Clinical effect of defocus incorporated multiple segments (DIMS) spectacles combined with low-concentration atropine in fast-progressing myopic children

doi:10.21203/rs.3.rs-3201754/v1

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Clinical effect of defocus incorporated multiple segments (DIMS) spectacles combined with low-concentration atropine in fast-progressing myopic children

https://doi.org/10.21203/rs.3.rs-3201754/v1

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Purpose

To compare the clinical efficacy of DIMS spectacles combined with 0.01% or 0.05% atropine in fast-progressing myopic children with DIMS spectacles alone.

Methods

We conducted a retrospective study of 93 patients aged 8–12 years who attended the optometry clinic at Shenzhen Aier Eye Hospital between January 2021 and February 2023. The subjects were selected based on their use of DIMS spectacles alone in the first year. In the second year, the patients were divided into three groups: continued to use DIMS spectacles alone (S Group), combined DIMS spectaeles with 0.01% atropine (SA1 Group), and combined DIMS spectacles with 0.05% atropine (SA5 Group).

Results

After a 2-year review, it was found that there was no significant difference in the growth of myopia and axial elongation among the three groups in the first year (P = 0.91; P = 0.23). In the second year, there were no significant differences in the growth of myopia and axial elongation between the S group and the SA1 group (P = 0.50; P = 0.35). Similarly, no significant differences were found between the S group and the SA5 group (P = 0.00; P = 0.00). However, significant differences were observed between the SA1 group and the SA5 group (P = 0.00; P = 0.00).

Conclusions

For children with rapid myopia growth using DIMS spectacles alone, the effects of combining 0.01% atropine were not obvious. However, when combined with 0.05% atropine, the effects were noticeable.

defocus incorporated multiple segments

0.01% atropine

0.05% atropine

myopia progression

With the change of lifestyle in recent years, the prevalence of myopia among children is increasing at a younger age, especially in Asia. By 2050, the global prevalence of myopia is predicted to reach fifty percent, with high myopia reaching ten percent^[1]. Over the past decade, there has been a non-linear increase in the prevalence of myopia among school students in China. This trend has been particularly pronounced among high school students, with the prevalence of high myopia reaching alarming levels^[2-3]. High myopia is a high-risk factor for various eye diseases that can cause visual impairment, including retinal degeneration, retinal detachment, myopic macular disease and vitreous liquefaction etc. Studies have shown that each 1D increase in myopia increases the risk of macular degeneration by 58%, open-angle glaucoma by 20%, posterior subcapsular cataract by 21%, and retinal detachment by 30%^[4]. Thus, controlling the progression of myopia and slowing down the elongation of the axial at an early stage is vital to avoid later ocular complications. DIMS spectacles and low-concentration atropine are widely used in clinical practice, but their clinical effects vary widely among individuals^[5-6]. For patients with rapid myopia growth using DIMS spectacles alone, combined use of low-concentration atropine is generally recommended. However, there is currently no relevant study on the effects of combined use of different concentrations of atropine. The primary objective of this study is to compare the clinical effects of combining 0.01% atropine or 0.05% atropine with DIMS spectacles alone in controlling myopia growth in fast-progressing myopic children.

Patients

In this retrospective study, the medical records of 93 children (right eyes) aged from 8 to 12 years old who visited our optometry clinic between Jay 2021 and Feb 2023 were reviewed. In the first year when DIMS spectacles were used alone, SE increased ≥ 0.75D or AL increased ≥ 0.4mm. In the second year, according to the choice of treatment, patients were divided into the S group (continued use of DIMS spectacles alone), the SA1 group (DIMS spectacles combined with 0.01% atropine), and the SA5 group (DIMS spectacles combined with 0.05% atropine). All patients and their parents or guardians were informed about the effects and side effects of using DIMS spectacles, 0.01% atropine and 0.05% atropine to control the development of myopia before treatment. Informed consent was obtained from the patients and their parents or guardians before data collection.

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) Aged 8–12 years; (2) Cycloplegic SE between −1.00 D and −6.00 D; (3) Myopic astigmatism ≤ − 1.00 cylinder (DC) and less than or equal to half the spherical diopter; (4) Anisometropia of no more than 1.50 D; (5) When DIMS spectacles were used alone in the first year, the SE increased ≥ 0.75D or the AL increased ≥ 0.4mm after one year; (6) The patient is in good health.

The exclusion criteria were as follows: (1) Children with ocular disorders such as glaucoma, cataract, keratopathy, strabismus, and amblyopia, and systemic disorders such as cardiac and respiratory illnesses; (2) Low birth weight (≤ 1500 g); (3) Intraocular pressure (IOP) > 21 mmHg and the difference between the eyes > 8 mmHg; (4) with systemic diseases; (5) Use of other therapies that may affect the evaluation of efficacy, such as low-level red-light therapy; (6)History of hypersensitivity to atropine or anticholinergic drugs.

Methods

The 0.5% compound tropicamide was administered three times with an interval of 10 min and waited for 20 min for cycloplegic autorefraction. Subsequently, all enrolled patients underwent comprehensive ophthalmic examinations every six months after treatment, which included assessments of visual acuity, intraocular pressure, mydriatic refraction, axial length, slit lamp examination, among others. SE was measured using an autorefractor (KR-800, TOPCON, TOKYO, JAPAN), while AL was measured using the non-contact Biometer(IOL master, Zeiss, Germany).

In the S group, participants were instructed to wear DIMS spectacles throughout the day. In the SA1 and SA5 groups, participants were prescribed either 0.05% or 0.01% atropine to be applied once per night before bedtime in both eyes, and were also required to wear DIMS spectacles throughout the day. In this study, the 0.05% atropine used was produced by the Aier Ophthalmology Company (Changsha, Hunan; no preservatives), the 0.01% atropine used was produced by the Xingqi Eye Hospital (Shenyang, Liaoning; no preservatives) and the DIMS spectacles were all from Xinlexue (Haoya, Japan).

All of the patients included in the study met the semi-annual review requirement, during which 0.5% compound tropicamide eye drops were used for mydriasis optometry. Additionally, DIMS spectacles were adjusted when the SE decreased by 0.5 diopters (D).

Statistical methods

We used SPSS 26.0 (IBM Corp., Armonk, NY) statistical analysis software for data analysis. The results of age, SE and AL were described by mean ± SD (standard deviation). Pearson chi-square test was used to analyze gender differences among the three groups. Independent sample one-way ANOVA was used to analyze the age among three groups and to analyze base values and changes of SE and AL. Independent sample t-tests were used for comparison between the two groups. P value ＜ 0.05 was considered to indicate statistical significance.

There were no statistically significant differences in gender between the S (n = 33), SA1 (n = 31), and SA5 (n = 29) groups (P = 1.00, Pearson Chi-square test), nor was there a statistically significant difference in mean age among the three groups (P = 0.88, one-way ANOVA of independent samples). Furthermore, there was no statistically significant difference in the baseline of SE and AL among the three groups of patients (P = 0.44, P = 0.94; independent sample one-way ANOVA). (Table 1)

Table 1

The baseline values of gender, age, SE and AL, and the changes of SE and AL in the S group, SA1 group, and SA5 group
	S	SA1	SA5		P	-Value
Gender(M: F)	16:17	15:16	14:15	1		.00b
Age, year, mean (SD)
	10.12(1.08)	10.13(1.02)	10.24(1.05)		0	.88a
SE, D, mean (SD)
Baseline	-3.54(0.85)	-3.72(0.74)	-3.79(0.76)		0	.44a
The first year	-1.03(0.25)	-1.06(0.25)	-1.05(0.24)	0		.91a
The second year AL, mm, mean (SD)	-0.40(0.12)	-0.42(0.13)	-0.15(0.13)	0		.00a
Baseline	24.70(0.68)	24.69(0.57)	24.74(0.65)	0		.94a
The first year	0.44(0.07)	0.47(0.08)	0.47(0.08)		0	.23a
The second year	0.35(0.03)	0.35(0.03)	0.20(0.02)	0		.00a
a = independent sample one-way ANOVA
b = Pearson Chi-square test

One year later, Group S showed changes of -1.03 D and 0.44 mm in SE and AL, respectively. Group SA1 exhibited changes of -1.06 D and 0.47 mm in SE and AL, respectively, while Group SA5 had changes of -1.05 D and 0.47 mm in SE and AL, respectively. However, there was no statistically significant difference in the changes of SE and AL among the three patient groups (P = 0.91, P = 0.23; independent sample one-way ANOVA). The changes in SE ≥ 0.75D or AL ≥ 0.4 mm were considered satisfactory. (Table 1)

In the second year, the changes of SE and AL were − 0.40 D and 0.35 mm in group S, -0.42 D and 0.35 mm in group SA1, and − 0.15 D and 0.20 mm in group SA5. There were statistical differences in the changes in SE and AL among the three groups (P = 0.00, P = 0.00; independent sample one-way ANOVA). (Table 1)

There were no statistically significant differences in the changes of SE and AL between the S group and the SA1 group (P = 0.50, P = 0.35; independent sample t-test); compared with the SA5 group, there were statistically significant differences in the changes in SE and AL (P = 0.00, P = 0.00; independent sample t-test); compared with the SA1 group and the SA5 group, there were statistically significant differences in the changes in SE and AL (P = 0.00, P = 0.00; independent sample t-test). (Table 2)

Table 2

Comparison of the variation of SE andAL in the S group, SA1 group, and SA5 group
	S	SA1	SA5	P1-Value	P2-Value	P3-Value
The changes of SE, D,
mean (SD)	-0.40(0.12)	-0.42(0.13)	-0.15(0.13)	0.50c	0.00c	0.00c
The changes of AL, mm,
mean (SD)	0.35(0.03)	0.35(0.03)	0.20(0.02)	0.35c	0.00c	0.00c
P1 = S vs SA1
P2 = S vs SA5
P3 = SA1 vs SA5
c = independent sample t-test

Due to the increasing prevalence of myopia in young children and the increasing phenomenon of visual impairment caused by high myopia, controlling the occurrence and development of myopia in young children is currently a highly valued issue in the field of ophthalmology and the whole country^[7–8]. 2–3 hours of outdoor activities a day is effective in preventing the onset of myopia and delaying its development^[9] and is also the most economical and practical method. However, due to the lifestyle changes nowadays, few children are able to adhere to it. Clinically, there are many methods to control myopia, such as drug treatment (M choline receptor antagonists, such as low-concentration atropine, etc.), optical treatment (such as DIMS spectacles and OK, etc.), and physical treatment (such as low-energy red light therapy and outdoor activity)^[10–13].

DIMS spectacles and low-concentration atropine are two widely used methods to control the development of myopia^[14]. DIMS spectacles are used for multi-point defocus frames (D.I.M.S: Defocus Incorporated Multiple Segments). These spectacles contain 396 microlenses that are evenly distributed in a honeycomb shape within an area of approximately 32mm in diameter around the optical center of the lens. Each microlens is capable of producing myopic defocus^[15]. The multi-zone forward optical defocus design provides continuous myopic defocus, even when the eye rotates^[16]. Moreover, spectacle lenses represent a safe and easy-to-administer option for myopia control, which is widely accepted by patients in clinical practice. However, the effect of myopia control and axial elongation varies greatly among individuals.

Atropine is a non-selective muscarinic receptor blocker whose possible mechanism controls the development of myopia through direct action on M receptors in the retina and sclera^[17–18]. It has also been found to stimulate the production of new chemicals, such as dopamine, in pigment epithelial cells of the retina, which in turn controls the elongation of the AL^[19–20]. At present, the most widely used concentrations of low-concentration atropine eye drops in clinical practice are 0.01% and 0.05%, with studies showing acceptable side effects for patients. However, 0.05% atropine eye drops have been found to be more effective in controlling myopia development and axial elongation^[21–23]. Compared with 0.01% atropine eye drops, 0.05% atropine eye drops can significantly reduce the incidence of myopia^[24].

Clinically, for children with rapid myopia growth using DIMS spectacles alone, we generally recommend combining with low-concentration atropine eye drops or using OK lenses to control myopia. However, the effect of combining atropine eye drops with different concentrations on myopia development and AL elongation has not been clear. In this retrospective study, it was discovered that the growth of myopia was not effectively controlled when DIMS spectacles were combined with 0.01% atropine, but when combined with 0.05% atropine, significant control of myopia growth was observed. This finding holds important implications for guiding our clinical approach.

Other studies have indicated that the use of 0.01% atropine in combination with OK did not improve myopia control and axial elongation in children with poor control of myopia development with OK alone. However, the growth of myopia and axial elongation of the eye can be significantly controlled after the combination of 0.05% atropine^[25]. Both this report and our study suggest that a combination of 0.05% atropine should be preferred in patients whose use of a method to control the growth of myopia is not ideal. It is important to note that further clinical studies are necessary to confirm this conclusion. Additionally, for patients who do not experience satisfactory myopia control with DIMS spectacles alone, further clinical studies should be conducted to evaluate the effectiveness of switching to OK.

The study has a few limitations that should be noted. Firstly, we utilized atropine with concentrations of 0.01% and 0.05%, but it would be beneficial to investigate the effects of different concentrations such as 0.02%, 0.025%, and 0.1%. Secondly, the clinical effects of combining low-concentration atropine were only studied for a year, and it would be valuable to confirm the longer-term clinical effects through further studies. As a result, we plan to continue monitoring the enrolled patients to observe the clinical efficacy over an extended period.

Ethics approval and consent to participate This study was reviewed and approved by the Institutional Review Board of the Shenzhen Aier Eye Hospital (Guangdong, China). And this study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from the patients and their parents or guardians before data collection.

Consent for publication Informed consent was obtained from the patients and their parents or guardians before data collection, and all authors and patients agree to the publication of the paper.

Data availability All of the data in this article is available through [email protected].

Conflict of interest declaration There is no conflict of interest in this study.

Fund The study was funded by the Science and Technology Innovation Program of Hunan Province (Grant No. 2021SK50102) and the Science Research Grant of Aier Eye Hospital Group(AF2108D3).

Author contribution statement QH participated in the design of the study, carried out the study and drafted the manuscript and performed the statistical analyses. JX has participated in the study’s coordination and has helped to draft the manuscript.

,Holden, Brien A, Fricke Timothy R, Wilson David A, Jong Monica, Naidoo Kovin S, Sankaridurg Padmaja W, Tien Y, Naduvilath Thomas J, Resnikoff Serge. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123:1036–42.
,Wang, Jianyong YGui-Shuang, Xiaojin Fu, Ronghua Z, Jia M, Fang Gu, Li Juanjuan. Prevalence of myopia and vision impairment in school students in Eastern China. BMC Ophthalmol. 2020;20(1):2.
,Chen M, Wu A, Zhang L, Wang W, Chen X, Yu X, Wang K. The increasing prevalence of myopia and high myopia among high school students in Fenghua City, Eastern China: a 15-year population-based survey. BMC Ophthalmol. 2018;18(1):159.
4, Bullimore MA, Ritchey ER, Shah S, Leveziel N, Bourne RRA, Flitcroft DI. The risks and benefits of myopia control. Ophthalmology. 2021;128(11):1561–79.
,Chen Z, Zhou J, Xue F, Qu X, Zhou X. Two-year add-on effect of using low concentration atropine in poor responders of orthokeratology in myopic children. Br J Ophthalmol. 2021;106(8):1069–72.
,Naidoo KS, Fricke TR, Frick KD, Jong M, Naduvilath TJ, Resnikoff S, Sankaridurg P. Potential lost productivity resulting from the global burden of myopia: systematic review, meta-analysis, and modeling. Ophthalmology. 2019;126:338–46.
,Yam JC, Zhang XJ, Zhang Y, Yip BHK, Tang F, Wong ES, Bui CHT, Kam KW, Ng MPH, Ko ST, et al. Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial. JAMA. 2023;329(6):472–81.
,Wong YL, Sabanayagam C, Ding Y, Wong CW, Yeo AC, Cheung YB, Cheung G, Chia A, Ohno-Matsui K, Wong TY, Wang JJ, et al. Prevalence, risk factors, and impact of myopic macular degeneration on visual impairment and functioning among adults in Singapore. Invest Ophthalmol Vis Sci. 2018;59:4603–13.
,Sherwin JC, Reacher MH, Keogh RH, Khawaja AP, Mackey DA, Foster PJ. The association between time spent outdoors and myopia in children and adolescents: a systematic review and meta-analysis. Ophthalmology. 2012;119:2141–51.
Wen 10HuangJ, Wang D, McAlinden Q, Flitcroft C, Chen I, Saw H, Chen SM, Bao H, Zhao F. Efficacy Comparison of 16 Interventions for Myopia Control in Children: A Network Meta-analysis. Ophthalmology. 2016;123(4):697–708.
,Chen H, Jiang Q. Advances of muscarinic antagonists slowing the progression of myopia. Chin J Exp Ophthalmol. 2017;35(6):556–60.
,Walline JJ, Myopia Control. Rev Eye Contact Lens. 2016;42(1):3–8.
Zhu 13DongJ, Xu Z, He H. Myopia Control Effect of Repeated Low-Level Red-Light Therapy in Chinese Children: A Randomized, Double-Blind, Controlled Clinical Trial. Ophthalmology. 2023;130(2):198–204.
,Morgan, Ian G, He Mingguang, Rose Kathryn A, EPIDEMIC OF PATHOLOGIC MYOPIA. What Can Laboratory Studies and Epidemiology Tell Us? Retina. 2017;37(5):989–97.
,Lam CSY, Tang WC, Tse DY, Lee RPK, Chun RKM, Hasegawa K, Qi H, Hatanaka T, To CH. Defocus incorporated multiple segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial. Br J Ophthalmol. 2020;104:363–8.
,Lam CS, Tang WC, Tse DY, Tang YY, To CH. Defocus incorporated soft contact (disc) lens slows myopia progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial. Br J Ophthalmol. 2014;98:40–5.
,Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors in mouse scleral fibroblasts: Prior to and after induction of experimental myopia with atropine treatment. Mol Vis. 2011;9:17:680–92.
.,18, Lin HJ, Wan L, Chen WC, Lin JM, Lin CJ, Tsai FJ. Muscarinic acetylcholine receptor 3 is dominant in myopia progression. Invest Ophthalmol Vis Sci 2012; 21;53(10):6519-25.
,Dong F, Zhi Z, Pan M, Xie R, Qin X, Lu R, Mao X, Chen JF, Willcox MD, Qu J, Zhou X. Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs. Mol Vis. 2011;17:2824–34.
Chaurasia 20BarathiVA, Poidinger SS, Koh M, Tian SK, Ho D, Iuvone C, Beuerman PM, Zhou RW. Involvement of GABA transporters in atropine-treated myopic retina as revealed by iTRAQ quantitative proteomics. J Proteome Res. 2014;13(11):4647–58.
,Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. 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):113–24.
,Yam JC, Li FF, Zhang X, Tang SM, Yip BHK, Kam KW, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report. Ophthalmology. 2020;127:910–9.
,Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP. 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;126:113–24.
,Yam JC, Zhang XJ, Zhang Y, Yip BHK, Tang F, Wong ES, Bui CHT, Kam KW, Ng MPH, Ko ST, et al. Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial. JAMA. 2023;329(6):472–81.
,Chen Z, Zhou J, Xue F, Qu X, Zhou X. Two-year add-on effect of using low concentration atropine in poor responders of orthokeratology in myopic children. Br J Ophthalmol. 2021;106(8):1069–72.

No competing interests reported.

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Clinical effect of defocus incorporated multiple segments (DIMS) spectacles combined with low-concentration atropine in fast-progressing myopic children

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