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Efficacy and safety of traditional Chinese
medicine decoction in the treatment of adolescent
myopia
A protocol for systematic review and network meta-analysis
Xiurong Tian, MD, Zhongli Sun, MD, Yonghua Li, PhD, Xianglin Jiang, MD, Xingying Li, MD,
Penglong Yu, PhD
∗
Abstract
Background: Adolescent myopia has become a major public health problem in Asian countries and even the world. Due to its
unstable prognosis and numerous complications, it has caused serious social and economic burden. As a common treatment in
Asia, Chinese medicine has been shown to be effective in controlling the development of myopia, but its evidence-based medical
evidence is not sufficient. Therefore, the purpose of this study is to evaluate the efficacy and safety of traditional Chinese medicine
(TCM) in the treatment of adolescent myopia through network meta-analysis, and to provide evidence for clinical and scientific
research.
Methods: We searched seven databases for randomized controlled trials of TCM decoction for adolescent myopia, including
PubMed, the Cochrane Library, EMbase, China National Knowledge Infrastructure, China Biological Medicine, Chinese Scientific
Journals Database, and wan-fang databases, from the date of the establishment of each database to January 31, 2022. The network
meta-analysis will be implemented through Aggregate Data Drug Information System 1.16.8 and Stata 13.0 software. Primary
outcomes include distant vision, intraocular pressure, and diopter. Mean differences or odds ratios will be used for statistical analysis.
We will ensure the reliability of the results through node-split model and heterogeneity analysis. In addition, the Cochrane
Collaboration’s tool and Grading of Recommendations Assessment, Development and Evaluation system will be used for the
methodological quality and the evidence quality.
Results: This study will provide reliable evidence for the clinical selection of TCM decoction in the treatment of adolescent myopia.
Conclusion: The results of this study will evaluate the efficacy and safety of TCM decoction in the treatment of adolescent myopia,
and provide decision-making references for future clinical and scientific research.
Ethics and dissemination: This study did not require ethical approval. We will disseminate our findings by publishing results in a
peer-reviewed journal.
OSF registration number: DOI 10.17605/OSF.IO/VXQUP.
Abbreviations: NMA =network meta-analysis, PSRF=potential scale reduced factor, RCTs =randomized controlled trials, TCM
=traditional Chinese medicine.
Keywords: adolescent, myopia, network meta-analysis, protocol, systematic review, traditional Chinese medicine
1. Introduction
Currently, myopia has become a major global public health
problem in Asian countries.
[1]
Around the world, 475.8 million
people suffer from myopia by 2050.
[2]
Myopia is also one of the
main causes of visual impairment and has caused serious social
and economic burden.
[3]
Now, in China, the number of myopia
patients remains high and continues to increase.
[4]
Complications
caused by excessive axial elongation caused by myopia, such
as myopia macular, glaucoma, choroidal neovascularization,
acquer cracks, etc., seriously affect the prognosis of myopia,
which can lead to irreversible visual damage and heavy economy
burden.
[5,6]
In fact, in China, myopia macular degeneration is one
of the main causes of low vision in adults and the second leading
cause of blindness.
[7,8]
Numerous studies have shown that low-dose (0.01%) atropine
is effective in reducing the increase in myopia in adolescents, and
topical atropine drops have been used for 150 years to relieve
This research was funded by the Science and Technology Project of Chongqing
Education Commission (grant number: KJQN202002706).
The authors have no conflicts of interest to disclose.
Data sharing not applicable to this article as no datasets were generated or
analyzed during the current study.
Chongqing Three Gorges Medical College, Chongqing, China.
∗
Correspondence: Penglong Yu, Chongqing Three Gorges Medical College,
Chongqing 404120, China (e-mail: penglong_yu@163.com).
Copyright ©2022 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
How to cite this article: Tian X, Sun Z, Li Y, Jiang X, Li X, Yu P. Efficacy and
safety of traditional Chinese medicine decoction in the treatment of adolescent
myopia: a protocol for systematic review and network meta-analysis. Medicine
2022;101:6(e28733).
Received: 11 January 2022 / Accepted: 13 January 2022
http://dx.doi.org/10.1097/MD.0000000000028733
Study Protocol Systematic Review Medicine®
OPEN
1
myopia.
[9–11]
However, long-term use can cause photosensitivity
and rebound effects after drug withdrawal due to concentration-
dependent side effects, so higher concentrations of atropine drops
are still not widely used.
[12]
At present, a large number of classic Chinese medicine
decoctions have been used in clinical treatment of adolescent
myopia, and they have been made into different dosage forms at
the same time, with good effects.
[13]
However, there are many
types of traditional Chinese medicine (TCM) decoctions in
clinical application, and there is no interactive comparison
between them. Therefore, the purpose of this study is to evaluate
the efficacy and safety of different TCM decoctions in the
treatment of adolescent myopia through network meta-analysis
(NMA), and to provide reference and evidence for clinical
application.
2. Methods
2.1. Protocol and registration
The NMA protocol has been registered on the Open Science
Framework platform (https://osf.io/vxqup), registration number:
DOI 10.17605/OSF.IO/VXQUP. This protocol follows the
Preferred Reporting Items for Systematic Reviews and Meta-
Analyses Protocols guidelines.
[14]
2.2. Ethics
Since personal information of subjects is not required to be
collected in this study, ethical permission is not applicable. In
addition, adolescent subjects and their family members will sign
informed consent during the study.
2.3. Eligibility criteria
The review will be conducted through the PICOS principle,
including Participant (P), Intervention (I), Comparator (C),
Outcome (O), and Study Design (S).
2.3.1. Type of participant. All participants included in this
study will meet the following criteria:
(a) be 18 years of age or younger;
(b) in this study, myopia will be defined as: equivalent spherical
lens -1.00 diopter after dilated eye examination;
[15]
(c) not accompanied by any organic diseases of organs or eye
diseases;
(d) those who have participated in any surgery or treatment
related to vision correction will not be included.
2.3.2. Type of interventions and comparators. The treatment
group was treated with TCM alone or integrated traditional
Chinese and Western medicine, while the control group was
treated with conventional western medicine or placebo or
waiting for treatment. TCM treatment mainly selects the rel evant
dosage forms of TCM, not limited to decoction, pill, injection,
etc.
2.3.3. Type of outcomes
2.3.3.1. Primary outcomes.
Distant vision;
Intraocular pressure;
Diopter;
2.3.3.2. Secondary outcomes.
Interpupillary distance and axis of eyeball;
Adverse reaction.
2.3.4. Study design. This study is a systematic review with
NMA of randomized controlled trials (RCTs) on TCM decoction
for the adolescent myopia. All relevant RCTs using TCM
decoction for the adolescent myopia will be included. Quasi-
RCTs will be excluded such as those allocating by medical record
number. The specific participants, interventions, comparators,
and outcomes criteria are as follows.
2.4. Literature retrieval strategy
Computer retrieval of published RCTs of TCM decoction for the
adolescent myopia is conducted in PubMed, the Cochrane
Library (issue 1, 2022), EMbase, China National Knowledge
Infrastructure, China Biological Medicine, Chinese Scientific
Journals Database (VIP), and wan-fang databases. The time
limit of document retrieval is from the establishment of each
database to January 31, 2022. The language is limited to English
and Chinese. In addition, inclusive literature from the field
and references from previous evaluations will be manually
retrieved to find other potentially relevant articles. Search terms
mainly include: “Myopia,”“Nearsightedness,”“Adolescent
myopia,”“Traditional Chinese Medicine,”“Injection,”“Pill,”
“Decoction,”“Powder,”“Eye ointment,”etc. Taking PubMed as
an example, the initial retrieval strategy is shown in Table 1 and
will be adjusted according to the specific database.
2.5. Literature selection and data extraction
As shown in Figure 1, Xiurong T and Zhongli S will independently
screen literatures according to inclusion and exclusion criteria: (a)
After importing the retrieved literature into EndNote X9.0, the
duplicate literature was eliminated; (b) Conduct a preliminary
screening by reading the headline summary to exclude literature
that does not meet the inclusion criteria; (c) Reading the full text
and making final selections; (d) Data extraction using a pre-
designed data extraction table for the included literature and cross-
checking the results; (e) In case of disagreement, the third
researcher Penglong Y will be called upon to assist in judgment.
Table 1
Search strategy of the PubMed.
Number Search terms
#1 Myopia[Mesh]
#2 Myopia[Title/Abstract] OR Nearsightedness[Title/Abstract]
#3 #1 OR #2
#4 Adolescent[Title/Abstract]
#5 Traditional Chinese medicine[Title/Abstract]
#6 Injection[Title/Abstract] OR Pill[Title/Abstract] OR
Decoction[Title/Abstract] OR Powder[Title/Abstract] OR
Eye ointment[Title/Abstract]
#7 #5 OR #6
#8 randomized controlled trial[Publication Type]
#9 controlled clinical trial[Publication Type]
#10 randomized[Title/Abstract]
#11 randomly[Title/Abstract]
#12 #8 OR #9 OR #10 OR #11
#13 #3 AND #4 AND #7 AND #12
Tian et al. Medicine (2022) 101:6 Medicine
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Data extraction mainly included basic information of the literature
(first author name, year of publication), basic information of study
subjects (gender, average age, sample size, information of
intervention and control group, intervention time, outcomes and
follow-up time). At the same time, the key factors of bias risk
assessment are extracted. We will contact the corresponding
authors for additional information if necessary.
2.6. Quality assessment/methodological quality of
included studies
Methodological quality will be assessed based on the bias tool
(ROB) in Cochrane Handbook 5.1.0. Two trained researchers
Yonghua L and Xianglin J will independently evaluate the risk of
bias of the included studies. In case of dispute, submit to the third
researcher Xingying L for arbitration. Cochrane bias risk
assessment tool will be used to assess the risk of RCTs being
included in NMA, 7 items are included
[16]
:
(a) random sequence generation, allocation concealment possi-
bility;
(b) blinding of participants and personnel;
(c) blinding of outcome assessment;
(d) incomplete outcome data;
(e) selective reporting;
(f) other bias.
Based on the above 7 items, the included studies will be
classified into three grades: low risk of bias, high risk of bias, and
unclear risk of bias.
2.7. Data synthesis and statistical methods
2.7.1. Network meta-analysis. This study uses Aggregate Data
Drug Information System 1.16.8 for NMA, and uses Markov
Chain-Monte Carlo algorithm to make Bayesian inference.
[17]
Iteration operations were performed according to the following
preset model parameters: 4 chains were used for simulation
analysis, with initial value of 2.5, a step size of 10, annealing
times of 20,000, and 50,000 simulation iteration times.
Aggregate Data Drug Information System software is used to
draw network evidence diagrams of different outcome indicators,
and odds ratio or standardized mean differences is used for
statistical analysis, both with 95% credible intervals. According
to the results of the NMA, rank probability plot of various TCM
decoction is generated and sorted by dominance, with Rank1
being the optimal sort.
Records identified through database
searching
(n = )
Screening
Included Eligibility Identification
Additional records identified
through other sources
(n = )
Records after duplicates removed
(n = )
Records screened
(n = )
Records excluded
(n = )
Full-text articles assessed
for eligibility
(n = )
Full-text articles excluded,
with reasons
(n = )
Studies included in
qualitative synthesis
(n = )
Studies included in
quantitative synthesis
(meta-analysis)
(n = )
Figure 1. PRISMA flow diagram of the study selection process. PRISMA =Preferred Reporting Items for Systematic Reviews and Meta-Analysis.
Tian et al. Medicine (2022) 101:6 www.md-journal.com
3
2.7.2. Statistical model selection. In this study, node-split
model was used to analyze the consistency of data. When the
statistical difference was compared directly and indirectly
(P>.5), the consistency model was used for analysis. On the
contrary, inconsistent model is adopted for analysis. If the
consistency model is adopted, then the stability of the results is
verified by the inconsistency model: when the inconsistency
factors including 0, at the same time inconsistency standard
deviation including 1 says the result of inconsistency model is
more stable and reliable. At the same time, the pre-set
parameters are used for iterative operation, and the conver-
gence degree of iteration is judged by the potential scale reduced
factor (PSRF). When the PSRF value is close to or equal to 1
(1 PSRF 1.05), the convergence is complete, indicating
good stability of the model and reliable analysis results. If
the PSRF is not in this range (1 PSRF 1.05), the iteration will
continue manually until the PSRF value reaches the range
standard.
2.7.3. Heterogeneity test. Before the combination of effect size,
the heterogeneity of the included literature is tested using STATA
15.0 software. Evaluate the heterogeneity between studies
through I
2
. When I
2
>50%, it indicates that the heterogeneity
between studies is large, using a random effect model; when I
2
<
50%, it indicates that the heterogeneity between studies is small
or there is no qualitative difference, using a fixed effect model.
When the heterogeneity is greater, the source of heterogeneity
should be further sought.
2.7.4. Sensitivity analysis. If necessary, sensitivity analysis will
be used to assess the impact of the studies on the random effects
model. After each study was excluded one by one, the data
analysis was carried out again to determine the stability of the
results. If there is no qualitative change in the combined effect
showed in the results, the results are stable.
2.7.5. Subgroup analysis. If there is clinical and methodologi-
cal heterogeneity, we will conduct a subgroup analysis of the
patient’s age, the degree of myopia, duration of treatment, or
study quality.
2.7.6. Publication bias. If 10 or more studies are included in the
NMA, a comparison-adjusted funnel plot is developed using
Stata to evaluate the presence of small sample effects or
publication bias in the intervention network. If the plot is
asymmetric and there is no inverted funnel shape, it indicates that
there may be publication bias. The reasons may be related to the
small sample size, allocation concealment, and insufficient
implementation of blind method.
2.7.7. Dealing with missing data. If the literature information is
clearly incorrect or incomplete, we will contact the first author or
the first author of the literature via email address. If no response is
received, the document should be deleted.
2.7.8. Evaluating the quality of the evidence. To grade
evidence quality and understand the current situation of evidence
rating thereby analyzing possible problems, The Grading of
Recommendations Assessment, Development and Evaluation
instrument will be used to assess the quality of evidence in the
NMA.
[18]
Based on bias, inconsistent, inaccurate, indirect, and
the risk of publication bias (5 degradation factors), the quality
classification for the four level of evidence: high, medium, low,
and very low.
2.7.9. Patient and public involvement. There was no patient or
public involvement in the preparation of this protocol.
3. Discussions
Myopia has gradually become one of the leading eye diseases in
the world. Studies have shown that TCM treatment with TCM
decoction can effectively slow down the occurrence and
development of myopia. Therefore, we hope to understand
the efficacy and safety of various TCM decoction in the
treatment of adolescent myopia through this study. Due to the
diversity of clinical medication and to avoid large heterogeneity
in the study, we could not include all categories of TCM
decoction. There is a potential risk of bias. We will further
optimize and deepen the research scheme according to actual
needs. We will promptly disclose the reasons and timing of any
changesthatmaybemade.
Author contributions
All the authors have approved the publication of the protocol.
Conceptualization: Xiurong Tian, Zhongli Sun, Penglong Yu.
Data curation: Xiurong Tian, Zhongli Sun, Yonghua Li.
Formal analysis: Xiurong Tian, Zhongli Sun.
Funding acquisition: Yonghua Li.
Methodology: Yonghua Li, Xianglin Jiang, Xingying Li.
Project administration: Xiurong Tian, Zhongli Sun, Yonghua Li.
Writing –original draft: Xiurong Tian, Zhongli Sun.
Writing –review & editing: Xiurong Tian, Zhongli Sun,
Yonghua Li, Xianglin Jiang, Xingying Li, Penglong Yu.
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