Hindawi

Computational and Mathematical Methods in Medicine

Volume 2022, Article ID 2935992, 9 pages
https://doi.org/10.1155/2022/2935992

Research Article
The Efficacy of Glucocorticoids in the Treatment of Nonarteritic
Anterior Ischemic Optic Neuropathy: A Systematic Review
and Meta-Analysis

Pingping Zhou , Jian Zhang, and Yanxiu Qi

Department of Ophthalmology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China

Correspondence should be addressed to Pingping Zhou; 171843155@masu.edu.cn

Received 20 January 2022; Revised 30 January 2022; Accepted 2 February 2022; Published 18 March 2022

Academic Editor: Min Tang

Copyright © 2022 Pingping Zhou et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

Background. To evaluate the clinical effects and safety of glucocorticoids for patients with nonarteritic anterior ischemic optic
neuropathy (NAION). Methods. The databases MEDLINE, Embase, PubMed, Cochrane Database, and Web of Science were
used to search for the relevant studies, and full-text articles that reported on the evaluation of glucocorticoids vs. no-treatment
or placebo for patients with NAION. Review Manager 5.4 was used to estimate the pooled effects of the results among selected
studies. Forest plots, funnel plots, and Begg’s rank correlation were also performed on the included articles. Results. A total of
983 patients were contained in the 9 studies that satisfied the eligibility criteria. The meta-analysis showed that, compared with
the control group, the glucocorticoid group had significantly improved the VA (MD: -0.25, 95% CI [-0.45, -0.05], P = 0:02), VF
(MD: -0.50, 95% CI [-0.94, -0.07], P = 0:02), and RNFL (MD: -14.10, 95% CI [-26.41, -1.79], P = 0:02) in NAION patients and
had a high improvement rate of VA (RR 1.31, 95% CI [1.12, 1.52], P = 0:0005). No significant publication bias was observed in
our study. Discussion. Our research preliminarily confirmed the effectiveness of glucocorticoids for NAION treatment, but
more high-quality RCTs focusing on the hormone adverse reactions should be performed to verify our conclusions.

1. Introduction
Ischemic optic neuropathy (ION) is a vascular disease [1]. It
occurs when the nutrient blood vessels of the optic nerve
have circulatory disturbances [2]. The disease primarily
occurs in one eye, but it can also occur in both eyes simulta-
neously or successively [3]. The incidence rate in the popu-
lation is 0.5 per 100,000, and the disease most often occurs
in people over 50, whose incidence is up to 2.3 ~ 10.2 per
100,000 [4, 5]. Pathologically, ION is divided into arteritis
and nonarteritic ION, and 95% of ION is nonarteritic ante-
rior ischemic optic neuropathy (NAION) [6, 7].
The pathological mechanism of NAION is still unclear
[8, 9]. Some studies believe that the posterior ciliary artery
that supplies the anterior part of the optic disc (i.e., the ante-
rior and lamina area) has stenosis, occlusion, or perfusion
pressure decrease, resulting in local microcirculation disor-
ders, and the decreased optic papillary perfusion pressure
will lead to insufficient blood supply to the optic disc, result-
ing in optic nerve ischemic disease [10, 11]. Optic disc
edema often occurs in the acute phase. Although the edema
will eventually disappear without any treatment, clinical
observations have found that it does not change rapidly
within 2 weeks [12]. The ischemic location and the degree
of edema are important reasons that affect the central vision
of NAION patients [13].
Glucocorticoids are anti-inflammatory and can reduce
edema [14]. They can reduce capillary permeability and
inhibit free radical injury. They have been used in the treat-
ment of diseases with angiogenic edema as the main patho-
genesis, such as intracerebral hemorrhage, brain tumor, and
craniocerebral trauma [15, 16]. The pathological mechanism
of NAION is often considered to be hypoperfusion or small
vessel embolism in pathological mechanism. The optic disc
edema caused by NAION cannot be completely defined as
angiogenic or cytotoxic edema. Systemic hypoperfusion,
2 Computational and Mathematical Methods in Medicine
nocturnal hypotension, local autoregulation dysfunction,
vasospasm, venous obstruction, and thrombosis been identi-
fied as the inducing factors of NAION, and the application
of hormones often leads to the rise of blood pressure and
blood glucose. Therefore, clinicians use hormones to quickly
reduce optic disc edema and restore visual function. At the
same time, they often worry about the impact of its adverse
effects on NAION patients and the accuracy of curative
effect [17].
Literature has shown that the application of glucocorti-
coids in the treatment of NAION can achieve better curative
effects [14, 18]. We used the meta-analysis method to syste-
matically evaluate the clinical efficacy of glucocorticoids in
the treatment of NAION and objectively evaluate the effec-
tiveness and safety of glucocorticoids, so as to provide refer-
ences for its further clinical research and application.
2. Methods
2.1. Literature Search Strategy. We used comprehensive
databases (MEDLINE, Embase, PubMed, Cochrane Data-
base, and Web of Science) to search for previous studies that
investigated the effects of glucocorticoids on the clinical out-
comes in patients with ION. The literature search was per-
formed from inception up to November 30th, 2021, using
the following keywords and MeSH terms: (1) glucocorti-
coids; (2) ION; (3) corticosteroid; and (4) optic neuropathy.
Numerous combinations of words and strings were applied
with Boolean operators “AND” and “OR” to broaden the
search. Our literature search was carried out without any
consideration for publication status limitations or language
restrictions. The reference lists of the retrieved studies and
review articles were examined manually to identify further
relevant studies not identified by the search strategy.
2.2. Study Selection. A study was included if it satisfied the
following criteria:
(1) Researches compared patients who received gluco-
corticoids and other therapy
(2) The study contained patients with ION
(3) The study contained indicators evaluating efficacy
between glucocorticoids and other therapy
(4) The study was available in full text
The exclusion criteria were as follows:
(1) Researches did not meet the inclusion criteria
(2) The outcomes of interest were not reported or were
impossible to use
(3) The document was a review, abstract, letter, or a
duplicate publication
2.3. Data Extraction. Data extraction was conducted inde-
pendently by two reviewers (Zhou and Zhang), and the dis-
agreements were resolved in consultation with a third
reviewer. The number of patients in each study group was
recorded. We also extracted data for study location, study
design, intervention mode, patients’ characteristics (age
and gender), year of outset, and time of follow-up.
2.4. Quality Assessment. To qualitatively evaluate the quality
of the included studies, the Cochrane Collaboration’s tool
was used to assess the quality of randomized controlled trials
(RCTs), and the Newcastle–Ottawa Scale (NOS) was used to
assess the quality of nonrandomized trials.
2.5. Statistical Analysis. The review manager (Version 5.4,
Cochrane Collaboration, 2020) was used to estimate the
pooled results in the selected studies. Chi-square test and
I 2 statistics were used to test the heterogeneity. An I 2 value
of 0%-50% indicated that heterogeneity was not relevant/
important; 30%-50% suggested moderate heterogeneity;
50%-90% represents substantial heterogeneity; and 75%-
100% represented considerable heterogeneity. A fixed effects
model was applied in the absence of heterogeneity, while a
random effect model was used when heterogeneity was
observed. If there were more than 5 studies included in the
meta-analysis, the data would be evaluated for publication
bias by viewing the symmetry of the funnel plot and using
the Begg rank correlation method.
3. Results
3.1. Search Process. The search yielded 1263 titles. After
removal of duplicates, 1027 articles were identified. After
manually inspecting the titles and abstracts, 920 articles were
excluded. From these, 98 articles were further excluded due
to various reasons including that they had a different study
design, insufficient data available, or because they were
review articles. Ultimately, 9 studies included in our present
meta-analysis strictly met our selection criteria [19–27].
Figure 1 illustrates the search process, with the associated
inclusion and exclusion criteria.
3.2. Characteristics of Included Studies. The detailed charac-
teristics of these 9 eligible studies are summarized in Table 1.
In total, 983 patients were included, of which 504 were in an
intervention group and 479 were in the control group; the
age of most patients was over 50s. All included studies were
published from 2007 to 2021. The sample size ranged from
10 to 613. These studies contained 6 retrospective cohort
studies, two RCTs and 1 prospective cohort study.
3.3. Results of Quality Assessment. After identifying the
included articles, the abstract and full text of each article
were carefully read and the publication’s quality was evalu-
ated according to Cochrane Collaboration’s tools and NOS
(Tables 2 and 3). For the 2 RCTs, there was no risk of bias.
The risk of bias of the non-RCTs showed that all studies
were rated over 6, which indicated no significant risk of bias.
3.4. Results of the Meta-Analysis for Outcomes
3.4.1. Visual Acuity. The pooled analysis indicated that,
compared with the control group, the glucocorticoid group
resulted in a significant improvement in the visual acuity
(VA, calculated by the logarithm of the minimum angle of
Computational and Mathematical Methods in Medicine
Records identified through
Identification
database search
(n = 1258)
Records after duplicates removed
(n = 1027)
Screening
Eligibility
Full-text articles assessed for eligibility
(n = 107)
Included
Studies included in meta-analysis
(n = 9)
Figure 1: PRISMA flow diagram of study selection process.
resolution, logMAR) with a mean difference (MD) of -0.25
(95% CI [-0.45,-0.05], P = 0:02; Figure 2). However, signifi-
cant heterogeneity among the studies was detected
(I 2 = 89%, P < 0:00001).
3.4.2. Visual Field. A fixed effects model was used to evaluate
the heterogeneity of visual field (VF, calculated by the mean
deviation), as insignificant heterogeneity was found among
the included studies (P = 0:46, I 2 = 0%). The results showed
that the glucocorticoid group had a better improvement in
evaluation of visual field than the control group (MD = -
0.50 with 95% CI [-0.94, -0.07], P = 0:02) (Figure 3).
3.4.3. Retinal Nerve Fiber Layer (RNFL). For retinal nerve
fiber layer (RNFL), 6 studies involving 303 patients reported
it. Meta-analysis showed that compared to the control
group, the glucocorticoid group had a higher decrease of
RNFL (MD: -14.10, 95% CI [-26.41, -1.79], P = 0:02, fixed
effects model), without significant heterogeneity (I 2 = 0%, P
= 0:61) (Figure 4).
3.4.4. Improvement Rate of VA. Change ≥3 lines in the Snel-
len VA chart was considered to be a significant change,
which corresponded to a change in logMAR of at least 0.30
[20]. Some articles analyzed the improvement rate of VA
(change ≥3 lines), we performed a pooled analysis on these
studies. Overall, the pooled estimate showed that compared
to the control group, the glucocorticoid group had a signifi-
cantly higher improvement rate of VF (RR 1.31, 95% CI
[1.12, 1.52]; P = 0:0005, fixed effects model), with insignifi-
3
Additional records
identified
through other resources
(n = 5)
Irrelevant research was excluded
after reading title and abstract
(n = 920)
Articles excluded due to the
following reasons (n = 98):
(i) Review article
(ii) No relevant data
(iii) Ineligible article design
cant heterogeneity among the included studies (I 2 = 15%, P
= 0:32) (Figure 5).
3.4.5. Adverse Reactions. Since there were not enough litera-
ture reports on the comparison of adverse reactions between
the two groups, we could not make a combined analysis. We
made a descriptive analysis about adverse reactions, and the
specific results were shown in Table 4. Adverse reactions
included gastrointestinal reactions, headache, weight gain,
and anxiety. From the current results, there was no signifi-
cant difference in adverse reactions between two groups.
3.5. Publication Bias. The funnel plots for all four outcomes
are shown in Figure 6. The shape showed some evidence of
asymmetry, but the P value of the Egger test was not statis-
tically significant (VA, P = 0:293; VF, P = 0:123; RNFL, P =
0:727; improvement rate of VA, P = 0:324). This indicated
that there was no significant publication bias in our meta-
analysis.
4. Discussion
Optic nerve edema is an important factor in the decline of
visual function, and the timely application of glucocorticoids
in a timely manner can help to eliminate edema, reduce the
crowded state of optic disc, improve the blocking state of
axial plasma flow, reduce the crowded pressure of capillaries
at the optic nipple, improve the blood flow state, and
improve the degree of nerve ischemia, so as to reduce some
damage to visual function in a certain sense [14, 28, 29]. At
 4

Table 1: Characteristics of the eligible studies.

Study Treatment No. of patients Gender (M/F) Age Follow-

Study Country Duration
design Intervention Control Intervention Control Intervention Control Intervention Control up
June 2004
Kaderli Retrospective Triamcinolone intravitreal injection No >9
Turkey 4 6 2/2 3/3 56-74 56-74 to January
2007 [21] cohort study of 4 mg/0.1 mL treatment months
2005
Prednisone 80 mg daily for 2 weeks,
Hayreh Retrospective and then tapered down to 70 mg for No 175/ 3 1973 to
US 312 301 188/124 59:2 ± 12:6 62:0 ± 12:2
2008 [20] cohort study 5 days, 60 mg for 5 days, and then treatment 126 months 2000
cutting down by 5 mg every 5 days
Prednisone 80 mg daily for 2 weeks, September
Rebolleda Retrospective and then tapered down to 70 mg for No 6 2008 to
Spain 10 27 7/3 14/13 73:5 ± 11:6 68:0 ± 10:4
2012 cohort study 5 days, 60 mg for 5 days, and then treatment months September
cutting down by 5 mg every 5 days 2009
Methylprednisolone (1 g/day) for 3
Kinori Retrospective No
Israel days, followed by oral prednisone 24 24 14/10 16/8 54:4 ± 12:3 55:4 ± 9:6 6 months —
2014 [22] cohort study treatment
(1 mg/kg) for 11 days
February
Radoi Retrospective Triamcinolone intravitreal injection No 2009 to
France 21 15 NR NR 59-91 59-91 6 months
2014 [25] cohort study of 4 mg/0.1 mL treatment November
2012
December
Randomized Methylprednisolone 500 mg twice a
Pakravan 2010 to
controlled Iran day for 3 days, followed by 2 weeks Placebo 30 30 20/7 21/9 63:3 ± 4:7 64:1 ± 7:3 6 months
2016 [23] November
trial of oral prednisolone 1 mg/kg/day
2013
Methylprednisolone 500 mg twice a May 2012
Pakravan Prospective Suggested
Iran day for 3 days followed with oral 43 30 32/11 21/9 63:2 ± 4:9 64:1 ± 7:3 6 months to October
2017 [24] cohort study treatments
prednisolone 1 mg/kg for 10 days 2015
Prednisone 80 mg daily for 2 weeks, March
Randomized
Saxena and then tapered down to 70 mg for 2015 to
controlled India Placebo 19 19 13/6 11/8 55:6 ± 4:2 58:0 ± 7:1 6 months
2018 [27] 5 days, 60 mg for 5 days, and then August
trial
cutting down by 5 mg every 5 days 2016
Durbant Retrospective Triamcinolone intravitreal injection No 2009 to
France 41 27 — — 66 68 6 months
2021 [19] cohort study of 4 mg/0.1 mL treatment 2017
Computational and Mathematical Methods in Medicine
Computational and Mathematical Methods in Medicine 5

Table 2: Risk of bias of randomized controlled trial studies.

Random Hidden Blind Incomplete outcome Selective reporting of Other Quality

Study
allocation distribution method data results bias level
Saxena 2018
Low risk Low risk Low risk Low risk Low risk Low risk High
[27]
Pakravan 2016
Low risk Low risk Low risk Low risk Low risk Low risk High
[23]

Table 3: Risk of bias of cohort studies.

Selection Outcomes
Selection of Outcome Comparability Sufficient Follow-
Study Representativeness Ascertainment Outcome Score
nonexposed lacking at the of cohorts follow-up up
of cohort of exposure assessment
cohort beginning time adequacy
Kaderli
★ ★ ★ ★ ★★ ☆ ★ ★ 8
2007 [21]
Radoi
★ ★ ★ ★ ★★ ★ ★ ★ 9
2014 [25]
Hayreh
★ ★ ★ ★ ★☆ ☆ ★ ★ 7
2008 [20]
Pakravan
★ ★ ★ ☆ ★★ ★ ★ ★ 8
2017 [24]
Rebolleda
★ ★ ★ ★ ★☆ ★ ★ ★ 8
2012
Kinori
★ ★ ★ ★ ★☆ ★ ★ ★ 8
2014 [22]
Durbant
★ ★ ★ ★ ★★ ★ ★ ★ 9
2021 [19]

Intervention Control Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% Cl IV, random, 95% Cl
Durbant 2021 −0.3 0.6 41 0.23 0.58 27 12.7% −0.53 [−0.82, −0.24]
Kaderli 2007 −0.06 0.21 24 −0.12 0.13 24 16.5% 0.06 [−0.04, 0.16]
Pakravan 2016 −0.38 0.46 30 0.28 0.53 30 13.5% −0.66 [−0.91, −0.41]
Pakravan 2017 −0.2 0.48 43 −0.22 0.51 30 14.0% 0.02 [−0.21, 0.25]
Radoi 2014 −0.33 0.19 21 −0.01 0.26 15 15.6% −0.32 [−0.47, −0.17]
Rebolleda 2012 −0.032 0.21 10 0 0.84 27 11.4% −0.03 [−0.37, 0.31]
Saxena 2018 −0.5 0.17 19 −0.2 0.21 19 16.2% −0.30 [−0.42, −0.18]

Total (95% Cl) 188 172 100.0% −0.25 [−0.45, −0.05]

Heterogeneity: Tau2 = 0.06; Chi2 = 52.74, df = 6 (P < 0.00001); I2 = 89%
Test for overall effect: Z = 2.41 (P = 0.02) −1 −0.5 0 0.5 1
Favours [intervention] Favours [control]

Figure 2: Forest plot evaluating the outcomes of VA. VA: visual acuity.

Intervention Control Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% Cl IV, random, 95% Cl
Kinori 2014 −2.6 0.9 24 −2.2 0.7 24 91.4% −0.40 [−0.86, 0.06]
Pakravan 2016 −3.56 5.58 30 −2.21 6.35 30 2.1% −1.35 [−4.37, 1.67]
Pakravan 2017 −2.71 4.58 43 −2.21 6.35 30 2.7% −0.50 [−3.15, 2.15]
Radoi 2014 −3.09 4.25 21 −0.34 3.85 15 2.7% −2.75 [−5.41, −0.09]
Rebolleda 2012 −0.56 5.03 10 1.27 6.9 27 1.2% −1.83 [−5.89, 2.23]

Total (95% Cl) 128 126 100.0% −0.50 [−0.94, −0.07]

Heterogeneity: Chi2 = 3.64, df = 4 (P = 0.46); I2 = 0%
−10 −5 0 5 10
Test for overall effect: Z = 2.26 (P = 0.02)
Favours [intervention] Favours [control]

Figure 3: Forest plot evaluating the outcomes of VF. VF: visual field.
6 Computational and Mathematical Methods in Medicine

Intervention Control Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, random, 95% Cl IV, random, 95% Cl
Durbant 2021 −160 62 41 −126 50 27 21.2% −34.00 [−60.76, −7.24]
Pakravan 2016 −62 50 30 −56 37 30 30.6% −6.00 [−28.26, 16.26]
Pakravan 2017 −101 53 43 −92 59 30 21.8% −9.00 [−35.39, 17.39]
Radoi 2014 −154 62.2 20 −120 69 7 4.5% −34.00 [−91.93, 23.93]
Rebolleda 2012 −150 64.9 10 −148.5 55.7 27 7.4% −1.50 [−46.88, 43.88]
Saxena 2018 −62 58 19 −52 42 19 14.6% −10.00 [−42.20, 22.20]

Total (95% Cl) 163 140 100.0% −14.10 [−26.41, −1.79]

Heterogeneity: Chi2 = 3.59, df = 5 (P = 0.61); I2 = 0%
Test for overall effect: Z = 2.24 (P = 0.02) −100 −50 0 50 100
Favours [intervention] Favours [control]

Figure 4: Forest plot evaluating the outcomes of RNFL. RNFL: retinal nerve fiber layer.

Intervention Control Risk ratio Risk ratio

Study or subgroup Events Total Events Total Weight M-H, fixed, 95% Cl M-H, fixed, 95% Cl
Durbant 2021 29 41 11 27 8.0% 1.74 [1.06, 2.85]
Hayreh 2008 159 312 120 301 74.1% 1.28 [1.07, 1.52]
Kaderli 2007 4 4 2 6 1.3% 2.52 [0.89, 7.10]
Pakravan 2016 13 30 12 30 7.3% 1.08 [0.59, 1.97]
Pakravan 2017 16 43 12 30 8.6% 0.93 [0.52, 1.67]
Radoi 2014 6 21 1 15 0.7% 4.29 [0.57, 32.01]

Total (95% Cl) 451 409 100.0% 1.31 [1.12, 1.52]

Total events 227 158
Heterogeneity: Chi2 = 5.88, df = 5 (P = 0.32); I2 = 15%
Test for overall effect: Z = 3.46 (P = 0.0005) 0.02 0.1 1 10 50
Favours [intervention] Favours [control]

Figure 5: Forest plot evaluating the outcomes of improvement rate of VA. VA: visual acuity.

Table 4: Summary of adverse reactions in the included studies.

Rate (%)
Complication RR 95% CI
Intervention Control
Gastrointestinal symptoms 52.63 31.58 2.41 (0.64, 9.03)
Headache 26.32 21.05 1.34 (0.30, 6.02)
Weight gain 21.05 15.79 1.42 (0.27, 7.44)
Anxiety 10.53 0 5.57 (0.25, 124.19)
RR: risk ratio.

the same time, glucocorticoids can also inhibit the expres-
sion of endothelin 21 [30, 31].
Our study systematically evaluated the therapeutic effect
of glucocorticoids on NAION patients with VA, VF, RNFL,
and adverse reactions as outcome indicators. A total of 9
studies were included in this paper. The results of meta-
analysis showed that the application of glucocorticoids could
improve VA (MD: -0.25, 95% CI [-0.45, -0.05], P = 0:02), VF
(MD: -0.50, 95% CI [-0.94, -0.07], P = 0:02), and RNFL
(MD: -14.10, 95% CI [-26.41, -1.79], P = 0:02) in NAION
patients.
Chen et al. conducted a meta-analysis of the literature on
the treatment of NAION with corticosteroids, and they
found that corticosteroids did not significantly improve the
vision of NAION patients [32]. However, our study strived
to objectively analyze the effectiveness and safety of hor-
mone treatment of NAION; therefore, some studies on hor-
mone combined with other treatment methods and the
literature that failed to clearly define arteritic or nonarteritic
ION have been excluded to avoid the possible potential bias
risk [33–35].
The adverse reactions of glucocorticoid drugs used in the
treatment of NAION deserve clinicians’ attention, such as
monitoring blood glucose changes, nausea, indigestion,
headaches, and weight gain, Anxiety and depression are eas-
ily overlooked, and intraocular hypertension is the most
common adverse reactions [36, 37]. By summarizing the
adverse reactions of included literatures and comparing the
differences with the control group in a descriptive way, we
found that the differences between the two groups were
not significant.
This study had some limitations. First, among the
included studies, 7 were nonrandomized studies and only 2
were RCTs. As the “gold standard” for clinical efficacy eval-
uation, RCTs have more objective guiding significance,
which may reduce the reliability of the results of this study.
Second, there were few reports of adverse reactions in the
original studies included in the meta-analysis, so it was
Computational and Mathematical Methods in Medicine 7

Begg’s funnel plot with pseudo 95% confidence limits Begg’s funnel plot with pseudo 95% confidence limits
.5 5

0
Effect size

Effect size
0

−.5

−.1 −5
0 .1 .2 0 0.5 1 1.5 2
s.e. of: effect size s.e. of: effect size
(a) (b)
Begg’s funnel plot with pseudo 95% confidence limits Begg’s funnel plot with pseudo 95% confidence limits
50
2

1
0
Effect size

Effect size
0

−50
−1

−100 −2
0 10 20 30 0 .5 1
s.e. of: effect size s.e. of: effect size
(c) (d)

Figure 6: Funnel plot showing the publication bias. (a) visual acuity; (b) visual field; (c) retinal nerve fiber layer; and (d) improvement rate
of visual acuity.

impossible to accurately evaluate the safety of glucocorti- Conflicts of Interest

coids in NAION treatment.
The authors have no conflicts of interest to declare.

5. Conclusions Authors’ Contributions

Our meta-analysis found that the application of glucocorti-
coids in the treatment of NAION was safe and effective
and can effectively improve VA and VF of NAION patients.
However, the effect of glucocorticoids on the improvement
of vision in NAION patients should be verified by more
large sample RCTs and should focus on its hormone adverse
reactions.
Data Availability
No data were used to support this study.
Ethical Approval
The authors are accountable for all aspects of the work in
ensuring that questions related to the accuracy or integrity
of any part of the work are appropriately investigated and
resolved.
Pingping Zhou and Jian Zhang contributed equally to this
work.
References
[1] M. A. Nagel, A. N. Russman, H. Feit et al., “VZV ischemic
optic neuropathy and subclinical temporal artery infection
without rash,” Neurology, vol. 80, pp. 424–426, 2012.
[2] C. Salgado, F. Vilson, N. R. Miller, and S. L. Bernstein, “Cellu-
lar inflammation in nonarteritic anterior ischemic optic neu-
ropathy and its primate model,” Archives of Ophthalmology,
vol. 129, no. 12, pp. 1583–1591, 2011.
[3] C. Kernstock, F. Beisse, S. Wiethoff et al., “Assessment of func-
tional and morphometric endpoints in patients with non-
arteritic anterior ischemic optic neuropathy (NAION),” Grae-
fe's Archive for Clinical and Experimental Ophthalmology,
vol. 252, no. 3, pp. 515–521, 2014.
[4] A. M. Gruener, J. R. Chang, T. M. Bosley, Z. M. al-Sadah,
C. Kum, and T. J. McCulley, “Relative frequencies of arteritic
8 Computational and Mathematical Methods in Medicine
and nonarteritic anterior ischemic optic neuropathy in an
Arab population,” Journal of Neuro-Ophthalmology, vol. 37,
no. 4, pp. 382–385, 2017.
[5] E. W. Mayes, E. D. Cole, S. Dang et al., “Optical coherence
tomography angiography in nonarteritic anterior ischemic
optic neuropathy,” Journal of Neuro-Ophthalmology, vol. 37,
no. 4, pp. 358–364, 2017.
[6] S. L. Bernstein, M. A. Johnson, and N. R. Miller, “Nonarteritic
anterior ischemic optic neuropathy (NAION) and its experi-
mental models,” Progress in Retinal and Eye Research,
vol. 30, no. 3, pp. 167–187, 2011.
[7] M. I. Boone, G. G. Massry, R. A. Frankel, J. B. Holds, and S. M.
Chung, “Visual outcome in bilateral nonarteritic anterior
ischemic optic neuropathy,” Ophthalmology, vol. 103, no. 8,
pp. 1223–1228, 1996.
[8] N. Desai, M. R. Patel, L. M. Prisant, and D. A. Thomas, “Non-
arteritic anterior ischemic optic neuropathy,” Journal of Clini-
cal Hypertension, vol. 7, pp. 130–133, 2010.
[9] M. Storoni, C. Chan, A. Cheng, N. C. Y. Chan, and C. K. S.
Leung, “The pathogenesis of nonarteritic anterior ischemic
optic neuropathy,” Asia-Pacific Journal of Ophthalmology,
vol. 2, no. 2, pp. 132–135, 2013.
[10] E. J. Atkins, “Nonarteritic anterior ischemic optic neuropa-
thy,” Current Treatment Options in Neurology, vol. 13, no. 1,
pp. 92–100, 2011.
[11] C. S. Chen, M. A. Johnson, R. A. Flower, B. J. Slater, N. R.
Miller, and S. L. Bernstein, “A primate model of nonarteritic
anterior ischemic optic neuropathy,” Investigative Ophthal-
mology & Visual Science, vol. 49, no. 7, pp. 2985–2992, 2008.
[12] A. J. Bella, W. O. Brant, T. F. Lue, and G. B. Brock, “Non-
arteritic anterior ischemic optic neuropathy (NAION) and
phosphodiesterase type-5 inhibitors,” The Canadian Journal
of Urology, vol. 13, no. 5, pp. 3233–3238, 2006.
[13] A. A. Nanji, K. S. Klein, V. S. Pelak, and M. X. Repka, “Nonar-
teritic anterior ischemic optic neuropathy in a child with optic
disk drusen,” Journal of AAPOS, vol. 16, no. 2, pp. 207–209,
2012.
[14] P. M. Aries, B. Hellmich, and W. L. Gross, “The role of gluco-
corticoids in the treatment of vasculitis,” Zeitschrift für Rheu-
matologie, vol. 64, no. 3, pp. 155–161, 2005.
[15] B. Bakbak, B. T. Ozturk, S. Gedik, B. E. Koktekir, and S. Gonul,
“Can intramuscular corticosteroid injection cause nonarteritic
anterior ischemic optic neuropathy?,” Clinical Ophthalmology,
vol. 2013, pp. 633–635, 2013.
[16] G. Rebolleda, M. Pérez-López, P. Casas-Llera, and F. J. Muñoz-
Negrete, “Treatment of non-arteritic anterior ischemic optic
neuropathy with high-dose systemic corticosteroids,” Graefe's
Archive for Clinical and Experimental Ophthalmology,
vol. 251, no. 3, pp. 1031-1032, 2013.
[17] Y. Cai, Y. Wu, and H. Yu, “Clinical observation of the effects of
combined therapy on nonarteritic anterior ischemic optic neu-
ropathy,” Journal of Clinical Ophthalmology, vol. 5, pp. 152–
156, 2005.
[18] T. L. Huang, K. H. Lin, and R. K. Tsai, “Treatment strategy for
non-arteritic anterior ischemic optic neuropathy,” Tzu Chi
Medical Journal, vol. 25, no. 3, pp. 135–138, 2013.
[19] E. Durbant, C. Radoi, T. Garcia, A. Denoyer, and C. Arndt,
“Injection intravitreenne de triamcinolone dans les neuropa-
thies optiques ischemiques anterieures aigues non-
arteritiques - Une etude retrospective,” Journal Français
d'Ophtalmologie, vol. 44, no. 6, pp. 777–785, 2021.
[20] S. S. Hayreh and M. B. Zimmerman, “Non-arteritic anterior
ischemic optic neuropathy: role of systemic corticosteroid
therapy,” Graefe's Archive for Clinical and Experimental Oph-
thalmology, vol. 246, no. 7, pp. 1029–1046, 2008.
[21] B. Kaderli, R. Avci, A. Yucel, K. Guler, and O. Gelisken, “Intra-
vitreal triamcinolone improves recovery of visual acuity in
nonarteritic anterior ischemic optic neuropathy,” Journal of
Neuro-Ophthalmology, vol. 27, no. 3, pp. 164–168, 2007.
[22] M. Kinori, I. Ben-Bassat, Y. Wasserzug, A. Chetrit, and
R. Huna-Baron, “Visual outcome of mega-dose intravenous
corticosteroid treatment in non-arteritic anterior ischemic
optic neuropathy - retrospective analysis,” BMC Ophthalmol-
ogy, vol. 14, no. 1, pp. 62–66, 2014.
[23] M. Pakravan, N. Sanjari, H. Esfandiari, P. Pakravan, and
M. Yaseri, “The effect of high-dose steroids, and normobaric
oxygen therapy, on recent onset non-arteritic anterior ische-
mic optic neuropathy: a randomized clinical trial,” Graefe's
Archive for Clinical and Experimental Ophthalmology,
vol. 254, no. 10, pp. 2043–2048, 2016.
[24] M. Pakravan, H. Esfandiari, K. Hassanpour, S. Razavi, and
P. Pakravan, “The effect of combined systemic erythropoietin
and steroid on non-arteritic anterior ischemic optic neuropa-
thy: a prospective study,” Current Eye Research, vol. 42,
no. 7, pp. 1079–1084, 2017.
[25] C. Radoi, T. Garcia, C. Brugniart, A. Ducasse, and C. Arndt,
“Intravitreal triamcinolone injections in non-arteritic anterior
ischemic optic neuropathy,” Graefe's Archive for Clinical and
Experimental Ophthalmology, vol. 252, no. 2, pp. 339–345,
2014.
[26] G. Rebolleda, M. Pérez-López, P. Casas-LLera, I. Contreras,
and F. J. Muñoz-Negrete, “Visual and anatomical outcomes
of non-arteritic anterior ischemic optic neuropathy with
high-dose systemic corticosteroids,” Graefe's Archive for Clin-
ical and Experimental Ophthalmology, vol. 251, no. 1,
pp. 255–260, 2013.
[27] R. Saxena, D. Singh, M. Sharma, M. James, P. Sharma, and
V. Menon, “Steroids versus No Steroids in Nonarteritic
Anterior Ischemic Optic Neuropathy: A Randomized Con-
trolled Trial,” Ophthalmology, vol. 125, no. 10, pp. 1623–
1627, 2018.
[28] S. S. Hayreh and M. B. Zimmerman, “Non-arteritic anterior
ischemic optic neuropathy: role of systemic corticosteroid
therapy,” Survey of Ophthalmology, vol. 37, pp. 349–354, 2017.
[29] S. Berry, W. V. Lin, A. Sadaka, and A. G. Lee, “Nonarteritic
anterior ischemic optic neuropathy: cause, effect, and manage-
ment,” Eye & Brain, vol. 9, pp. 23–28, 2017.
[30] S. S. Hayreh, “Posterior ischaemic optic neuropathy: clinical
features, pathogenesis, and management,” Eye (London,
England), vol. 18, no. 11, pp. 1188–1206, 2004.
[31] S. Lessell, “Nonarteritic anterior ischemic optic Neuropathy,”
Archives of Ophthalmology, vol. 117, no. 3, pp. 386–388, 1999.
[32] J. Chen, J. Zhu, L. Chen, C. Hu, and Y. du, “Steroids in the
treatment of nonarteritic anterior ischemic optic neuropathy,”
Medicine, vol. 98, no. 46, article e17861, 2019.
[33] A. K. Schuster, P. Steinmetz, T. M. Forster, F. C. Schlichten-
brede, B. C. Harder, and J. B. Jonas, “Choroidal thickness in
nonarteritic anterior ischemic optic neuropathy,” American
Journal of Ophthalmology, vol. 12, pp. 898–904, 2014.
[34] S. S. Hayreh and M. B. Zimmerman, “Nonarteritic anterior
ischemic optic neuropathy: natural history of visual outcome,”
Ophthalmology, vol. 115, no. 2, pp. 298–305.e2, 2008.
Computational and Mathematical Methods in Medicine 9

[35] A. Yaman, O. B. Selver, A. O. Saatci, and M. F. Soylev, “Intra-

vitreal triamcinolone acetonide injection for acute non-
arteritic anterior ischaemic optic neuropathy,” Clinical &
Experimental Optometry, vol. 91, no. 6, pp. 561–564, 2008.
[36] R. Khanna, R. Hage, A. Lecler, T. Sené, C. Vignal-Clermont,
and G. Clavel-Refregiers, “Giant cell arteritis with ocular
involvement successfully treated with tocilizumab and very
short-course glucocorticoids: A case report,” Journal Français
d'Ophtalmologie, vol. 44, no. 4, pp. 481–484, 2021.
[37] C. Zhang, Y. Guo, B. J. Slater, N. R. Miller, and S. L. Bernstein,
“Axonal degeneration, regeneration and ganglion cell death in
a rodent model of anterior ischemic optic neuropathy
(rAION),” Experimental Eye Research, vol. 91, no. 2,
pp. 286–292, 2010.