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OPEN

Nasal and temporal curvaturesof lamina CRIBROSA in myopic
eyes
Sooyeon Choe1,2, Yoon Ha Joo3, Yong Woo Kim1,2, Young Kook Kim1,2, Jin Wook Jeoung1,2,
Jung Chan Lee4,5 & Ki Ho Park1,2*
Little is known about the myopic characteristics of lamina cribrosa (LC) curvature. As such, weinvestigated nasal and temporal LC curvatures in myopia. In this retrospective, cross-sectional
study, 144 myopic eyes (refraction < − 2D) and 88 non-myopic eyes (refraction > − 0.5D) underwent
swept-source optical coherence tomography scanning of the LC. The anterior border of LC curvature
was delineated with 17 points and interpolated with the “cardinal spline” curve-fitting method. The
average curvature indices of the temporal and nasal sides were presented as the temporal and nasal
curvatures. Myopic eyes had a mean refraction of − 6.7 ± 2.8D, while for non-myopic eyes, the value
was 0.3 ± 1.0D. Nasal LC curvature was visible in 54 myopia (37.5%) and 42 non-myopia (47.7%)
cases (P = 0.126), and temporal LC curvature was visible in 142 myopia (98.6%) and 68 non-myopia(77.3%) cases (P = 0.001). The nasal LC curvature was significantly larger in myopia than in non-myopia(P < 0.001). Contrastingly, the temporal LC curvature was significantly smaller in myopia than in nonmyopia (P < 0.001). Axial length was associated with larger nasal LC curvature, smaller temporal LC
curvature, and larger nasal–temporal LC curvature difference (all P’s < 0.05). In myopic relative to nonmyopic eyes, LC curvature was decreased temporally and increased nasally.
Abbreviations
BCVA	Best-corrected visual acuity
BMO	Bruch’s membrane opening
cpRNFL	Circumpapillary retinal nerve fiber layer
IOP	Intraocular pressure
LC	Lamina cribrosa
MD	Mean deviation
MRW	Minimum rim width
OCT	Optical coherence tomography
ONH	Optic nerve head
RGC​	Retinal ganglion cell
SS-OCT	Swept-source optical coherence tomography
Myopia is becoming a more important issue in direct proportion to its dramatically increasing prevalence.1,2 In
myopic eyes, optic discs develop characteristic features. A tilted appearance of the optic disc and temporal crescent, which is now well known as parapapillary atrophy, was the first known feature, as identified by funduscopic
examination and optic disc photography.3–5 Currently, myopic optic nerve head (ONH) features are being further
studied by optical coherence tomography (OCT). Kim et al.6 demonstrated that as axial elongation procedes, thetemporal border tissue changes to externally oblique, the Bruch’s membrane opening (BMO) enlarges, and thenasal minimum rim width (MRW) elevates.

1

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republicof Korea. 2Department of Ophthalmology, Seoul National University Hospital, Seoul, Republic ofKorea. 3Interdisciplinary Program in Bioengineering, Seoul National University Graduate School, Seoul,
Republic of Korea. 4Department of Biomedical Engineering, College of Medicine and Institute of Medical andBiological Engineering, Medical Research Center, Seoul National University, Seoul, Republic of Korea. 5Instituteof BioEngineering, Bio‑Max Institute, Seoul National University, Seoul, Republic of Korea. *email: kihopark@
snu.ac.kr
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Figure 1.  Schematic illustration of hypothetical three-dimensional view of LC in myopic optic nerve head.
The above image depicts myopic optic disc, well-known as ‘tilted disc,’ in a two-dimensional view. This ‘twodimensional tilted disc’ may be, in the three-dimensional view, either (A) tilt-like disc appearance or (B) realdisc tilt.

Some efforts to explain myopic change to the deep structure of the ONH (i.e., lamina cribrosa [LC]), havebeen made. Lee et al.7 emphasized nasal shifting of LC indicated by nasal dragging of the central retinal vasculartrunk as a consequence of axial elongation. However, their report could not explain the well-known concept of‘disc tilt’. At this point the most pertinent question is whether, in myopic eyes, there is real disc tilt or just a tilt-likedisc appearance due to nasal shifting of the LC (Fig. 1). To the best of our knowledge, the myopic characteristics
of LC curvature, especially including the nasal part of the LC, have yet to be fully elucidated.
In the present study, we aimed to evaluate nasal and temporal curvatures of the LC in myopic eyes and tocompare them with those in non-myopic eyes.

Results

Subject demographics. Initially, 180 candidate subjects were enrolled. Among them, 64 subjects were
excluded due to increased intraocular pressure (IOP), existence of cataract with best-corrected visual acuity(BCVA) less than 20/40, history of ocular surgeries, comorbid retinal diseases, or poor OCT scan quality. Thus, a
total of 116 subjects (232 eyes) were involved in this study. All of the subjects were Korean by ethnicity.
The patients were classified into two groups based on refraction: myopia (n = 144; refraction < − 2 D) andnon-myopia (n = 88; refraction > − 0.5 D). The refraction of the myopia group was − 6.7 ± 2.8 D, while that of thenon-myopia group was 0.3 ± 1.0 D (P < 0.001). The myopia group was of significantly younger age (52.2 ± 6.7 vs.
60.3 ± 9.5 years; P < 0.001), had a smaller proportion of females (50.0 vs. 65.9%; P = 0.018), longer axial length(26.1 ± 1.1 vs. 23.6 ± 0.8; P < 0.001), and lesser circumpapillary retinal nerve fiber layer (cpRNFL) thickness(71.4 ± 14.4 vs. 82.6 ± 19.5; P < 0.001). There were no significant intergroup differences in sex, laterality of eye,
BCVA (in logMAR), disc area, cup area or percentage of glaucoma (all P > 0.05). The nasal side of the LC wasvisible in 54 myopic eyes (37.5%) and 42 non-myopic eyes (47.7%) (P = 0.126), while the temporal side of the LC
was visible in 142 myopic eyes (98.6%) and 68 non-myopic eyes (77.3%) (P = 0.001) (Table 1).
The baseline demographics and descriptive characteristics of the eyes with visible nasal and temporal LC areshown in Table 2. If both eyes of a candidate were eligible, the eye without glaucoma (or less severe glaucoma
with a higher mean deviation [MD] value) was selected for the subsequent analysis. Forty-five myopic eyes of
45 subjects and 30 non-myopic eyes of 30 subjects were included for the subsequent analysis. The refraction of
the myopia group was − 6.6 ± 2.6 D, while that of the non-myopia group was 0.5 ± 1.1 D (P < 0.001). The myopia
group was of younger age (52.3 ± 7.2 vs. 60.5 ± 10.4), and had longer axial length (26.3 ± 1.2 vs. 23.5 vs. 0.8) andthinner cpRNFL thickness (71.7 ± 13.6 vs. 86.8 ± 20.5) (all P’s < 0.001).
Comparison of LC curvature. The nasal and temporal curvatures of the LC were compared between the

myopic and non-myopic eyes with visible LC. Nasal LC curvature in myopic eyes (2.3 ± 0.5 [1/mm]) was significantly larger than that in-non myopic eyes (1.8 ± 0.3 [1/mm]) (P < 0.001). Meanwhile, temporal LC curvature
in myopic eyes (0.9 ± 0.7 [1/mm]) was smaller than that in non-myopic eyes (1.7 ± 0.6 [1/mm]), with statisticalsignificance (P < 0.001). The difference between nasal–temporal curvature was significantly larger in myopic eyes
than in non-myopic eyes (P < 0.001) (Table 3).

Factors associated with LC curvature. The factors associated with the LC curvature parameters wereanalyzed using a multivariate linear regression model. Multicollinearity was checked, and all of the varianceinflation factors (VIFs) were less than 2.5. Axial length was significantly associated with larger nasal LC curvature (β = 0.128, P = 0.011), smaller temporal LC curvature (β = − 0.278, P < 0.001) and larger nasal–temporal

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Myopia(n = 144)

Non-myopia(n = 88)

Age (yrs)

52.2 ± 6.7

60.3 ± 9.5< 0.001*

Female, n (%)

72 (50.0)58 (65.9)

0.018†

Right eye, n (%)

72 (50.0)44 (50.0)

1.000†BCVA (logMAR)

0.02 ± 0.1

0.03 ± 0.1

0.345*

Refraction (Diopter)− 6.7 ± 2.8

0.3 ± 1.0

< 0.001*

Axial length (mm)26.1 ± 1.1

23.6 ± 0.8< 0.001*

IOP (mmHg)

13.0 ± 2.7

13.3 ± 2.4

0.421*

Average cpRNFL thickness (μm)

71.4 ± 14.4

82.6 ± 19.5

< 0.001*

MD (dB)− 5.7 ± 6.4− 4.7 ± 6.4

0.284*

Disc area ­(mm2)‡

2.0 ± 0.7

1.9 ± 0.7

0.496*

Cup area (­ mm2)‡

1.3 ± 0.8

1.3 ± 0.7

0.905*

Glaucoma, n (%)

100 (69.9)

59 (68.6)

0.835†

Nasal LC visibility, n (%)

54 (37.5)

42 (47.7)

0.126§

Temporal LC visibility, n (%)

142 (98.6)

68 (77.3)

0.001§

P value

Table 1.  Baseline demographics and descriptive characteristics. Except where indicated otherwise, values
are mean ± standard deviation or number (%). *Comparison was performed using the Student t test.
†
Comparison was performed using the two proportion z-test. ‡ Corrected area calculated in considerationof the magnification factors related to the SD-OCT camera and the eye by substituting the subject’s axial
length. § Comparison was performed using the chi-squared test. Statistically significant values are shown inbold (P < 0.05). BCVA: best-corrected visual acuity; cpRNFL: circumpapillary retinal nerve fiber layer; IOP:
intraocular pressure; LC: lamina cribrosa; MD: mean deviation.

Myopia(n = 45)

Non-myopia(n = 30)

Age (yrs)

52.3 ± 7.2

60.5 ± 10.4

< 0.001*

Female, n (%)

25 (55.6)

22 (73.3)

0.121†

Right eye, n (%)

15 (33.3)

11 (36.7)

0.764†BCVA (logMAR)

0.007 ± 0.1

0.048 ± 0.1

0.056*

Refraction (Diopter)− 6.6 ± 2.6

0.5 ± 1.1

< 0.001*

Axial length (mm)26.3 ± 1.2

23.5 ± 0.8< 0.001*

IOP (mmHg)

13.0 ± 2.1

13.5 ± 2.5

0.351*

Average cpRNFL thickness (μm)

71.7 ± 13.6

86.8 ± 20.5

< 0.001*

MD (dB)− 5.0 ± 6.3− 4.3 ± 5.9

0.645*

Disc area ­(mm2)‡

2.0 ± 0.5

1.8 ± 0.4

0.076*

Cup area (­ mm2)‡

1.1 ± 0.5

1.0 ± 0.5

0.514*

Glaucoma, n (%)

32 (71.1)

20 (66.7)

0.689†

P value

Table 2.  Baseline demographics and descriptive characteristics with visible nasal LC. Except where indicatedotherwise, values are mean ± standard deviation or number (%). *Comparison was performed using theStudent t test. † Comparison was performed using the two proportion z-test. ‡ Corrected area calculated inconsideration of the magnification factors related to the SD-OCT camera and the eye by substituting the
subject’s axial length. Statistically significant values are shown in bold (P < 0.05). BCVA: best-corrected visualacuity; cpRNFL: circumpapillary retinal nerve fiber layer; IOP: intraocular pressure; LC: lamina cribrosa; MD:mean deviation.

LC curvature difference (β = 0.406, P < 0.001). Smaller disc area was associated with larger nasal LC curvature(β = − 0.034, P = 0.021) and larger nasal–temporal LC curvature difference (β = − 0.648, P = 0.027) (Table 4).

Representative cases. Figure 2 shows representative cases of myopic and non-myopic eyes with visible

nasal LC. In the first row are the findings for the eye of a 51-year-old myopic female. The axial length was
26.1 mm and the refraction was − 7.0 D. The nasal LC curvature was 1.80 (1/mm) and the temporal LC curvature
was 0.78 (1/mm). In the second row are the results for the eye of a 66-year-old non-myopic female. The axial
length was 23.9 mm and the refraction was + 2.6 D. The nasal LC curvature was 1.56 (1/mm) and the temporal
LC curvature was 1.75 (1/mm).

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Myopia with visible nasal LC(n = 45)

Non-myopia with visible nasal LC(n = 30)

Nasal LC curvature (1/mm)

2.3 ± 0.5

1.8 ± 0.3

< 0.001*

Temporal LC curvature (1/mm)

0.9 ± 0.7

1.7 ± 0.6

< 0.001†

LC curvature difference(nasal–temporal) (1/mm)

1.4 ± 0.9

0.1 ± 0.8

< 0.001*

P value

Table 3.  Comparison of nasal and temporal curvatures of LC between myopia and non-myopia. Except whereindicated otherwise, values are mean ± standard deviation. *Comparison was performed using the Student
t test. † Comparison was performed using the Wilcoxon signed-rank test. Statistically significant values areshown in bold (P < 0.05). LC: lamina cribrosa.

ßStandard Error

95% CI

P value*

Nasal LC curvature (1/mm)
Age (yrs)− 0.0130.008− 0.029 to 0.003

0.110

Sex (female)− 0.2440.145− 0.537 to 0.049

0.101
0.011

Axial length (mm)

0.128

0.048

0.031 to 0.226

IOP (mmHg)− 0.0120.027− 0.067 to 0.042

0.651

Disc area ­(mm2)†− 0.0340.161− 0.708 to − 0.060

0.021

Average cpRNFLT (μm)

0.004

0.004

− 0.004 to 0.013

0.370

MD (dB)− 0.0100.011− 0.032 to 0.012

0.358

Glaucoma

0.002

0.162

− 0.325 to 0.329

0.989

Temporal LC curvature (1/mm)
Age (yrs)

0.005

0.010

− 0.016 to 0.026

0.650

Sex (female)

0.174

0.187

− 0.203 to 0.551

0.357

Axial length (mm)

− 0.278

0.062− 0.403 to − 0.153< 0.001

IOP (mmHg)− 0.0070.035− 0.078 to 0.063

0.832

Disc area ­(mm2)†

0.264

0.207

− 0.153 to 0.681

0.208

Average cpRNFLT (μm)

− 0.005

0.006− 0.016 to 0.007

0.404

MD (dB)− 0.00002

0.014− 0.029 to 0.029

0.999

Glaucoma

0.114

0.208

− 0.306 to 0.535

0.587

LC curvature difference (nasal–temporal) (1/mm)
Age (yrs)− 0.0180.014− 0.047 to 0.011

0.214

Sex (female)− 0.4180.256− 0.935 to 0.099

0.110< 0.001

Axial length (mm)

0.406

0.085

0.235 to 0.577

IOP (mmHg)− 0.0050.048− 0.101 to 0.092

0.919

Disc area ­(mm2)†− 0.6480.283− 1.219 to − 0.077

0.027

Average cpRNFLT (μm)

0.009

0.008

− 0.007 to 0.025

0.265

MD (dB)− 0.0100.020− 0.050 to 0.029

0.601

Glaucoma− 0.1120.285− 0.688 to 0.464

0.697

Table 4.  Factors associated with LC curvature parameters. *Statistical analysis was performed using
multivariate linear regression model. † Corrected area calculated in consideration of the magnification factors
related to the SD-OCT camera and the eye by substituting the subject’s axial length. Statistically significant
values are shown in bold (P < 0.05).

Discussion

This study investigated the nasal and temporal LC curvatures of myopic and non-myopic eyes. We found that thenasal side of LC curvature is larger and the temporal side is smaller in myopia relative to non-myopia. Additionally, we evaluated the factors associated with nasal and temporal LC curvatures.
The association of myopia with morphologic ONH change (i.e., of the LC) has been investigated widely. Lee
et al.7 found that during myopic progression, the position of the central retinal vascular trunk, which is embeddedin the LC, was dragged nasally. Another ­study8 from the same group demonstrated that during axial elongation,
the temporal border tissue length stretches to the nasal side while its angle changes from internally oblique toexternally oblique. Kim et al.6 previously discovered that with elongation of axial-length, nasal MRW increases,
which suggests that nasal peripapillary tissue elevation occurs with progression of myopia. Our findings can
supplement results from previous studies on myopic ONH change, especially with regard to three-dimensionalchange of LC curvature. We can postulate that as axial elongation proceeds during myopic change, the central
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Figure 2.  Representative cases with visible nasal LC. Representative images of myopic eyes (A–C) and nonmyopic eyes (D–F) are presented. The images of myopic eye are from a 51-year-old female with refraction of− 7.0 D and an axial length of 26.1 mm. The images of non-myopic eye are from a 66-year-old female withrefraction of + 2.6 D and an axial length of 23.9 mm. The first column (A,D) shows disc photographs. The
second column (B,E) provides horizontal SS-OCT optic disc B-scans. The third column (C,F) provides thecalculated vectors of LC curvature (green arrows), as measured from each equally-divided dot (red dots). The
nasal LC curvature was 1.80 (1/mm) and the temporal LC curvature was 0.78 (1/mm) for the myopic eye and1.56 (1/mm) and 1.75 (1/mm), respectively for the non-myopic eye.

Figure 3.  Schematic illustration showing nasal and temporal LC curvature in non-myopic and myopic eyes.
Unlike non-myopic eyes, in myopic eyes, the nasal LC curvature shows an abruptly tilted appearance while thetemporal LC curvature shows a flattened appearance.

part of the LC moves nasally and causes the nasal part to tilt abruptly and curve. At the same time, the temporal
LC would be stretched, thereby coming to take on a more flattened appearance (Fig. 3).
The LC plays a primary role in the pathogenesis of g­ laucoma9–14. Deformation of the LC causes retinal ganglion cell (RGC) axonal injury, which leads in turn to glaucoma. LC deformation contributory to glaucoma has
manifested mainly as localized laminar d­ efects15–19 and LC t­ hickness20,21 or depth c­ hange11,22–26. The findings ofthe present study possibly explain the phenomenon of topographic distribution of localized LC defect and its
association with glaucoma. Previous studies have shown that large LC pores and LC defects are located mostly
on the temporal rather than the nasal ­side27,28. We can postulate that axial-elongation-associated stretching of thetemporal LC generates tensile force that results in localized LC defect on the temporal side. Also, compromised
LC structure can lead to vulnerability of RGC axons. On the other hand, it may also be postulated that as the nasal
part of the LC tilts, compression of LC structures therein is incurred, and optic nerves running through nasal
LC pores might be injured, thus generating temporal visual-field defects. This explanation supports a previous­report29 that a temporal visual-field defect group with myopia showed a higher optic disc tilt ratio than did a
typical glaucomatous-field defect group.
In regard to morphologic deformation of the LC, previous studies have focused mainly on LC depth andthinning to explain the association with g­ laucoma20,21,26,30,31. However, in order to understand this association,
three-dimensional deformation of the LC in the myopic ONH should be investigated. Our study is novel inhaving evaluated nasal LC curvatures where visualization of the LC is relatively difficult on OCT images due toshadowing from the nasal neuroretinal rim. As such, it can further elucidate previous assumptions regarding
axial-elongation-associated ONH changes and myopic optic neuropathies such as myopic glaucoma.
Our study has several limitations. First, although swept-source OCT (SS-OCT) is comparable to enhanced
depth imaging OCT in LC i­maging32, it sometimes has a limitation in visualizing deep ONH structures that
include the LC. To reduce selection bias, we excluded cataract eyes with vision worse than 20/40, ocular surgery
history and/or poor-quality OCT images. Also, to overcome the ambiguity inherent in delineating the anteriorborder of the LC, we performed a reliability test to assess inter-rater difference (Kappa = 0.90; almost perfect).
Second, both patients with and without glaucoma were included in this study. To minimize the effect of glaucoma
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and IOP on LC curvature, we excluded patients with IOP over the normal range (> 21 mmHg) and performed a
multivariate linear regression analysis for IOP, cpRNFL thickness, MD and presence of glaucoma as covariates.
Third, all of the subjects were Korean by ethnicity. Since optic disc head properties manifest racial ­differences33,34,
our results cannot be generalized to all ethnicities. Fourth, the cross-sectional nature of this study implies that it
can show only the association of myopia with features of LC curvature. Further longitudinal cohort study shouldbe performed to more fully elucidate the causal relationship between myopia and LC curvature and its effecton glaucoma. Lastly, the imbalances of age, size, and percentage of LC visibility between the myopic and nonmyopic groups may have caused selection bias. One therefore should be cautious in interpreting the results; infact, further study with a larger cohort will be needed to minimize bias. Also, multiple factors should be sought
out and grouped by PCA plot when investigating the factors associated with LC curvature.
In conclusion, myopic eyes show characteristic features of LC curvature. The nasal LC bends more and thetemporal LC flattens as axial length elongates. This finding can help to broaden understanding of myopic LC
configurations and the pathophysiology of myopic optic neuropathy.

Methods

This was a single-center retrospective study performed at Seoul National University Hospital. The study wasapproved by the Institutional Review Board of Seoul National University Hospital (IRB number: 2202-0371298), which adhered to the tenets of the Declaration of Helsinki. Written informed consent was waived due tothe retrospective nature of the study by the Institutional Review Board of Seoul National University Hospital.

Study subjects. All of the subjects had visited the Seoul National University Hospital Glaucoma Clinic in
Seoul, Korea, between January 2015 and July 2022. We reviewed medical records retrospectively, and included
eligible adult (over 40 years old) subjects. Based on refraction, the patients were classified into two groups: myopia (refraction < − 2 D) and non-myopia (refraction > − 0.5 D).
Patients were excluded from further analysis for any of the following reasons: (1) IOP over 21 mmHg by
Goldmann applanation tonometry, (2) existence of cataract with BCVA worse than 20/40 in Snellen equivalent,(3) history of intraocular surgery or trauma, (4), any evidence of pathologic myopia or high-myopia-associatedoptic neuropathy, or (5) poor optical coherence tomography scan quality. Patients for whom both eyes qualified
for inclusion were enrolled.
All of the enrolled patients underwent a complete ophthalmic examination, including BCVA assessment,
refraction by keratorefractometry (KR-800A, Topcon, Tokyo, Japan), axial-length measurement (Axis II PR;
Quantel Medical, Inc., Bozeman, MT, USA), slit-lamp biomicroscopy, Goldmann applanation tonometry (HaagStreit, Koniz, Switzerland), dilated fundus examination, stereo optic disc photography, red-free retinal nerve
fiber layer photography (TRC-50IX; Topcon Corporation, Tokyo, Japan), and 24-2 SITA Standard protocols of
Humphrey VF (Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA). Additionally, Cirrus HD-OCT (Carl Zeiss
Meditec) and SS-OCT (Deep Range Imaging [DRI] OCT, Triton, Topcon) were performed at the same visit.
The disc area and cup area were obtained from Cirrus OCT. The corrected disc and cup areas were calculated,in consideration of OCT-camera- and human-eye-related magnification factors, with the following equation,
which calculation process is described in detail in previous r­ eports35–37.

2Corrected area mm2 = 3.3822 × 0.013062 × axial length−1.82

× OCT − computed area
SS‑OCT imaging.

SS-OCT imaging was performed after dilation of the pupil. Three-dimensional discscans, covering 6 mm × 6 mm area and comprising 512 A-scans × 256 B-scans, were obtained. The protocol captures color fundus photos as well as optic disc scans, allowing for simultaneous evaluation between OCT B-scansand color optic disc photos with the built-in review program (IMAGEnet 6 Version 1.25, Topcon). The cpRNFL
thickness was automatically measured with the built-in review program (IMAGEnet 6 Version 1.25, Topcon).
The obtained OCT scans were reviewed, and those of poor quality, that included, for example, motion artifacts,
defocusing and/or poor centration, were excluded from further analysis.

Evaluation of LC curvature. In the present study, three horizontal B-scans were selected and analyzed
from the center (middle one-third), superior (upper one-third), and inferior (lower one-third) horizontal
meridians, and then averaged for the analysis. To improve LC visibility, we enhanced the OCT images using theadaptive compensation ­technique38–40. In the enhanced images, the two BMO points were connected to define
the BMO reference plane. The middle point of the BMO distance was identified, from which a perpendicular line
was drawn. The meeting point of this line and the anterior surface of the LC was marked as the midline reference point. The anterior surface of the LC between the midline reference point and the nasal and temporal end
points, respectively, was divided into 8 equivalently spaced points. The points were interpolated with the “cardinal spline” curve-fitting ­method41. To separate the spline into 17 points at regular intervals, arc length parameterization was performed. The circumcenter of the triplet of adjacent points along the curve was calculated as
the curvature index. The average curvature indices of the temporal and nasal sides were presented as the temporal and nasal curvatures (Fig. 4). The above-referenced calculations were performed using MATLAB R2021(MathWorks, Inc., MA, USA). To determine the interobserver measurement reproducibility of LC curvatures,the intraclass correlation coefficient (ICC) with its confidence interval (CI) was calculated by two independent
examiners (S.C. and Y.K.K.) in a masked fashion. The strength of agreement was almost perfect (Kappa: 0.90).

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Figure 4.  Diagram describing methodology of LC curvature measurement. (A) BMO points (blue dots) with
17 yellow dots delineating the anterior surface of the LC are shown. The yellow dots were interpolated withthe cardinal spline curve-fitting method (blue curve). The blue curve was separated into 17 points at regularintervals (red points). The circumcenter of the triplet of adjacent red points along the blue curve was calculated
as the curvature index (green arrow). The average of the nasal side is presented as the nasal LC curvature, andthe average of the temporal side is presented as the temporal LC curvature. (B) The right column provides aschematic version of each corresponding left-column image.

Data analysis. Continuous variables (age, BCVA, refraction, axial length, IOP, cpRNFL thickness, disc area,
cup area and LC curvatures) were compared by Student t test or by Wilcoxon signed-rank test. Categorical variables (sex, laterality, presence of glaucoma and percentage of LC visibility) were compared using the two proportion z-test or the chi-squared test. A multivariate linear regression model was used to identify factors associatedwith nasal or temporal LC curvature (scatterplots of variables are provided in Supplementary Information Fig.
S1). The statistical analysis was performed by MATLAB R2021 (MathWorks, Inc.) and STATA 13.0 (StataCorp
LP, College Station, TX, USA). Except where stated otherwise, the data are presented herein as the mean ± standard deviation, and the level of statistical significance was set at 2-sided P < 0.05.

Data availability

The datasets analysed during the current study are not publicly available due to patient data privacy policy, but
are available from the corresponding author (K.H.P.) on reasonable request.

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Received: 16 June 2022; Accepted: 13 September 2022

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Acknowledgements

The authors thank Michael J. A. Girard (Ophthalmic Engineering & Innovation Laboratory, Singapore Eye
Research Institute, Singapore) and Jean Martial Mari (Université de la Polynésie Française, Tahiti, French Polynesia) for providing the adaptive compensation software.

Author contributions

K.H.P. had full access to all the data in the study and takes responsibility for the integrity of the data and theaccuracy of the data analysis. S. C. wrote the main manuscript text. S.C, Y.H.J., Y.K.K and K.H.P. performed thedata review and analysis and prepared Fig. 1. The critical revision of the manuscript was done by Y.W.K., Y.K.K,
J.W.J., J.C.L. and K.H.P. All authors reviewed the manuscript.

Competing interests

The authors declare no competing interests.

Additional information

Supplementary Information The online version contains supplementary material available at https://​doi.​org/​
10.​1038/​s41598-​022-​20372-8.
Correspondence and requests for materials should be addressed to K.H.P.
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