Clinical efficacy of electroacupuncture in controlling myopia in children and its influence on retinal blood flow

HAN Rong (韩榕), WANG Xuejun (王雪君), KONG Xiehe (孔谐和), ZHANG Xiaopeng (张小芃), CAO Yaojiani (曹姚佳妮),LU Yunqiong (卢云琼), LIU Li (刘力), ZHOU Xingtao (周行涛), ZHAO Feng (赵峰), MA Xiaopeng (马晓芃)

1 Shanghai Qigong Research Institute, Shanghai 200030, China

2 Taiji Health Center, Shanghai University of Traditional Chinese Medicine/Shanghai Academy of Traditional Chinese Medicine,Shanghai 200030, China

3 Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine,Shanghai 200437, China

4 Eye and ENT Hospital of Fudan University, Shanghai 200031, China

5 Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Abstract

Keywords: Acupuncture Therapy; Electroacupuncture; Auricular Acupressure; Axial Length; Eye; Retina; Microcirculation;Myopia

Myopia, the most common refractive disorder, has a persistently high incidence and a trend of lower age[1-2].How to prevent and control the development of myopia has become an important problem that needs to be solved. Myopia has been recognized in traditional Chinese medicine (TCM) for a long time, and acupuncture and auricular acupressure are commonly used TCM treatments for myopia and have gradually become one of the hot spots in myopia treatment in recent years[3-4]. The causes and mechanisms of myopia are influenced by a variety of factors[5-6]. Some researchers have suggested that there may be a potential relationship between the development of myopia and changes in retinal blood flow: retinal vessel density (VD) and mean retinal blood flow are significantly lower in myopic eyes compared with emmetropic eyes and may consequently affect the development of visual function[7]. Optical coherence tomography angiography (OCTA) is a new imaging technique that has emerged in recent years and can be used to quantify superficial retinal blood flow, offering more possibilities for the study of ocular diseases[8]. A previous study by our group found that 6 months of auricular acupressure was able to delay the progression of myopia by 0.13 D[9]. In this study, we observed the effect of add-on electroacupuncture (EA) to auricular acupressure on myopia control in children and observed its effect on retinal blood flow by OCTA technique in order to provide a clinical basis for the use of EA in myopia control.

1 Clinical Materials

1.1 Study subjects

All 68 subjects in this study were myopic patients aged 7 to 12 years attending the Ophthalmology Department, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, and were observed between November 2020 and May 2021. The SPSS version 25.0 software was used to generate random numbers and random assignment tables, and group information was placed in opaque envelopes according to the random sequence formed. After obtaining verbal informed consent from the children and written informed consent from their guardians, subjects would be given envelopes according to their order of enrollment and randomly divided into an observation group and a control group, with 34 subjects in each group. The study was reviewed and approved by the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (Ethical Approval No. 2020-893-102-01).

1.2 Diagnostic criteria

This study referred to the diagnostic criteria for simple myopia in theChinese Ophthalmology[10].

1.3 Inclusion criteria

Met the diagnostic criteria for simple myopia; aged 7-12 years; cycloplegic myopic refraction was between-3.00 D and -0.50 D; corneal curvature: 40-46 D;intraocular pressure: 10-21 mmHg.

1.4 Exclusion criteria

Those who had other ocular diseases or systemic diseases; had undergone eye surgery; had used other myopia prevention or control methods such as atropine and orthokeratology; had received acupuncture treatment within 1 month; had opening wounds on the auricular points or allergies to adhesive tapes; and those whose guardians held unreasonable expectations.

1.5 Criteria for dropout

Those who experienced serious adverse events or other specific physiological changes that made the study unsustainable; those who did not receive treatment according to the trial protocol; those who voluntarily requested to withdraw.

1.6 Criteria for elimination

Those who did not meet the inclusion criteria or met the exclusion criteria but were mistakenly included;those who missed one or more post-baseline efficacy assessments.

1.7 Statistical analysis

Only data from the right eyes were used for ocularrelated statistical analyses. The data were processed using the SPSS version 25.0 statistical software with a full analysis set for statistical analysis. The measurement data were described as mean ± standard deviation(±s), mean ± standard error (±SE), or median(lower quartile, upper quartile) [M (QL, QU)], and the two independent samplest-test or Wilcoxon Mann-WhitneyUrank-sum test was used for between-group comparisons. The enumeration data were described by the number of cases (percentage), and Chi-square test was used for between-group comparisons. All statistical results were considered statistically significant atP＜0.05.

2 Treatment Methods

2.1 Control group

The control group received auricular acupressure treatment.

Points: Eye (LO5), Liver (CO12), Kidney (CO10), Heart(CO15), Spleen (CO13), and Shenmen (TF4).

Method: After routine disinfection of the skin at the auricular points, the plasters with magnetic beads were applied to each point. A guardian was instructed to help the child apply acupressure to each point three times a day (morning, evening, and before bedtime), 20 times each session, with pressure as strong as the child could tolerate and the auricle feeling slightly warm and painful. One auricle was treated each time (alternated at each visit), and the auricular patches were changed by the acupuncturist each week. Three months was one course of treatment, with a total of two courses.

2.2 Observation group

The observation group received EA treatment in addition to the same auricular acupressure used in the control group.

Points: Baihui (GV20) and bilateral Cuanzhu (BL2),Sibai (ST2), Taiyang (EX-HN5), Sizhukong (TE23),Muchuang (GB16), Fengchi (GB20), Hegu (LI4), Zusanli(ST36), Guangming (GB37), and Taichong (LR3).

Method: The needles of 0.25 mm in diameter and 25 mm in length were used. After disinfection of the skin at the points, the needles were inserted into Cuanzhu (BL2), Sibai (ST2), Taiyang (EX-HN5), Sizhukong(TE23), Muchuang (GB16), and Baihui (GV20) to a depth of about 0.3 Cun; Fengchi (GB20), Hegu (LI4), Zusanli(ST36), Guangming (GB37), and Taichong (LR3) to a depth of about 0.5 Cun. After obtaining the needling sensation (Deqi), Cuanzhu (BL2) and Taiyang (EX-HN5)were connected to the Hwato SDZ-II electrical stimulator, and a pair of electrodes were connected to the same side of the points, and a continuous wave with a frequency of 2 Hz was selected. Each time the needle was retained for 30 min, the needle was slowly withdrawn according to the direction of needle entry,and the needle hole was pressed with a sterile dry cotton ball after the needle was completely removed.The treatment was carried out once a week, for 3 months as one course of treatment, with a total of two courses.

3 Outcome Observation

3.1 Observation items

The relevant indicators were tested before treatment,and after 3 months and 6 months of treatment,respectively. All tests were performed by the same personnel in strict accordance with the rules.

3.1.1 Spherical equivalent refraction (SER)

The ciliary muscle was paralyzed using compound tropicamide eye drops for both eyes, one drop every 5 min for a total of 5 drops, and the refractive error was measured using the NIDEK ARK-1 autorefractor 20 min later. SER = Spherical power + 1/2 cylinder power.

3.1.2 Axial length (AL)

The AL was measured using the IOL-master 700. The system would automatically measure several times and calculate the average value.

3.1.3 Retinal blood flow

Measurements were performed using the CIRRUS HD-OCT 5000, and the Angio Scan mode was selected for scanning the blood flow images in the range size of 3 mm × 3 mm, with a signal intensity ≥8 being considered a valid image. The machine’s built-in software program automatically calculates retinal surface VD and retinal surface perfusion density (PD)[11].

3.2 Results

3.2.1 Comparison of the baseline data

During the study, 2 subjects in the observation group and 3 subjects in the control group did not complete the 3-month follow-up; these five subjects had only baseline data and were excluded according to the criteria for elimination. In addition, one subject in the observation group and one subject in the control group dropped out after completing the 3-month follow-up,and the missing 6-month follow-up data of these two subjects were imputed by the last-observationcarry-forward method. A total of 32 subjects in the observation group and 31 subjects in the control group were finally included in the statistical analysis. The differences were statistically insignificant (P＞0.05) when comparing the age and gender of the children between the two groups, as shown in Table 1. The differences were statistically insignificant in baseline SER, AL, and the retinal surface VD and PD between the two groups(P＞0.05). Please see Table 2.

3.2.2 Comparison of the change in SER

After 3 months and 6 months of treatment, there were no statistically significant differences in the change in SER from the baseline between the two groups(P＞0.05). It is suggested that auricular acupressure combined with EA failed to show a better effect in slowing down the progression of SER compared with auricular acupressure treatment alone. Please see Table 3.

3.2.3 Comparison of the change in AL

After 3 months of treatment, the difference in the change of AL from baseline between the two groups was not statistically significant (P＞0.05); after 6 months of treatment, the change from baseline in the AL was smaller in the observation group than in the control group, showing statistical significance (P＜0.05). It is suggested that in the present study, compared with auricular acupressure alone, additional EA treatment can better delay the axial elongation in myopic children.Please see Table 4.

3.2.4 Comparison of the change in the retinal blood flow

The change from baseline in the retinal blood flow was compared between the two groups, and the results showed that after 3 months of treatment, the changes from baseline in the retinal surface VD and PD were significantly greater in children in the observation group than in the control group (P＜0.01); after 6 months of treatment, the changes from baseline in the retinal surface VD and PD were still more significant in the observation group than in the control group (P＜0.01).The results suggest that auricular acupressure combined with EA may more significantly increase retinal surface blood flow compared with auricular acupressure treatment alone. Please see Table 5 and Table 6.

Group n Age[M (QL, QU), year]Gender (case)Male Female Observation 32 9.00 (8.00, 9.75) 18 14 Control 31 9.00 (8.00, 10.00) 18 13 Statistical value 0.781) 0.022)P-value 0.43 0.88

Group n SER[M (QL, QU), D]AL(images/BZ_7_1311_2835_1350_2881.png±s, mm)VD in retinal surface layer[M (QL, QU), mm-1]PD in retinal surface layer[M (QL, QU)]Observation 32 -1.48 (-2.00, -1.25) 24.15±0.75 18.97 (17.38, 19.78) 0.33 (0.31, 0.35)Control 31 -1.29 (-2.08, -1.00) 24.24±0.66 19.17 (18.35, 20.02) 0.34 (0.32, 0.36)Statistical value 1.111) 0.542) 1.141) 1.161)P-value 0.27 0.59 0.25 0.25

Group n After 3-month treatment After 6-month treatment Observation 32 -0.18±0.04 -0.41±0.06 Control 31 -0.17±0.04 -0.46±0.04 t-value 0.05 -0.64 P-value 0.95 0.52

Group n After 3-month treatment After 6-month treatment Observation 32 0.13±0.01 0.22±0.02 Control 31 0.12±0.01 0.28±0.02 t-value 0.33 2.13 P-value 0.74 0.04

Group n After 3-month treatment After 6-month treatment Observation 32 1.78±0.42 3.21±0.41 Control 31 -0.60±0.50 1.23±0.42 t-value -3.64 -3.41 P-value ＜0.01 ＜0.01

After 6-month treatment 0.05 (0.03, 0.07)0.01 (-0.01, 0.05)3.21＜0.01

4 Discussion

A survey in 2020 showed that the myopia rate among Chinese adolescents reached 52.7%, and the problem of low myopia age is still prominent[12]. At present, the main ways to delay myopia progression in Western medicine are optical therapy, medication, and surgery,but all of them have different degrees of adverse effects[13-14], so there is still a need to find safe and effective methods for myopia prevention and treatment.

“Can see things near, but cannot see far” is an ancient term for myopia[15]. Auricular acupressure is one of the common methods used in TCM to prevent and control myopia, and it is easy to operate and has few side effects[3,16]. Previous studies have shown that auricular acupressure can slow down the progression of myopia to a certain extent compared to blank controls,but the effect is not very satisfactory[3,17]. EA is based on traditional acupuncture, and it helps to improve the efficacy of acupuncture by enhancing the stimulation to points in the form of electrical pulses. It is worth exploring whether the addition of EA to auricular acupressure treatment can further improve the myopia control effect in children.

In this study, we compared the effect of auricular acupressure combined with EA with the application of auricular acupressure alone on the control of myopia in children, and the results showed that after 6 months of treatment, additional EA treatment slowed the rate of axial elongation compared to the auricular acupressure treatment alone. Most of the previous studies had an acupuncture treatment duration of shorter than 3 months and concluded that acupuncture treatment could not slow down the axial elongation[18-20]. In the present study, there was again no statistical difference in AL progression between the two groups at 3 months,which was consistent with the results of previous studies. However, the 6-month results suggest that the effect of EA on slowing AL progression relies on relatively long-term treatment. The mismatch of the results between AL and SER at 6 months may be related to the small sample size and short observation time. In addition, the routinely used autorefractor with an accuracy of 0.25 D was unable to detect subtle SER change, use of an autorefractor with 0.01 D accuracy would be desirable to verify the current results[21].

The mode of action of acupuncture in myopia control is unclear, and most of the previous studies focused on the investigation of accommodation[22-23]. In recent years, as research intensifies, more and more researchers have redirected their research from the anterior to the posterior segment of the eye. The compensatory increase in AL caused by the production and transmission of abnormal visual signals in the retina is fundamental to the pathogenesis of axial myopia, and retinal blood perfusion is one of the bases for maintaining normal visual function[10,24]. Reduced retinal perfusion leads to oxygen deficiency, restricted retinal adenosine triphosphate supply, and abnormal message transmission, resulting in abnormal visual function[25]. Studies have shown that compared with emmetropic eyes, myopic eyes have narrower retinal vessel diameters, decreased VD, reduced blood perfusion, and retinal VD is negatively correlated with AL[7,26]. In addition, it has been shown that a decrease in mean light sensitivity is associated with a decrease in retinal VD[27]. Therefore, the development of myopia is closely related to retinal blood perfusion. However,clinical studies exploring the control of myopia by acupuncture from the perspective of ocular blood flow changes are relatively rare, and one of the reasons may be that previous methods of ocular blood flow measurement were not convenient enough. Doppler ultrasound, one of the more clinically applied methods to measure ocular blood flow in the past, is mostly used to measure large vessels but shows significant limitations in measuring microvessels[28]. Compared with large vessels, microvessels are closer to the macula,so microvascular perfusion is more significant for visual function[29]. OCTA has the advantages of non-invasive,fast, and clear imaging, and it can clearly display the surface retinal blood flow images, breaking the limitations of previous ocular blood flow imaging methods and providing the possibility and convenience of quantitative analysis of macular blood perfusion[8].

Studies showed that AL and retinal blood perfusion were negatively correlated, and an increase in eye axis length led to a decrease in retinal blood perfusion[30].The results of the present study showed that 6 months of add-on EA increased retinal surface VD and PD compared with auricular acupressure therapy alone.Combined with the results of AL changes in both groups,it is suggested that 6 months of EA therapy may improve abnormal visual signals in the retina by increasing retinal blood flow perfusion, thereby delaying the axial elongation.

The following limitations existed in this study: the sample size was relatively small, and further validation by clinical trials on a larger scale is needed. A blank control group was not set up in this study, and the efficacy of EA plus auricular acupressure was unknown.Considering the increasing attention of guardians to myopia in China and the rapid myopia progression in Chinese children, it is highly likely that the guardians of the subjects would decline randomization to a design including a blank control or drop out during the study period and commence myopia control treatment. We will gradually collect data from children with untreated myopia in the clinic and use historical controls to supplement the results of this study, so as to provide more powerful evidence for the clinical prevention and control of myopia in children.

Conflict of Interest

Author MA Xiaopeng is a member of the Editorial Board ofJournal of Acupuncture and Tuina Science. The paper was handled by other editors and has undergone a rigorous peer review process. Author MA Xiaopeng was not involved in the journal’s review or decisions related to this manuscript.

Acknowledgments

Three-year Development Project for Inheritance and Innovation of Traditional Chinese Medicine of Shanghai[上海市进一步加快中医药传承创新发展三年行动计划(2021 年-2023 年) 项 目, No. ZY(2021-2023)-0105];Shanghai Municipal Health Commission Research Project of Traditional Chinese Medicine (上海市卫生健康委员会中医药科研项目, No. 2020LP017); Sailing Program of Shanghai Science and Technology Committee [上海市科学技术委员会启明星培育( 扬帆专项), No.22YF1444400].

Statement of Informed Consent

Informed consent was obtained from the guardians of the recruited children in this study.

Received: 28 July 2021/Accepted: 28 October 2021