Comparison of the long-term effects of atropine in combination with Orthokeratology and defocus incorporated multiple segment lenses for myopia control in Chinese children and adolescents

Abstract

Purpose

The aim of this study was to evaluate the efficacy of Orthokeratology (Ortho-K), defocus incorporated multiple segment (DIMS) lens, combined Ortho-K/atropine, and combined DIMS/atropine for myopia control in children.

Methods

A retrospective study included 167 myopic children aged 6–14 years with a spherical equivalent refraction (SER) of −0.75 to −4.00 diopter treated with Ortho-K (OK, n = 41), combined Ortho-K/atropine (OKA, n = 43), DIMS (n = 41), or combined DIMS/atropine (DIMSA, n = 42). Axial length (AL) was measured at baseline and at 3, 6, 9 and 12 months. Axial elongation over time and between groups were analysed.

Results

After 12 months, the AL change was 0.20 ± 0.12 mm, 0.12 ± 0.14 mm, 0.22 ± 0.14 mm, and 0.15 ± 0.15 mm in the OK, OKA, DIMS, and DIMSA, respectively. There was no significant difference in AL change between OK and DIMS. OKA and DIMSA significantly slowed axial elongation compared to OK and DIMS monotherapy. After stratification by age, in the subgroup aged 6–10 years, there was significant difference in AL change between OKA and DIMS (p = 0.013), and no difference between other groups, while in the subgroup aged 10–14 years, the difference between OKA and DIMS became insignificant (p = 0.237), and the difference between OK and OKA, OK and DIMSA, DIMS and DIMSA became significant.

Conclusions

Ortho-K and DIMS lenses show similar reductions in myopia progression among children with low initial myopia. Atropine can significantly improve the efficacy of myopia control of both Ortho-K and DIMS lenses, and this add-on effect is better in older children.

Backgrounds

Myopia is a common eye disorder in humans [1, 2], and has emerged as a serious health problem worldwide [3–7]. It is predicted that approximately half of the world’s population will suffer myopia by 2050, and that 19.7% of the population will have high myopia [8]. Early onset of myopia not only impacts children’s quality of life, such as academic performance, physical activity and employment choices [9], but is also associated with high myopia in adulthood, leading to various vision-threatening complications [10–12]. Therefore, the need for effective interventions to inhibit the progression of myopia in children and prevent future complications resulting from high myopia in adulthood is urgent.

Comprehensive clinical treatments, including optical, pharmaceutical, and behavioural interventions, have been used for myopia control [13–16]. Optical intervention mainly includes spectacles and contact lenses. Several studies have reported that the defocus incorporated multiple segment (DIMS) lens, a novel type of spectacle lens with peripheral myopic defocus [17–19], can retard 52% of myopic refractive errors and 62% of in axial elongation compared to children wearing SV spectacle lenses [17]. The DIMS lenses comprise a central correction zone surrounded by multiple segments of constant myopic defocus (+3.50 dioptres) at the midperiphery, which can provide clear central vision and peripheral myopic defocus, retarding the progression of myopia [18]. Among contact lenses, Orthokeratology (Ortho-K) is an effective treatment at controlling myopia in children and adolescents [20–23]. Previous studies have revealed that wearing Ortho-K lenses can slow myopia progression in children (by 32% to 55%) compared with wearing SV spectacle lenses [20, 23–26]. The Ortho-K lens is considered to slow the progression of myopia by flattening the central cornea while steepening the midperipheral cornea to reduce relative peripheral hyperopia and increase higher order aberrations [22, 27].

Pharmacological interventions include atropine [28], 7-methylxanthine [29], and pirenzepine [30], which are promising treatments for controlling myopia progression. Atropine eye drops, a nonselective muscarinic antagonist, have demonstrated good efficacy and are an emerging therapy for controlling myopia, with control effects varying from 45% to 77% across different studies [21, 28, 31, 32]. Various concentrations of atropine were investigated, and concentration-dependent effects were observed for their clinical efficacy and adverse side effects. The low-concentration atropine for myopia progression (LAMP) Study revealed a concentration-dependent response to low-concentration atropine at 0.05%, 0.025%, and 0.01%, which confer respective reductions of 67%, 43%, and 27%, respectively, in spherical equivalent (SE) progression compared with that of the placebo group over 1 year [28]. According to the Atropine for the Treatment of Myopia 2 (ATOM 2) trial, 0.5%, 0.1%, and 0.01% atropine can retard myopia progression to −0.30 ± 0.60 D, −0.38 ± 0.60 D, and −0.40 ± 0.69 D, respectively, over 2 years [33]. Regarding adverse vision-related effects and rebound after drop discontinuation, a low concentration of 0.01% atropine was considered the common dose for slowing myopia progression in children [33, 34].

Although various interventions have been explored for myopia control, their efficacy is accompanied by significant individual variability among these treatments. The age of myopia onset [14, 25, 35], baseline refractive error [18, 21, 36], and pupil size [37] have been proposed to be influencing factors. Previous studies have confirmed that 0.01% atropine eye drops have additive effect on Ortho-K lenses, and Ortho-K combined with atropine (OKA) treatment has been considered a method for improving treatment efficacy in slowing myopia progression [14, 38]. Several studies have also reported that myopia progression and axial elongation are slower in children receiving a combination of 0.01% atropine and DIMS than in those receiving DIMS or SV alone [39, 40]. However, the additive effect of atropine seems to be influenced by initial refractive error. Kinoshita et al. reported that an additive effect of OKA was found in children with low initial myopia but not in those with moderate to high initial myopia [41]. A study performed by Xu et al. revealed that the efficacy of OKA was similar to that of Ortho-K lenses in children aged 8–10 years, while in those aged 10–12 years, the efficacy of OKA was similar to that of atropine [14], which indicated that the improvement in OKA might also be influenced by age. Therefore, a personalised myopia control strategy based on initial age, myopic refractive error and the rate of myopia progression may be able to better control myopia in children and adolescents.

To investigate whether the effectiveness of the Ortho-K lens differs from that of the DIMS lens and to better elucidate the timing of atropine administration, in the present study, we first directly compared the efficacy of myopia control among the Ortho-K lens, DIMS lens, combined Ortho-K/atropine, and combined DIMS/atropine over a 1-year period. Our age-stratified analysis provides additional information on the effect of age on these treatments, which can help clinicians to make optimum prescriptions for myopia control in children and adolescents.

Methods

Participants

This was a retrospective clinical study. The involved subjects were treated with DIMS spectacle lenses, Ortho-K lenses, combined Ortho-K/atropine or combined DIMS/atropine and followed up for more than 1 year at the Peking University People’s Hospital optometry centre between January 2021 and September 2022. The axial length (AL) was measured at baseline and every 3 months over one year. The changes in AL among different subgroups were compared over the study period.

A total of 292 subjects who underwent a comprehensive ophthalmological examination and 167 who fulfilled the following inclusion criteria were enroled in the study: (1) continuous wearing of Ortho-K (8–10 h/day) or DIMS lens (≥10 h/day) and regular follow-up for more than 1 year; (2) continuous using 0.01% atropine (≥6 days/week); (3) initial wearing age 6 to 14 years; (4) baseline SER between −4.00 D to −0.75 D; (5) astigmatism and anisometropia of 1.50 D or less; (6) best-corrected visual acuity of ≤0.10 (logMAR value); (7) the absence of any ocular and systemic diseases, such as cataracts, glaucoma, and strabismus.

This study was approved by the institutional research ethics committee of Peking University People’s Hospital. All examinations and management procedures were performed in accordance with the Declaration of Helsinki. Because all the data were anonymized and the study was retrospective, no informed permission was necessary for patient enrolment.

Biometric measurements

Refraction and ocular biometry examinations were performed for all subjects. First, ocular biometric parameters were measured with an optical biometer. AL, central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (CLT), and vitreous chamber depth (VCD) were measured with noncontact partial-coherence laser interferometry (IOL Master; Carl Zeiss Meditec, Oberkochen, Germany). A corneal topography system (Sirius, Italy) was used to obtain the pupil diameter (PD), eccentricity value (e value), and mean keratometry reading (mean K, mean K= (flat keratometry + steep keratometry)/2). The measurements were taken by the same experienced technical staff, and five valid measurements were taken and averaged for statistical analysis. The ocular parameters presented here are presented as the mean ± standard deviation (SD).

After the biometry measurements, cycloplegia were performed on each subject after the administration of 0.5% compound tropicamide eye drops (Santen Pharmaceutical Co. Ltd., Japan; 0.5% tropicamide combined with 0.5% phenylephrine). Three drops of 0.5% compound tropicamide eye drops were administered at least 25 min before refractive error measurement. Cycloplegia was considered complete if the pupil was dilated to 6 mm or more and if there was no pupillary reflex. The average of five measurements automatically performed by the autorefractor (KP8800; Topcon Corp., Tokyo, Japan) was used for analyses. Slit-lamp and fundus examinations were performed.

Procedure

The Ortho-K group (OK) was fitted with a vision shaping treatment (VST) design Ortho-K lens, which was a Euclid orthokeratology (Euclid Inc, Charlotte, NC) with a BOSTON Equalens II lens material, an oxygen transmission coefficient of 127, a refractive index of 1.435, a wetting angle of 36°, and a back optic zone diameter (BOZD) of 6.6 mm. Lens fitting was performed by the same experienced ophthalmic technician based on subjective refraction, the flat keratometry value and the HVID. In general, the ideal fit requires that the lens have good central positioning, and that the tears gather into a narrow deep stain zone under the reverse curve, resulting in the whole “bull’s eye” after fluorescence staining. At the same time, the lens had appropriate motion of 1–2 mm at normal blink. After 30 min of simulated sleep, the visual acuity was examined and the fitting effect was evaluated with a corneal topographic map. If the subject wore the lens without obvious discomfort and obtained an ideal fit state, the prescription was determined and the lens parameters were ordered. The subjects were advised to wear the lenses for at least 8 h every night. Subjects underwent regular follow-up examinations at 1 day, 1 week, 1 months, 3 months, 6 months, and 12 months after lens wear. During regular follow-up, the examinations were performed within 3 h after removing the lenses and included measurements of the subjects’ VA, refraction, AL, corneal topography examination, fluorescein staining of the corneal epithelium, lens fit assessment, etc.

The DIMS group (DIMS) wore a custom-made plastic spectacle lens. The lens comprises a central optical zone (9 mm in diameter) for correcting distance refractive errors, and an annular multiple focal zone with multiple segments (33 mm in diameter) having a relative positive power (+3.50 D). The diameter of each segment is 1.03 mm [18]. DIMS spectacle prescriptions were given based on subjective refraction with corrected visual acuity of 20/25 or better in both eyes. In addition to physical activities, the subjects were advised to wear the lenses for at least 10 h in daily life. Subjects underwent regular follow-up examinations at 1, 3, 6, and 12 months after lens wear. During regular follow-up, the examinations included measurements of the subjects’ VA, refraction and AL.

The subjects in combined Ortho-K/atropine group (OKA) used Ortho-K lenses and one drop of 0.01% atropine (Shenyang Xingqi Pharmaceutical Co., China) once every night at least 15 min before Ortho-K lens wear. In the combined DIMS/atropine group (DIMSA), DIMS spectacle lenses were used in daily life and one drop of 0.01% atropine once nightly was administered. The subjects in the combination groups were instructed to instil the 0.01% atropine eye drop into both eyes without their eyelids or eyelashes touching the tip of the bottle.

Myopic progression was estimated based on the change in the AL in the four treatment groups. AL measurements were obtained using the same IOL Master instrument each time by the same blinded examiner. Five valid measurements were taken and averaged for statistical analysis.

Statistical analysis

Statistical analysis was performed using the SPSS statistical software package (version 22.0, IBM Corp., US). As biometric data for the right and left eyes were strongly correlated (Pearson correlation coefficient, r = 0.91), analyses were performed using data for the right eye only. The Chi-squared test was used to compare gender among the groups. The data of age, SER and e value were not normally distributed according to the Kolmogorov–Smirnov test. The Kruskal–Wallis test was used to compare age, SER and e value analysis among groups. Baseline ocular biometrics including the mean K, HVID, PD, AL, CCT, ACD, CLT and VCD and changes in AL every 3 months were compared among the four groups using independent sample one-way ANOVA analyses and among two different subgroups using post hoc tests (LSD). A p < 0.05 was considered to be statistically significant.

Results

Subject demographics

A total of 292 participants were assessed in this retrospective study, of whom 203 passed the initial screening. Only 167 subjects (80 boys and 87 girls) met the inclusion criteria and were grouped into four treatment groups. There were 41 subjects in the DIMS group, 42 subjects in the DIMSA group, 41 subjects in the OK group, and 43 subjects in the OKA group (Supplementary Fig. 1). The overall mean age of all the subjects was 9.30 ± 1.84 years, and the initial mean SER and AL were −2.08 ± 1.05 D (ranging from −4.00 to −0.75 D) and 24.39 ± 0.72 mm (ranging from 22.05 to 27.75 mm), respectively. There was no statistically significant difference in sex at baseline among the four groups (χ2 = 1.050, p = 0.306). The baseline age, initial SER, initial AL, and initial ocular parameters (including the mean K, HVID, e value, PD, CCT, ACD, CLT, and VCD) were compared among the four groups, and no statistically significant differences were found in any baseline data (independent sample one-way ANOVA, all P > 0.05). The detailed subjects’ characteristics are provided in Supplementary Table 1.

Axial length change after 1 year of treatment

Figure 1B and Supplemental Table 2 show the axial length changes in the four treatment groups after 1 year of follow-up. After 1 year of treatment, the overall AL changes were 0.20 ± 0.12 mm, 0.12 ± 0.14 mm, 0.22 ± 0.14 mm, and 0.15 ± 0.15 mm in the OK, OKA, DIMS, and DIMSA groups, respectively. There were significant differences in the AL change between OK and OKA groups (p = 0.042), between DIMS and OKA groups (p = 0.008) and between DIMS and DIMSA groups (p = 0.039). The AL changes were significantly different among the four treatment groups at 3 and 12 months (all p < 0.05, Supplementary Table 2), but not at 6 and 9 months. AL significantly changed over time (all p < 0.01), and increased in the four groups (Fig. 1A). On average, 1-year AL elongation was slower by 0.08 mm in the OKA group than in the OK group, and by 0.07 mm in the DIMSA group than in the DIMS group.

Fig. 1. Changes in AL in the four treatment groups.

A Line chart showing the change in AL for 1 year in the four treatment groups. B Histograms showing the 1-year AL elongation in the four treatment groups. AL axial length. The data are expressed as the means and standard errors of the means. Unpaired t test; *P < 0.05 indicates significant differences between the different groups. DIMS defocus incorporated multiple segment spectacle lens, DIMSA defocus incorporated multiple segment spectacle lens combined with 0.01% atropine, OK Orthokeratology, OKA Orthokeratology combined with 0.01% atropine.

Figure 2 shows the AL change between the different treatment groups over a 1-year period. The AL changes were significantly different between OK group and OKA group at 3, 6, 9, and 12 months (all p < 0.05). A significantly different in AL change was observed between OK group and DIMSA group at 3 and 6 months, but not at 9 and 12 months. There were significant differences in AL changes between OKA group and DIMS group and between DIMS group and DIMSA group at 12 months, but not at 3, 6, and 9 months. No significant differences in AL change were found between other groups including DIMS and OK, OKA and DIMSA at 3, 6, 9 and 12 months (all p > 0.05) (Supplementary Table 3).

Fig. 2. Pairwise comparison of AL changes in the OK, OKA, DIMS and DIMSA groups at 1 month, 3 months, 6 months, and 12 months of follow-up. AL, axial length.

a OK vs. OKA; b DIMS vs. DIMSA; c OK vs. DIMS; d OK vs. DIMSA; e DIMS vs. OKA; f OKA vs. DIMSA. The data are expressed as the means and standard errors of the means. Unpaired t test were used; *P < 0.05 and **P < 0.01 indicate significant differences between the different groups. DIMS defocus incorporated multiple segments spectacle lens, DIMSA defocus incorporated multiple segment spectacle lens combined with 0.01% atropine, OK Orthokeratology, OKA Orthokeratology combined with 0.01% atropine.

Factors associated with treatment efficacy

As shown in Table 1, in the univariate analysis, older age was significantly associated with shorter axial length elongation in DIMS (p = 0.008) and DIMSA group (p = 0.047), but not in OK and OKA group. The baseline SER had no significant association with AL elongation in DIMS, DIMSA, OK, and OKA groups (all P > 0.05). Sex and baseline ocular parameters were not significantly associated with AL elongation in the four treatment groups.

Table 1.

Univariate regression analyses of the factors associated with AL change at 1 year in the four groups.

	DIMS		DIMSA		OK		OKA
	r	p	r	p	r	p	r	p
Sex (M/F)	−0.219	0.229	−0.062	0.737	0.071	0.713	0.049	0.799
Age (Y)	−0.463	0.008	−0.354	0.047	0.034	0.863	−0.170	0.370
SER (D)	−0.138	0.429	0.086	0.640	0.092	0.634	−0.224	0.235
Mean K (D)	0.010	0.958	−0.046	0.801	0.060	0.757	0.138	0.467
HVID (mm)	0.022	0.903	−0.053	0.772	−0.083	0.669	−0.147	0.439
e value	0.051	0.783	<0.001	0.998	0.008	0.965	−0.182	0.337
PD (mm)	0.124	0.489	0.122	0.506	0.163	0.397	<0.001	0.998
AL (mm)	0.199	0.275	−0.135	0.461	−0.178	0.356	−0.350	0.058
CCT (um)	−0.046	0.804	−0.288	0.110	−0.114	0.557	−0.029	0.877
ACD (mm)	−0.225	0.215	0.014	0.942	−0.188	0.330	−0.022	0.907
CLT (mm)	0.313	0.082	−0.241	0.184	0.265	0.214	0.288	0.123
VCD (mm)	0.197	0.279	−0.082	0.655	−0.222	0.246	−0.274	0.116

Bold text indicates a significant difference (p value < 0.05).

SER spherical equivalent refraction error, Mean K mean keratometry reading, HVID horizontal visible iris diameter, e value eccentricity value, PD pupil diameter, AL axial length, CCT central corneal thickness, ACD anterior chamber depth, CLT crystalline lens thickness, VCD vitreous chamber depth, M male, F female, D dioptres, DIMS defocus incorporated multiple segment spectacle lens, DIMSA defocus incorporated multiple segment spectacle lens combined with 0.01% atropine, OK Orthokeratology, OKA Orthokeratology combined with 0.01% atropine.

Axial length change at 1 year stratified by age

There was no statistically significant difference at baseline for age, sex or ocular parameters among the four groups in the two age subgroups (Supplementary Tables 4 and  5). In the 6–10 years old group, the overall AL changes were 0.20 ± 0.13 mm, 0.14 ± 0.14 mm, 0.27 ± 0.18 mm, and 0.19 ± 0.15 mm in OK, OKA, DIMS, and DIMSA groups, respectively. There was a significant difference in the AL change between OKA and DIMS groups (p = 0.013), but there was no statistical difference between other groups. In the 10–14 years old group, the overall AL changes were 0.20 ± 0.12 mm, 0.11 ± 0.11 mm, 0.16 ± 0.09 mm, and 0.07 ± 0.12 mm in OK, OKA, DIMS, and DIMSA groups, respectively. Significant differences in AL changes were found between OK and OKA groups (p = 0.046), between OK and DIMSA groups (p = 0.005), and between DIMS and DIMSA groups (p = 0.040). The difference between OKA and DIMS groups became insignificant (p = 0.237) (Fig. 3 and Supplementary Table 6).

Fig. 3. Comparison of axial length changes in the four treatment groups in the two age subgroups after 1 year of follow-up.

A Age 6–10 years old; B Age 10–14 years old. AL axial length. The data are expressed as the means and standard errors of the means. *P < 0.05 indicates significant differences between the different groups. DIMS defocus incorporated multiple segment spectacle lens, DIMSA defocus incorporated multiple segment spectacle lens combined with 0.01% atropine, OK Orthokeratology, OKA Orthokeratology combined with 0.01% atropine.

Rates of axial length elongation

Orthokeratology combined with 0.01% atropine demonstrated myopia control with axial length elongation ≤0.15 mm in 53.33% of the subjects. 43.75%, 47.06%, and 37.93% of subjects with DIMS, DIMSA, and OK, respectively, also have no significant change in axial length. Axial length elongation ranging from 0.15 mm to 0.40 mm was found in the 46.87%, 47.06%, 55.17%, and 43.33% of subjects with DIMS, DIMSA, OK, and OKA, respectively. We found that 9.38% of the subjects with DIMS have more than 0.40 mm axial elongation, while only 3.34% of the subjects with OKA experienced rapid myopic progression. Overall, Ortho-K combined with atropine achieved the best efficacy of myopia control over 1 year of treatment (Table 2).

Table 2.

Comparison of rates of axial elongation for the four groups over 1 year of follow-up.

Interventions	ΔAL ≤ 0.15 mm	0.15 mm <ΔAL ≤ 0.40 mm	ΔAL > 0.40 mm
DIMS	43.75%	46.87%	9.38%
DIMSA	47.06%	47.06%	5.88%
OK	37.93%	55.17%	6.90%
OKA	53.33%	43.33%	3.34%

ΔAL the change of AL in the four groups after 1 year of treatment, DIMS defocus incorporated multiple segment spectacle lens, DIMSA defocus incorporated multiple segment spectacle lens combined with 0.01% atropine, OK Orthokeratology, OKA Orthokeratology combined with 0.01% atropine.

Discussion

In this retrospective study, we found that children with low initial myopia receiving DIMS lens achieve similar reduction in myopia progression as children receiving Ortho-K lens. Ortho-K combined with 0.01% atropine achieved the best myopia control efficacy, and 53.33% of the subjects in the OKA group had axial elongation less than 0.15 mm over 1-year follow-up period. 0.01% atropine can significantly improve the efficacy of myopia control of Ortho-K and DIMS lenses, and this addictive effect is better in older children. On average, 1-year AL elongation was slower by 0.08 mm in the OKA group than in the OK group, and by 0.07 mm in the DIMSA group than in the DIMS group.

Supplementary Table 7 shows a comparison of the mean axial elongation over 1 year between patients treated with Ortho-K, DIMS lenses, or/and atropine in the present study and other studies. Chia et al. reported that the axial length of children receiving 0.5%, 0.1%, and 0.01% atropine increased by 0.11 mm, 0.13 mm, and 0.24 mm, respectively [33]. Yam et al. reported that the axial length of children receiving 0.05%, 0.025%, and 0.01% atropine increased by 0.20 mm, 0.29 mm, and 0.36 mm, respectively [28]. In the present study, the increase in axial length over 1 year in the OK group was similar to that in the 0.05% atropine group, and the increase in axial length over 1 year in the OKA, DIMS, and DIMSA groups was between subjects receiving 0.1% atropine and 0.5% atropine, 0.01% atropine and 0.05% atropine, and 0.05% atropine and 0.1% atropine, respectively. Supplementary Table 7 shows that, compared with that of controls receiving single-vision spectacles, the 1-year reduction in axial elongation in subjects wearing Ortho-K lens was ranged from 24% to 57% [23, 26, 42], and in subjects wearing DIMS lens was ranged from 21% to 45% [39, 40]. In this study, compared with those in historical SV spectacle-wearing controls, the 1-year reduction rate was 49% in OK group and 44% in DIMS group [23, 26, 42]. Moreover, the mean changes in the AL in the OK and DIMS groups over the 1-year period were 0.20 ± 0.12 mm and 0.22 ± 0.14 mm, respectively. However, there was no significant difference in AL change between these two treatment groups. This may be because most of the children in this study had low initial myopia; therefore, the Ortho-K and DIMS lenses had the same efficacy in controlling myopia. In addition, compared with those in historical SV spectacle-wearing controls, the 1-year reduction rate was 69% in OKA group and 62% in DIMSA group, [23, 26, 42]. These findings indicated that axial elongation was retarded by an additional 20% when 0.01% atropine was combined with Ortho-K lens, and 18% when 0.01% atropine was combined with DIMS lens.

Kinoshita et al. reported that subjects treated with OKA had a slower increase in axial length by 53% compared with that of subjects wearing Ortho-K monotherapy [43]. Xiao et al. [44] and Tan et al. [45] reported similar findings; a slower increase in axial length was 38% and 56%, respectively, in OKA patients than in Ortho-K lens-treated individuals. In this study, compared with subjects wearing Ortho-K lens alone, subjects receiving OKA had a 40% slower increase in axial elongation (0.12 ± 0.14 mm vs. 0.20 ± 0.12 mm). Huang et al. [39] and Nucci et al. [40] reported that subjects treated with DIMSA had a 32% and 58% slower increase in axial length, respectively, than did subjects receiving DIMS monotherapy. In our study, compared with subjects wearing DIMS lenses, subjects receiving DIMSA had a 32% slower increase in axial elongation (0.15 ± 0.15 mm vs. 0.22 ± 0.14 mm). Notably, however, the additive effect of 0.01% atropine on Ortho-K or DIMS lenses appeared in subjects aged 10–14 years, but not in subjects aged 6–10 years, and this additive effect occurred within the last three months. Hence, it is speculated that the addictive effect of atropine has a cumulative effect over time and that initial age affects this effect.

The Ortho-K lens is considered to retard the progression of myopia in children by an optical mechanism, and the possible mechanism involves a reduction in peripheral hyperopic defocus [36] and/or an increase in higher order aberrations through a redistribution of the corneal epithelium, which may be affected by the suppressive effect of the Ortho-K lens [41]. Kinoshita et al.’s study revealed that the initial SER affects the suppressive effect of the Ortho-K lens [41]. Kakita et al. and Hiraoka et al. reported that the Ortho-K lens is less effective at slowing axial elongation in individuals with lower myopia than in those with higher myopia [25, 26]. Li et al. also reported that Ortho-K therapy alone slowed axial elongation more effectively in children with moderate to high initial myopia than in those with low initial myopia [46]. Therefore, the effect of Ortho-K lens monotherapy in controlling myopia progression may be greater in children with moderate-to-high initial myopia than in children with low initial myopia. However, in our study, there was no significant correlation between the change in AL over 1-year and the initial SER in the OK or OKA group because 88% of the children in the OK group and 86% of the children in the OKA group had low initial myopic refraction.

Atropine may involve the blockade of muscarinic receptors, with an enhanced optical effect of OK by pupil enlargement, facilitating the ability of Ortho-K lens to slow myopia progression [47, 48]. In this study, we also found that atropine has an additive effect on subjects wearing Ortho-K lenses, and this additive effect was greater in older children (aged 10–14 years). We speculate that these variations in the additive effect of atropine may be because younger patients tend to respond poorly to treatment with low-concentration of atropine (0.01%) for myopia control because of the greater inherent risk of myopia progression; thus, younger children require higher concentrations of atropine to achieve efficacy similar to that of older children using lower concentrations of atropine. These findings were confirmed by a study conducted by Li et al. [49]. They suggested that a higher concentration (i.e., 0.05%), rather than a 0.01% concentration should be administered as a starting dose for younger children, given that they have a greater risk of myopia progression. Notably, although the difference was not statistically significant, the overall 1-year AL elongation was 0.06 mm shorter in the OKA group than in the OK group for children aged 6–10 years.

The DIMS lens is designed to control myopia in children, based on the principle of myopic defocus. It is a dual-focus spectacle lens consisting of a central optical zone for correcting distance refractive error, and a batch of tiny circular segments with a relative positive power of 3.50 D equally distributed throughout the mid-peripheral area in a honeycomb pattern. Therefore, compared to the Ortho-K lens, the DIMS lens provides constant myopic defocus (+3.50 D). In this study, the efficacy of myopia control using DIMS lens was comparable to that using Ortho-K lens. Furthermore, 0.01% atropine had an additive effect on the DIMS lens, and this additive effect was comparable to that of Ortho-K combined with 0.01% atropine. Univariate regression analysis indicated that initial age was the only factor influencing myopia progression in the DIMS and DIMSA groups, and the effect of myopia control using DIMS lens was greater in older subjects (aged 10–14 years). In contrast, no such correlation was found in subjects wearing Ortho-K lenses. We speculate that the variations in the treatment effects of DIMS and Ortho-K lenses may be due to difference in the retinal profile or peripheral refraction among these children [50]. Moreover, younger children receiving Ortho-K monotherapy had similar myopia control efficacy as children receiving DIMS lenses combined with 0.01% atropine, while older children receiving DIMS lenses combined with 0.01% atropine had better myopia control than children receiving Ortho-K monotherapy. These findings suggested that initial age affects the addictive effect of atropine on the DIMS lens, and when the DIMS lens is used to control myopia in younger children, atropine may be used in combination when myopia progresses too rapidly.

This novel 1-year study included DIMS lenses, Ortho-K lenses and atropine; we made direct comparisons among them, and our results provide clues for clinicians in guiding myopia control in children. Younger children might be treated with Ortho-K lenses, and if myopia is growing quickly, a combination of 0.01% atropine can be administered. However, if patients consider the adverse effects of Ortho-K lenses or economic reasons, younger children can receive DIMS lenses combined with 0.01% atropine. For older children, DIMS monotherapy might tend to be used first for myopia control. To develop a more precise myopia control strategy, a randomised clinical trial is warranted.

There were several limitations to our study. First, this was a retrospective study and not a prospective randomised controlled trial, which may have resulted in confounding factors that may have affected the results. A randomised clinical trial with a larger sample size is warranted to further compare the treatment effects of single and combined modalities. Second, several parameters, including pupil size, accommodation and peripheral refractive status may influence myopia control with Ortho-K or DIMS lenses, which were not considered. Third, our follow-up time was only 1 year, and the combined longer-term effects require further study. Finally, the number of subjects with moderate-to-high myopia included in this study was too small. In further investigations, we will stratify the subjects by SER at enrolment (−0.75 to −3.00 D vs. −3.01 to −6.00 D) and compare the changes in AL between the combination and monotherapy groups, to determine the optimal treatment for controlling myopia progression and to help clinicians make optimum prescriptions for myopia control in children and adolescents.

In conclusion, our study showed that the Ortho-K and DIMS lenses had similar effects on slowing myopia progression in children aged 6–14 years with low initial myopia. Treatment with 0.01% atropine eye drops can improve the efficacy of myopia control of Ortho-K and DIMS lenses, and this additive effect is better in older children. Overall, during the 1-year follow-up period, the combination of Ortho-K and 0.01% atropine achieved the best myopia control efficacy. Further RCTs are warranted to validate these findings.

Summary

What was known before

• Both Orthokeratology (Ortho-K)and defocus incorporated multiple segment(DIMS) lenses can be used to control myopia in children.

• The low concentration of 0.01% atropine was considered to be the commonly used dose for slowing the myopia progression in children.

What this study adds

• Ortho-K and DIMS lenses show similar reduction in myopia progression among children with low initial myopia.

• Atropine can significantly improve myopia control efficacy of both Ortho-K and DIMS lenses, and this additive effect is greater in older children.

Author contributions

KW conceived and designed the experiments. YL and MWZ conceived the work and performed data analysis. TT conceived and designed the experiments, collected data, performed the experiments, analysed the data and wrote the manuscript. YCL, XWL and HZ collected data. All authors read and approved the final version of the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (Grant No. 82171092, 82371087), Capital’s Funds for Health Improvement and Research (No. 2022-1G-4083), National Key R&D Program of China (No.2021YFC2702100).

Data availability

All data generated or analysed during this study are included in this published article.

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by the institutional research ethics committee of Peking University People’s Hospital. All examinations and management were performed in accordance with the Declaration of Helsinki. Because all data were anonymized and the study was retrospective, no informed permission was necessary for patient enrolment.

Supplementary information

The online version contains supplementary material available at 10.1038/s41433-024-02987-5.