A Prospective Study on the Efficacy of Different Interventions for Progressive Myopia in Children After Orthokeratology Lens Wear
Conditions: Progressive Myopia, Pediatric Myopia, Orthokeratology-related Myopia Progression
Sponsor: Tianjin Medical University Eye Hospital

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Observational Study Protocol Template
Project Title: Study on the Efficacy of Different Intervention Methods for
Progressive Myopia After Wearing Orthokeratology Lenses
Research protocol version: 1.0, March 9, 2026
Project Leader: He Meinan
1. Research Background and Project Justification
Myopia has become a major global issue affecting the visual health of children and
adolescents. Research by Holden BA et al. estimates that by 2050, the prevalence of myopia and
high myopia will significantly increase worldwide, affecting nearly 5 billion and 1 billion people
respectively, with particularly prominent impacts in East Asia. Data from the China CDC show that
in 2022, the overall myopia rate among Chinese children and adolescents was 51.9% (elementary
school students: 36.7%, junior high school students: 71.4%, senior high school students: 81.2%).
The continuous rise in myopia prevalence and the increasing incidence of complications
associated with high myopia will have multifaceted socioeconomic impacts2. The elongation of the
eye axis caused by high myopia elevates the risk of various ocular diseases, such as cataracts and
glaucoma, not only exacerbating the healthcare burden but also increasing the incidence of ocular
complications3. Therefore, preventing myopia onset and controlling axial length progression have
become critically important4.
Orthokeratology lenses (Ortho-k) represent the only non-surgical method that does not
require daytime optical correction and are currently regarded as a first-line intervention for
myopia control5-7. These lenses induce temporary corneal surface remodeling and reduce
daytime myopia by wearing specially designed, breathable contact lenses with reverse geometric
patterns at night8-9. In children with mild to moderate myopia, they have demonstrated excellent
visual correction efficacy ranging from 80% to 92%10-11. However, their efficacy in myopia
control may be inferior to that in myopia correction. Compared to the control group,
orthokeratology lenses show therapeutic effects of 43–63% in slowing axial length progression.
Despite lens use, approximately 15% of children still exhibit annual axial length progression
exceeding 0.36 mm12-13.
Currently, interventions for myopia control in children primarily include orthokeratology
(OK), repeated low-level red-light therapy (RLRL), and low-dose atropine (AT). In recent years,
researchers have begun exploring whether the combined use of these methods can produce
synergistic effects to more effectively delay myopia progression.

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Tang Wenting et al. reported that low-concentration atropine (0.01%) combined with
orthokeratology lenses for myopia correction in adolescents resulted in significant improvements
in parameters such as refractive error, corneal curvature, and CCT compared to orthokeratology
lenses alone, with good safety profiles. The 0.01% atropine eye drops used in combination may
exert an effect on controlling further progression of axial length (AL) by altering scleral
morphology and thickening the nerve fiber layer. In other related studies, Zhu Xianfeng et al.
reported that the combination of 0.01% atropine eye drops and orthokeratology lenses for treating
high myopia in adolescents showed reduced AL progression compared to orthokeratology lenses
alone. Kinoshita et al. conducted a study on children aged 8–12 years, demonstrating that the
AOK group exhibited more effective AL growth retardation (0.09 mm–0.19 mm) compared to the
0K lens group. Additionally, Tan et al. investigated children aged 6–11 years with standard error
of measurement (sE) ranging from –1.00 to –4.00 D, finding that AL growth in the AOK group
was delayed by 0.09 mm in the first year of treatment compared to the 0K lens group, and by 0.17
mm after two years of treatment. Zhao et al. reported that AL growth in children aged 5–14 years
treated with AOK or 0K lenses for one year was 0.14 mm and 0.29 mm, respectively. Another
study involving children aged 8–12 years22 demonstrated that after a 1-year treatment course, the
AOK group achieved a 17% delay in axial length (AL) progression (0.20 mm in the AOK group
vs. 0.24 mm in the control group). However, the 2-year study results from Zhou et al.23 showed
that compared to monotherapy with 0.1 g·L⁻ ¹ atropine, the AOK group exhibited significantly
better efficacy in delaying refractive progression. In terms of AL growth control, however, the two
groups showed comparable outcomes, with values of (0.50±0.17) mm and (0.61±0.21) mm,
respectively.
The posterior optical zone diameter (BOZD) of orthokeratology lenses is one of the most
critical parameters in custom orthokeratology lens design. Studies have demonstrated that
reducing BOZD can effectively decrease the treatment area while increasing the steepening area
and degree in the central corneal region24-26. However, in 2013, Kang et al.24 first modified lens
design parameters to attempt orthokeratology lenses with a smaller BOZD (5 mm) and steeper
peripheral tangents, but failed to observe significant changes in peripheral refractive error or
corneal topography morphology among subjects. Guo et al.272021 found during 6-month and
12-month follow-ups that patients wearing KATT orthokeratology lenses with a 5 mm BOZD
exhibited significantly less axial length progression compared to those with a 6 mm BOZD group.
Although the correlation between axial length progression and treatment area size was weak (r² =
0.15), the results indicated that orthokeratology lenses with a smaller 5 mm BOZD were more
effective in controlling axial length growth. Li et al.282023 reported that at 12-month follow-up,
patients in the 5 mm BOZD group showed significantly lower axial length progression than those
with a 6.2 mm BOZD group, with axial length progression reduced by 53.6% in the smaller
BOZD group.

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The study by Xiong et al. demonstrated that for children who experienced at least 0.50 mm of
axial length progression within one year of Ortho-k wear, combining RLRL therapy with Ortho-k
significantly outperformed Ortho-k alone in slowing axial length growth. While the safety profile
of this combined approach appears promising, further long-term research is required for
comprehensive evaluation. Clinically, these findings hold significant implications, as they indicate
that although Ortho-k treatment enables children to achieve clear daytime vision without glasses,
incorporating RLRL therapy may yield greater efficacy in reducing axial length progression
compared to Ortho-k monotherapy, thereby achieving satisfactory myopia control.
Current studies indicate that combination therapies involving orthokeratology lenses,
low-intensity red light therapy, and low-concentration atropine exhibit a synergistic trend in
enhancing myopia control effects.
2. purpose of research
Myopia prevention and control is not only a critical issue in ophthalmology but also an
essential component of public health. With the rising prevalence of myopia, effective strategies to
manage its progression, particularly slowing axial length growth, have become a focal point of
current research. Although orthokeratology (OK) lenses demonstrate certain efficacy in myopia
control, suboptimal outcomes have been observed in some pediatric patients, necessitating novel
therapeutic approaches. Low-intensity red light therapy (LLRT), as an emerging treatment
modality, has garnered significant attention in recent years; however, its application in
combination therapies remains inadequately studied. Consequently, this study holds substantial
theoretical and practical significance. The objective of this study was to conduct a comparative
analysis of different prevention and control strategies for myopia management in 8-12-year-old
children at Tianjin Medical University Eye Hospital who exhibited suboptimal axial length control
(annual growth>0.3 mm) after one year of orthokeratology lens wear, aiming to provide real-world
clinical data and scientific evidence for progressive myopia management protocols.
3. research design
3.1 Study Site and Study Population

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This study aims to evaluate the efficacy of orthokeratology (OK) lenses used alone versus
combined with other myopia control methods in children aged 8-12 years through systematic review
and comparative analysis, with particular focus on axial length increase exceeding 0.3 mm after 1
year of OK lens wear. By comprehensively analyzing the advantages and limitations of different
strategies, this study provides a scientific basis for developing personalized myopia control plans.
3.2 Method for Determining Required Sample Size in Research
This study screened children who had undergone follow-up for at least one
year
and
exhibited
annual
axial
length
progression>0.3
mm
from
3,890
individuals who visited the optometry clinic and myopia prevention clinic at the
Ophthalmology Hospital of Tianjin Medical University between November 2019
and
June
2023,
and
who
were
fitted
with
orthokeratology
lenses.
These
participants were included in the study.
Inclusion criteria were:
1) Age 8 to 12 years;
2) Binocular SE range: 0 to-6.00 D;
3) Best corrected visual acuity in both eyes ≥1.0;
4) It ensures nightly wearing of orthokeratology lenses for 8 to 10 hours;
5) No history of ocular trauma or surgical intervention;
6) No history of acute or chronic ocular inflammation, such as keratoconjunctivitis or
lacrimal dysfunction;
7) Care for the lenses as prescribed by the physician and undergo regular standardized
follow-up examinations;
8) Standardize the use of 0.1 g·L-1 atropine, red light therapy, and other medications or
interventions for myopia progression control;
9) Complete follow-up data.
Exclusion criteria:
1）After one year of wearing orthokeratology (OK) lenses, the axial length increase in both eyes
was less than 0.30 mm.
2）Severe complications occurred during this period (such as recurrent corneal inflammation);
3）Cases with incomplete data or lost to follow-up;
4）The equivalent spherical refractive error (SE) of both eyes ranges below-6.00D, with
astigmatism below-2.00D.
5）During the use of orthokeratology (OK) lenses, visual acuity was unstable, with multiple
readings below 0.2 (LogMAR).

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6）Change the brand of orthokeratology lenses.
3.3 Survey Content
1. Evaluate the overall myopia prevention and control outcomes for children aged 8-12 years
wearing orthokeratology lenses at Tianjin Medical University from November 2019 to June 2023.
2. Evaluate children who experience an axial length increase exceeding 0.3 mm after one
year of orthokeratology lens wear, selecting different prevention and control strategies. Monitor
axial length growth at 3 months, 6 months, and 12 months, compare the control efficacy between
groups after combined prevention and control measures, and conduct intergroup comparisons prior
to implementing combined prevention and control strategies.
3. Analysis of parental myopia history (e.g., whether parents have myopia or high myopia),
age of onset of myopia in children, and the impact of initial myopia degree on refractive error and
axial length in children with myopia.
3.4 Data Management and Statistical Analysis Plan
1. Data Sources and Collection
This study was an observational clinical study, with all data derived from routine diagnostic
and treatment records of participants, including ophthalmic examination data, medical history
records, intervention measures documentation, and follow-up materials, without additional
unnecessary examinations. All data were collected promptly, accurately, and comprehensively by
investigators who underwent standardized training, following uniform criteria and standardized
forms.
2. Data Recording and Entry
The study data were recorded using paper case report forms or electronic data systems to
ensure legible handwriting and complete content. Data entry was performed by designated
personnel, with critical data undergoing dual-entry verification to minimize errors. Logical and
scope checks were implemented during the entry process, and any abnormal data were promptly
cross-checked against original records for correction.
3. Data Traceability and Authenticity
All research data can be traced back to original medical records, examination reports,

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imaging materials, and equipment logs. Any data modifications shall retain modification traces,
specifying the modifier, modification date, and rationale, to ensure data authenticity and
traceability, with no arbitrary deletion or alteration of data.
Statistical Analysis Section: Statistical analysis was performed using SPSS v.25 statistical
software (SPSS Corporation, USA). Quantitative parameters were expressed as mean ± standard
deviation. The normality of data distribution was assessed using the Shapiro-Wilk test. Qualitative
parameters were presented as frequency and percentage. Differences in gender distribution
between groups were compared using the chi-square test. Differences in baseline age, baseline
equivalent spherical curvature, baseline axial length, baseline annual axial length growth rate, and
axial length growth rates at 6 months and 12 months post-treatment were analyzed using one-way
ANOVA. Post-hoc Bonferroni analysis was employed to compare pairwise differences. The
proportion of patients with stable progression (AL growth ≤
0.18 mm/year) was compared
among OK group, OKA group, OKBC group, and OKRL group using the chi-square test. A
P-value <0.05 was considered statistically significant.
3.5 Bias Control
This study is a retrospective observational study, with bias control primarily achieved through the
following measures:
1. Selection bias: Cases were strictly screened according to predefined inclusion/exclusion
criteria, with only pediatric patients who underwent complete ophthalmology follow-up of ≥12
months at our hospital from November 2019 to June 2023 being included to avoid baseline
imbalance between groups caused by selective enrollment.
2. Confounding bias: Collect and balance baseline characteristics between groups (age,
gender, baseline refractive error, corneal curvature, axial length, etc.). If significant differences
exist between groups, propensity score matching (PSM) or multivariate regression analysis will be
employed for correction. Standardize follow-up time windows and examination procedures to
avoid measurement bias caused by variations in follow-up intervals or examination equipment.
3. Information bias: All clinical data were obtained from the hospital's medical record system
and standardized examination database, with independent data extraction performed by two

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investigators. Inconsistent data were reviewed by a third party to ensure accuracy. Examination
equipment underwent regular calibration, and operators received standardized training to
minimize measurement errors.
4. Loss-to-follow-up bias: Only cases with complete follow-up data were included. Cases
with loss-to-follow-up were explicitly excluded from the eligibility criteria, and the reasons for
loss-to-follow-up as well as potential impacts were explained in the discussion section.
3.6 Quality Management
1. Data Management: Establish standardized electronic data entry forms and implement
logical validation rules for key parameters such as refractive power, axial length, intraocular
pressure, and corneal topography to prevent input errors. Adopt a dual-entry system with
cross-verification, and have senior physicians review critical data (e.g., axial length variation) for
confirmation.
2. Process Standardization: Develop a unified Standard Operating Procedure (SOP) for Case
Screening and Data Extraction, specifying inclusion/exclusion criteria, data extraction fields, and
time nodes. Regularly conduct quality control meetings and perform random sampling of 10%
cases for data traceability to ensure the study process is traceable.
3. Equipment and Personnel Quality Control: Devices such as optometers, axial length meters,
and tonometers are calibrated regularly in accordance with national metrological requirements,
with self-inspections conducted prior to each inspection. All researchers involved in data
extraction and analysis undergo standardized training and are only permitted to participate in the
study after passing the assessment to minimize operational variability.
3.7 Safety Evaluation
1. Definition of adverse events: The adverse events of interest in this study included corneal
epithelial injury, conjunctivitis, dry eye, elevated intraocular pressure, rapid progression of myopia
(axial length increase>0.3 mm/6 months), and other ocular abnormalities associated with
orthokeratology lenses, low-concentration atropine, or low-intensity red light.
2. Adverse event collection: By reviewing electronic medical records, extract ocular
discomfort, physical sign changes, and management measures recorded during each follow-up

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visit, and classify them according to severity (mild/moderate/severe) and relevance (definitely
relevant/likely relevant/may be relevant/irrelevant).
3.8 Ethical Review and Informed Consent
1. Subject Protection: This study is a retrospective observational study that exclusively
utilizes de-identified clinical routine diagnostic and treatment data, without involving additional
interventions or invasive examinations, in compliance with the ethical requirements of the
Declaration of Helsinki and China's Measures for the Ethical Review of Biomedical Research
Involving Human Subjects.
2. Ethics Committee Application: The research protocol, data acquisition statement, and
informed consent exemption application have been submitted to the Ethics Committee of our
institution, clearly outlining the research objectives, methods, scope of data usage, and
confidentiality measures. The study may only commence after approval by the Ethics Committee.
3. Benefits and Risks:
Risks: There is only an extremely low risk of information leakage, which has been mitigated
through data de-identification, encrypted storage, and access control management. Benefits: The
research findings will provide real-world evidence for optimizing myopia control strategies in
children, benefiting more pediatric patients and their families.
4. Confidentiality Measures: All cases are assigned unique study identifiers, with personal
identifiers such as names, ID numbers, and contact information removed, retaining only clinically
relevant data related to the study. The research data is stored on encrypted servers, accessible
exclusively by the principal investigator and data administrator. After study completion, data must
be retained for at least 5 years in accordance with regulations. When publishing papers, only
aggregated data is utilized, with no disclosure of any personally identifiable information.
4. References
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Trends from 2000 through 2050. Ophthalmology 2016;123(5):1036-42.
2. Lim MC, Gazzard G, Sim EL, Tong L, Saw SM. Direct costs of myopia in Singapore.Eye. (2009) 23:1086
–9. doi: 10.1038/eye.2008.225
3. Saw SM, Gazzard G, Shih-Yen EC, Chua WH. Myopia and associated pathological complications. Ophthalmic

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Physiol Opt. (2005) 25:381 –91. doi: 10.1111/j.1475-1313.2005.00298.x
4. Queirós A, Amorim-de-Sousa A, Fernandes P, Ribeiro-Queirós MS, Villa- CollarC, González-Méijome JM.
Mathematical estimation of axial length increment in the control of myopia progression. J Clin Med. (2022)
11:6200. doi: 10.3390/jcm11206200
5. Wildsoet CF, Chia A, Cho P, et al. IMI - Interventions Myopia Institute: Interventions for Controlling Myopia
Onset and Progression Report. Invest Ophthalmol Vis Sci 2019;60(3):M106-M31.
6. Huang J, Wen D, Wang Q, et al. Efficacy Comparison of 16 Interventions for Myopia Control in Children: A
Network Meta-analysis. Ophthalmology 2016;123(4):697-708.
7. Lawrenson JG, Shah R, Huntjens B, et al. Interventions for myopia control in children: a living systematic
review and network meta-analysis. Cochrane Database Syst Rev 2023;2(2):CD014758.
8. Swarbrick HA, Alharbi A, Watt K, et al. Myopia control during orthokeratology lens wear in children using a
novel study design. Ophthalmology 2015;122(3):620-30.
9. VanderVeen DK, Kraker RT, Pineles SL, et al. Use of Orthokeratology for the Prevention of Myopic
Progression in Children: A Report by the American Academy
of Ophthalmology. Ophthalmology
2019;126(4):623-36.
10. Cheung SW, Cho P. Subjective and objective assessments of the effect of orthokeratology--a cross-sectional
study. Curr Eye Res 2004;28(2):121-7.
11. Wan K, Lau JK, Cheung SW, Cho P. Refractive and corneal responses of young myopic children to short-term
orthokeratology treatment with different compression factors. Cont Lens Anterior Eye 2020;43(1):65-72.
12. Charm J, Cho P. High myopia-partial reduction ortho-k: a 2-year randomized study. Optom Vis Sci
2013;90(6):530-9.
13. Cho P, Cheung SW. Retardation of myopia in Orthokeratology (ROMIO) study: a 2-year randomized clinical
trial. Invest Ophthalmol Vis Sci 2012;53(11):7077-85.
14. Tang Wenting, Tian Mei, Li Shibei, et al. Clinical observation of low-dose atropine combined with
orthokeratology lenses for myopia treatment. International Journal of Ophthalmology 2020;20(6):1044–1047
15. Mok AK, Chung CST. Seven-year retrospective analysis of the myopic control effect of orthokeratology in
children: a pilot study. Clin Optom 2011;3:1–4
16. Zhu Xianfeng, He Tao, Wang Jianchao, et al. Observation on the effect of 0.01% atropine eye drops combined
with orthokeratology lenses in controlling high myopia in adolescents. China Rural Medicine 2020;27(3):3–4
17. KINOSHITA N,KONNO Y,HAMADAN,KANDAY,SHIMMU- RA-TOMITAM,KABURAKI T,et al.Efficacy
of combined or- thokeratology and 0.01%atropine solution for slowing axial elongation in children with
myopia:a 2-year randomised trial [J].Sci Rep,2020,10(1):12750.
18. KINOSHITA N,KONNO Y,HAMADAN,KANDAY,SHIMMU- RA-TOMITA M,KAKEHASHI A.Additive
effects of orthoker- atology and atropine 0.01%ophthalmic solution in slowing axial
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in children
with myopia:first year results [J].Jpn
J Ophthalmol,2018,62(5):544-553.
19. TAN Q,NG A L,CHOY BN,CHENG GP,WOOVC,CHO P. One-year
results
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Opt,2020,40(5):557-566.
20. TAN
Q,NG A
L,CHENG GP,WOOV C,CHO P.Combined
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in
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myopia control(AOK)study:a
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JOphthalmol,2022.[Online
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24. MARCOTTE-COLLARD R, SIMARD P, MICHAUD L. Analysis of two orthokeratology lens designs and
comparison of their optical effects on the cornea [J]. Eye Contact Lens，2018，44( 5) : 322-329
25. KANG P, SWARBRICK H. New perspective on myopia control with orthokeratology [J]. Optom Vis Sci 2016，
93(5): 497–503.
26. KANG P, GIFFORD P, SWARBRICK H. Can manipulation of orthokeratology lens parameters modify
peripheral refraction? [J]. Optom Vis Sci 2013，90(11): 1237–1248.
27. GUO B, CHEUNG S W, KOJIMA R, CHO P. One-year results of the Variation of Orthokeratology Lens
Treatment Zone (VOLTZ) study: a prospective randomised clinical trial [J]. Ophthalmic Physiol Opt 2021，
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28. LI N, LIN W, ZHANG K, LI B, SU Q, DU B, et al. The effect of back optic zone diameter on relative corneal
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29. Xiong R,Wang W,Tang X, et al. Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined
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5. appendix
Signature of the principal investigator: Meinan He
Date: 9 March 2026
Recommended reference materials: 1. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
Statement: Guidelines for Reporting Observational Studies. http://www.equator-network.org/reporting-guidelines/strobe/

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Waiver of Informed Consent Application
project name
Effectiveness of Different Interventions for Progressive Myopia After Wearing
Orthokeratology Lenses
Project source
IIT study
Solution version number
1.0
Version date of the solution 9 March 2026
Responsible Department Optometry Center
Principal Investigator
He Meinan
1. Application for exemption from informed consent based on research utilizing
medical
records/biochemical
specimens
obtained
from
previous
clinical
diagnosis and treatment
·This study is an observational study utilizing medical records/biological specimens obtained
from previous clinical diagnosis and treatment: ☑Yes, No
·The research purpose is significant: ☑Yes, or No
The study poses no greater risk to subjects than that encountered in daily life,
routine physical examinations, or psychological testing: ☑Yes, No
·Exemption from informed consent will not adversely affect the rights and health of
subjects: ☑Yes, No
·Subject privacy and personal identity information are protected: ☑Yes, No
· If obtaining informed consent is stipulated, the study cannot proceed (patients
have the right to be informed that their medical records/samples may be used for
research; their refusal or disagreement to participate does not constitute evidence of
study non-implementation or exemption from informed consent): Verbal consent

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(Please specify:
），☑deny
·This study does not utilize medical records or specimens that the patient/subject has previously
explicitly refused to provide: ☑Yes, No
II. Research on secondary utilization of medical records/biological specimens
and application for exemption from informed consent
· This study aims to explore the secondary utilization of medical records and
biological specimens, specifically utilizing medical records or specimens collected
through prior research projects with informed consent. Application for exemption
from informed consent: yes, no
· Previous studies have obtained written consent from participants, permitting
other research projects to utilize their medical records or specimens: yes, no
·This study complies with the original informed consent requirements: yes, no
·The privacy and confidentiality of subjects' identity information are guaranteed:
yes or no
Signature of
the applicant
Meinan He
date
9March 2026