Multi-Factor Analysis of the Inuence of Orthokeratology on Controlling Myopia in Adolescents

Background To investigate which baseline factors are predictive for axial length growth over an average period of 1 years in a group of adolescents wearing orthokeratology (OK) contact lenses. Methods In this retrospective study, the clinical records of 189 new OK wearers (378 eyes) between 2014 and 2018 at Xiangya Hospital of Central South University were reviewed. The primary outcome measure was axial length change from baseline to the time of 1 year. Independent variables included baseline measures of age at initiation of OK wear, refractive error (spherical equivalent), corneal thickness, corneal curvature. (1) Age group, 8 ~ 10 years old is the rst group, 10 ~ 13 years old is the second group, ≥ 13 years old is the third group; (2) Myopia degree group, ≥ -3.00D is the rst group, -3.00 ~ -6.00D is the second group, <-6.00D is the third group; (3) corneal thickness group, ≤ 550μm is the rst group,> 550μm is the second group; (4) corneal curvature group, ≤ 42.0D is The rst group, 42.0 ~ 44.0D is the second group,> 44.0D is the third group.


Background
Myopia, as the highest incidence of refractive error, has an increasing incidence and a trend toward the younger. Currently, most myopia is produced by axial elongation and orthokeratology as a treatment to control the progression of myopia by controlling the axial elongation has attracted the attention of many medical institutions. Clinically, the role of orthokeratology in controlling myopia progression has been widely a rmed, but there are individual differences and related factors affecting treatment effect. Therefore, it is very necessary to understand the relevant factors. This article summarizes the effect of age, myopia degree, corneal thickness, and corneal curvature on the difference between the basic axial length and the axial length after one year of continuous wearing of orthokeratology.

Methods
Subjects A total of 189 subjects (n = 279 eyes), all of whom continuously wore orthokeratology for 1 year were enrolled. All subjects visited the Xiangya Hospital of Central South University, Changsha, China, from 2014 to 2018. Inclusion criteria comprised of patients with no amblyopia, no strabismus, no history of wearing orthokeratology and other contact lenses, no ocular in ammation, no ocular organic diseases, and good compliance.
Methods The selected subjects were grouped according to age, myopia degree, corneal thickness and corneal curvature, and the basic axial length and the axial length after 1 year of continuous wearing of orthokeratology were collected. (1) Age group, 8 ~ 10 years old is the rst group, 10 ~ 13 years old is the second group, ≥ 13 years old is the third group; (2) Myopia degree group, ≥-3.00D is the rst group, -3.00 -6.00D is the second group, <-6.00D is the third group; (3) corneal thickness group, ≤ 550 µm is the rst group,> 550 µm is the second group; (4) corneal curvature group, ≤ 42.0D is The rst group, 42.0 ~ 44.0D is the second group,> 44.0D is the third group.The following pre-orthokeratology examinations are carried out in accordance with standard operations: External eye and Anterior segment (Slit-lamp microscope), Intraocular pressure (Non-contact tonometer), Fundus (Fundus photography), Breakup time of lacrimal lm (BUT), Corneal morphology (Corneal curvometer and Corneal topography), Corneal endothelial cells (Non-contact corneal endothelial microscope), Axial length (IOL-MASTER), Corneal thickness (Coeneal pachymeter), Diopter (Automatic refractometer, Comprehensive refractometer).After excluding nonindications, subjects wore the appropriate OKs whose oxygen permeability coe cient was above 90, and physical properties also meet the relevant regulations of the State Food and Drug Administration. After wearing OKs, rugular examinations were performed every 1 to 3 months, including visual acuity, refractive changes, corneal curvature, corneal topography, the ocular surface and lens condition. The tear membrane, corneal endothelial cells, axial length and corneal thickness were reviewed regularly every 3 to 6 months.The baseline axial length before wearing OKs and the axial length after continuous wearing of OKs for 1 year were included in the statistical data, and the statistical analysis were performed according to the group of age, myopia degree, corneal thickness and corneal curvature.
Statistical Analysis Data analysis was performed using version 23.0 SPSS software (SPSS, Inc., Chicago, IL, USA).The comparison of the axial length difference between different groups was performed by independent sample t test (two classi cation) or analysis of variance (three classi cation), and further pairwise comparisons were performed by LSD-t test. A P-value of < 0.05 was considered statistically signi cant.

Results
The relationship between age and the mean difference of axial length The mean difference of axial length in the three age groups are 0.173 ± 0.488 mm, 0.109 ± 0.426 mm and − 0.008 ± 0.105 mm. By pairwise comparison, the mean difference between the rst group and the third group is statistically signi cant (P = 0.041). The relationship between myopia degree and the mean difference of axial length The mean difference of axial length in the three myopia degree groups are 0.251 ± 0.317 mm, 0.033 ± 0.515 mm and 0.112 ± 0.203 mm. By pairwise comparison, the difference between the rst group and the second group is statistically signi cant (P = 0.000) and the difference between the rst group and the third group is statistically signi cant(P = 0.016).  The relationship between corneal thickness degree and the mean difference of axial length The mean axial difference between different corneal thickness groups are 0.148 mm and 0.113 mm, and the difference of the two groups is not statistically signi cant (F = 0.664,P = 0.507).

Discussion
Orthokeratology has been shown to be the most effective non-pharmacological method for controlling the progression of myopia. OKs make corneal epithelial cells to migrate and redistribute and atten the central cornea while steeping the midperipheral cornea to reduce relative peripheral hyperopia, which may slow the elongation of the axial length [1,2]. At present, the axial length is considered to be an effective parameter for monitoring the progression of myopia [3,4], and the effect of the orthokeratology in controlling the axial elongation is certain [5][6][7], but there are many factors that affect the development of the axial length, such as age, myopia degree, corneal thickness and corneal curvature. The study has analyzed multiple factors and multiple grades and found that the axial elongation is highly correlated with the initial age and myopia degree of OK wearers.
Wong et al researched the eye growth tting curve and found that the annual growth of the axial length decreased with age, especially after 10 years old [8]; Fledelius et al found that the average elongation of the axial length was less than 0.1 mm/year between the age of 7 to 8 and less than 0.01 mm/year between the age of 10 to 12, during their researches, axial length was about 16 mm at birth, grew to 23 mm at 3 years old, and 24 mm at adulthood [9]. The above studies have proved that the growth rate of the axial length slows down with the age. This study found that the axial elongation rate of the older children (≥ 13 years old) is slower than that of the younger children (8-10 years old). Studies at home and abroad support that the initial age of OK wearers is negatively correlated with the axial elongation [10][11][12][13][14][15] and consider that the effect of age may be due to the slower eyeball growth of older children. Cho et al proved that OKs can signi cantly reduce the risk of rapid progression of myopia and younger wearer can bene t more in the long term, although younger children have a higher axial growth rate [16].
The results of current researches on the relationship between initial myopia degree and axial elongation are contradictory. A small number of studies show that there is no correlation between initial myopia degree and axial elongation [17,18]. Kakita et al obtained a negative correlation between initial myopia degree and axial elongation, however, they compared the distribution of axial elongation in different grade of myopia degree and concluded that the axial elongation wound be slower only in the higher myopia degree [19]. A large number of studies still believe that the the axial elongation is negatively correlated with the initial myopia degree [12,20,21]. Wang et al considered that this was related to the possible existence of the maximum threshold of myopia degree and axial length, there is a lot of room for axial elongation in lower myopia degree, and the axial length grow fast, but once it approaches the threshold, the axial elongation naturally slows down [12]. Most studies believe that this may be related to the relative peripheral hyperopia defocus which can cause axial elongation and myopia progression [22,23], the hypothesis is that, the higher the myopia degree, the steeper the central and peripheral cornea will be, and the less harmful effects of relative peripheral hyperopia will be on the retina which can reduce the stimulation to axial length and myopia progression [24][25][26]. This article compares the mean value of the axial length between baseline and the follow-up time of 1 year among the low, medium, and high myopia groups and supports that the bene t in OK wearers of the moderate and high myopia is better than that of the low myopia.
This study proves that the initial corneal thickness has no correlation with the axial elongation, which is consistent with the conclusions of the current literature [12,27]. Lee et al concluded that the initial corneal thickness was negatively correlated with the axial elongation, but they proposed that this correlation is highly dependent on the age, and believed that the younger wearers had thinner and more exible corneal thickness which is less likely to be affected by the cornea shape changes caused by the orthokeratology lens [11].
At present, there are few studies on the relationship between initial corneal curvature and axial elongation. Some studies believe that the initial corneal curvature has nothing to do with the axial elongation [15]. Xie Jing et al believe that the initial corneal curvature is negatively correlated with the axial elongation [28], but there is no similar report in China. In this study, the initial corneal curvature is not related to the axial elongation.
In summary, the orthokeratology lens can effectively control the elongation of the axial length and is an effective method to control the progression of myopia. The initial age and myopia degree signi cantly affect the axial elongation. Although the older initial age and the higher myopia degree OK wearers achieve the better effect in controlling the progression of myopia, but in the long term, the earlier the treatment for myopia, the higher bene t the children will obtain.
Abbreviations OK: Orthokeratology Declarations Ethics approval and consent to participate This study was approved by the ethics committee of Xiangya Hospital of Central South University. The whole procedure strictly complied with the tenets of the Declaration of Helsinki, and the written informed consent was obtained from all subjects and their guardians before joining in the project.

Consent for publication
Not applicable.
Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that there is no con ict of interest regarding the publication of this paper.

Funding
Not applicable.
Author's contribution SW and XZ designed the study, analyzed the data, and write the manuscript. SM, CX, SH, XR, XT and XX performed the examinations, collect the data, and managed the whole study. XZ instructed the whole study and revised the manuscript. The authors read and approved the nal manuscript.