Biodegradable microneedle acupuncture has equivalent efficacy to traditional intradermal acupuncture for dry eye disease: A pilot single-blinded, randomized controlled trial

Abstract

Background:

Dry eye disease (DED) is a common ocular disorder in which the tear film cannot maintain homeostasis. Acupuncture has been used to treat DED in Korean medicine. Particularly, intradermal acupuncture (IDA) is less painful and enables free movement after treatment. However, it can also provoke allergic reactions to metal. To overcome this, biodegradable microneedle acupuncture (BMA) has been developed. This study compared BMA with traditional IDA in terms of efficacy and safety in patients with DED.

Methods:

This study was designed as an investigator-initiated, assessor-blinded, single-center, parallel randomized controlled trial. Thirty patients with DED were enrolled and randomized to one of the treatments. One group was treated with BMA on the acupoints, including bilateral BL2, GB14, TE23, EX-HN5, and ST1. The other group was treated with traditional IDA at the same acupoints. Treatments were conducted 3 times a week for 4 weeks. The major endpoint was ocular surface disease index (OSDI). The minor endpoints were subjective symptoms visual analog scale (VAS), quality of life (QoL), and tear production measured by the Schirmer I test.

Results:

All enrolled participants successfully completed the trial, and all of their data was analyzed. Both treatments remarkably improved the OSDI score, VAS score, QoL score, and tear secretion after 4 weeks (P < .05). Except for tear production in the left eye (P < .05), there were no statistical differences between the 2 treatments on the final visit (P > .05). No adverse events were observed.

Conclusion:

BMA and IDA had the same therapeutic effect for improving DED and both were safe. BMA can be used in patients with DED as an alternative to traditional IDA.

1. Introduction

Dry eye disease (DED) is a complex ocular surface disorder characterized by an unstable tear film. It is accompanied by ocular symptoms including inflammation, ocular surface damage, and patient-subjective discomfort.^[1] Patients with DED complain of various symptoms including eye strain, blurry eyes, poor accommodation, dryness, excessive tear secretion, eye congestion, foreign body sensation, dazzle, and itching.^[2] The worldwide prevalence of DED is estimated to vary between 5% and 50%,^[3] and the domestic prevalence in Korea is also consistently increasing.^[4] In 2020, the number of patients with DED in Korea was 2.45 million people compared with 1.86 million people 10 years ago, representing an increase of 31.7%.^[5] Furthermore, the impact of the 2019 coronavirus disease pandemic has also contributed to an increase in DED because of prolonged facial mask wearing and excessive digital media use.^[6,7]

Conventional medicine has presented diverse therapies for DED, including artificial tears (AT), topical corticosteroids, immunosuppressants, intranasal agents, and punctal occlusion.^[8] However, these are not considered fundamental therapies, and they have several side effects. Meanwhile, Korean medicine has traditionally used acupuncture or herbal medicine for DED.^[9] Acupuncture is the most commonly used Korean medical therapy for DED in clinical practice. Prior studies have also consistently demonstrated the efficacy of acupuncture for DED,^[10–13] but these have been mainly published as case reports.

Intradermal acupuncture (IDA) is a kind of traditional acupuncture in Korean medicine. This acupuncture technique involves embedding a special small needle, such as a thumbtack needle, into the skin for 1 to 3 days in order to treat various chronic conditions.^[14] Owing to its merits, including less pain and simplicity of procedure, IDA has been commonly used to treat DED in clinical practice. However, IDA has a few shortcomings, such as the potential for allergic reactions. As an alternative, a novel medical device called biodegradable microneedle acupuncture (BMA) has been developed. Thus, we compared BMA to traditional IDA in patients with DED in terms of efficacy and safety.

2. Methods

This study was conducted according to a previously published study protocol in 2022.^[15] The descriptions in this section partly reproduce the wording of this protocol.

2.1. Study design, sample size, and enrollment

This study was an investigator-initiated, assessor-blinded, single-center, parallel, pilot randomized controlled trial (RCT). Recruitment and trials were conducted at a single hospital. Because this study was planned as a pilot trial, the sample size was set as 12 people per group according to a previous suggestion.^[16] Taking into account a dropout rate of 20%, 15 participants were needed for each group. Thus, a total of 30 participants were enrolled.

For recruitment of participants, invitations to participate were advertised at a single hospital. A volunteer who was willing to participate received detailed information about the study from the investigators. Then, the participants submitted written consent and were screened for eligibility. If eligible, the participant received a unique identification number.

2.2. Eligible population

Adult patients with DED symptoms aged between the ages of 19 and 65 years were included. Their ocular surface disease index (OSDI) scores had to be ≥ 13. Their tear secretion had to be ≤ 10 mm/5 min as measured by the Schirmer I test (SIT). However, patients were excluded if their DED symptoms were due to ocular problems other than the ocular surface, systemic skin disorders, or blinking difficulty caused by facial palsy. Patients were excluded if they had recently received treatments that could affect tear secretion, including ophthalmic surgery via the anterior chamber, punctal plugs, punctal occlusion, anti-inflammatory eye drops, systemic corticosteroids, or immunosuppressants. Patients were also excluded if they had vitamin A deficiency, ocular injury, active ocular infection, ocular allergy, viral conjunctivitis, high intraocular pressure ≥ 25 mmHg, or glaucoma. Women who were pregnant, breastfeeding, or planning to become pregnant were not permitted to participate.

2.3. Random allocation

Block randomization using statistical software (IBM SPSS Statistics 21, IBM, Armonk, NY) was used to randomize the participants into 2 groups. With a block size of 4, a total of 30 people were randomly allocated to one of 2 groups (50% chance). Therefore, 15 participants were allocated to each intervention.

For eligible participants, the investigators opened a sealed opaque envelope to assign the intervention in front of them. The used envelope was kept in a separate location.

2.4. Interventions

No concomitant treatments other than the 2 interventions were permitted during the study. If a participant used any unauthorized medications, he/she was excluded from the final analysis.

2.4.1. Experimental group.

The experimental group (BMA group) was treated with BMA (RMD-PN1; Raphas Co. Ltd., Seoul, Republic of Korea). Five biodegradable hyaluronic acid microneedles were fixed to a hydrocolloid film. BMA was attached to both sides of 5 acupoints, including BL2, GB14, TE23, EX-HN5, and ST1. The attached BMAs were removed after 4 hours. The participants received the treatment a total of 12 times over 4 weeks.

2.4.2. Control group.

The control group (IDA group) was treated with an IDA needle (T-press needle DB130A; Dongbang Medical, Seongnam, Republic of Korea). The same therapists in the BMA group treated the IDA group on both sides of the aforementioned 5 acupoints. The needles were removed after 4 hours. The participants received the same number of treatments as the BMA group.

2.5. Study procedure

2.5.1. Screening visit.

Patients who wanted to participate received detailed information for this study from the investigators. After obtaining written consent, the investigators conducted interviews and physical examinations to assess eligibility. The data collected were medical and medication history, vital signs, visual acuity, OSDI score, and tear secretion. Based on the eligibility criteria, eligible participants received an identification code. At the end of each visit, the participants were informed of the date of the next visit.

2.5.2. Visit 1.

Visit 1 was arranged within 7 days from the screening visit. On this visit, eligible participants were randomized and received initial treatment. They were permitted to arrange this visit at the same time as the screening visit. Prior to treatment, the investigators examined the participants for changes in medical and medication history. Outcome measures were examined. Some assessments, including vital signs, changes in medical and medication history, visual acuity, and adverse events (AEs), were examined at each visit. Prior to treatment, the participants were randomized to the BMA or IDA group. The therapist treated the patients with the assigned interventions.

2.5.3. Visits 2-12.

During this period, investigators recorded the changes in regular examinations. The assigned interventions were continuously delivered to the participants during this period. On visit 7, midterm assessment, except for the SIT, was performed before treatment.

2.5.4. Visit 13.

Visit 13 was arranged 4 weeks after visit 1. Some participants were permitted to complete visit 13 on the same day as visit 12. Investigators examined the changes in regular checkups since visit 12. The final examination was made for all endpoints. General assessment and participants’ compliance were also examined during this visit.

2.6. Endpoints

2.6.1. OSDI.

The primary endpoint was the OSDI.^[17] The OSDI consists of a total of 12 questions on visual acuity, ocular symptoms, and aggravated environments.^[18] Severity was rated from 0 to 4 according to the frequency of symptoms. The following formula was used to calculate the overall score.^[19]

$${\displaystyle \begin{array}{l}{\displaystyle \mathrm{O}\mathrm{S}\mathrm{D}\mathrm{I}\mathrm{s}\mathrm{c}\mathrm{o}\mathrm{r}\mathrm{e}=\frac{\left(\begin{array}{lll}& {\displaystyle \mathrm{s}\mathrm{u}\mathrm{m}\mathrm{o}\mathrm{f}\mathrm{s}\mathrm{c}\mathrm{o}\mathrm{r}\mathrm{e}\mathrm{s}\mathrm{f}\mathrm{o}\mathrm{r}\mathrm{a}\mathrm{l}\mathrm{l}}& {\displaystyle \mathrm{q}\mathrm{u}\mathrm{e}\mathrm{s}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}\mathrm{s}\mathrm{a}\mathrm{n}\mathrm{s}\mathrm{w}\mathrm{e}\mathrm{r}\mathrm{e}\mathrm{d}}\end{array}\right)\times 100}{\left(\begin{array}{lll}& {\displaystyle \mathrm{t}\mathrm{o}\mathrm{t}\mathrm{a}\mathrm{l}\mathrm{n}\mathrm{u}\mathrm{m}\mathrm{b}\mathrm{e}\mathrm{r}\mathrm{o}\mathrm{f}}& {\displaystyle \mathrm{q}\mathrm{u}\mathrm{e}\mathrm{s}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}\mathrm{s}\mathrm{a}\mathrm{n}\mathrm{s}\mathrm{w}\mathrm{e}\mathrm{r}\mathrm{e}\mathrm{d}}\end{array}\right)\times 4}}\end{array}}$$

If a participant did not respond to a question, the question was marked as “not applicable.” The score ranges from 0 to 100. Higher scores indicated greater discomfort.

2.6.2. Subjective symptoms visual analog scale (VAS).

The VAS was scored by rating the discomfort caused by DED in the past week on a 100-mm line. The left end of the scale indicated “no symptoms,” and the right end indicated “the worst discomfort.” When the participants marked a point on the line, the length from the left end to the point was measured as the score.

2.6.3. Quality of life (QoL).

The QoL evaluated the life of the participants related to DED symptoms in the past week. It was rated from 0 (best) to 6 (worst) by the participants themselves. The participants were asked the following question: “During the last week, how was the overall quality of your life related to dry eye symptoms?”

2.6.4. SIT.

The SIT was used to evaluate tear production. The folded tip of a Schirmer strip (BIO Color Tear Test; Bio Optics, Seongnam, Republic of Korea) was placed at the lateral 1/3 point of the lower conjunctival sac. Immediately after insertion, the participants closed their eyes for 5 minutes with their eyes facing upward. The investigators then measured the distance of the tear-soaked strip.

2.6.5. Safety assessment.

AE was defined as any unintended result that occurred despite appropriate use of the medical device. The expected AEs of IDA were local pain and/or bleeding at the treated area, skin allergy, infections, headache, and/or faint symptoms due to acupuncture.^[20,21] For BMA, in addition to the expected AEs of IDA, redness, irritation, and/or erosion in the treated area were also expected. Investigators checked and recorded the occurrence of AEs in the CRF at each visit.

2.7. Endpoints analysis

The same analysis was done for all endpoints. For within-group comparisons, the differences before and after treatment were compared using the Student’s paired t test or Wilcoxon signed-rank test depending on normality. The differences between the 2 groups at each visit were compared using the two-sample t test or Mann–Whitney U test depending on the normality.

2.8. Ethics

This study was approved by the Institutional Review Board of Naju Dongshin University Korean Medicine Hospital (approval no. NJ-IRB-015). The study protocol using an experimental medical device was approved by the Ministry of Food and Drug Safety, Republic of Korea (approval No. 1337). This study was registered with the Clinical Research Information Service of the Republic of Korea (registration no. KCT0007358). The investigators abided by the tenets of the Declaration of Helsinki. The investigators provided detailed information about the study to the patients and commenced the study after obtaining their informed consent.

3. Results

3.1. General characteristics of the participants

The first participant was enrolled on July 6, 2022, and the study ended on September 19, 2022. Thirty participants completed the trial and there were no dropouts. All participants were analyzed (Fig. 1). The mean age was 34.3 ± 12.36 years. There were slightly more women than men. The mean height and weight were 165.6 ± 8.60 cm and 63.2 ± 13.93 kg, respectively. Apart from one, all participants were nonsmokers. The ratio of drinkers to nondrinkers was similar. There were no statistical differences in the general characteristics between the participants in the BMA and IDA groups (Table 1).

Figure 1.

The CONSORT diagram. Thirty participants are recruited and all finish the trial (no dropouts). BMA group = biodegradable microneedle acupuncture treatment group, IDA group = intradermal acupuncture treatment group, ITT = intention-to-treat, PP = per protocol.

Table 1.

Participants’ general characteristics.

	BMA group (n = 15, mean ± SD)	IDA group (n = 15, mean ± SD)	Total (n = 30, mean ± SD)	P value*
Age (years)	32.4 ± 11.51	36.3 ± 12.86	34.3 ± 12.36	.283
Sex				.717
Male (%)	7 (46.7)	6 (40.0)	13 (43.7)
Female (%)	8 (53.3)	9 (60.0)	17 (56.7)
Height (cm)	165.5 ± 8.86	165.7 ± 8.34	165.6 ± 8.60	.884
Weight (kg)	63.1 ± 15.20	63.2 ± 12.53	63.2 ± 13.93	1.000
Smoking				.317
Smoker (%)	0 (0.0)	1 (7.1)	1 (3.3)
Nonsmoker (%)	15 (100.0)	14 (92.9)	30 (96.7)
Drinking				.277
Drinker (%)	5 (33.3)	8 (53.3)	13 (43.7)
Nondrinker (%)	10 (66.7)	7 (46.7)	17 (56.7)

BMA group = biodegradable microneedle acupuncture treatment group, IDA group = intradermal acupuncture treatment group, SD = standard deviation.

^*Comparisons between the BMA group and the IDA group.

3.2. Decline in the OSDI score

For 4 weeks, the OSDI scores of both groups steadily declined. On visit 1, the scores of both groups indicated a severe condition.^[18] On visit 7, the scores declined by about 15 points, but the severity of both groups remained severe. On visit 13, the scores declined by approximately 35 points, indicating a moderate condition.^[18] However, there were no statistically significant differences between the 2 groups at any visit (Table 2).

Table 2.

Shifts in the endpoints.

Endpoint	Visit	BMA group (n = 15, mean ± SD)	IDA group (n = 15, mean ± SD)	P value†
OSDI	Visit 1	57.1 ± 20.42	60.8 ± 14.47	.633
	Visit 7	43.5 ± 17.73	45.5 ± 15.20
	Difference‡	−13.6 ± 8.40	−15.3 ± 9.29	.479
	P value§	.001*	.001*
	Visit 13	22.4 ± 16.22	25.6 ± 13.35
	Difference‖	−34.7 ± 12.34	−35.2 ± 14.77	.983
	P value§	.001*	.001*
Subjective symptoms VAS (unit: mm)	Visit 1	62.7 ± 14.86	68.7 ± 15.98	.209
	Visit 7	48.0 ± 15.68	55.3 ± 15.52
	Difference‡	−14.7 ± 8.34	−13.3 ± 4.88	.900
	P value§	.000*	.000*
	Visit 13	30.7 ± 13.35	38.0 ± 15.21
	Difference‖	−32.0 ± 11.46	−30.7 ± 11.00	.758
	P value§	.001*	.001*
QoL	Visit 1	3.7 ± 0.88	3.9 ± 0.83	.729
	Visit 7	2.9 ± 0.64	2.9 ± 0.70
	Difference‡	−0.9 ± 0.52	−0.9 ± 0.46	.694
	P value§	.001*	.000*
	Visit 13	1.5 ± 0.64	1.8 ± 0.68
	Difference‖	−2.2 ± 0.77	−2.1 ± 0.59	.699
	P value§	.000*	.000*
SIT, OS (unit: mm)	Visit 1	4.1 ± 2.05	5.3 ± 2.35	.119
	Visit 13	15.9 ± 9.47	9.5 ± 6.05
	Difference‖	11.81 ± 9.41	4.1 ± 6.99	.025*
	P value§	.001*	.025*
SIT, OD (unit: mm)	Visit 1	5.7 ± 2.31	4.7 ± 2.05	.216
	Visit 13	14.6 ± 10.08	12.7 ± 7.71
	Difference‖	8.9 ± 9.82	7.9 ± 7.22	.868
	P value§	.002*	.001*

BMA group = biodegradable microneedle acupuncture treatment group, IDA group = intradermal acupuncture treatment group, OD = oculus dexter, OS = oculus sinister, OSDI = ocular surface disease, QoL = quality of life, SD = standard deviation, SIT = Schirmer I test, VAS = visual analog scale.

^*P < .05.

^†Comparisons between the BMA group and the IDA group.

^‡Visit 7-visit 1.

^§Comparisons between before and after treatments.

^‖Visit 13-visit 1.

3.3. Decline in the subjective symptoms VAS score

For 4 weeks, the VAS scores of both groups steadily declined. On visit 1, the scores of the BMA and IDA groups were 62.7 ± 14.86 mm and 68.7 ± 15.98 mm, respectively. On visit 7, the scores declined by approximately 14 mm. On visit 13, the final scores of both groups were 30.7 ± 13.35 mm and 38.0 ± 15.21 mm, respectively. However, there were no statistically significant differences between the 2 groups at any visit (Table 2).

3.4. Enhancement of the QoL

A lower QoL score represents a better QoL. For 4 weeks, both treatments steadily enhanced the QoL of the participants. On visit 1, the QoL scores of the BMA and IDA groups represented a moderate decrease in QoL due to DED. On visit 7, the scores declined by 0.9 points. On visit 13, the final scores of both groups were 1.5 ± 0.64 and 1.8 ± 0.68 points, respectively. However, there were no statistically significant differences between the 2 groups at any visit (Table 2).

3.5. Increase in tear secretion

In the left eye, the SIT results of both groups were less than 10 mm on visit 1, which corresponded with the diagnostic criterion of SIT for DED. On visit 13, the BMA raised tear secretion to a normal level. IDA also raised tear secretion compared with visit 1, but the final secretion was slightly below the normal level. Statistical analysis suggested a significant difference between the 2 groups on visit 13 (Table 2).

In both groups, the right eye also secreted tears that amounted to less than 10 mm of soaking of the test strip, which was sufficient to diagnose DED. In the left eye, the final secretion of both groups increased to normal levels at visit 13. However, there were no statistical differences between the 2 groups at visit 13 (Table 2).

3.6. Safety

No AEs were reported during the trial.

4. Discussion

From July 6, 2022, to September 19, 2022, 30 participants with DED were treated with BMA or IDA for 4 weeks. The results show that both treatments remarkably improved the OSDI score, VAS score, QoL score, and tear secretion. Despite remarkable improvements after treatment, there were no statistical differences between the 2 groups on visit 13. The participants safely completed the trial without any AEs.

This study only blinded an investigator who met with the participants in assessing the endpoints. Double-blinding is challenging because of the appearance of BMA and IDA. They could be distinguished by the participants when they were treated. Instead, the assessor was blinded to the study. The assessor was only allowed to meet the participants when examining the endpoints. In addition, the assessor was provided with a separate form to record the results that could not identify the participant.

To treat DED, this study stimulated 5 acupoints including BL2, GB14, TE23, EX-HN5, and ST1 for 4 hours in both groups. The treatments were conducted 3 times a week for 4 weeks. Five acupoints were selected according to previous studies on DED,^[9,22,23] and these acupoints have been commonly used to treat ocular diseases. Treatment time and frequency were determined according to a multicenter RCT on the efficacy of acupuncture for DED^[23] and our previous RCT on IDA for patients with DED (not yet published).

Acupuncture and moxibustion therapy in Korean medicine have shown remarkable efficacy for DED in many studies. Domestic and foreign studies on DED have suggested that Korean medicine therapies are more effective than AT in terms of the major endpoints for DED, including the OSDI, tear film breakup time (TFBUT), and tear secretion.^[23–26] IDA is a type of acupuncture technique that gently stimulates acupoints for a long time by embedding a small needle in the skin. This therapy originated from “shallow needling in classical acupuncture and “needle retention method in “Huangdi’s Internal Classic.”^[27] IDA has several merits owing to its small size. IDA is less painful than conventional body acupuncture and enables children or adults who fear needles or pain to receive acupuncture therapy. The small needle used in IDA does not disturb physical movement, even when the needle is attached to the body. Until now, previous studies on IDA have primarily concentrated on the analgesic effects.^[28–30] Recent studies are investigating the potential application of IDA in the treatment of neuropsychiatric diseases, such as major depressive disorder and insomnia.^[31–33]

Regarding the use of IDA on DED, several studies have been published. Lu and Chen^[34] suggested that the combination of IDA and AT has a greater therapeutic effect than AT alone in 88 patients with DED, which is worthy of being widely adopted in clinical practice. Ma et al^[35] also compared the combination of IDA and AT with the use of AT alone in a study involving 80 patients with DED, which demonstrated that combination of IDA and AT was superior in terms of subjective symptoms, tear secretion, TFBUT, and corneal fluorescein staining. Wu et al^[36] suggested that both IDA and AT were effective in improving OSDI, noninvasive TFBUT, and tear secretion in 20 patients with DED, but IDA promoted greater tear secretion than AT. Qian et al^[37] observed the efficacy of IDA in 76 patients with DED after pterygium excision, and IDA significantly improved the VAS score 3 days after excision, symptoms of DED, tear secretion, and TFBUT. The acupoints mainly used in those studies were BL2, TE23, ST2, EX-HN4, and EX-HN5, which are located in the periocular region and are similar to those in this study.

However, IDA has a few shortcomings. It can cause irritation to the patient when attached for a long time. Additionally, IDA can trigger allergic symptoms in patients who are sensitive to metals. BMA, a novel medical device, overcomes the shortcomings of traditional IDA. The material used in the microneedles of the BMA was hyaluronic acid. Hyaluronic acid is a natural macromolecule that degrades in the body, and the safety of injecting it into the body has been well established.^[38,39] Thus, the microneedles of the BMA do not trigger allergic skin irritations when compared with the stainless steel needle of the IDA.^[40] In addition, the number of needles in BMA was increased to 5 in order to enhance the therapeutic effect.

The original form of the BMA is based on a microneedle patch that promotes percutaneous drug delivery by perforating the skin barrier with microneedles.^[41,42] Meanwhile, the BMA and traditional IDA needles are alike in terms of appearance. The BMA consists of 5 microneedles fixed on a film. The IDA needle consists of a small needle fixed on a small plaster. Given their similarity, the BMA was expected to have equivalent therapeutic effects to the IDA needle.

Including the results of this study, the therapeutic effects of acupuncture on DED have been supported by numerous previous studies.^{[10–13,23,25,26,34–37]} However, the detailed mechanisms that can explain how acupuncture improves DED are still unclear.^[43] Until now, the proposed mechanisms of acupuncture for DED include promoting tear secretion, providing analgesic effects for neuropathic pain, suppressing inflammatory responses, improving ocular blood flow, and regulating the nervous and immune systems.^[43,44] In this study, IDA is one of the traditional acupuncture techniques, while BMA is a newly developed medical device based on the IDA technique. Therefore, both BMA and IDA may have functioned as the proposed mechanisms of acupuncture in patients with DED. Furthermore, stimulating periocular acupoints with BMA or IDA in this study may have alleviated DED by stabilizing the tear film, as IDA has improved the results of TFBUT and SIT in similar studies.^[35–37]

This clinical trial, which observed the efficacy and safety of a newly developed medical device, is significant because it can serve as evidence or a basis for further studies to register the BMA with the “New Health Technology” of the National Evidence-based Healthcare Collaborating Agency. Furthermore, this study will enhance the safety of acupuncture treatment. Acupuncture has already been recognized as a relatively safe treatment option.^[45] However, numerous minor local AEs, such as local inflammation, itching, and redness, have been reported,^[46] which may also be involved in the shortcomings of IDA. If BMA becomes more popular through this study, the safety of acupuncture will be enhanced by reducing the incidence of AEs. This study is also noteworthy because BMA is the product of the convergence of traditional IDA and modern microneedle patch technology.

On the other hand, this study has a few limitations. One limitation was the small sample size. This study only enrolled 15 participants for each group. However, this study was planned as an explanatory trial prior to a larger confirmatory clinical trial. Further studies will recruit more participants to aim to confirm the superiority of BMA based on this study. Another limitation was the absence of additional follow-up after treatment termination. Additional follow-up may have enabled the comparison of the persistence of the efficacy of the 2 treatments. The other limitation was the absence of the positive control group that received conventional treatment, such as AT. Because this study aimed to observe the efficacy of BMA, it focused on comparing BMA to a similar medical device. Further studies would include a control group that receives a representative Western medical treatment.

In conclusion, BMA and IDA remarkably improved the OSDI score, subjective symptoms VAS score, QoL score, and tear secretion in patients with DED after 4 weeks of treatment. As there were no differences between the 2 treatments, we concluded that BMA and IDA have the same therapeutic effect on DED. Moreover, the 2 treatments were safe because there were no AEs. These findings suggest that BMA can be used as an equivalent alternative for patients with DED who are sensitive to the metal used in traditional acupuncture.

Acknowledgments

We would like to thank Editage (www.editage.co.kr) for English language editing.

Author contributions

Conceptualization: Soo-Yeon Park.

Data curation: Soo-Yeon Park.

Formal analysis: Soo-Yeon Park.

Funding acquisition: Soo-Yeon Park.

Investigation: Ji-Hoon Song, Soo-Yeon Park.

Methodology: Soo-Yeon Park.

Project administration: Soo-Yeon Park.

Supervision: Soo-Yeon Park.

Visualization: Ji-Hoon Song.

Writing – original draft: Ji-Hoon Song.

Writing – review & editing: Ji-Hoon Song, Soo-Yeon Park.