region, including optic disc tilt and torsion and parapapillary
atrophy. Because LC is a deep component of the optic nerve
head, it is reasonable to think that the LC, too, is deformed
in myopic eyes and that it affects axonal injury in glaucoma.
Myopic glaucoma exhibits characteristic clinical features
such as prevalence at a relatively young age and develop-
ment of paracentral scotoma (PCS) from an early stage.
Together with these clinical characteristics, we hypothesized
that there may be a unique mechanism to myopic glaucoma
that induces axonal injury apart from previously described
glaucomatous mechanisms.
Deformation of the LC in glaucoma includes focal loss of
laminar beams. The association of focal LC defects with
neuroretinal rim thinning and visual field (VF) loss was
demonstrated previously.10,11 In addition, recent studies
have described the association of focal LC defects with

1600 ª 2017 by the American Academy of Ophthalmology http://dx.doi.org/10.1016/j.ophtha.2017.04.027

Published by Elsevier Inc. ISSN 0161-6420/17
 Sawada et al 
Temporal LC Defects in Myopic Glaucoma
factors related to myopic deformation of the parapapillary
region.20,21 These findings suggest that LC defects related to
the myopic deformation of the parapapillary region may
contribute to glaucomatous defects. However, there is not
enough data regarding how LC defects in myopic eyes
contribute to the glaucomatous defects spatially and quan-
titatively. Therefore, the present study aimed to investigate
the characteristics of LC defects in myopic eyes with
glaucoma and to determine their association with location
and extent of glaucomatous VF defects.
Methods
This cross-sectional observational study was approved by the
institutional review board of Akita University Graduate School of
Medicine, Akita, Japan, and followed the tenets of the Declara-
tion of Helsinki. All participants provided written informed
consent.
We prospectively recruited myopic patients with open-angle
glaucoma (OAG) from the outpatient clinic of Akita University
Graduate School of Medicine from June 2015 through December
2016. Myopic participants without glaucoma were recruited among
hospital staff and their friends and family as control participants.
All participants underwent comprehensive ophthalmic assessment,
including refraction test, measurement of best-corrected visual
acuity, measurement of central corneal thickness and axial length
by ultrasound pachymetry (Tomey Corporation, Nagoya, Japan),
Goldmann applanation tonometry, slit-lamp biomicroscopy,
gonioscopy, dilated fundus stereoscopic examination, color fundus
stereo photography (Canon, Tokyo, Japan), spectral-domain (SD)
OCT (Spectralis version 5.4.6; Heidelberg Engineering GmbH,
Heidelberg, Germany), and standard automated perimetry (Hum-
phrey Field Analyzer II 750; 24-2 Swedish interactive threshold
algorithm; Carl Zeiss Meditec, Dublin, CA). Untreated IOP was
determined as the average of at least 2 measurements before the use
of IOP-lowering medication, and last IOP was determined as the
average of the last 3 IOP measurements.
The inclusion criteria were as follows. Eyes were included that
had OAG, an open iridocorneal angle, glaucomatous optic disc
changes such as localized or diffuse rim thinning and retinal nerve
fiber defects, and glaucomatous VF defects corresponding to the
glaucomatous structural changes. Glaucomatous VF defects were
defined by glaucoma hemifield test results outside the normal range
or presence of at least 3 contiguous test points within the same
hemifield on the pattern deviation plot at less than 5%, with at least
1 of these points at less than 1%, confirmed by 2 consecutive
reliable tests (fixation loss rate, 20%; false-positive and false-
negative error rates, 15%). A spherical equivalent (SE) of 2
diopters (D) or less and axial length of 24.0 mm or more also were
required. Pseudophakic eyes were evaluated for eligibility on the
basis of preoperative SE. The exclusion criteria were as follows:
ocular injury or intraocular diseases other than glaucoma;
congenital optic disc abnormalities; extremely high myopia (axial
length >28.5 mm or SE <10 D) because of the increased risk of
myopic degeneration of the fundus that may affect the VF; and
eyes with poor-quality OCT images that did not present a clear
image of anterior LC surface because of media opacity, irregular
tear film, or poor patient cooperation. Poor-quality OCT images
were defined by less than 80% visibility of the anterior LC surface
within Bruch’s membrane opening in more than 2 of 48 of radial
scans.14 Myopic eyes without glaucoma were included as controls
when they exhibited SE of 2 D or less and axial length of 24.0
mm or more, an open iridocorneal angle, IOP between 10 and 21
mmHg, a nonglaucomatous optic disc, and no VF defects.
Enhanced Depth Imaging Optical Coherence
Tomography
For optic disc evaluation, images were acquired using the
enhanced depth imaging (EDI) SD OCT. Imaging was performed
within 3 months of VF evaluation. The EDI OCT images were
acquired using 65 serial horizontal and vertical lines (interval
between images, 30 mm) and 48 radial lines centered on the optic
disc in the infrared fundus image, each at an angle of 3.75 .
During the study, we found that LC pores in myopic eyes often
were stretched and elongated toward the temporal direction,
particularly at the temporal periphery of the LC. These elongated
pores exhibited parallel arrangement, as observed in infrared
images in the Spectralis viewer (Fig 1). In eyes where such
parallel arrangements of elongated pores were identified on
infrared images, lines parallel to the pore arrangement also
were scanned, because they often captured clear images of the
LC defects (Fig 1). They were used to measure the accurate
size of the defects. Among these OCT images, the ones that
captured the best view of LC defects were used for analysis.
Each section had 42 OCT frames averaged. Magnification error
was corrected using a formula provided by the manufacturer, on
the basis of results of autorefraction keratometry and focus
setting during image acquisition. The scaling of OCT images
was corrected to 1:1 before evaluation.
The EDI OCT images were reviewed carefully for the focal LC
defects violating the smooth contour that is observed in healthy
eyes, and the number of LC defects in each eye was counted. A
focal LC defect was required to exhibit a diameter of 100 mm or
more and a depth of 30 mm or more in cross-sectional OCT
images.10e14 An LC defect detected in an OCT image was required
to have at least 1 additional adjacent OCT image with a similar
finding to avoid a false-positive characterization. This image
review was performed by 2 experienced glaucoma specialists (Y.S.
and M.I.) masked to the clinical information of the participants.
Disagreements were dealt with by discussion between the 2
reviewers to achieve consensus, and failing that, disagreements
were resolved by a third adjudicator (T.Y.). In a preliminary
analysis of healthy nonmyopic eyes, the diameter of LC pores
usually ranged from 10 to 30 mm, and rarely exceeded 60 mm.
Therefore, we defined an LC pore with a diameter between 60 and
100 mm as a large pore and counted them, also.
The circumferential location of LC defects was evaluated using
the foveaeBruch’s membrane opening center axis as a reference
line.22 It was categorized as supratemporal (>0 e45 ), superior
(>45 e135 ), nasal (>135 e225 ), inferior (>225 e315 ), or
inferotemporal (>315 e360 ). A defect located on the border
between 2 areas was fitted into the area containing a greater
proportion of the defect area. The LC defects also were
categorized as peripheral or middle defects. A peripheral LC
defect was defined as a defect adjusted to the insertion, with the
anterior LC visible only on the central side of the defect and the
peripheral LC not visible. A middle LC defect was defined as a
defect with the LC visible on either side.14
Measurement of Optic Disc Tilt and Torsion
Optic disc tilt and torsion were measured in accordance with the
previously described methods with some modification.21,23,24 Optic
disc tilt angle was measured using EDI OCT B-scan21,23 (Fig S2,
available at www.aaojournal.org). It was defined as the angle
between the reference plane, which connects the inner edge of
the nasal and temporal Bruch’s membrane, and the optic disc
canal plane, which connects the inner edge of the nasal Bruch’s
membrane and temporal margin of the optic disc canal that was
defined as the end of externally oblique border tissue. Optic disc
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Figure 1. Images of a myopic eye with open-angle glaucoma. A, Fundus photograph. B, Infrared fundus image demonstrating that lamina cribrosa (LC)
pores at the temporal margin of the optic disc are elongated in the temporal direction and exhibit parallel arrangement. C, Enhanced depth imaging (EDI)
optical coherence tomography (OCT) scan lines aligned with the parallel arrangement of LC pores at the temporal margin of the optic disc (blue arrows).
These lines correspond to the images presented in (DeH). DeH (Upper rows), B-scan EDI OCT images demonstrating defects at the temporal far periphery
of the LC. This eye exhibits 5 LC defects. DeH (Bottom rows), Same images as the top rows, with the LC defects (arrows) and surface of the anterior LC
and LC defects (green lines) labeled.

torsion angle was defined as the deviation of the long axis of the
optic disc from the vertical meridian,24 which was identified as a
vertical line at a 90 angle to a horizontal line connecting the
fovea and the center of the optic disc in the infrared images.
Positive and negative torsion angles indicated inferotemporal and
supratemporal torsion, respectively.
Assessment of Spatial Relationship between
Lamina Cribrosa Defects and Visual Field
Defects
The spatial relationship between LC and VF defects was assessed
in both PCS and hemifield VF defects. Paracentral scotoma was
defined as a glaucomatous VF defect in 1 hemifield within 10 of
fixation, with at least 1 point at less than 1% lying at the 2 inner-
most paracentral points, regardless of the presence of VF defects
outside the central 10 .25 Eyes were categorized on the basis of
presence or absence of PCS, and factors associated with presence
of PCS were determined. Because eyes with advanced glaucoma
exhibit large areas of VF defects that often include paracentral
area, only eyes with early to moderate glaucoma (mean deviation
[MD], >8 dB) were considered for analysis of PCS.
Additionally, eyes with VF defects only within 26 points of the
superior or inferior hemifield were assigned to the superior or
inferior VF defect group,24 and factors associated with presence
of hemifield defects were analyzed. Eyes with VF defects
involving both superior and inferior hemifields were excluded
from analysis.

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Temporal LC Defects in Myopic Glaucoma

Table 1. Demographic Data of Myopic Eyes with Open-Angle Glaucoma and Those without Glaucoma

Myopic Eyes with Open-Angle Myopic Eyes without

Demographic Feature Glaucoma (n [ 133) Glaucoma (n [ 83) P Value*
Gender (male/female) 73/60 40/43 0.3403
Age (yrs) 52.513.4 49.416.1 0.1299
IOP (mmHg)
Untreated 19.75.6 n/a
At last examination 14.63.1 14.93.1 0.5854
Spherical equivalent (diopter) 6.152.31 5.701.96 0.1382
Axial length (mm) 25.991.14 25.830.99 0.2889
Central corneal thickness (mm) 524.932.0 528.730.2 0.3866
Torsion angle (degree) 4.48.8 4.110.3 0.8020
Tilt angle (degree) 8.44.5 9.04.7 0.2621
Mean deviation (dB) 10.417.85 1.061.17 <0.0001
Proportion of eyes with at least 1 lamina cribrosa defect (%) 90.0 24.1 <0.0001
No. of lamina cribrosa defect per eye 3.83.0 0.80.9 <0.0001
No. of large pore per eye 1.91.9 1.61.5 0.1058

IOP ¼ Intraocular pressure; n/a ¼ not applicable.

Values are mean  standard deviation.
*Student t test. Statistically significant values are noted in boldface.

Statistical Analysis Results

Differences in continuous valuables between groups were assessed
by Student t test or ManneWhitney U test, depending on the
normality of data distribution. Relationships between the number of
LC defects and possible confounders were assessed by multiple
regression analysis. Factors associated with the presence of PCS and
hemifield VF defects were assessed by multivariate logistic
regression analysis. Interobserver reproducibility of measurement
of the number of LC defects and tilt and torsion angles was assessed
by 2 independent observers (Y.S. and M.I.) in a separate group of
30 OAG eyes, and the corresponding intraclass correlation co-
efficients and 95% confidence intervals (CIs) were calculated. All
analyses, with 2-sided P values, were performed using SPS software
version 9.66.26 The level of significance was set at P < 0.05.
From among 286 eyes of 143 myopic patients with OAG, 72 eyes
were excluded for the following reasons: poor quality of OCT
images that did not exhibit a clear image of the anterior LC surface
(n ¼ 33), unreliable VF test results (n ¼ 14), and optic disc
appearance suggestive of any congenital anomaly including tilted
disc syndrome (n ¼ 12), macular degeneration (n ¼ 11), and
diabetic retinopathy (n ¼ 2). One eye was eligible in 52 patients
and both eyes were eligible in 81 patients. For patients with both
eyes eligible, one eye was chosen randomly. As a result, 133 eyes
of 133 patients were included in the analysis. In addition, 83 eyes
of 83 myopic participants without glaucoma were included as
controls. All of the participants were Japanese.

Figure 3. Diagram showing the circumferential location of lamina cribrosa (LC) defects and large pores in myopic eyes with open-angle glaucoma (OAG)
and those in myopic eyes without glaucoma. The inner (gray) and outer (white) circles indicate the middle and peripheral areas of the LC. Numbers inside
circles indicate the average numbers of LC defects per eye in that area, whereas those in parentheses indicate the average numbers of large pores per eye in
that area.

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Figure 4. Images from the myopic left eye of a 26-year-old woman without glaucoma, showing multiple large pores at the temporal periphery of the lamina
cribrosa (LC). Refractive error was 6.25 diopters and axial length was 25.85 mm. A, Fundus photograph demonstrating a tilted myopic optic disc.
B, Infrared fundus image demonstrating the parallel arrangement of LC pores at the temporal margin of the optic disc. C, The same image as (B), but with
labels. The blue lines represent the scan lines of enhanced depth imaging (EDI) optical coherence tomography (OCT) images shown in (FeJ). The scan lines
are parallel to the arrangement of pores at the temporal margin of the optic disc. D, Retinal nerve fiber layer thickness is within the normal range.
E, Standard automated perimetry 24-2 pattern deviation map showing a normal visual field. FeJ, B-scan EDI OCT images of the scan lines in (C),
demonstrating large pores at the temporal far periphery of the LC. Some of these pores appear wedge-shaped, as if the LC was torn off the adjacent sclera.
The inner surfaces of the large pores are irregular because of the pie sheet-like structure of the LC. I, One of the large pores exhibits a width of 100 mm or
more and consequently is classified as an LC defect. The figures in the lower rows are the same as those in the upper rows, but with the surface of the anterior
LC and large pores (green lines) labeled. INF ¼ inferior; N and NAS ¼ nasal; NI ¼ nasal inferior; NS ¼ nasal superior; SUP ¼ superior; T and
TMP ¼ temporal; TI ¼ temporal inferior; TS ¼ temporal superior.

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Temporal LC Defects in Myopic Glaucoma
Table 2. Relationship of Tilt Angle, Mean Deviation, and
Possible Cofounders to Number of Lamina Cribrosa Defects:
Results of Multiple Regression Analysis
Standard Regression
Coefficient P Value
Tilt angle 0.315 <0.001
Mean deviation 0.378 <0.001
Gender 0.099 0.1345
Age 0.009 0.8881
IOP
Untreated 0.086 0.2053
At last examination 0.008 0.9021
Axial length 0.069 0.2798
Central corneal thickness 0.053 0.3912
Torsion angle 0.020 0.7415
R2 0.536 <0.001
IOP ¼ intraocular pressure; R ¼ multiple regression coefficient;
R2 ¼ contribution rate.
Statistically significant values are noted in boldface.
The intraclass correlation coefficients for interobserver repro-
ducibility of the measurement of number of LC defects, tilt angle,
and torsion angle were 0.85 (95% CI, 0.78e0.89), 0.93 (95% CI,
0.91e0.95), and 0.93 (95% CI, 0.90e0.96), respectively. Among
myopic participants with OAG, the mean age, SE, and axial length
were 52.513.4 years, 6.152.31 D, and 25.991.14 mm,
respectively (Table 1); there were no statistical differences in these
parameters between myopic eyes with or without glaucoma. The
average MD of the VF in myopic eyes with OAG
was 10.417.85 dB. Among myopic eyes with glaucoma, 119
(90.0%) exhibited at least 1 LC defect, and the mean numbers of
LC defects and large pores per eye were 3.83.0 and 1.91.9,
respectively. Among myopic eyes without glaucoma, 24.1%
exhibited at least 1 LC defect, and the mean numbers of LC
defects and large pores were 0.80.9 and 1.61.5 per eye,
respectively. Among myopic eyes without OAG, eyes with LC
defects exhibited significantly greater tilt angles than those
without LC defects (P ¼ 0.021), although there was no
significant difference in patient age between the 2 groups (data
not shown).
The quadrant-wise distribution of LC defects in myopic eyes
with OAG was as follows: 2.8 of 3.8 temporal (73.7%), 0.5 inferior
(13.2%), 0.4 superior (10.5%), and 0.1 nasal (2.6%; Fig 3).
Although 3.1 LC defects (81.6%) were located at the periphery,
0.7 (18.4%) were located in the middle of the LC; thus, 2.5
(65.8%) of all LC defects were located at the temporal periphery
of the LC. In myopic eyes without glaucoma, 0.5 of 0.8 LC
defects (62.5%) and 1.1 of 1.6 large pores (68.8%) were located
at temporal periphery of the LC (Fig 3). Figure 4 presents a
representative case of a myopic eye without glaucoma that
exhibited LC defects and large pores.
The number of LC defects in myopic eyes with OAG was
correlated significantly with tilt angle of the optic disc and MD of
the VF after considering the effects of possible cofounders (both,
P < 0.001; Table 2). It demonstrated that eyes with higher optic
disc tilt angle and worse MD exhibited a larger number of LC
defects. Figures 5 and 6 present representative cases of eyes with
early and advanced VF defects, respectively.
In comparison with eyes without PCS, those with PCS
exhibited significantly greater optic disc tilt angle and number of
temporal LC defects (Table 3). Upon multivariate logistic
regression analysis, these parameters were found to be associated
significantly with presence of PCS (both P < 0.05; Table 4).
Eyes with superior and inferior hemifield VF defects exhibited
significant differences in torsion angle and number of superior and
inferior LC defects (Table 5). In multivariate logistic regression
analysis, positive torsion angle and low and high numbers of
superior and inferior LC defects, respectively, were found to be
associated with the presence of superior hemifield defects
(all P < 0.01; Table 6), and the exact opposite was true for
factors associated with presence of inferior hemifield defects
(all P < 0.01; Table 7).
Discussion
This study evaluated focal LC defects in myopic eyes with
OAG. Myopic eyes with OAG exhibited an average of 3.8
LC defects per eye, 66% of which were located at the
temporal periphery of the LC. Myopic eyes without
glaucoma exhibited multiple large pores at the temporal
periphery of the LC, which suggests that large pores in
myopic eyes may evolve into LC defects when glaucoma
develops in the eye. The number of LC defects was greater
in eyes with higher optic disc tilt angle and worse MD, and
their location corresponded spatially with that of VF defects.
As far as we are ware, this is the first study to identify
multiple LC defects at the temporal periphery in myopic
eyes with OAG and to demonstrate their association with
glaucomatous VF loss in both severity and location. Our
findings suggest that optic disc tilt may influence glau-
comatous VF defect by way of an increased number of LC
defects at the temporal periphery.
Kiumehr et al10 previously described the correspondence
of focal LC defects with neuroretinal rim thinning and
notching and acquired optic disc pitting in glaucoma, as
well as the correlation between the number of focal LC
defects and MD of the VF. The present results are
compatible with these findings in that focal LC defects
occurred in tandem with glaucomatous loss. However, the
characteristics of LC defects observed in myopic eyes
with glaucoma in this study were quite different from
those reported in nonmyopic eyes with glaucoma in the
previous study.10e14 The LC defects in myopic glaucoma
were located predominantly in the temporal area (74%),
whereas those in nonmyopic glaucoma were located mostly
in the inferior or superior area, with the temporal area being
spared (0%).10,14 The incidence of LC defects (90% vs.
22%e45%)10e12 and the number of LC defects per eye (3.8
vs. 0.3)14 among eyes with myopic glaucoma were greater
compared with those among eyes with nonmyopic
glaucoma. Furthermore, the configuration of LC defects in
nonmyopic glaucoma was classified as a laminar hole or
laminar disinsertion.11 A laminar hole was defined as a
localized discontinuity of the LC tissue. A laminar
disinsertion was defined as a posteriorly displaced laminar
insertion with a downward slope toward the neural canal
at the far periphery of the LC.10e13 In the eyes with
myopic glaucoma, most LC defects were located at the far
periphery of the LC, which was the same location as the
laminar disinsertion. However, they did not exhibit the
conventional laminar disinsertion features. Instead, they
appeared as if the LC was torn off the adjacent sclera,
creating clefts between the two. These differences led us to
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Figure 5. Images from the myopic left eye of a 52-year-old woman with early-stage glaucoma. The refractive error was 6.5 diopters and the axial length was
26.16 mm. A, Fundus photograph. B, Infrared fundus image. C, The same image as (B), but with labels. The blue lines represent the scan lines of enhanced
depth imaging (EDI) optical coherence tomography (OCT) images shown in (FeH). The scan lines are parallel to the arrangement of pores at the temporal
margin of the optic disc. D, The retinal nerve fiber layer thickness exhibits thinning in the temporal section. E, Standard automated perimetry 24-2 pattern
deviation map demonstrating paracentral scotoma and inferior nasal step. The mean deviation is 3.5 dB. FeH, B-scan EDI OCT images of the scan lines
in (C), demonstrating 3 lamina cribrosa (LC) defects at the temporal periphery of the LC (arrows), with their location corresponding with that of visual field
defects. The figures in the bottom rows are the same as those in the top rows, but with the LC defects (arrows) and the surface of the anterior LC and LC
defects (green lines) labeled. INF ¼ inferior; N and NAS ¼ nasal; NI ¼ nasal inferior; NS ¼ nasal superior; SUP ¼ superior; T and TMP ¼ temporal;
TI ¼ temporal inferior; TS ¼ temporal superior.

realize that LC defects in myopic glaucoma may arise from
a different mechanism and may possess a different nature
than those in nonmyopic glaucoma. Considering its signif-
icant association with glaucomatous VF defects, we propose
multiple LC defects at the temporal periphery as a unique
mechanism that causes VF defects in myopic eyes with
glaucoma.
Evidence is accumulating that myopia influences glau-
comatous damage through deformation of the parapapillary
region. The present findings demonstrating a significant
association between the optic disc tilt and the number of LC
defects are in accordance with this hypothesis. The present
results further confirmed the findings of our recent studies,
where we described the association of optic disc tilt with the
severity18 and progression19 of VF defects in myopic
glaucoma and provided evidence that optic disc tilt affects
VF defects by way of an increased number of temporal
LC defects. In addition, a previous study demonstrated
development of PCS from the early stage of glaucoma in
highly myopic eyes.27 The present results are in line with
them by presenting a larger tilt angle and a greater
number of temporal LC defects in eyes with PCS.
Furthermore, our results support the findings of a previous
study that demonstrated an association between optic disc
torsion direction and the location of VF defects in myopic
eyes with glaucoma25 by showing a greater number of LC
defects in the same half of the LC area as the torsion
direction.
Among previous studies of LC defects in myopic glau-
coma, one study using swept-source OCT reported LC
defects in 54% of highly myopic eyes with glaucoma, with
all of the LC defects being present in the temporal area of

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Temporal LC Defects in Myopic Glaucoma

Figure 6. Images from the myopic eye left eye of a 60-year-old woman with advanced-stage glaucoma. The refractive error was 5.25 diopters and the axial
length was 25.38 mm. A, Fundus photograph. B, Infrared fundus image. C, The same image as (B), but with labels. The blue lines represent the scan lines of
enhanced depth imaging (EDI) optical coherence tomography (OCT) images shown in (FeQ). The scan lines are parallel to the arrangement of pores at the
temporal edge of the optic disc. Because the arrangement of pores in the upper and lower portions of the lamina cribrosa (LC) differs from each other in this
eye, the alignment of scan lines is varied accordingly. D, The retinal nerve fiber layer thickness exhibits overall thinning. E, Standard automated perimetry
24-2 pattern deviation map revealing advanced-stage VF defects with a mean deviation of 20.50 dB. FeQ, B-scan EDI OCT images of the scan lines
shown in (C), demonstrating 12 LC defects at the far periphery of the LC (arrows). It appears as if all of the pores at the temporal periphery of the LC
became enlarged and evolved into LC defects. INF ¼ inferior; N and NAS ¼ nasal; NI ¼ nasal inferior; NS ¼ nasal superior; SUP ¼ superior; T and TMP ¼
temporal; TI ¼ temporal inferior; TS ¼ temporal superior.

the LC.20 Another study investigated LC defects in myopic
eyes with and without OAG using radial scan SD OCT and
reported LC defects in 66% and 28% of the myopic eyes
with and without OAG, respectively.21 Although the
present results correspond with these previous findings,
participants in the previous studies did not exhibit
multiple LC defects. The former study did not mention the
number of LC defects per eye. From their method of
categorizing participants on the basis of presence or
absence of LC defects, we assume most of the eyes with

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Table 3. Comparison of the Eyes with and without Paracentral Scotoma

With Paracentral Without Paracentral

Scotoma (n [ 35) Scotoma (n [ 37) P Value*
Gender (male/female) 16/19 21/16 0.3328
Age (yrs) 52.713.8 54.612.7 0.5367
IOP (mmHg)
Untreated 18.25.6 18.64.3 0.6936
At last examination 14.12.1 14.92.2 0.1273
Spherical equivalent (diopter) 6.201.66 6.101.67 0.7876
Axial length (mm) 26.021.08 25.900.95 0.6168
Central corneal thickness (mm) 522.938.1 530.231.2 0.3491
Torsion angle (degree) 5.49.3 0.911.9 0.0713
Tilt angle (degree) 9.24.3 7.03.1 0.0083
Mean deviation (dB) 5.262.95 4.552.89 0.2791
Lamina cribrosa defects (no.) 3.72.5 2.62.0 0.0252
Temporal lamina cribrosa defects (no.) 2.92.0 1.71.5 0.0020

IOP ¼ intraocular pressure.

Values are mean  standard deviation.
*Student t test. Statistically significant values are noted in boldface.

LC defects might have exhibited a single defect. In the latter
study, the average number of LC defects in myopic eyes
with OAG was 0.9, which is lower than the corresponding
number (3.8) in the present study. Although the reason for
these differences is uncertain, it may be explained by the
difference in the alignment of scan lines among the 3
studies. The former study used swept-source OCT, in
which scan lines are set vertically and horizontally. This
might have led to a failure to detect several LC defects in
myopic optic discs with various deformations. The latter
study used radial scan, where the scan lines might have been
aligned across the parallel arrangement of the temporally
elongated pores, thus failing to detect the maximum diam-
eter of the LC defects except along a few lines in the tem-
poral area. In contrast, we used SD OCT and varied the
alignment of scan lines in accordance with the arrangement
of LC pores in each eye. This method is suitable for
capturing the feature of the LC defects in myopic eyes and
allowed us to detect multiple defects.
The mechanism behind the development of multiple LC
defects at the temporal periphery in tilted optic discs may be
explained as follows. Optic disc tilt occurs along with the
axial elongation of the globe in childhood myopic shift.28
With this change, the temporal part of the optic disc is
stretched, and the laminar pores consequently are
elongated in the temporal direction. The temporal margin
of the LC is a junction of the LC and sclera, and therefore
is vulnerable to mechanical forces. If the stretching force
of axial elongation exceeds the tolerance of the optic disc,
the LC might be torn off the adjacent sclera, creating a

Table 4. Factors Associated with Presence of Paracentral Scotoma

Univariate Analysis Multivariate Analysis 1 Multivariate Analysis 2

95% Confidence 95% Confidence 95% Confidence
Factors Odds Ratio Interval P Value Odds Ratio Interval P Value Odds Ratio Interval P Value
Gender 1.55 0.64e3.78 0.330
Age 0.99 0.96e1.02 0.530
IOP
Untreated 0.98 0.90e1.08 0.690
At last examination 0.85 0.69e1.05 0.130 0.91 0.72e1.15 0.442 1.07 0.84e1.37 0.590
Spherical equivalent 0.96 0.73e1.26 0.790
Axial length 1.12 0.72e1.75 0.610
Central corneal thickness 0.99 0.98e1.01 0.350
Torsion angle 1.04 0.99e1.09 0.084 1.04 0.99e1.09 0.116 1.05 0.99e1.10 0.062
Tilt angle 0.84 0.74e0.97 0.014 0.85 0.73e0.99 0.040
Mean deviation 0.92 0.79e1.07 0.280
No. of total LC defects 1.27 1.02e1.58 0.033
No. of temporal LC defects 1.51 1.14e2.00 0.005 1.44 1.07e1.93 0.016

IOP ¼ intraocular pressure; LC ¼ lamina cribrosa.

Statistical analysis was performed using logistic regression analysis. Statistically significant values are noted in boldface. Factors with P < 0.20 in the
univariate analysis were included in the multivariate analysis. The multivariate analysis was performed separately using tilt angle and number of temporal LC
defects because of the multicollinearity between them. The number of total LC defects was not included in the multivariate analysis because of the
multicollinearity with the number of temporal LC defects.

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Temporal LC Defects in Myopic Glaucoma

Table 5. Comparison of the Eyes with Superior and Inferior Hemifield Defects

Superior Defect (n [ 32) Inferior Defect (n [ 15) P Value*

Gender (male/female) 17/15 7/8 0.6876
Age (yrs) 52.413.9 54.913.8 0.5692
IOP (mmHg)
Untreated 17.84.2 18.84.8 0.5388
At last examination 14.32.2 15.33.4 0.2953
Spherical equivalent (diopter) 5.732.05 5.952.34 0.7496
Axial length (mm) 26.001.06 25.800.88 0.5106
Central corneal thickness (mm) 521.830.6 525.929.5 0.6633
Torsion angle (degree) 10.510.8 2.66.7 <0.0001
Tilt angle (degree) 8.63.8 6.93.8 0.1438
Mean deviation (dB) 6.124.04 4.283.55 0.1374
No. of lamina cribrosa defects
Total 2.82.1 2.92.3 0.7554
Superior defects 0.81.1 2.01.7 0.0171
Inferior defects 2.01.4 0.91.0 0.0109

IOP ¼ intraocular pressure.

Values are mean  standard deviation unless otherwise indicated.
*Student t test. Statistically significant values are noted in boldface.

cleft between the 2 structures, which may be observed as a
large pore at the far temporal periphery of the LC. Because
local strain within the LC is determined by laminar
density,29 when myopic eyes are involved in the IOP-
related stress of glaucoma, the large pores in the temporal
periphery may experience greater strain than pores in the
other areas of the LC. Consequently, the large pores with
sparse laminar beams may become the foci of glaucomatous
strain. As soon as the temporal area gains greater suscepti-
bility, it enters a vicious cycle of glaucomatous change, and
initial large pores may enlarge further and evolve into LC
defects. The laminar beams are sheathed with astrocytes,
which provide structural and cellular support to retinal
ganglion cells (RGCs).15 In addition, capillaries running
inside the laminar beams are considered to provide
oxygen and nutrition to the laminar portion of the
RGCs.30 When defects develop in the laminar tissue, the
RGC axons may lose their structural and metabolic
support, leading to the loss of RGCs.
The present study has limitations. First, the LC was
obscured by overlying tissues such as blood vessels, partic-
ularly in areas other than the temporal region. Therefore, the
possibility remains that the small number of LC defects in
these areas may be because of the poor visibility of the LC.
This is the limitation of currently used OCT devices, which
may be overcome by the invention of devices that allow

Table 6. Factors Associated with Presence of Superior Hemifield Defect

Univariate Analysis Multivariate Analysis 1 Multivariate Analysis 2

95% Confidence 95% Confidence 95% Confidence
Factors Odds Ratio Interval P Value Odds Ratio Interval P Value Odds Ratio Interval P Value
Gender 0.78 0.23e2.61 0.680
Age 0.99 0.94e1.03 0.560
IOP
Untreated 0.96 0.83e1.10 0.540
At last examination 0.86 0.68e1.09 0.220
Spherical equivalent 1.02 0.76e1.36 0.750
Axial length 1.24 0.66e2.33 0.510
Central corneal thickness 0.99 0.97e1.02 0.660
Torsion angle 1.26 1.09e1.46 0.002 1.32 1.11e1.56 0.002
Tilt angle 1.14 0.95e1.38 0.150
Mean deviation 0.88 0.74e1.05 0.140 0.80 0.63e1.02 0.073 0.92 0.74e1.15 0.472
No. of LC defects
Total 0.96 0.72e1.27 0.750
Superior defects 0.54 0.33e0.87 0.012 0.14 0.04e0.60 0.008
Inferior defects 2.17 1.13e4.17 0.019 9.90 1.82e53.9 0.008

IOP ¼ intraocular pressure; LC ¼ lamina cribrosa.

Statistical analysis was performed using logistic regression analysis. Statistically significant values are noted in boldface. Factors with P < 0.20 in the
univariate analysis were included in the multivariate analysis. The multivariate analysis was performed separately using torsion angle and the number of
superior or inferior LC defects because of the multicollinearity between them.

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Table 7. Factors Associated with Presence of Inferior Hemifield Defect

Univariate Analysis Multivariate Analysis 1 Multivariate Analysis 2

95% Confidence 95% Confidence 95% Confidence
Factors Odds Ratio Interval P Value Odds Ratio Interval P Value Odds Ratio Interval P Value
Gender 1.29 0.38e4.34 0.680
Age 1.01 0.97e1.06 0.560
IOP
Untreated 1.05 0.91e1.20 0.540
At last examination 1.16 0.92e1.48 0.220
Spherical equivalent 0.95 0.71e1.27 0.750
Axial length 0.81 0.43e1.52 0.510
Central corneal thickness 1.00 0.98e1.03 0.660
Torsion angle 0.79 0.68e0.92 0.002 0.76 0.64e0.91 0.002
Tilt angle 0.87 0.73e1.05 0.150
Mean deviation 1.14 0.96e1.36 0.140 1.25 0.98e1.59 0.073 1.08 0.87e1.34 0.472
No. of LC defects
Total 1.05 0.79e1.39 0.750
Superior defects 1.87 1.15e3.05 0.012 6.98 1.68e29.0 0.008
Inferior defects 0.46 0.24e0.88 0.019 0.10 0.02e0.55 0.008

IOP ¼ intraocular pressure; LC ¼ lamina cribrosa.

Statistical analysis was performed using logistic regression analysis. Statistically significant values are noted in boldface. Factors with P < 0.20 in the
univariate analysis were included in the multivariate analysis. The multivariate analysis was performed separately using torsion angle and the number of
superior or inferior LC defects because of the multicollinearity between them.

better visibility of underlying tissues. Second, the association
of multiple temporal LC defects with factors that were re-
ported previously to induce susceptibility to myopic eyes,
such as increased distance from the arterial circle of Zinn-
Haller31 and thinning of the peripapillary sclera,32 was not
taken into account in the present analysis. Future studies
are needed to clarify the association. Third, the relationship
between large pores and VF defects was not determined. It
is possible that large pores may represent LC defects and
may contribute to create VF defects. However, because
eyes with large pores also exhibited LC defects, we could
not estimate the extent of the contribution of large pores to
the VF defects. Further studies are required to investigate
pore size that is related to the VF defects in eyes with
glaucoma. Finally, the present study design was cross-
sectional, which does not allow evaluation of whether the
numbers and locations of large pores and LC defects change
with disease progression. Further longitudinal studies are
required to determine it.
In conclusion, we identified multiple defects at the
temporal periphery of the LC in myopic eyes with OAG and
demonstrated its association with VF defects in both
severity and location. Our results suggest that this is a
unique feature that results in VF defects in these eyes, and
optic disc tilt may contribute to the glaucomatous VF
defects by way of an increased number of LC defects in the
temporal periphery.
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Footnotes and Financial Disclosures
Originally received: January 30, 2017.
Final revision: April 24, 2017.
Accepted: April 24, 2017.
Available online: May 24, 2017. Manuscript no. 2017-163.
1 Abbreviations and Acronyms:
Department of Ophthalmology, Akita University Graduate School of
Medicine, Akita, Japan.
2 IOP ¼ intraocular pressure; LC ¼ lamina cribrosa; MD ¼ mean deviation;
Department of Ophthalmology, Kanto Central Hospital of the Mutual Aid
Association of Public School Teachers, Tokyo, Japan.
Financial Disclosure(s):
The author(s) have no proprietary or commercial interest in any materials
discussed in this article.
Author Contributions:
Conception and design: Sawada, Yoshitomi
Analysis and interpretation: Sawada, Araie, Ishikawa, Yoshitomi
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optic disc vertical tilt angle with spectral-domain optical
coherence tomography and influencing factors. Am J Oph-
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the location of glaucomatous damage in normal-tension glau-
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1021-1029.
Data collection: Sawada, Ishikawa
Obtained funding: none
Overall responsibility: Sawada, Araie
CI ¼ confidence interval; D ¼ diopter; EDI ¼ enhanced depth imaging;
OAG ¼ open-angle glaucoma; OCT ¼ optical coherence tomography;
PCS ¼ paracentral scotoma; RGC ¼ retinal ganglion cell; SD ¼ spectral-
domain; SE ¼ spherical equivalent; VF ¼ visual field.
Correspondence:
Yu Sawada, MD, PhD, Department of Ophthalmology, Akita University
Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. E-mail:
sawadayu@doc.med.akita-u.ac.jp.
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