Interocular symmetry of the peripapillary choroidal thickness and retinal nerve fibre layer thickness in healthy adults with isometropia
Yang et al. BMC Ophthalmology
Interocular symmetry of the peripapillary choroidal thickness and retinal nerve fibre layer thickness in healthy adults with isometropia
Mo Yang 0 2
Wei Wang 1
Quangang Xu 0 3
Shaoying Tan 0
Shihui Wei 0
0 Department of Ophthalmology, Chinese PLA General Hospital , Fuxing Road NO.28, Beijing, Haidian District , China
1 Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University , Guangzhou , China
2 Department of Ophthalmology, Shanxi Grand Hospital , Taiyuan , China
3 Department of Neurology, Chinese PLA General Hospital , Beijing , China
Background: The aim of this study was to determine the interocular differences in the peripapillary retinal nerve fibre layer (RNFL), peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) in healthy adults with isometropia, using enhanced depth imaging optical coherence tomography (EDI SD-OCT). Methods: One hundred healthy Chinese adults with spherical equivalents of ≤ ±3 dioptres and interocular differences of <0.5 dioptres were prospectively enrolled in this study. They underwent RNFL and PCT measurements via EDI SD-OCT, with a 3.4 mm scan circle centred on the optic nerve head. Subfoveal choroidal thickness (SFCT) measurements were also taken with a horizontal line scan centred on the macula. Right and left eyes were compared by a paired t-test, and the interocular differences were calculated. The agreement and correlations of the RNFLs, PCTs and SFCTs between the right and left eyes were analysed. Results: Eighty-six subjects (172 eyes) were included in the final analysis, consisting of 44 (51.6 %) males and 42 (48.8 %) females; 55 (63.9 %) had emmetropia and 33 (36.1 %) had ametropia. The RNFL was statistically significantly thicker in the right eyes when compared to the left eyes in the temporal quadrant, and thinner on average in the nasal superior quadrant (p < 0.05). However, the differences in the choroidal thicknesses in all of the quadrants between the right and left eyes were not statistically significant. The tolerance limits of the average RNFL were −21.1 μm and 7.1 μm, and the mean and standard deviation of the interocular difference in the average PCT was −2.2 ± 24.2 μm. The RNFLs and PCTs in all of the locations in the right eyes were significantly correlated with those in the left eyes. However, no significant associations between the age, sex, interocular asymmetry of spherical the equivalent or interocular differences in the RNFL and PCT were detected. Conclusion: The PCT did not differ significantly between the right and left eyes, although interocular asymmetry of the RNFL existed in this Chinese population with isometropia.
Symmetry; Emmetropia; RNFL; Choroidalthickness; EDI SD-OCT
Because paired organs are not always perfectly
symmetrical, an analysis of interocular symmetry can be a useful
tool in clinical practice. Numerous studies have
evaluated the role of asymmetrical parameters in various
conditions, including the diagnosis of disease, detection of
pathological abnormalities and prediction of disease
progression. For example, interocular differences of greater
than 2.0 in the cup to disc ratio have been shown to be
a sign of glaucomatous damage, and have been widely
used in clinical practice . Similarly, other studies have
reported that interocular asymmetry in the intraocular
pressure (IOP) and retinal nerve fibre layer (RNFL) is
associated with glaucomatous visual field defects [2, 3].
Moreover, in refractive or cataract surgery, high
interocular symmetry of the spherical equivalent and visual
acuity may be helpful in predicting the outcome of
surgery on the fellow eye. In age-related macular
degeneration, the severity in one eye affects the severity in its
fellow eye .
Since the landmark study by Spaide and associates
reporting choroid imaging in vivo with enhanced depth
imaging using spectral domain optical coherence
tomography (EDI SD-OCT), recent studies have focused on
the measurement of choroidal thickness in healthy and
disease conditions. In addition, it has greatly expanded
our understanding of the pathogenesis of various retinal
and optic diseases, such as age-related macular
degeneration, pathological myopia, ischemic optic neuropathy
and glaucoma [5–7].
Understanding the normal range of differences
between eyes will help inform analysis of what degree of
asymmetry between eyes can be considered possibly
pathologic. Recently, several studies have detected the
degree of interocular symmetry in the RNFL thickness
and macular choroidal thickness in both adults and
children, but the results were controversial [8–13]. The
discrepancy may caused by different OCT devices,
variation of inclusion criteria, ethnic variation, or different
refractory status. These studies may also have been
biased by the inclusion of subjects with isometropia and
anisometropia. It was suggested that difference in
refractive error between eyes would be expected to change
the RNFL thickness and macular choroidal thickness
[14, 15]. Moreover, no study has reported interocular
differences in the peripapillary choroidal thickness
(PCT) of healthy subjects. Therefore, the aim of the
present study was to determine the range of
interocular variation in the RNFL and PCT, as well as the
factors associated with the interocular differences in
normal Chinese adults with isometropia. This
information may help to provide an indication of possible
pathology, if there is some degree of asymmetry
between a patient’s eyes.
This prospective, cross-sectional study was conducted
from July through August of 2015 in the Department of
Neuro-ophthalmology at the General Hospital of the
People’s Liberation Army (PLAGH) in China. This study
adhered to the tenets of the Helsinki Declaration, and
was approved by the PLAGH institutional review board.
Written informed consent was obtained from all of the
subjects before they entered the study.
Healthy adults were recruited from the staff, students
and relatives of the patients at the PLAGH. The
inclusion criteria in this study were as follows: 1) best
corrected visual acuity (BCVA) on the Snellen chart of ≥1.0;
2) spherical equivalent (SE) of ≤ ±3.0 dioptres,
astigmatism of <1.0 dioptre and interocular difference in the SE
of < 0.5 dioptres (isometropia); 3) anterior segment and
fundus appeared normal; 4) the RNFL thickness was
within normal ranges. The SE was calculated by the
sphere plus one-half of the cylinder degree. The adults
with isometropia were further divided into emmetropia
(SE ≤ ±0.5 dioptres) and ametropia (SE > ±0.5 dioptres).
The major exclusion criteria were as follows: 1)
intraocular pressure (IOP) ≥ 21 mmHg (Goldmann
applanation tonometry); 2) interocular difference in the
BCVA (Snellen chart) of > 0.1; 4) history of laser
therapy, intraocular surgery or rigid contact lens wear.
Those subjects with a history of diabetes, smoking,
systemic hypertension, prematurity or other systemic
diseases were also excluded from this study.
All of the subjects underwent complete ophthalmic
evaluations, which included visual acuity measurements,
slit-lamp biomicroscopy, gonioscopy, IOP measurements
(Goldmann applanation tonometry), fundus
examinations and refractive error examinations using an
autorefractometer (KR-8900 version 1.07; Topcon Corporation,
Optical coherence tomography imaging and analysis
All of the OCT scans were performed by the same
experienced technician who was blind to the subject
assignment. A commercial SPECTRALIS®SD-OCT (Heidelberg
Engineering, Heidelberg, Germany) was used to obtain
the RNFL and choroidal images, and the detailed
methodology and standard protocol have been reported
previously [16, 17]. Briefly, a 3.4 mm scan circle centred on
the optic nerve head was used to obtain the RNFL and
PCT measurements. In addition, a horizontal line scan
centred on the macula was used to obtain the
subfoveal choroidal thickness (SFCT) . The RNFL
values were automatically displayed for 6 quadrants
(Fig. 1): nasal (N), temporal (T), nasal superior (NS),
Fig. 1 Illustration of retinal nerve fiber layer (RNFL) and peripapillarychoroidal thickness (PCT) measurements in isometropia eyes using enhanced
depth imaging optical coherence tomography (EDI-OCT). a RNFL thickness in right eye; b PCT in right eye. The circle were segmented into six
quadrants: nasal (N), temporal (T), nasal superior (NS), temporal superior (TS), nasal inferior (NI) and temporal inferior (TI)
temporal superior (TS), nasal inferior (NI) and
temporal inferior (TI). The RNFL and PCT
measurements were obtained via SD-OCT in the enhanced
depth imaging (EDI) mode.
The automatic averaging and eye-tracking features
were used to better visualize the choroid, while the
keratometry readings were entered into the Heidelberg
machine to adjust for the magnification during the OCT
examination. The resultant images were viewed and
measured using Heidelberg Eye Explorer software (version
184.108.40.206; Heidelberg Engineering, Heidelberg, Germany).
The choroidal thickness was measured manually as the
distance between the inner edge of the retinal pigment
epithelium and the outer aspect of the lamina fusca/inner
border of the sclera. Like the RNFL, the PCTs in the six
quadrants were presented after the identification of the
two borderlines (Fig. 1). The averages of RNFL and PCT
measurements were also calculated and used in the final
statistical analyses. To avoid diurnal variations, all of the
scans were obtained in the afternoon, between 17:00 and
20:00. Those subjects with inadequate image quality or
segmentation failure in one or both eyes were excluded
from the statistical analyses.
All of the statistical analyses were performed using SPSS
software (version 20.0; SPSS, Chicago, IL), and the data
was presented as the mean and standard deviation (SD).
Based on data from previous studies, we estimated that
26 healthy adults would be required to detect a
significant difference in average PCT of at least 60.0 μm
between right eyes and left eyes at a significance level of
0.05 and a power of 0.90, for a standard deviation of
40.3 μm [13, 15–17]. The normality of the parameter
measurements was confirmed using a one sample
Kolmogorov–Smirnov test, and the categorical variables
were evaluated using Fisher’s exact test. The intraclass
correlation coefficients (ICC) and Pearson’s coefficients
were computed to measure the interocular agreement/
correlation. Either the paired Student’s t-test or
Wilcoxon paired test was used to compare the right eyes
and left eyes, depending on whether normality could be
assumed. Pearson’s correlation and a regression analysis
were used to explore the relationship between the
interocular differences (Δ, right eyes minus left eyes)
between the RNFL or PCT and the other variables (e.g.,
age, sex, ΔSE). A P-value < 0.007 (0.05/7) was considered
significant for associations for RNFL or choroidal
thickness measurements. Otherwise, a P value of <0.05 was
considered to be statistically significant.
A total of 100 healthy Chinese adults with isometropia
were recruited for this research; however, 14 were
excluded due to image artefacts or segment failure. Finally,
86 eligible subjects (172 eyes) were entered into the final
statistical analyses. The mean age was 32.7 ± 11.7 years
old (range 18 to 69), forty-four (51.6 %) were male, and
42 (48.8 %) were female. There were 55 (63.9 %) patients
with emmetropia and 33 (36.1 %) with ametropia. The
demographic characteristics and main clinical features of
the right and left eyes are listed in Table 1. The mean SE
Table 1 Demographic and ocular characteristics of subjects
SE in all subjects, diopter
32.7 ± 11.7 (18–69)
−0.65 ± 0.96
−0.59 ± 0.93
SD standard deviation, SE spherical equivalent
*P-value comparing right and left eyes by paired Student t test
was −0.65 ± 0.96 dioptres in the right eyes and −0.59 ±
0.93 dioptres in the left eyes (P = 0.123).
Table 2 shows the data for the RNFLs and choroidal
thicknesses in the right and left eyes, and their
interocular differences. The RNFL in NS quadrant was thinner
in the right eyes (120.3 ± 19.7 μm) than in the left eyes
133.9 ± 21.3 μm) (P < 0.001). Although the right eyes had
thinner average RNFL (119.1 ± 11.1 versus 120.3 ±
11.2 μm, P = 0.034), it is worth noting that a difference
in means of only one micrometer may not be
particularly clinically significant. The right eyes had thicker
RNFLs in the T quadrant and thinner RNFLs in the NS
quadrant, when compared to the left eyes; however, no
significant differences in the other quadrants were
observed. With regard to the SFCT and PCT, highly
interocular symmetry was observed. As Table 2 shows,
the interocular differences in the SFCT and PCT in each
quadrant were not significant (all P < 0.05). The 95 %
confidence interval was −21.1 μm to 7.1 μm,
respectively, depending on whether the RNFL was greater in
the left eye or the right eye. The cut-off points for the
average PCT were −74.1 μm and 46.4 μm.
When the subjects were divided into emmetropia or
ametropia subgroups, the analyses of interocular
symmetry produced consistent results of RNFL thickness
in the NS quadrant and choroidal thickness
measurements (Table 3). Both emmetropes and ametropes
showed asymmetry of RNFL thickness in NS
quadrant. Significant interocular difference of RNFL
thickness in the N quadrant was observed among
emmetropia eyes, but not among ammetropia eyes. In
addition, the interocular difference in the temporal
quadrant exists only among emmetropia eyes and not
The interocular correlations between the right and left
eyes are shown in Table 4. Overall, the SFCT and PCT
were highly correlated in both eyes, with ICCs of >0.9
for all of the measurements of choroidal thickness. The
RNFLs of the homonymous quadrants were not
Table 2 Measurements of peripapillary retinal nerve fibre layer thickness and choroidal thickness for right and left eyes and
Table 3 Interocular differences of peripapillary retinal nerve fiber layer thickness and choroidal thickness in emmetropia and
correlated as well as the choroidal thicknesses were,
although all of the ICCs for the RNFLs were >0.8.
Table 5 shows the results of the linear regression
analysis of the interocular differences in the RNFLs and
choroidal thicknesses. The interocular differences in the
RNFLs were not correlated with the age or ΔSE. With
regard to sex, no significant associations with the RNFL
were detected, with the exception of the TS quadrant. In
the interocular differences in the choroidal thickness, no
correlations with the sex, ΔSE or age were noted (all P >
0.05), but the PCT and ΔNI were related to the age.
This study aimed to assess the interocular symmetry of
the RNFL and PCT, as measured via EDI SD-OCT in an
adult Chinese population with isometropia. We did not
find a significant interocular difference in the PCT in
any of the quadrants in the emmetropia or ametropia
subgroups, and the normal limit for the interocular
difference in the average PCT was 46.4 μm. With regard to
the RNFL, we found that the interocular differences in
the RNFLs for the average and two of the quadrants
were statistically significant. Moreover, the interocular
correlation was higher for the PCT than for the RNFL
measurements. The interocular differences in the RNFLs
Table 4 Agreement and correlations of retinal nerve fiber layer
and choroidal thickness between right and left eye
Parameters Pearson association* ICC (95 % CI)*
−0.13 (−0.41 to 0.14)
−0.01 (−0.30 to 0.28)
0.08 (−0.11 to 0.28)
0.09 (−0.25 to 0.42)
−0.12 (−0.35 to 0.10)
−0.02 (−0.18 to 0.14)
−0.02 (−0.12 to 0.08)
0.24 (−0.37 to 0.84)
0.04 (−0.58 to 0.66)
−0.23 (−0.82 to 0.36)
−0.60 (−1.15 to −0.04)
−0.46 (−1.07 to 0.15)
−0.15 (−0.70 to 0.40)
−0.19 (−0.64 to 0.25)
0.33 (−0.51 to 1.18)
8.26 (1.97 to 14.55)
0.70 (−6.08 to 7.48)
0.06 (−4.52 to 4.64)
−0.87 (−8.60 to 6.86)
4.28 (−0.94 to 9.49)
1.18 (−2.55 to 4.91)
2.27 (0.01 to 4.53)
−0.59 (−14.74 to 13.57)
−0.74 (−15.19 to 13.71)
5.19 (−8.66 to 19.05)
8.19 (−5.07 to 21.44)
5.49 (−8.85 to 19.83)
−2.99 (−15.87 to 9.90)
2.45 (−7.96 to 12.86)
−8.55 (−28.60 to 11.50)
−3.02 (−11.47 to 5.42)
1.93 (−6.85 to 10.71)
2.42 (−3.49 to 8.33)
4.36 (−5.62 to 14.33)
1.29 (−5.57 to 8.15)
−2.84 (−7.64 to 1.97)
0.69 (−2.30 to 3.68)
8.32 (−9.93 to 26.57)
9.61 (−9.00 to 28.22)
−5.62 (−23.58 to 12.35)
−2.14 (−19.46 to 15.19)
−2.38 (−21.02 to 16.26)
8.82 (−7.79 to 25.42)
2.79 (−10.71 to 16.29)
11.65 (−13.96 to 37.26)
Δ, interocular difference (right eye minus left eye), SE spherical equivalent, 95%CI 95 % confidential interval, RNFL retinal nerve fibre layer, TS temporal superior
quadrant, NS nasal superior quadrant, N nasal quadrant, NI nasal inferior quadrant, TI temporal inferior quadrant, T temporal quadrant, SFCT subfoveal
*P value <0.007 was considered significant
and PCTs could not be explained by age, sex or the
interocular differences in the SE.
Previous studies have focused on the physiological
interocular differences in the RNFLs, but varied in their
methodologies and populations [8–10, 18–31]. We
found that the RNFL thickness in N and T quadrants
was thicker in the right eyes for emmetropia subjects,
and the RNFL thickness in the NS quadrant was thicker
in the right eyes for both emmetropia and ametropia
subjects. Our observations were in agreement with the
recent studies [9, 10, 19, 20, 24, 27]. Using iVue100
OCT, Chen and colleagues showed that the RNFL
was thinner in the right eyes in the NS for 2,324
young Chinese students . Al-Haddad et al. 
demonstrated that the RNFL thickness in the N and
T quadrants showed thicker RNFLs in the right eyes,
as measured via the high definition Cirrus OCT.
Similarly, Park and associates reported that the RNFL
thickness in N and T quadrants were thicker in the
right eyes than that in left eyes for healthy Korean
subjects using Stratus OCT . We also found that
the right eyes had similar average RNFL thickness
compared to the left eyes, which is highly consistent
with the previous studies [9, 10, 19, 20, 27]. Huynh found
no significant interocular difference of average RNFL .
Chen and colleagues showed highly symmetrical in
average in 2324 young Chinese students .
However, in a population-based study of 1,765
Australian children, Huynh found that the right eyes had
significantly thicker RNFLs in the S and I quadrants, and
thinner RNFLs in N and T quadrants . Their
observations were inconsistent with our results. This
discrepancy may be associated with several factors: (1) the
previous study included healthy children with mixed
ethnicity, while we included only Chinese adults; (2) the
old version Stratus OCT was used in their study, while
the latest EDI SD-OCT was used to obtain RNFL
measurements; (3) subjects with severe refractory errors
were not excluded in their study, but strictly isometropia
subjects were included in the present study.
There has been intense interest in the measurements of
choroidal thickness in vivo in recent years, since the
introduction of EDI SD-OCT [7, 32]. However, the interocular
symmetry of the PCT has remained elusive. In this study,
we found that the interocular differences in the PCT were
not statistically significant, but large differences of up to
93.9 μm were observed at the individual level (Table 4).
The choroid is a highly vascular structure with variable
thickness regulated by various parameters including
sympathetic nerve pathway and blood perfusion. An abnormal
choroidal thickenss has been identified as indicator for
several retinal and choroidal diseases . The differences may
related to interocular differences in blood perfusion.
However, Rawji et al.  did not detect interocular difference
in perfusion. Furthermore, the demographic factors and
refractive status between both the eyes are highly similar in
the present study. The difference at individual level may be
a variation of normal phenomenon or underling indicators
for some diseases, calling for further studies . Though
causative factors or significance of the large individual
interocular differences was not identified currently, we
believe further longitudinal studies may unveil the mystery.
One strength of this study was its strict inclusion of
subjects with isometropia (ΔSE < 0.5 dioptres). Previous
symmetrical analyses of the RNFL and macular
choroidal thickness using EDI SD-OCT have included
participants with large variations in the SE. Another strength
of this study was its standardized protocol. To eliminate
the factors that may affect choroidal circulation, those
subjects with systemic or ocular disease, smokers and
pregnant women were excluded, and the diurnal
variation was controlled.
Nevertheless, the present study had some limitations.
First, the majority of the subjects had emmetropia (SE ≤
±0.5 dioptres), which may make the results less
generalizable to patients with refractive error. Second,
the lack of ethnic diversity limits the generalizability of
our results. However, we believe that these findings can
be extrapolated to other Asian populations. Third, all of
the subjects were recruited from a tertiary care centre
and underwent strict screening; therefore, the observed
results may not be generalizable to the larger population.
Forth, the PCTs were obtained semi-manually, which
may introduce measurement bias, warranting future
studies using a swept source OCT equipped with
automatic segmentation software [35–37]. Finally, in addition
to the age, sex and SE, other potential factors warrant
investigation in future studies.
In conclusion, this study explored the interocular
differences in the RNFL and PCT in the adult Chinese
population with isometropia. There was no significant
difference in the PCT between the right and left eyes, but
large degrees of asymmetry were observed at the
individual level. In addition, the findings did show the interocular
asymmetry of the RNFL. Future studies with larger
populations and different ethnic groups are needed to confirm
or refute the findings of the present study.
95 % CI: 95 % confidential interval; BCVA: Best corrected visual acuity;
EDI-OCT: Enhanced depth imaging optical coherence tomography;
ICC: Intraclass correlation coefficient; IOP: Intraocular pressure; N: Nasal
quadrant; NI: Nasal inferior quadrant; NS: Nasal superior quadrant;
PCT: Peripapillarychoroidal thickness; RNFL: Peripapillary retinal nerve
fiber layer; RNFL: Retinal nerve fibre layer; SD: Standard deviation;
SE: Spherical equivalent; SFCT: Subfovealchoroidal thickness; T: Temporal
quadrant; TI: Temporal inferior quadrant; TS: Temporal superior quadrant;
Δ: Interocular difference (right eye minus left eye)
We are very grateful to all the study participants.
This study was supported by the Chinese 863 Plan Biological and Medical
Technology project “Development of equipments in diagnosis and visual
function evaluation for optic neuritis” (Number: 2015AA020511). The funders
had no role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
Availability of data and materials
All the data supporting the findings is contained within the manuscript.
MY and WW wrote the proposal. QX, ST, and SW revised and approved the
protocol. MY and WW collected the data. All authors were involved in the
analysis (MY, WW, QX, ST, SW). MY and WW wrote the first draft of the
manuscript. MY, WW, ST, QX, and SW reviewed and revised the manuscript
and produced the final version. All authors read and approved the final
manuscript (MY, WW, QX, ST, SW).
Consent for publication
Ethics approval and consent to participate
This study adhered to the tenets of the Helsinki Declaration and was
approved by the ethics review board of the Chinese People’s Liberation
Army General Hospital. Written informed consent was obtained from all
subjects before they entered the study.
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