Original Article

Choroidal Thickness in Acute Non-arteritic Anterior
Ischemic Optic Neuropathy

Homayoun Nikkhah1,2, MD; Mohadeseh Feizi1,2, MD; Naser Abedi2, MD; Saeed Karimi1,2, MD
Mehdi Yaseri3, PhD; Hamed Esfandiari4, MD

1Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Department of Ophthalmology, Torfeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, USA

ORCID:
Homayoun Nikkhah: https://orcid.org/0000-0002-2414-4661
Mohadeseh Feizi: https://orcid.org/0000-0002-7589-4550

Abstract
Purpose: To compare the choroidal thickness in eyes with acute non-arteritic anterior
ischemic optic neuropathy (NAION) with healthy contralateral eye and normal controls.
Methods: Thirty-eight eyes with NAION, thirty-eight unaffected fellow eyes, and seventy-
four eyes from 37 healthy, age- and sex-matched subjects were included in this
prospective comparative case-control study. Choroidal thickness was measured by
enhanced depth imaging (EDI) of spectral domain optical coherence tomography (SD-
OCT). Peripapillary choroidal thickness (PCT) was measured at 1000 and 1500 𝜇m from
Bruch’s membrane opening (BMO). Subfoveal choroidal thickness (SFCT) was measured
in central subfoveal area, and 500 microns apart in temporal and nasal sides. Choroidal
thickness among NAION eyes, uninvolved fellow eyes, and control eyes were compared.
Results: The mean of PCT at 1000 𝜇m was significantly thicker in NAION and fellow eyes
compared to control eyes (169.7 ± 47, 154.4 ± 42.1, and 127.7 ± 49.9 𝜇m, respectively,
P < 0.001 and P = 0.42). The mean PCT at 1500 𝜇m was also significantly thicker in
NAION and fellow eyes compared to control eyes (178.6 ± 52.8, 162.6 ± 46.1, and 135.1
± 59 𝜇m, respectively, P = 0.007 and P = 0.048). The mean PCT at 1000 and 1500 𝜇m
was significantly greater in NAION compared to fellow eyes (P = 0.027 and P = 0.035,
respectively). The mean of SFCT was significantly thicker in NAION compared to control
eyes (P = 0.032); however, there was no significant difference between uninvolved fellow
and control eyes (P = 0.248).
Conclusion: Thicker choroidal thickness in acute NAION and uninvolved fellow eyes
compared to normal eyes suggests a primary choroidal role in NAION pathophysiology.

Keywords: Choroidal Thickness; Non-arteritic Ischemic Optic Neuropathy; Optic Nerve Head;
Swept Source Optical Coherence Tomography

J Ophthalmic Vis Res 2020; 15 (1): 59–68

Correspondence to:

Mohadeseh Feizi, MD. Department of Ophthalmology,
Torfeh Hospital, Shahid Beheshti University of Medical
Sciences, Ibn Sina St., Tehran 11498, Iran.
E-mail: mohadeseh_feizi@yahoo.com
Received: 24-11-2018 Accepted: 19-06-2019

Access this article online

Website: https://knepublishing.com/index.php/JOVR

DOI: 10.18502/jovr.v15i1.5946

This is an open access journal, and articles are distributed under the terms of
the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which
allows others to remix, tweak, and build upon the work non-commercially, as
long as appropriate credit is given and the new creations are licensed under the
identical terms.

How to cite this article: Nikkhah H, Feizi M, Abedi N, Karimi S, Yaseri M,
Esfandiari H. Choroidal Thickness in Acute Non-arteritic Anterior Ischemic
Optic Neuropathy. J Ophthalmic Vis Res 2020;15:59–68.

© 2020 JOURNAL OF OPHTHALMIC AND VISION RESEARCH | PUBLISHED BY KNOWLEDGE E 59

http://crossmark.crossref.org/dialog/?doi=10.18502/jovr.v15i1.5946&domain=pdf&date_stamp=2019-07-17
https://knepublishing.com/index.php/JOVR


Choroidal Thickness in Acute NAION; Nikkhah et al

INTRODUCTION

Although the role of choroid in several
sight-threatening ocular conditions such as
polypoidal choroidal vasculopathy or choroidal
neovascularization[1–4] is well-studied, it is only
recently that the details of the choroid have
been evaluated with enhanced depth imaging
optical coherence tomography (EDI-OCT). EDI-
OCT provides in vivo cross-sectional image of the
choroidal layer.[5] Since choroid is located adjacent
to optic nerve and shares interconnected blood
supply with optic disc, investigators have started
to look at its possible role in two of the most
common optic neuropathies, that is, non-arteritic
anterior ischemic optic neuropathy (NAION) and
glaucoma.[6–9] NAION is the most common acute
optic neuropathy[10] and, as the name implies,
it is presumed to be secondary to the vascular
insufficiency within optic disc space, but the nature
of the vasculopathy and its pathophysiologic
mechanism is not definitely known yet.[11]

Evaluating choroidal thickness in acute NAION
may help identify choroidal role in NAION and
clarify if the choroidal thickness changes in NAION
is a predisposing factor for this condition or the
consequence of acute optic neuropathy.

The purpose of this case-control study was
to evaluate the peripapillary choroidal thickness
(PCT) and subfoveal choroidal thickness (SFCT)
in eyes with acute NAION and compare them
with uninvolved fellow eyes and eyes of healthy
controls.

METHODS

This prospective comparative case-control study
was carried out at Torfeh Hospital as a university-
based tertiary eye center. The study protocol was
approved by the Ethics Committee and Review
Board of Shahid Beheshti University of Medical Sci-
ences. All investigations were carried out in accor-
dance with the Declaration of Helsinki. Patients
with acute NAION and less than 14 days of clinical
presentation were included from January 2014 to
June 2015.

The diagnosis of NAION was based on the
presence of a history of sudden painless visual
loss associated with a relative afferent pupillary
defect that was not attributed to any other ocular,
neurologic, or systemic disease, optic disc swelling

detected by biomicroscopic examination at the
time of presentation and confirmed by peripapillary
retinal nerve fiber layer thickness measurement
using OCT, visual field testing compatible with
ischemic optic neuropathy, and resolution of disc
swelling and appearance of optic atrophy within
two months.

The exclusion criteria were clinical symptoms of
giant cell arteritis, high erythrocyte sedimentation
rate (ESR) or C-reactive protein (CRP) level, any
history or clinical evidence of retinal or neurologic
disease, previous retinal procedure (e.g., laser
photocoagulation), intraocular pressure (IOP) > 21
mmHg, or usage of glaucoma medication, pres-
ence of glaucomatous optic nerve damage, any
other optic nerve disease, and bilateral NAION
cases. Healthy volunteers from the optometry clinic
with a refractive error in the range of –4 to +4, and
no history of intraocular surgery were recruited as
the control group. For all cases and controls, com-
prehensive ophthalmic examination including best
corrected visual acuity (BCVA) assessment, slit-
lamp examination, Goldmann applanation tonome-
try, gonioscopy, fundus examination, and perime-
try (Humphrey visual field analyzer; model 750;
Carl Zeiss Meditec, Dublin, California, USA) were
performed. Axial length was measured using IOL
Master (ZEISS IOLMaster, Carl Zeiss Meditec AG,
Germany).

OCT imaging

All OCT measurements were performed using
Heidelberg spectral domain OCT (Spectralis; Hei-
delberg Engineering, Heidelberg, Germany) by the
same experienced operator. For each eye, three
OCT images were acquired.

PCT was measured using horizontal and vertical
raster EDI-OCT scans centered at optic nerve
head (ONH) [Figure 1]. SFCT was determined using
horizontal raster EDI-OCT scans centered at the
fovea. Macular OCT scan: 25 horizontal optical
coherent tomographic sections were obtained in
a 20𝜇× 20𝜇 rectangle centered around the fovea.
Three circular lines demonstrating 1, 3, and 6 mm
of the central macula (Early Treatment Diabetic
Retinopathy Study (ETDRS) macular grid) were
obtained. The data of central 1 mm circle was
defined as central macular thickness (CMT). In
addition, ganglion cell-inner plexiform layer (Gc-IPL)
thickness in central 1 mm circle and inner macular

60 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020



Choroidal Thickness in Acute NAION; Nikkhah et al

area (between the central and middle circles) were
measured in four superior, inferior, temporal, and
nasal quadrants, using instrument segmentation
software. It has been shown that the Spectralis
software has an excellent reproducibility in the
measurement of each individual retinal layer.[12]

Choroidal thickness was measured along the
perpendicular distance from posterior border of
retinal pigment epithelium to anterior scleral border
(choroidal–scleral interface) using the OCT manual
measurement tool. For peripapillary choroid, we
measured the choroidal thickness at 1000 (±10) and
1500 (±10) 𝜇m from Bruch’s membrane opening
(BMO) in superior, inferior, temporal, and nasal
parts on vertical and horizontal raster scans (eight
points). To compare the choroidal thickness at
1000 and 1500 𝜇m from BMO among the eyes
with NAION, uninvolved fellow eyes and control
eyes, we calculated the mean of measurements at
1000 and 1500 𝜇m in superior, inferior, temporal,
and nasal parts. In the subfoveal area, choroidal
thickness was measured at the foveal center as
well as 500 (±5) 𝜇m from the foveal center in both
temporal and nasal sides [Figure 2]. The mean
of these three measurements was defined as the
mean SFCT. To better determine the choroidal–
scleral interface, we changed the contrast and
resolution scales of the OCT device several times
until we could find the exact borders. Considering
reports of diurnal variation in choroidal thickness,
all OCT images were carried out between 10 and 12
am. All choroidal measurements were done by the
same surgeon (HN) and re-evaluated by two other
co-authors (MF, HE).

Statistical method

To present data, we used mean, standard
deviation, median, and range. To assess
normal distribution of quantitative data, we
used Kolmogorov–Smirnov test and Q–Q plot.
To compare the results between groups at
baseline, we used t-test, Mann–Whitney test, and
Chi-square test. Considering the probability
correlation of the measures, Generalized
Estimating Equation (GEE) analysis was used
to compare the groups. Furthermore, adjusted
results for hypertension and diabetes were
obtained using another GEE model. To consider
the multiple comparisons, issue in pairwise
comparisons, we used the Bonferroni method.

The correlation of variables was obtained by the
Pearson method. All statistical analyses were
performed by SPSS software (IBM Corp. Released
2014. IBM SPSS Statistics for Windows, Version
23.0. Armonk, NY: IBM Corp.). All tests were two-
sided and P < 0.05 was considered statistically
significant.

RESULTS

Among 46 enrolled eyes, 38 eyes with acute
NAION were included for final analysis. Eight eyes
were excluded because of poor-quality OCT and
inability to determine choroidal–scleral junction.
Thirty-eight uninvolved fellow eyes and seventy-
four eyes of 37 healthy, age- and sex-matched
subjects were included as the control group. The
mean age of NAION patients and control subjects
were not significantly different (62 ± 11 and 61
± 30 years, respectively, P = 0.95). The mean
interval between the initiation of symptoms and
OCT acquisition was 6.7 ± 3.7 days (range, 1 to
14). There was no difference between NAION, unin-
volved contralateral, and control eyes regarding
spherical equivalent (P = 0.64) and mean axial
length (P = 0.87). Affected cases were more likely
to have diabetes mellitus (DM), but the prevalence
of systemic hypertension was comparable in both
affected and healthy individuals [Table 1].

Intraobserver and interobserver reproducibility
of PCT and SFCT are shown in Table 2. There was
excellent reproducibility in the intraobserver and
interobserver tests (ranging from 0.934 to 0.992 for
the intraobserver and from 0.874 to 0.961 for the
interobserver reproducibility).

The mean PCT at 1000 𝜇m from BMO (PCT1000)
was 169.7 ± 47, 154.4 ± 42.1, and 127.7 ± 49.9 𝜇m
in NAION eyes, uninvolved fellow eyes, and con-
trol eyes, respectively. PCT1000 was significantly
thicker in the involved eyes and uninvolved fellow
eyes compared to the control eyes (P < 0.001
and P = 0.042, respectively). Moreover, PCT1000
was significantly thicker in involved eyes than
uninvolved fellow eyes (P = 0.025) [Table 3].

The mean PCT at 1500 𝜇m from BMO (PCT1500)
was also significantly thicker in the NAION and
uninvolved fellow eyes than the control eyes (P
= 0.007 and P = 0.048, respectively). In addition,
PCT1500 was significantly thicker in the eyes with
NAION than the uninvolved fellow eyes (P = 0.035)
[Table 3].

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020 61



Choroidal Thickness in Acute NAION; Nikkhah et al

Figure 1. Delineated SD-OCT from affected eye: Bruch’s membrane (dotted red line), anterior sclera (dotted yellow line), BMO,
Bruch’s membrane opening.

Figure 2. Choroidal thickness at the center of the fovea and 500 𝜇m from the center at temporal and nasal side.

The mean SFCT was 275 ± 71.7, 258.3 ± 65, and
225.9 ± 91.2 𝜇m in eyes with NAION, uninvolved
fellow eyes, and control eyes, respectively. The
mean SFCT was thicker in the eyes with NAION
than the control eyes (P = 0.038), however, there
was no statistically significant difference between
the fellow and control eyes (P = 0.248) [Table
4].

CMT was significantly higher in the NAION than
the uninvolved and control eyes (P < 0.001 and P
< 0.001, respectively), but there was no significant
difference between the fellow and control eyes (P
= 1.000).

Central Gc-IPL thickness was significantly thicker
in the eyes with NAION eyes than the uninvolved
fellow and control eyes (P < 0.001 for both). Central
Gc-IPL thickness in the eyes with NAION was

negatively correlated with the BCVA (r = 0.31,
P = 0.006). There was no statistically significant
difference among the NAION, uninvolved fellow,
and control eyes regarding the Gc-IPL thickness in
the inner macular area [Table 4].

The differences persisted once adjusted for DM
and systemic hypertension [Table 5].

DISCUSSION

In the present study, we found significantly thicker
choroid in both acute NAION and unaffected fellow
eyes compared to controls, both in peripapillary
and subfoveal areas.

All previous studies evaluated the PCT in the
chronic phase of NAION.[8, 9] This study is the

62 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020



Choroidal Thickness in Acute NAION; Nikkhah et al

Table 1. Demographic data of NAION patients and healthy control subjects

Study groups P

NAION eyes Uninvolved fellow eyes Control eyes

Number (n) 38 38 74 (37)
Age (Years) Mean ± SD 62 ± 11 61 ± 30 0.959†

Median (range) 61 (30 to 87) 87 (62 to 10)
Sex M 20 (52.6%) 18 (48.6%) 0.525*

F 18 (47.4%) 19 (51.4%)
Interval (Days)1 Mean ± SD 6.74 ± 3.82

Median (range) 6.5 (1 to 14)
DM No 21 (55.3%) 29 (78.4%) 0.010*

Yes 17 (44.7%) 8 (21.6%)
HTN No 21 (55.3%) 27 (73.0%) 0.077*

Yes 17 (44.7%) 10 (27.0%)
SE Mean ± SD 0.39 ± 1.11 0.46 ± 1.16 0.27 ± 0.99 0.641†

Median (range) 0.38 (–2 to 3.75) 0.5 (–2 to 3.5) 0.25 (–3 to 3)
Axial length Mean ± SD 22.74 ± 0.76 22.74 ± 0.78 22.83 ± 0.84 0.873†

Median (range) 22.98 ) 22.88 (21.05 to 23.85) 22.97 (21.09 to 24.31)

1: Interval between initial symptom and ophthalmic evaluation
DM, diabetes mellitus; HTN, systemic hypertension; NAION, nonarteritic anterior ischemic optic neuropathy; SE, spherical
equivalent
†Based on t-test
‡Based on Mann–Whitney test
*Based on Chi-square test

Table 2. Intraclass correlation coefficients for PCT and SFCT in a random subset of 15 eyes

Intraobserver Variability (95% Confidence Interval) Interobserver Variability (95% Confidence Interval)

PCT 1000 (temporal) 0.934 (0.841–0.973) 0.874 (0.710–0.948)

PCT 1000 (nasal) 0.971 (0.940–0.992) 0.963 (0.920–0.984)

PCT 1500 (temporal) 0.966 (0.914–0.986) 0.933 (0 .831–0.973)

PCT 1500 (nasal) 0.968 (0.922–0.985) 0.941 (0.853–0.974)

SFCT (temporal) 0.959 (0.910–0.981) 0.981 (0.960–0.992)

SFCT (nasal) 0.992 (0.951–0.996) 0.961 (0.912–0.983)

PCT, peri-papillary choroidal thickness; SFCT, subfoveal choroidal thickness

first one that measured PCT in acute phase.
By adjusting the contrast and resolution scale
of the OCT device, we were able to measure
choroidal thickness despite edema and disc
swelling.

Although the exact mechanism of NAION is
yet to be understood, ischemia and the so called
“compartment syndrome” in optic disc space are

the main determinants for the loss of visual
function.[14, 15]

Whatever the mechanism of vascular insuf-
ficiency in NAION, persistent hypoperfusion is
required for the development of ischemic optic
neuropathy. The paraoptic branches of the short
posterior ciliary arteries are responsible for ONH
blood supply and the infarction in NAION is

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020 63



Choroidal Thickness in Acute NAION; Nikkhah et al

Table 3. Measurements of PCT in different areas in NAION, uninvolved and control eyes

NAION eyes(1) Uninvolved eyes(2) Control eyes(3) Diff (1 vs 2) P1* Diff (1 vs 3) P2* Diff (2 vs 3) P3*

Mean ± SD Mean ± SD Mean ± SD
PCT S 1000 173.2 ± 59.4 164.9 ± 47.4 135.7 ± 57.3 8.2 1.000 37.4 0.007 29.2 0.065
PCT I 1000 151.2 ± 62.4 131.5 ± 47.5 112.2 ± 51.7 19.7 0.076 39.0 0.012 19.3 0.112
PCT T 1000 181.5 ± 69.9 167.9 ± 53.9 131.8 ± 58.7 13.7 0.429 49.7 0.001 36.1 0.043
PCT N 1000 172.8 ± 61.9 153.5 ± 52.2 131.2 ± 54.9 19.3 0.027 41.6 0.005 22.3 0.221
Mean PCT 1000 169.7 ± 47 154.4 ± 42.1 127.7 ± 49.9 15.2 0.027 41.9 < 0.001 26.7 0.042
PCT S 1500 175.3 ± 69.6 165.5 ± 51.3 141.2 ± 69.4 9.8 1.000 34.0 0.054 24.3 0.287
PCT I 1500 155.5 ± 71.4 132.7 ± 47.4 113.8 ± 62.5 22.8 0.059 41.7 0.015 18.9 0.395
PCT T 1500 208.7 ± 80.6 190.5 ± 67.7 144.9 ± 64.7 18.3 0.301 63.9 < 0.001 45.6 0.012
PCT N 1500 172.7 ± 64.1 161.7 ± 55.6 140.5 ± 64 11.0 0.314 32.2 0.073 21.2 0.442
Mean PCT 1500 178.6 ± 52.8 162.6 ± 46.1 135.1 ± 59 16.0 0.035 43.5 0.007 27.5 0.048

PCT, peri-papillary choroidal thickness; NAION, non-arteritic anterior ischemic optic neuropathy; S, superior; I, inferior; T, temporal; N,
nasal; 1000, at 1000micron from Bruch’s membrane opening; 1500, at 1500micron from Bruch’s membrane opening; SD, standard
deviation; Diff, difference
* P-for pairwise comparison, based on post hoc analysis of GEE, adjusted for the multiple comparison by Bonferroni method

Table 4. Measurements of GC-IPL, RFNL, SFCT and CMT in different areas in study groups (NAION, uninvolved, and control
eyes)

NAION eyes Uninvolved
eyes

Control
eyes

Diff (NAION
vs

Uninvolved
eyes)

P1* Diff (NAION
vs Control

eyes)

P2* Diff
(Uninvolved
vs Control

eyes)

P3*

Mean ± SD Mean ± SD Mean ± SD
GC-IPL C 20.1 ± 14.7 13.2 ± 5.3 13.1 ± 3.4 6.8 < 0.001 6.9 < 0.001 0.1 1.000
GC-IPL S 46.2 ± 14.1 45.8 ± 13 51.9 ± 5.4 0.4 1.000 –5.6 0.045 –6.0 0.019
GC-IPL I 45.8 ± 12.1 46.2 ± 12.8 51.4 ± 5.6 –0.3 1.000 –5.5 0.018 –5.2 0.033
GC-IPL T 41 ± 12.7 43.9 ± 13 45.7 ± 5.8 –2.9 0.687 –4.7 0.078 –1.8 1.000
GC-IPL N 45.7 ± 13.8 45.8 ± 12.5 49.6 ± 5.3 –0.1 1.000 –3.9 0.173 –3.8 0.167
SFCT C 286.7 ± 72.7 271 ± 68.2 237.2 ± 89.1 15.7 0.352 49.4 0.034 33.7 0.234
SFCT T 500 267.3 ± 72.9 250.8 ± 71 219.8 ± 99.6 16.6 0.701 47.5 0.032 30.9 0.323
SFCT N 500 271 ± 76.3 253.1 ± 63.2 220.6 ± 94.1 17.8 0.345 50.3 0.035 32.5 0.245
Mean SFCT 275 ± 71.7 258.3 ± 65 225.9 ± 91.2 16.7 0.123 49.1 0.038 32.4 0.248
CMT 339.9 ± 131 274.8 ± 54.1 266 ± 25 65.1 < 0.001 73.9 < 0.001 8.8 1.000

GC-IPL, ganglion cell-inner plexiform layer; SFCT, subfoveal choroidal thickness; CMT, central macular thickness; NAION, non-arteritic
anterior ischemic optic neuropathy; C, central; S, superior; I, inferior; T, temporal; N, nasal; T 500, 500micron temporal to fovea; N 500,
500micron nasal to fovea; SD, standard deviation; Diff, difference.
*P-for pairwise comparison, based on post hoc analysis of GEE, adjusted for the multiple comparison by Bonferroni method

suggested to be predominantly located in the
retrolaminar portion of the ONH.[16] Therefore, since
the choroid mainly supplies – to a limited extent
– more anterior optic nerve head regions, it is
less likely that choroid has a substantial role in
the pathogenesis of NAION. However, several

studies reported changes in choroidal thickness in
NAION,[7–9] which is consistent with the findings of
the current study.

Fard et al evaluated the PCT in chronic NAION
and reported increased thickness in both affected
and unaffected fellow eyes compared to normal

64 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020



Choroidal Thickness in Acute NAION; Nikkhah et al

Table 5. PCT, GC-IPL, and SFCT values adjusted for hypertension and diabetes mellitus

Diff (NAION vs Control eyes) SE P* Diff (Uninvolved vs Control eyes) SE P*

PCT S 1000 37.966* 11.5 0.007 31.075* 11.5 0.032

PCT I 1000 44.470* 11.0 < 0.001 23.5 11.0 0.121
PCT T 1000 50.309* 12.6 < 0.001 35.958* 12.6 0.019
PCT N 1000 42.085* 11.6 0.001 22.6 11.6 0.167

Mean 43.708* 9.7 < 0.001 28.282* 9.7 0.025
PCT S 1500 38.097* 13.5 0.013 28.3 13.5 0.127

PCT I 1500 45.619* 12.8 0.012 22.9 12.8 0.237

PCT T 1500 63.130* 14.6 < 0.001 44.698* 14.6 0.013
PCT N 1500 33.351* 12.9 0.044 23.4 12.9 0.321

Mean 45.049* 11.3 < 0.001 29.826* 11.3 0.034
GC-IPL C 6.924* 1.7 < 0.001 0.0 1.7 1.000
GC-IPL S –5.411* 2.2 0.043 –5.708* 2.2 0.034

GC-IPL I –6.383* 2.0 0.005 –5.437* 2.0 0.025

GC-IPL T –5.0 2.1 0.057 –1.9 2.1 1.000

GC-IPL N –3.3 2.1 0.331 –2.9 2.1 0.612

Mean GC-IPL –2.7 1.7 0.367 –3.2 1.7 0.201

SFCT C 49.586* 18.2 0.025 33.9 18.2 0.201

SFCT T 500 50.091* 17.4 0.012 34.4 17.4 0.172

SFCT N 500 75.364* 15.5 < 0.001 8.8 15.5 1.000
Mean SFCT 49.838* 16.8 0.012 34.9 16.8 0.123

PCT, peripapillary choroidal thickness; GC-IPL, ganglion cell- inner plexiform layer; SFCT, Subfoveal choroidal thickness; Diff,
difference; SE, standard error; NAION, non-arteritic anterior ischemic optic neuropathy; C, central; S, superior; I, Inferior; T,
temporal; N, nasal; T 500, 500 𝜇m temporal to fovea; N 500, 500 𝜇m nasal to fovea; SE, standard error; Diff, difference
*P-for pairwise comparison adjusted for the HTN and diabetes, based on post hoc analysis of GEE, multiple comparison
considered by Bonferroni method

controls.[8] Our finding also matches the finding of
Nagia et al that observed increased thickness of
the PCT, especially 1000 to 1500 𝜇m from BMO,
in chronically affected NAION and contralateral
eyes compared to controls.[10] Surprisingly, the
mean PCT in the affected eyes in our study was
lower than the aforementioned studies with chronic
NAION. Although one should be cautious to draw
any conclusion from these cross-sectional studies,
chronic cases were expected to have thinner
choroid compared to the eyes at the acute stage
if choroidal thickening was secondary to ischemic
damage. However, longitudinal studies are needed
to evaluate the changes of choroidal thickness
following the ischemic damage.

The lack of consistent choroidal filling defect
in angiographic studies[17] further reinforces the

primary role of choroid in the development of
NAION.

Crowded disc is known as a predisposing factor
for NAION, although the mechanism by which it
contributes to ischemia is unclear.[11] Increased PCT
may be a component of crowded disc morphology
as suggested by Fard et al.[8] They hypothesized
that the thicker choroid may strain the optic nerve
axon and its vessel within the narrow central cup
and further restrict the crowded optic nerve space.

Thicker peripapillary choroid in NAION eyes
may be a structurally predisposing factor or may
be a compensatory mechanism due to ischemia.
Thicker choroid, both in acute NAION and unin-
volved fellow eyes, rationally suggests the role
of choroid as a predisposing factor rather than a
compensatory mechanism. Moreover, if increased

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020 65



Choroidal Thickness in Acute NAION; Nikkhah et al

choroidal thickness was a compensatory factor, it
must be decreased after the acute phase, but as
mentioned earlier, the result of previous studies in
the chronic phase also showed thicker choroid.[8, 9]
The NAION progresses through asymptomatic
“incipient NAION” to full blown ischemic neu-
ropathy with characteristic clinical presentation
in more than two-third of cases[18, 19]. By fur-
ther contributing to “compartment syndrome”
in already constricted scleral canal, increased
choroidal thickness may have a role in the devel-
opment of symptomatic axonal damage. In that
sense, increased choroidal thickness acts as a
“catalyzer” for the progression of ischemic optic
neuropathy.

Moreover, Beijing Eye Study showed no associ-
ation between SFCT and optic disc size in normal
subjects, therefore choroidal thickness could affect
the incidence and progression of NAION indepen-
dent of optic disc size.[20] Thicker choroid may also
be a sign of local auto-regulation dysfunction of the
choroidal vessel.[21]

In contrast to our study and others,[8, 9] Garcia-
Basterra et al[10] reported thinner PCT in NAION
and unaffected fellow eyes compared to normal
subjects. The differing results may be because they
did not match the refractive state of control subjects
and NAION patients, and also they evaluated PCT
in chronic phase of AION.

Gonal et al[22] reported no difference between
sub-macular choroidal thickness in acute and
chronic NAION eyes and control subjects, they
included subjects with optic disc edema that had
occurred in a time period of less than one month
as an acute NAION, but we included patients with
initial symptoms occurring less than 14 days; they
also measured choroidal thickness in farther points
from the foveal center. Interestingly, Schuster et al
reported thinner SFCT in the affected and non-
affected fellow eyes of patients with NAION.[7]
Although the authors considered the enrolled
cases as acute NAION, the duration of the disease
that was considered acute is not reported in their
paper, so we cannot confidently compare our
findings with their results. Besides, they used one
horizontal line passing through fovea and CT was
measured on 1 point on this line. We argue that
measuring choroidal thickness at 1 selected point,
which is performed manually, could be affected
by irregularities of choroidal-scleral boundary.[23]
In addition, not all factors affecting the choroidal

thickness measurement were adjusted in that
study.

The thickening of central macular region in our
study is in line with previous reports that have
shown subretinal fluid accumulation in recent onset
NAION.[24–26] Since macular OCT is not routinely
obtained in NAION, the exact incidence of macular
edema is unknown in these eyes but it is estimated
to range from 10 to 50%.[23] There is no longitudinal
study that has evaluated the course of macular
edema after the NAION and its effect on the final
visual acuity.

In the present study, we found that the Gc-IP
layer in the central 1 mm was significantly thicker in
NAION eyes compared to uninvolved fellow eyes
and control eyes, while in all quadrants of 1 to 3
mm annulus, there was no significant difference
among NAION, uninvolved fellow, and control eyes
in terms of Gc-IP layer thickness. The thickening
of Gc-IPL in the central 1 mm may be due to
intracellular edema due to greater ischemic stress
on central fovea in the early phase of NAION and
contributes to vision deterioration. Fard et al[27]
reported that parafoveal Gc-IPL thinning present
in chronic NAION eyes was associated with worse
vision compared to glaucoma patients in which
central vision is preserved and has no Gc-IPL
thinning in this area. Parks et al reported the initial
thinning of Gc-IP layer in the macula occurring 46.1
± 23.2 days after the onset of NAION symptoms.[28]
We measured Gc-IPL thickness in the period of
less than two weeks from initial symptoms, which
showed thickening only in the affected eyes. The
ischemia induced axoplasmic flow stasis results in
axonal swelling[28] and is considered an early event
in the “sequence of events” in NAION.[29] In fact,
this early axonal swelling is the stage where timely
interventions such as anti-inflammatory and neuro-
protective agents proved to be promising.[14, 31, 32]

This study has several limitations. The sample
size was relatively small but is comparable to previ-
ous studies on this subject and necessitates further
longitudinal studies to clarify whether choroidal
thickening precedes NAION or it occurs following
the ischemic incidence.

Although anterior scleral border was delineated
manually, intra- and interobserver reproducibility
were excellent, which is in line with the high repro-
ducibility reported in previous studies.[8, 9] Further-
more, recent endeavors to quantify choroidal thick-
ness with automated segmentation have shown

66 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020



Choroidal Thickness in Acute NAION; Nikkhah et al

excellent consistency with manual labeling.[33]
Choroidal thickness has not been adjusted for IOP
in our study and it may have caused some random
errors, although the induced bias may be far from
significance.

In summary, we showed that the boundaries of
the choroid in acute NAION could be delineated
by excellent intra- and interobserver reproducibil-
ity. Moreover, our finding of increased choroidal
thickness in both eyes of the affected patients
compared to controls lends support to the theory
of primary choroidal role in the development of
NAION.

Acknowledgements

The authors would like to thank Ms. Marzieh
Mola Mohammad Rahimi and Ms. Masoumeh Zarei
(Torfeh Hospital, Tehran, Iran) for their technical
support.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.

REFERENCES

1. Yoshida T, Ohno-Matsui K, Yasuzumi K, et al. Myopic
choroidal neovascularization: a 10-year follow-up. Oph-
thalmology 2003;110:1297–1305.

2. Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced
depth imaging optical coherence tomography of the
choroid in central serous chorioretinopathy. Retina
2009;29:1469–1473.

3. Chung SE, Kang SW, Lee JH, Kim YT. Choroidal thick-
ness in polypoidal choroidal vasculopathy and exuda-
tive age-related macular degeneration. Ophthalmology
2011;118:840–845.

4. Spaide RF. Choroidal neovascularization. In: Pathologic
Myopia. New York, NY: Springer; 2014:211–230.

5. Spaide RF, Koizumi H, Pozzoni MC, Pozonni MC. Enhanced
depth imaging spectral-domain optical coherence tomog-
raphy. Am J Ophthalmol 2008;146:496–500.

6. Park H-YL, Lee N-Y, Shin H-Y, Park CK. Analysis of
macular and peripapillary choroidal thickness in glaucoma
patients by enhanced depth imaging optical coherence
tomography. J Glaucoma 2014;23:225–231.

7. Schuster AK, Steinmetz P, Forster TM, Schlichtenbrede FC,
Harder BC, Jonas JB. Choroidal thickness in nonarteritic

anterior ischemic optic neuropathy. Am J Ophthalmol
2014;158:1342–1347.e1.

8. Fard MA, Abdi P, Kasaei A, Soltani Mogaddam R, Afzali M,
Moghimi S. Peripapillary choroidal thickness in nonarteritic
anterior ischemic optic neuropathy. Invest Ophthalmol Vis
Sci 2015;IOVS-14-15661.

9. Nagia L, Huisingh C, Johnstone J, Kline LB, Clark M,
Girard MJ, et al. Peripapillary pachychoroid in nonarteritic
anterior ischemic optic neuropathy. Invest Ophthalmol Vis
Sci 2016;57:4679–4685.

10. García-Basterra I, Lahrach I, Morillo Sánchez MJ, Kamal-
Salah R, Ríus-Díaz F, Dawid Milner MS, et al. Analy-
sis of peripapillary choroidal thickness in non-arteritic
anterior ischaemic optic neuropathy. Br J Ophthalmol
2015;100:891–896.

11. Miller NR, Arnold AC. Current concepts in the diagnosis,
pathogenesis and management of nonarteritic anterior
ischaemic optic neuropathy. Eye 2015;29:65–79.

12. Arnold AC. Pathogenesis of nonarteritic anterior ischemic
optic neuropathy. J Neuroophthalmol 2003;23:157–163.

13. Ctori I, Huntjens B. Repeatability of foveal measurements
using spectralis optical coherence tomography segmenta-
tion software. PLOS ONE 2015;10:e0129005.

14. Pakravan M, Sanjari N, Esfandiari H, Pakravan P, Yaseri M.
The effect of high-dose steroids, and normobaric oxygen
therapy, on recent onset non-arteritic anterior ischemic
optic neuropathy: a randomized clinical trial. Graefes Arch
Clin Exp Ophthalmol 2016;254:2043–2048.

15. Pakravan M, Esfandiari H, Hassanpour K, Razavi S, Pakra-
van P. The effect of combined systemic erythropoietin and
steroid on non-arteritic anterior ischemic optic neuropathy:
a prospective study. Curr Eye Res 2017;42:1079–1084.

16. Bernstein SL, Johnson MA, Miller NR. Nonarteritic anterior
ischemic optic neuropathy (NAION) and its experimental
models. Prog Retin Eye Res 2011;30:167–187.

17. Oto S, Yilmaz G, Cakmakci S, Aydin P. Indocyanine
green and fluorescein angiography in nonarteritic anterior
ischemic optic neuropathy. Retina 2002;22:187–191.

18. Subramanian PS, Gordon LK, Bonelli L, Arnold AC. Pro-
gression of asymptomatic optic disc swelling to non-
arteritic anterior ischaemic optic neuropathy. Br J Ophthal-
mol 2017;101:671–675.

19. Hayreh SS, Zimmerman MB. Incipient nonarteritic
anterior ischemic optic neuropathy. Ophthalmology
2007;114:1763–1772.

20. Wei WB, Xu L, Jonas JB, Shao L, Du KF, Wang S, et al.
Subfoveal choroidal thickness: the Beijing Eye Study.
Ophthalmology 2013;120:175–180.

21. Dias-Santos A, Ferreira J, Abegão Pinto L, Vicente A,
Anjos R, Cabugueira A, et al. Choroidal thickness in
nonarteritic anterior ischaemic optic neuropathy: a study
with optical coherence tomography. Neuroophthalmology
2014;38:173–179.

22. Gonul S, Gedik S, Koktekir BE, Yavuzer K, Okudan S.
Evaluation of choroidal thickness in non-arteritic anterior
ischaemic optic neuropathy at the acute and chronic
stages. Neuro-Ophthalmology 2016;40:181–187.

23. Gonul S, Okudan S. Choroidal thickness in nonarteritic
anterior ischemic optic neuropathy. Am J Ophthalmol
2015;159:994–995.

JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020 67



Choroidal Thickness in Acute NAION; Nikkhah et al

24. Hedges TR 3rd, Vuong LN, Gonzalez-Garcia AO,
Mendoza-Santiesteban CE, Amaro-Quierza ML.
Subretinal fluid from anterior ischemic optic neuropathy
demonstrated by optical coherence tomography. Arch
Ophthalmol 2008;126:812–815.

25. Tomsak RL, Zakov ZN. Nonarteritic anterior ischemic optic
neuropathy with macular edema: visual improvement and
fluorescein angiographic characteristics. J Neuroophthal-
mol 1998;18:166–168.

26. Galvez-Ruiz A. Macular star formation in diabetic patients
with non-arteritic anterior ischemic optic neuropathy (NA-
AION). Saudi J Ophthalmol 2015;29:71–75.

27. Fard MA, Afzali M, Abdi P, Yasseri M, Ebrahimi KB, Moghimi
S. Comparison of the pattern of macular ganglion cell-inner
plexiform layer defect between ischemic optic neuropathy
and open-angle glaucoma. Invest Ophthalmol Vis Sci
2016;57:1011–1016.

28. Park SW, Ji YS, Heo H. Early macular ganglion cell–inner
plexiform layer analysis in non-arteritic anterior ischemic
optic neuropathy. Graefes Arch Clin Exp Ophthalmol

2016;254:983–989.

29. Hayreh SS. Fluids in the anterior part of the optic nerve in
health and disease. Surv Ophthalmol 1978;23:1–25.

30. Hayreh SS. Ischemic optic neuropathy. Prog Retin Eye Res
2009;28:34–62.

31. Hayreh SS, Zimmerman MB. Non-arteritic anterior
ischemic optic neuropathy: role of systemic
corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol
2008;246:1029–1046.

32. Sanjari N, Pakravan M, Nourinia R, Esfandiari H, Hafezi-
Moghadam A, Zandi S, et al. Intravitreal injection of a
rho-kinase inhibitor (fasudil) for recent-onset nonarteritic
anterior ischemic optic neuropathy. J Clin Pharmacol
2016;56:749–753.

33. Tian J, Marziliano P, Baskaran M, Tun TA, Aung T.
Automatic segmentation of the choroid in enhanced depth
imaging optical coherence tomography images. Biomed
Opt Express 2013;4:397–411.

68 JOURNAL OF OPHTHALMIC AND VISION RESEARCH VOLUME 15, ISSUE 1, JANUARY-MARCH 2020