Low concentration atropine combined with orthokeratology in the treatment of axial elongation in children with myopia: A meta-analysis

Abstract

Objective:

To evaluate the effect of low concentration atropine combined with Orthokeratology (OK) lens compared with the OK lens on the changes of axial length in children with moderate and low myopia by meta-analysis.

Methods:

Databases such as PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched to collect related studies on atropine combined with the OK lens in the treatment of children with moderate and low myopia. The retrieval time was from the establishment of the database to December 2020. The standardized mean difference (SMD) and its 95% confidence interval (CI) were selected as the effect to analyze the changes of the axial length of the eye axis in children with low and moderate myopia treated with low concentration atropine combined with OK lens.

Results:

A total of eight articles were included in this study. Compared with OK lens treatment, low concentration atropine combined with the OK lens significantly slowed down the axial elongation of low and moderate myopia, SMD = −0.68(95% CI: −0.86–−0.50, p < 0.05). According to the subgroup analysis of treatment time, when the treatment time was less than or equal to 6 months, SMD = −0.63(95% CI: −0.88–−0.37, p < 0.05), when the treatment time was 1 year, SMD = −0.76(95% CI: −1.08–−0.43, p < 0.05), and when the treatment time was 2 years, SMD = −0.69(95% CI: −1.07–−0.31, p < 0.05).

Conclusion:

Low concentration atropine combined with the OK lens is more effective than the OK lens in the treatment of children with low to moderate myopia in reducing axial elongation.

Keywords

Axial length orthokeratology myopia meta-analysis atropine

Introduction

Myopia has become a worldwide public health problem. In the past few decades, cases of myopia, especially myopia of school age, have shown a rapidly rising trend. In June 2016, Holden et al. predicted that by 2050, 4.758 billion of the world’s population, or 49.8% of the world’s total population, will have myopic ametropia.¹ Research by Vitale et al. found that the overall incidence of myopia among 12-to 54-year-olds in the United States increases from 25% in 1970 to 41.6% in 2009, with Asian Americans having a more significant increase in myopia, from 13.0% to 33.5%. Furthermore, some extensive sample studies also show that in Southeast Asia, such as China, Singapore, Japan, South Korea, and other countries, the incidence of myopia is higher than that in Europe and the United States.² A study in Singapore also showed that the incidence of myopia among Chinese children is higher than that of other ethnic groups.³ The increase in the proportion of myopic children in East Asia may be related to learning pressure, lifestyle changes, including reduced time for outdoor activities and other factors.⁴ Besides, myopia may also be related to genes, race and other factors.⁵ According to the survey of the World Health Organization, uncorrected refraction is one of the leading causes of vision loss and poses a substantial economic burden on society and families.⁶

Refractive state is a complex variable, which is determined by the refractive power of the refractive system of the eye, including the corneal and lens and the length of the eye axis (including the depth of the anterior chamber, the thickness of the lens, and the length of the vitreous body). Myopia is usually manifested as a too long eye axis, especially too long vitreous cavity. In the development of myopia, the elongation of the eyeball axis is the main change, which is the most closely related factor of myopia. The longer the axial length, the more likely it is to be myopic.⁷ Controlling the extension of axial length during development is not only the key factor in obtaining normal vision, but also the primary mechanism to prevent myopia.⁸

At present, the orthokeratology (OK) lens is considered to be a promising method to correct the development of myopia in children.^9,10 Also, orthokeratology, which has become a research focus with the advantages of low risk and reversibility, has been widely used in clinics,¹¹ due to its satisfactory effect in controlling the progression of myopia.¹² Atropine is a non-selective muscarinic acetylcholine (M) receptor antagonist. Doses of 0.5%–1% atropine are commonly used clinically for mydriasis and ciliary paralysis, and application of atropine in the treatment of myopia can be traced back to the 1970s.¹³ Currently, a large number of studies home and abroad have confirmed that different concentrations of atropine eye drops are effective in controlling myopia.^14–22 However, after local application of high concentrations (1%, 0.5%) of atropine preparations, the incidence of adverse reactions such as photophobia, blurred vision, allergic conjunctivitis, and dry face is high, which makes the clinical application of atropine controversial.^14,15 Recent studies have shown that the appliance of atropine at low concentrations (0.1%, 0.05%, 0.025%, 0.01%) and appropriate frequency can effectively delay the development of myopia and can also reduce the incidence of side effects such as photophobia, nearsightedness, and myopic diopter rebound after withdrawal. Meantime, the visual quality of the subjects is not affected.^16,17 Up to date, several studies have reported that low-concentration atropine combined with orthokeratology is more effective in controlling the axial elongation of myopic children than using an OK lens alone.^8,18 However, these studies all have limitations such as small sample size and single-center, so no definite conclusion can be drawn.

Therefore, this study used a meta-analysis to evaluate the changes of the axial length of low concentration atropine combined with the OK lens compared with the OK lens alone in the treatment of children with moderate and low-grade myopia, in order to provide evidence for clinical use of atropine combined with the OK lens in the treatment of myopia.

Methods

Literature retrieval

Databases such as PubMed, Web of Science, Embase, and Cochrane Library were searched to collect the related studies on the changes of ocular axis length after atropine combined with the OK lens in children with myopia. The search terms adopting Medical Subject Heading and free words were as follows: ortho-k, OK lens, orthokeratology lens, orthokeratologic procedures, orthokeratology, myopia, near sight, refractive errors, atropine sulfate, and atropine. The Randomized controlled trials (RCTs) or retrospective cohort studies were selected in the analysis. The retrieval time was from the establishment of each database to December 2020. All literature retrieval and screening were carried out independently by two researchers and finally cross-checked. When the two researchers encountered differences, they should resolve them through discussion.

Inclusion and exclusion criteria

Inclusion criteria

(1) The subjects were children under 18 years of age with acquired myopia. (2) The changes of ocular axis length after low concentration atropine combined with the OK lens in myopic children were studied. (3) The literature data included information such as axial length, myopic refraction, and astigmatism. (4) The ocular axis was measured by intraocular lens main optical biological instrument (IOL Master). (5) The concentration of atropine was not higher than 0.1%. (6) The language of publication was English. (7) The type of study included was a randomized controlled trial or a retrospective cohort study.

Exclusion criteria

(1) The studies were just abstracts, reviews, literature reviews, and editing reviews or case reports. (2) The studies whose research samples were studies in which other eye diseases (such as cataract, glaucoma, and amblyopia). (3) The studies did not have sufficient data or are unable to extract relevant raw data. (4) The subjects were children with high myopia. High myopia was defined as diopters less than −6.0D. Only children with moderate and low myopia with diopters greater than −6.0D were included in this study.

Literature quality evaluation

In accordance with Cochrane Collaboration,¹⁹ the quality of the included randomized controlled trials (RCT) was evaluated from the following seven aspects: random sequence generation, allocation hiding, blind method of participants and researchers, blind method of result evaluation, incomplete result data, selective reporting, and other biases. Each item was assessed as “low bias risk,” “high bias risk,” or “ambiguous bias risk.”

The quality of the retrospective cohort study was evaluated according to the Newcastle-Ottawa scale (NOS),²⁰ which adopted a star system consisting of three aspects: the selection of research objects (including four items), the comparability of the research group (including two items), and the determination of exposure or results (including three items). The answer to each question was set as “yes,” “no,” or “unclear.” “Yes” represented a low risk of bias, with a score of 1; “unclear” indicated a medium risk of bias, with a score of 0; “No” showed a high risk of bias, with a score of-1. The highest score was nine stars. When the NOS score was less than 6, it was considered a low-quality study; when the NOS was greater than or equal to six stars, it was considered a high-quality study. Only studies with NOS scores more than or equal to six stars were included in this study. The quality of the literature was evaluated independently by two researchers who resolved their disagreements through discussion.

Data extraction

Data were extracted independently by two researchers and finally cross-checked. The following information was withdrawn from the literature: the first author, country, year of publication, type of study, and clinical data such as follow-up time, sample number, age, axial length, myopic refraction, and astigmatism.

Statistical analysis

Stata 15.0 software was used to analyze the data. Standardized mean difference (SMD) and its 95% confidence interval (CI) were selected as effect size, to analyze the change of axial length in atropine combined with OK group relative to OK lens group. Cochran’s Q test and I² test were used to analyze the heterogeneity among the included literature. When the p-value of Cochran’s Q test was ⩽0.05, or I² ⩾ 50%, it indicated that there was heterogeneity, and a random-effects model (REM) was used. Otherwise, a fixed-effects model (FEM) would be used. The subgroup analysis was carried out according to the follow-up time after treatment. Publication bias was assessed by Funnel plot and Egger’s Test. Finally, a sensitivity analysis was carried out to evaluate the robustness of the conclusions.

Results

Results of literature retrieval

After the strict screening, a total of eight articles, among which there were articles of RCT^{8,18,21–23,24} and two articles of retrospective cohort study,^25,26 were included in this meta-analysis. In the included cases, there were 229 children in atropine combined with the OK lens group and 232 children in the simple OK lens group. All the studies were published in English. The specific flow chart of literature screening is shown in Figure 1. The basic characteristics of the study and the NOS score of the retrospective cohort study can be found in Table 1, which shows the NOS scores of the two retrospective studies were more than six, indicating they were high-quality studies. The quality evaluation of six RCT articles is as shown in Figure 2(a) and (b). Thus it could be seen that the six controlled trials included were of low risk in the random sequence generation, the incomplete outcome, and the blind evaluation of the outcome index. Only one study had a high risk of blindness among participants and personnel.

Table 1.

The basic characteristics of the inclusion studies.

First author	Country	Study design	Age (years)	Follow-up (month)	Group	Atropine concentration	Number (AOK/OK)	Myopia	Baseline		NOS
First author	Country	Study design	Age (years)	Follow-up (month)	Group	Atropine concentration	Number (AOK/OK)	Myopia	AOK	OK	NOS
Chen et al.²⁴	China	RE	5.6–11.6	12	AOK/OK	0.01	28/29	−1.0~−5.0D	24.34 ± 0.92	24.34 ± 0.92	8
Wan et al.²⁶ (2018)	China	RE	7–17	24	AOK/OK	0.025	20/20	<6D	24.08 ± 1.31	24.19 ± 1.24	8
Tan et al.²¹	China	RCT	6–11	1	AOK/OK	0.01	30/34	1.00~4.00D	24.45 ± 0.62	24.46 ± 0.79	NA
Kinoshita et al.⁸	Japan	RCT	8–12	12	AOK/OK	0.01	20/20	−1.0~−6.0D	24.73 ± 0.58	24.95 ± 0.92	NA
Vincent et al.²²	China	RCT	6–11	6	AOK/OK	0.01	25/28	1.00~4.00D	24.38 ± 0.62	24.44 ± 0.84	NA
Tan et al.²⁶	China	RCT	6–11	6, 12	AOK/OK	0.01	29/30	1.00~4.00D	24.43 ± 0.62	24.43 ± 0.81	NA
Kinoshita et al.²³	Japan	RCT	8–12	24	AOK/OK	0.01	38/35	−1.0~−6.0D	24.69 ± 0.58	24.86 ± 0.81	NA
Zhao et al.¹⁸	China	RCT	8–12	1	AOK/OK	0.01	39/36	−1.0~−6.0D	24.78 ± 0.98	24.69 ± 0.63	NA

AOK: atropine and orthokeratology; OK: orthokeratology; RE: retrospective cohort study; RCT: randomized controlled trial; NOS: Newcastle-Ottawa scale; NA: not applicable.

Meta-analysis Results

Changes of axial length after atropine combined with OK lens treatment

In this part, an overall analysis was conducted over all the included studies to compare the changes of the axial length of low concentration atropine combined with OK lens group compared with OK lens group in children with low and moderate myopia. According to the results of heterogeneity (I² = 10.3%, p > 0.05), a FEM was selected for data merging. As shown in Figure 3, the elongation of the eyeball axis of the low concentration atropine combined with the OK lens group was notably slower than that of the OK lens group, SMD = −0.68(95% CI: −0.86–−0.50, p < 0.05). The difference was statistically significant. The funnel chart (Figure 4) showed good symmetry, and Egger’s Test demonstrated that p > 0.05, indicating the publication bias was low.

Subgroup analysis based on treatment time

The follow-up time of myopia treatment was divided into three stages, which were less than or equal to 6 months, 12 months, and 24 months (Figure 3) for an independent analysis. There were four studies^18,21,22,24 including data that the duration of treatment was less than or equal to 6 months. The results indicated SMD = −0.63(95% CI: −0.88–−0.37, p < 0.05). There were three studies^8,25,26 including data on the duration of treatment for 12 months, of which the results showed SMD = −0.76(95% CI: −1.08–−0.43, p < 0.05). There were two studies^23,26 including data for 24 months of treatment, whose results indicated SMD = −0.69(95% CI: −1.07–−0.31, p < 0.05). The differences were statistically significant. These results further confirmed that a low concentration of atropine combined with the OK lens group significantly slowed down the axial elongation of eyes in children with low to moderate myopia compared with the OK lens group.

Sensitivity analysis

A meta-analysis was re-conducted after the included studies were removed one by one in order to observe the impact of a single study on the conclusion. The results showed that the overall conclusion did not change significantly when any single study was excluded (Figure 5), which suggested the conclusion of this study was stable.

Discussion

Online English databases were searched systematically in order to explore the effect of low concentration atropine combined with the OK lens on the length of eye axis in children with low and moderate myopia. The results showed that compared with the OK lens alone, the OK lens combined with low concentration atropine was able to remarkably slow down the axial elongation in children with low to moderate myopia. The efficacy of atropine in the treatment of adolescent myopia is related to the concentration of atropine. Many studies have confirmed that high concentrations of atropine are more effective in the treatment of myopia than low concentrations of atropine,²⁷ but the side effects increase with the increment of atropine dose.^15,28 Some studies suggested that topical use of 0.01% atropine can efficiently control transient myopia caused by work in adolescents.²⁹ However, the study of Larkin et al.³⁰ showed that 0.01% atropine eye drops considerably slows the progression of myopia in a group of American children who have been treated for more than 2 years. In a 6-month prospective study of Cheng et al.,³¹ atropine at a concentration of 0.01% shows no obvious side effects on the ocular surface in children with myopia. Although studies have demonstrated the efficacy of the OK lens in the treatment of myopia,^9,10 several adverse events exist, such as keratitis,³² the decline of tear film stability,³³ bacterial adhesion,³⁴ etc. Therefore, the efficacy of the OK lens combined with low concentration atropine in the treatment of myopic children, especially the change of axial length of the eye axis, is a problem worth studying in particular.

Screened by strict inclusion and exclusion criteria, eight published studies were selected from various English databases. Six of them were RCTs, while the other two were retrospective cohort studies. From the results of the literature quality evaluation, they were all high-quality studies. Among the cases in these studies, the shortest time was atropine combined with the OK lens for one month, and the longest was 2 years. The meta-analysis of these studies showed that compared with OK lens alone, low concentration atropine combined with the OK lens could notably slow down the axial elongation in children with low to moderate myopia. The funnel plot was basically symmetrical, and the Egger’s Test showed that the difference was not statistically significant, which indicated that there was no noticeable publication bias. Moreover, there was no significant heterogeneity among the included studies. A meta-analysis was conducted after each one study was excluded from the included studies in order to verify the robustness of the conclusions. The results of sensitivity analysis also confirmed that the conclusions of this study were robust.

Meanwhile, in order to explore the relationship between the treatment time and the treatment time of low concentration atropine combined with the OK lens in children with low concentration of atropine, we divided into three time periods for subgroup analysis. Subgroup analysis showed that in the treatment of low concentration atropine combined with the OK lens for 24 months, 12 months, and less than or equal to 6 months, it was more effective to slow down the elongation of the eye axis than to use the OK lens alone. Moreover, there was no obvious heterogeneity in these three subgroups. The meta-analysis of Wang et al.³⁵ and Gao et al.³⁶ showed that atropine combined with the OK lens is more effective than the OK lens alone in reducing axial elongation in children with myopia, which is consistent with our conclusion. Nonetheless, we imposed stricter restrictions on the inclusion of studies. For example, the research must be published in English; the concentration of atropine was no more than 0.1%; and children with myopia were moderate to low myopia. In addition, we also included the latest research and carried out a more detailed subgroup analysis of the treatment time, etc.

Naturally, this study also had some limitations. First, all the studies included in this meta-analysis were published in English, making it impossible for articles in other languages to be included in the analysis, which was likely to lead to a certain publication bias. Second, most of the subjects in the literature included in this study were Chinese people, with those of only two articles being Japanese. Hence, the scope of the research subject was relatively narrow, lack of research of other populations such as the Caucasian and African populations, which gave rise to doubt whether the conclusions of this study are equally applicable to people of other races. Third, the sample size was small. Fourth, there were only a few studies included, especially lacking studies in different treatment times of myopia.

In summary, low concentration atropine combined with the OK lens can delay axial elongation more effectively than the OK lens alone in the treatment of children with low and moderate myopia. However, considering the limitations of this study, more long-term follow-up researches are needed in order to draw a more accurate conclusion for low concentration atropine combined with OK lens in the treatment of eye axis elongation in children with low and moderate myopia.

Footnotes

Abbreviations

OK: Orthokeratology; SMD: standardized mean difference; CI: confidence interval; NOS: Newcastle-Ottawa scale; RCTs: randomized controlled trials; REM: random-effects model; FEM: fixed-effects model.

Author contributions

YN, BJX, LL: Critical revision of the manuscript; YN, BJX, LL: Substantial contribution to the conception and design of the work, manuscript drafting; YN, BJX: Acquisition, analysis, and interpretation of the data; YN, BJX, LL: Revising the manuscript critically, final approval of the version to be published. All authors have read and approved the final manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval and consent to participate

Ethical approval was not needed because this is a meta-analysis.

ORCID iD

Li Liu

Availability of data and material

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

Holden

Fricke

Wilson

, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 2016; 123(5): 1036.

Morgan

Rose

How genetic is school myopia?

Prog Retin Eye Res 2005; 24(1): 1–38.

Saw

Tong

Chua

, et al. Incidence and progression of myopia in Singaporean school children. Invest Ophth Vis Sci 2005; 46(1): 51–57.

Cheng

Wang

Wong

, et al. Prevalence and causes of vision loss in East Asia in 2015: magnitude, temporal trends and projections. Br J Ophthalmol 2020; 104(5): 616–622.

Vishweswaraiah

Swierkowska

Ratnamala

, et al. Epigenetically dysregulated genes and pathways implicated in the pathogenesis of non-syndromic high myopia. Sci Rep 2019; 9(1): 4145.

Ono

Hiratsuka

Murakami

Global inequality in eye health: country-level analysis from the Global Burden of Disease Study. Am J Public Health 2010; 100(9): 1784–1788.

Cruickshank

Logan

NS.

Optical ‘dampening’ of the refractive error to axial length ratio: implications for outcome measures in myopia control studies. Ophthalmic Physiol Opt 2018; 38(3): 290–297.

Kinoshita

Konno

Hamada

, et al. Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia: first year results. Jpn J Ophthalmol 2018; 62(5): 544–553.

Lee

Wang

Chiu

CJ.

Effect of orthokeratology on myopia progression: twelve-year results of a retrospective cohort study. Bmc Ophthalmol 2017; 17(1): 243.

10.

Walline

Lindsley

Vedula

, et al. Interventions to slow progression of myopia in children. Cochrane Database Syst Rev 2020; 1(1): D4916.

11.

Guan

Zhao

Geng

, et al. Changes in axial length after orthokeratology lens treatment for myopia: a meta-analysis. Int Ophthalmol 2020; 40(1): 255–265.

12.

Kang

, et al. Efficacy, safety and acceptability of orthokeratology on slowing axial elongation in myopic children by meta-analysis. Curr Eye Res 2016; 41(5): 600–608.

13.

Bedrossian

RH.

The effect of atropine on myopia. Ophthalmology 1979; 86(5): 713–717.

14.

Zhu

Tang

Guo

, et al. Efficacy and safety of 1% atropine on retardation of moderate myopia progression in Chinese school children. Int J Med Sci 2020; 17(2): 176–181.

15.

Tran

HDM

Tran

, et al. A Review of myopia control with atropine. J Ocul Pharmacol Ther 2018; 34(5): 374–379.

16.

Yam

Jiang

Tang

, et al. Low-concentration atropine for myopia progression (LAMP) study: a randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmology 2019; 126(1): 113–124.

17.

Sacchi

Serafino

Villani

, et al. Efficacy of atropine 0.01% for the treatment of childhood myopia in European patients. Acta Ophthalmol 2019; 97(8): e1136–e1140.

18.

Zhao

, et al. Short-term effects of atropine combined with orthokeratology (ACO) on choroidal thickness. Contact Lens Anterio Eye. Epub ahead of print 30 June 2020. DOI: 10.1016/j.clae.2020.06.006.

19.

Higgins

Green

. Cochrane handbook for systematic reviews of interventions. The Cochrane Collaboration. . Available at: http://handbook-5-1.cochrane.org/. (2011).

20.

Stang

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25(9): 603–605.

21.

Tan

Cheng

, et al. Combined atropine with orthokeratology for myopia control: study design and preliminary results. Curr Eye Res 2019; 44(6): 671–678.

22.

Vincent

Tan

ALK

, et al. Higher order aberrations and axial elongation in combined 0.01% atropine with orthokeratology for myopia control. Ophthal Physl Opt 2020; 40(6): 728–737.

23.

Kinoshita

Konno

Hamada

, et al. Efficacy of combined orthokeratology and 0.01% atropine solution for slowing axial elongation in children with myopia: a 2-year randomised trial. Sci Rep 2020; 10(1): 1.

24.

Tan

Choy

, et al. One-year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial. Ophthal Physl Opt 2020; 40(5): 557–566.

25.

Chen

Huang

Zhou

, et al. Adjunctive effect of orthokeratology and low dose atropine on axial elongation in fast-progressing myopic children—a preliminary retrospective study. Contact Lens Anterio Eye. Epub ahead of print 24 November 2018. DOI: 10.1016/j.clae.2018.10.026.

26.

Wan

Chen

, et al. The Synergistic Effects of Orthokeratology and Atropine in Slowing the Progression of Myopia. J Clin Med.2018;7(9):259.

27.

Shih

Chen

Chou

, et al. Effects of different concentrations of atropine on controlling myopia in myopic children. J Ocul Pharmacol Ther 1999; 15(1): 85.

28.

Gong

Janowski

Luo

, et al. Efficacy and adverse effects of atropine in childhood myopia: a meta-analysis. Jama Ophthalmol 2017; 135(6): 624–630.

29.

Guo

Fan

Tao

, et al. Use of topical 0.01% atropine for controlling near work-induced transient myopia: a randomized, double-masked, placebo-controlled study. J Ocul Pharmacol Ther 2020; 36(2): 97–101.

30.

Larkin

Tahir

Epley

, et al. Atropine 0.01% eye drops for myopia control in american children: a multiethnic sample across three US sites. Ophthalmol Ther 2019; 8(4): 589–598.

31.

Cheng

Yang

Kong

, et al. The effect of 0.01% atropine eye drops on the ocular surface in children for the control of myopia-the primary results from a six-month prospective study. Ther Clin Risk Manag 2020; 16: 735–740.

32.

Kam

Yung

GKH

, et al. Infectious keratitis and orthokeratology lens use: a systematic review. Infection 2017; 45(6): 727–735.

33.

Dong

Liu

Effect of overnight wear orthokeratology lenses on corneal shape and tears. Eye Contact Lens 2018; 44(5): 304–307.

34.

Choo

Holden

Papas

, et al. Adhesion of Pseudomonas aeruginosa to orthokeratology and alignment lenses. Optom Vis Sci 2009; 86(2): 93–97.

35.

Wang

Combined orthokeratology with atropine for children with myopia: a meta-analysis. Ophthalmic Res. Epub ahead of print 11 August 2020. DOI: 10.1159/000510779.

36.

Gao

Wan

Zhang

, et al. The efficacy of atropine combined with orthokeratology in slowing axial elongation of myopia children: a meta-analysis. Eye Contact Lens. Epub ahead of print 13 October 2020. DOI: 10.1097/ICL.0000000000000746.