Abstract
Background:
Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis.
Methods:
A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described.
Results:
Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = –2.08, 95% CI (–2.96, –1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups.
Conclusion:
The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.
Keywords: acupuncture, artificial tears, dry eye syndrome, meta-analysis
1. Introduction
Dry eye syndrome (DES) refers to a chronic inflammatory disease characterized by the infiltration of various inflammatory factors caused by internal and external factors. Dryness and abnormal eye sensations are the main clinical features, and low vision may occur in severe cases.[1] Various factors can cause decreased tear secretion and dysfunction of the meibomian gland, ultimately resulting in DES.[1–3] Eye discomfort that lasts for a long time can significantly impact people’s quality of life, and research has indicated a significant positive correlation between dry eye and levels of anxiety and depression.[4] With the influence of many factors, such as air pollution, long-term eye fatigue, or population aging, the prevalence of DES is increasing yearly. For example, in China, the prevalence of DED has reached 21% to 30%. With changes in the social environment and living environment, it is estimated that its incidence may increase in the future.[5] There are limited options for treating dry eye, such as using artificial tears (AT), undergoing hormone therapy, or taking anti-inflammatory measures.[6] Patients with dry eyes experience limited therapeutic benefits from using topical ophthalmic medications. Additionally, surgical treatment is often rejected due to high costs and potential complications. As a result, effective and complementary treatments are needed for DES.
Traditional Chinese medicine (TCM) is more convenient, less expensive, and more effective than Western medicine treatment in China. The efficacy and safety of acupuncture (AC) in treating diseases such as osteoarthritis, headache, and others have been explored.[7,8] Studies have shown that AC may have potential therapeutic significance for dry eye.[9,10] Over time, there have been more clinical studies focused on using a combination of AC and AT to treat dry eye. Based on clinical observations, patients have experienced some improvement in their symptoms, signs, and laboratory indicators without any harmful side effects. However, there have not been many large-scale multicenter randomized controlled clinical trials conducted. The current research is scattered, with mostly single reports and small sample sizes. Therefore, this study aims to provide useful evidence on the effectiveness of AC combined with AT in treating DES by systematically analyzing existing data. This review followed the PRISMA statement.[11]
2. Materials and methods
2.1. Literature source
A based online systematic search was conducted in databases including PubMed, Cochrane Library, Web of Science, Chinese Scientific Journal Database Journal, China National Knowledge Infrastructure, and Wanfang Data without language limits up to July 1st, 2023. The following medical terms were used for the search: “Dry Eye” or “Dry Eye Syndrome” or “Dry Eye Disease” or “Xerophthalmia” or “Keratoconjunctivitis Sicca” or “Bai se Zheng (description of Dry Eye Syndrome in Chinese Medicine)” and “Acupuncture” or “Acupuncture therapy” or “Electroacupuncture” or “Needling” and “Artificial tears” or “Lubricant Eye Drops” or “Sodium Hyaluronate Eye Drops.”
2.2. Selection criteria
The inclusion criteria of trials were as follows: study design: randomized or controlled trials. Patients met the diagnosis of DES classification criteria: the tear film breakup time (BUT) < 10 seconds and the Schirmer I test (SIT) with outcome < 10 mm per 5 min in either one or both eyes. The trial group was turned to AC combined with AT for treating DES, and the control group received AT or other therapy methods.
The exclusion criteria were as follows: noncontrolled studies; patients with the diagnostic criteria of DES, including defects of the eyelid or eyelashes; acute infections of the eyelid, eyeball, or ocular accessory; Stevens–Johnson syndrome; vitamin A deficiency; defects of the eye or accessory due to external injury, a history of surgical procedures related to the eye, punctal occlusion, current use of contact lenses, consequence of facial paralysis, current use of anti-inflammatory eye drops in the last 3 weeks, and pregnancy; clinical studies of poor quality; duplicate or incomplete publications; and letters, comments, reviews, and animal studies. As this study was based on the data available online, no ethical approval was applicable in this study.
2.3. Data extraction
Two authors independently reviewed the abstracts and article titles of each included study. The sample size, participant information, objective outcomes, and treatment protocol of the included studies were summarized, and the AC treatment details of each study were also extracted. We considered BUT and SIT as the main outcomes for evaluating the efficacy of clinical treatment and considered corneal fluorescein staining (CFL), ocular surface disease index assessed using a questionnaire, and clinical efficacy as the secondary outcome measures. The differences were settled via discussions with all authors. The authors were contacted by e-mail for additional information if data were unavailable. All analysis were based on previous published studies, thus no ethical approval and patient constent are required.
2.4. Data synthesis and statistical methods
The meta-analysis was performed using Review Manager 5.3. The standard mean difference (SMD) with 95% confidence interval (95% CI) was used for continuous data, and odds ratio with 95% CI was applied for dichotomous variables. A P value < .05 indicated a statistically significant difference. The heterogeneity in the studies was quantified using the chi-square test based on the P value and I2 statistic. The fixed-effects model was used for homogeneity (P > .1 or I2 < 50%); otherwise, the random-effects model was used. The funnel plot displayed publication biases.
3. Results
3.1. Literature source
We found 1207 potential correlations through a database search. To eliminate duplicates, we sifted through 584 studies that could be relevant based on their titles and abstracts. Out of those, we read the full text of 216 studies and analyzed 17 randomized or controlled trials which had 1517 participants in total for the evaluation.[12–28] The flow diagram presented in Figure 1 illustrates the process used to search for literature on this topic. All publications included in the search were published between 2012 and 2023. According to the original text, there were no significant differences in age and sex among the patients in these studies. Table 1 offers detailed information about the studies and treatments. The most outcomes described in all studies were BUT and SIT, subsequently followed the efficacy.
Figure 1.
Flow diagram of the study selection process.
Table 1.
Characteristics of the eligible studies.
| Studies author, year (Study period) | Total patients/Trl | Age, years Trl (Ctrl) | Genders, M/F total (Trl) | Intervention/Trl (Ctrl) | Treatment course | Outcomes | Follow-up |
|---|---|---|---|---|---|---|---|
| Bai, 2016[12] (2013.5–2014.5) | 70/35 | 31.6 ± 2.7 (34.5 ± 14.5) | 40/30 (20/15) | AC + AT (AT) | 21 d | Efficacy, BUT, SIT, CFL | 3 wk |
| Chen,2023[13] (2018.6–2022.12) | 200/100 | 52.79 ± 2.68 (52.82 ± 2.72) | 71/129 (36/64) | AC + AT (AT) | 8 wk | Efficacy, BUT, SIT, IL-6, TNF-α, SPS, tear meniscus height | 6 mo |
| Chu, 2019[14] (2017.5–2018.5) | 80/40 | 48.87 ± 5.85 (48.56 ± 5.82) | 49/31 (15/25) | AC + AT (AT) | 40 d | Efficacy, BUT, SIT, CFL, OSDI | NM |
| Huang, 2012[15] (2009.4–2009.12) | 92/38 | 51.3 ± 10.1 (53.8 ± 10.9) | 28/64 (12/26) | AC + AT (AT) | 21 d | Efficacy, BUT, SIT, CFL | 3 wk |
| Huang, 2020[16] (2016.1–2018.1) | 84/42 | 38.6 ± 4.7 (39.3 ± 4.5) | 29/55 (14/28) | AC + Moxibustion + AT (AT) | 4 wk | Efficacy, BUT, SIT, CFL, IL-1, IL-6, TNF-α, SPS | NM |
| Kim, 2012[17] (2010.4–2010.11) | 150/75 | 47.95 ± 11.11 46.05 ± 13.10 | 41/109 (22/53) | AC + AT (AT) | 12 wk | BUT, SIT, OSDI, QOL, Visual analogue scale | 8 wk |
| Li, 2023[18] (2022.1–2022.7) | 78/39 | NM. | NM. | AC + AT (AT) | 1 mo | Efficacy, BUT, SIT, CFL, SPS, self-rating anxiety scale score | NM |
| Lin, 2022[19] (2019.6–2021.6) | 80/40 | 43 ± 15 (42 ± 14) | 36/44 (17/23) | AC + AT (AT) | 5 wk | Efficacy, BUT, SIT, CFL, OSDI, IL-6, TNF-α | NM |
| Liu, 2014[20] (2013.1–2014.6) | 90/45 | 47.19 ± 12.21 | NM | AC + AT (AT) | 1 mo | Efficacy, BUT, SIT | NM |
| Liu, 2019[21] (2015.3–2018.2) | 60/30 | 34.82 ± 2.91 (35.27 ± 3.06) | 29/31 (15/15) | AC + AT (AT) | At least 10 d | Efficacy, BUT, SIT, CFL, Visual function score | NM |
| Mao, 2015[22] (2010.1–2013.12) | 84/42 | 51.8 ± 9.2 (53.4 ± 7.8) | 40/44 (19/23) | AC + Moxibustion + AT (AT) | 20 d | BUT, SIT, CFL, Visual function score | 1-6 mo |
| Qiu, 2019[23] (2015.3–2017.12) | 80/40 | 49 ± 3 (49 ± 3) | 0/80 (0/40) | AC + AT (AT) | 1 mo | Efficacy, BUT, SIT, OSDI, Lacrimal lactoferrin | NM |
| Que, 2022[24] (2019.1–2020.5) | 80/40 | 64.5 ± 7.6 (63.3 ± 7.7) | 42/38 (23/17) | AC + AT (AT) | 4 wk | Efficacy, BUT, SIT, CFL, OSDI | 4 wk |
| Shi, 2020[25] (2018.6–2019.12) | 60/30 | NM | NM | AC + AT (AT) | 2 wk | Efficacy, BUT, SIT | NM |
| Sun, 2022[26] (2015.10–2019.6) | 70/35 | 48 ± 12 (44 ± 11) | 27/38 (15/18) | AC + AT (AT) | 2 wk | Efficacy, BUT, SIT, CFL, SPS, Hamilton anxiety scale score | NM |
| Wang, 2021[27] (2015.11–2018.5) | 108/54 | 49/51 (27/22) | 42.7 ± 13.2 (41.8 ± 14.3) | AC + AT (AT) | 10 d | Efficacy, BUT, SIT, CFL, SPS, IL-6, TNF-α, Duration of photopic vision | NM |
| Zhao, 2019[28] (2013.10–2014.10) | 80/40 | 37.8 ± 10.7 (35.9 ± 11.5) | 36/44 (17/23) | AC + AT (AT) | 2 mo | Efficacy, BUT, SIT | NM |
Data presented as mean ± standard deviation.
AC+AT = acupuncture plus artificial tears, AT = artificial tears, BUT = tear breakup time, CFL = corneal fluorescein staining, Ctrl = control group, M/F = male/female, NM = not mentioned, OSDI = ocular surface disease index, SIT = Schirmer I test, SPS = subjective perception score, Trl = trial group, VRQOL = the symptom score and vision related quality of life.
In clinical practice, there are different acupuncture techniques available for treating dry eye syndrome. Table 2 lists the acupuncture methods and points used in each study. The most point selection for DES is proximal points combined with distal point. The top 3 proximal points of eye selected in these studies were BL1 (Jing Ming), BL2 (Zan Zhu), and EX-HN5 (Tai Yang). The top 3 distal points in all studies were LI4 (He Gu), SP6 (San Yin Jiao), and KI3 (Tai Xi).
Table 2.
Acupuncture treatment details of the included trials.
| Studies author, year (Study period) | Point selection | Insertion depths | Acupuncture rationale | Time retention of needle | Needle type |
|---|---|---|---|---|---|
| Bai, 2016[12] (2013.5–2014.5) | BL2, BL1, EX-HN5, LI4, ST2, SP6, KI3, GB20 | NM | Move qi and invigorate blood | 20 min | NM |
| Chen, 2023[13] (2018.6–2022.12) | Proximal point: BL1, BL2, ST23, ST2, GB1, ST1; distal point: LI4, ST36, SP6, SP9 | NM. | unblock the channels and quicken the collaterals | 30 min | 0.3 mm*40 mm for all points |
| Chu, 2019[14] (2017.5–2018.5) | Proximal point: BL1, SP6, ST2, BL2, GB20, DU20, EX-HN5; distal point: ST36, LR3, KI3, SJ5, RN6, LI11, RN12, LU9, ST25 | 1–2 cm for proximal point; 3–4 cm for distal point | invigorate blood and dissolve stasis | 20 min | NM |
| Huang, 2012[15] (2009.4–2009.12) | BL1, BL2, EX-HN5, ST2, LI4, SP6, B20, KI3 | NM | Move qi and invigorate blood | 20 min | NM |
| Huang, 2020[16] (2016.1–2018.1) | Host point:BL1, DU20, EX-HN5, BL2, GB20, ST2; Guest combination points: lung yin deficiency (LU5, BL13, LI4, LU7) liver-kidney yin deficiency (BL23, BL18, KI3, LR3) spleen and stomach damp-heat (ST36, BL20, SP6, ST40) | 2–3 cm for all points | Differentiation of syndrome | 25 min | 0.25*25 mm for host point;0.3*40 mm for guest combination points |
| Kim, 2012[17] (2010.4–2010.11) | bilateral BL2, GB14, TE 23, Ex1, ST1, GB20, LI4, and LI11 and single GV23 | 1.5–3 cm for BL2, TE23, Ex1; 0.9–1.5 cm for GB14, GV23; 3–4.5 cm for LI4, LI11; 0.6–0.9 cm for ST1 | NM. | 20 min | 0.20*30 mm acupuncture needles for all points |
| Li, 2023[18] (2022.1–2022.7) | Proximal point: BL1, BL2, ST23, ST1, EX-HN4, EX-HN5, DU24; distal point: LI4, SP6, SP9, LR3 | 1 cm for proximal point;1.5–3 cm for distal points | clear heat and open the orifices | 20 min | 0.25*25 mm for proximal point; 0.25*40 mm for distal points |
| Lin, 2022[19] (2019.6–2021.6) | Proximal point: BL1, BL2, ST23, ST1, ST2, EX-HN4, EX-HN5, DU20, GB20; distal point: LI4, SP6, LR3, GB37, SJ5, LI11 | 10–20 mm for proximal point; 18-20 mm for DU20; 25–30 mm for GB20; 20–30 for distal point | unblock the orifices and invigorate blood | 30 min | 0.25 mm*25 mm for BL1, 30 mm*25 mm and 0.30 mm*40 mm for the other points |
| Liu, 2014[20] (2013.1–2014.6) | BL1, DU20, BL2, SJ23, EX-HN5, ST2, GB20 | NM | NM | 30 min | 0.25*40 mm for all point |
| Liu, 2019[21] (2015.3–2018.2) | Host point:GB20, BL1, BL2, ST2, EX-HN5, DU20, DU24; guest combination points consistent with Huang 2020 | NM | Differentiation of syndrome | 20 min | NM |
| Mao, 2015[22] (2010.1–2013.12) | Host point:GB20, BL1, BL2, ST2, EX-HN5, DU20, DU24; combination points consistent with Huang 2020 | NM | Differentiation of syndrome | 20 min | NM |
| Qiu, 2019[23] (2015.3–2017.12) | Proximal point:GB20, BL1, BL2, ST2, EX-HN5, DU20, DU24; guest combination points consistent with Huang 2020 | NM | Differentiation of syndrome | 20 min | 0.3*25 mm for the host point;0.3*40 mm for guest combination points |
| Que, 2022[24] (2019.1–2020.5) | Lung yin deficiency point:LU9, PC7, LI4, SP3, ST42, SJ4, SI4; liver-kidney yin deficiency point:LR3, KI3, GB40, BL64, ST42 | 1–2 cm for all points | Differentiation of syndrome | 20–30 min | NM |
| Shi, 2020[25] (2018.6–2019.12) | Proximal point: DU20, ST8, EX-HN5, BL1, BL2, ST1; distal point: BL13, BL18, BL23, LI11, LI4, ST36, SP6, LR3 | 2–3 cm for all points | NM | 30 min | 0.3*25 mm for all point |
| Sun, 2022[26] (2015.10–2019.6) | DU24, TF4, GB13, KI3, LR3, GB37, GB20, GB1, EX-HN4, ST23 | 15–25 mm for DU24, GB13, LR3, KI3, GB1, GB37; 10–15 mm for TF4; 20–30 mm for GB20 | Enrich and nourish liver-kidney | 30 min | 0.25 mm*40 mm for all points |
| Wang, 2021[27] (2015.11–2018.5) | Proximal point: BL1, BL2, ST23, GB11, EX-HN5; distal point: LI4, ST36 | 15–20 mm for GB1; 10–12 mm for the other proximal point; 10–20 mm for distal point | Unblock the channels and invigorate blood | 30 min | 0.25*25 mm for proximal point; 0.25*40 mm for distal points |
| Zhao, 2019[28] (2013.10–2014.10) | SJ23, EX-HN5, BL1, DU20, BL2, GB20, LI4, ST1, LR3, BL18, SP6, BL26, BL23 | NM | NM | 30 min | 0.25*40 mm for all point |
Point selection was described according to WHO Standard Acupuncture Point Locations.
NM = not mentioned.
3.2. Quality assessment of the included studies
Table 3 and Figure 2 provide a summary of the assessment’s methodological quality. Out of the 9 studies, randomized control trials were mentioned and 5 of them discussed the appropriate method of sequence generation. Only 1 study mentioned allocation concealment and blinding.[20] No studies described withdrawals and dropouts.
Table 3.
Assessment of quality of the included studies.
| Studies (Author, year) | Randomization | Allocation concealment | Blinding | Incomplete outcome data | Withdrawals and dropouts |
|---|---|---|---|---|---|
| Bai, 2016[12] | Yes | NM | Subject blind | No | No |
| Chen, 2023[13] | Yes, RNT | NM | Subject blind | No | No |
| Chu, 2019[14] | Yes, RNT | NM | Subject blind | No | No |
| Huang, 2012[15] | NM | NM | Subject blind | No | No |
| Huang, 2020[16] | Yes, RNT | NM | Subject blind | No | No |
| Kim, 2012[17] | Yes, RD | Yes | Double blind | No | Yes |
| Li, 2023[18] | Yes, RD | NM | Subject blind | No | No |
| Lin, 2022[19] | Yes, RNT | NM | Subject blind | No | No |
| Liu, 2014[20] | Yes | Yes | Double blind | No | No |
| Liu, 2019[21] | Yes, RNT | NM | Subject blind | No | No |
| Mao, 2015[22] | NM | NM | Subject blind | No | No |
| Qiu, 2019[23] | Yes, RD | NM | Subject blind | No | No |
| Que, 2022[24] | Yes | NM | Subject blind | No | No |
| Shi, 2020[25] | Yes | NM | Subject blind | No | No |
| Sun, 2022[26] | Yes, RD | NM | Subject blind | No | Yes |
| Wang, 2021[27] | Yes | NM | Subject blind | No | Yes |
| Zhao, 2019[28] | Yes | NM | Subject blind | No | No |
NM = not mentioned, RD = random draw, RNT = random number table.
Figure 2.
Risk-of-bias graph (A) and risk-of-bias summary (B).
3.3. Tear breakup time
DES can cause instability in the tear film which can be measured using tear film BUT. The 12 studies included in this analysis looked at BUT after treatment. Due to differences in the studies, a random-effects model was used (I2 = 93%, P < .00001). The results showed that combining AC with AT therapy significantly improved BUT in treating DES compared to AT therapy alone [SMD = 1.25, 95% CI (1.14, 1.37), P < .0001] (Fig. 3).
Figure 3.
Forest plot of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome for BUT. AC= acupuncture, AT =artificial tears, BUT= tears break-up time.
3.4. Schirmer I test
The SIT determined whether the eye produced enough amounts of tears to keep the ocular surface moist. All eligible studies inquired into SIT when the treatment was over. Notably, the subgroup analysis revealed significant heterogeneity (I2 = 94%, P < .00001), and the random-effects model was used for the analysis. The results suggested that the therapeutic method of AC combined with AT significantly alleviated SIT while treating DES compared with the control group [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001] (Fig. 4).
Figure 4.
Forest plot of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome using Schirmer I test. AC= acupuncture, AT =artificial tears.
3.5. Corneal fluorescein staining
CFL has been used to visualize the distribution of corneal epithelium in dry eye disease. Six studies have examined the post-treatment CFL, while 1 study documented the patient outcomes based on the number of patients.[11] As significant heterogeneity existed across the studies (I2 = 96%, P < .00001), the random-effects model was used for the analysis. The meta-analysis showed that the therapeutic method of AC combined with AT significantly decreased CFL while treating DES compared with that in the control group [SMD = −2.08, 95% CI (−2.96, −1.20), P < .00001] (Fig. 5). Bai et al described the CFL results as negative or positive, and Sun et al used the median to record the detection index of CFL, both of which could not be included in the data analysis.[12,26]
Figure 5.
Forest plot of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome for CFL. AC= acupuncture, AT =artificial tears, CFL=cornealfluorescein staining.
3.6. Ocular surface disease index
The Ocular Surface Disease Index (OSDI) is a commonly used questionnaire for diagnosing dry eye. It evaluates the subjective symptoms and severity of the condition. In 5 separate trials, OSDI was compared between the AC + AT and AT groups. A random-effects model was used with I2 = 97%, P < 0. 00001. The results showed that there was no significant difference in OSDI between the 2 groups in treating DES (P = .15) (Fig. 6).
Figure 6.
Forest plot of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome for OSDI. AC= acupuncture, AT =artificial tears, OSDI= ocular surface disease index.
3.7. Inflammation indicator
DES is an inflammatory disease that affects the surface of the eye. Several studies investigated the levels of IL-6 and TNF-α, which are indicators of inflammation, in both trial subjects and control patients. The results showed that the AC + AT treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). These findings were based on a random-effects model analysis, which showed no significant differences (P > .1) or inconsistencies (I2 < 50%) between the studies (Fig. 7).
Figure 7.
Forest plot of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome for inflammation indicator. AC= acupuncture, AT =artificial tears.
3.8. Efficacy of clinical treatment
We analyzed 15 studies to compare the effectiveness of post-therapy for treating DES between the AC + AT and AT groups. We found some heterogeneity across the studies (I2 = 0%, P = .50), but overall, the AC + AT therapy was more effective than AT therapy with an odds ratio of 3.85 and a 95% confidence interval of 2.80–5.29 (P < .00001) (Fig. 8A). To check for bias, we used a funnel plot, which showed some heterogeneity due to differences in the use of AC points and small sample sizes (Fig. 8B).
Figure 8.
Forest plot (A) and funnel plot (B) of acupuncture plus artificial tears (AC + AT) compared with artificial tears (AT) while treating dry eye syndrome for efficacy. AC= acupuncture, AT =artificial tears.
3.9. Adverse events
According to the report from Sun in 2022,[26] 5 patients fell off during the treatment. Among them, 2 patients in the acupuncture combined with artificial tears group fell off due to personal reasons. Meanwhile, Wang’s literature reported 8 cases of shedding, with 5 cases in the acupuncture and artificial tear group.[27] One of these cases was due to fainting caused by needles. The reason for the remaining 4 cases was not explained, but no other adverse events were reported. In Kim’s report from 2012,[17] 17 cases of patients falling off were mentioned, including 3 cases of hematoma in the acupuncture treatment group. However, it is unclear whether these adverse events were related to the treatment.
4. Discussion
DES identified as an ocular surface inflammatory disease, is a significant public health problem globally and has become one of the most common eye diseases warranting ophthalmological support.[29,30] Currently available diagnostic tests for dry eye mainly include tear and ocular surface examinations.[31] BUT and SIT are commonly used in auxiliary clinical diagnosis to determine tear quantity and stability, which helps draw more objective conclusions.[32,33] Our study analyzed the BUT and SIT examinations showed that acupuncture is favor to get a clinical benefit in patients with DES, however, 1 study reported an opposite conclusion in BUT test.[34]
CFL is an index for assessing the integrity of the corneal and conjunctival epithelium and can be used to evaluate the physiological efficacy of treatment and determine the severity of dry eye.[35] OSDI evaluates the severity of the disease in patients with dry eyes based on the patient’s subjective perception.[36] CFL and OSDI mainly examine the ocular surface condition. This study suggested that the CFL index was less severe in the acupuncture combined artificial tear group than in the artificial group. However, no significant difference was observed in OSDI between the artificial tear and control groups. Additionally, 4 of these studies used a subjective perception score, with 2 studies presenting total scores and the other 2 reporting single item scores.
The abnormal regulation of tear secretion and drainage system function is closely related to the infiltration of inflammatory cells in the eye and the inflammatory process.[1] Patients with DES experience inhibition in their lacrimal gland’s secretion function. Research has shown that the severity of DES in patients can be linked to the levels of certain cytokines in their tears and conjunctival epithelium, including IL-1, IL-6, and TNF-α.[37] Specifically, high levels of TNF-α and IL-6 can cause local inflammation in the cornea and lacrimal gland tissue, potentially resulting in corneal damage and decreased lacrimal gland secretion.[38] In this study, 4 publications reported the inflammation indicator IL-6 and TNF-α in patients with DES, and the analysis results indicated a clinical benefit to acupuncture that inhibits the expression of IL-6 and TNF-α.
At present, dry eye therapy consists of moisturizing and lubricating the ocular surface, resulting in temporary symptom improvement.[39] The most common treatments for DES are AT, which mimic the composition of natural tears.[40] The current situations call for effective and complementary treatments for DES. In 2017, the Tear Film & Ocular Surface Society’s Dry Eye Workshop II (TFOS DEWS II) first reported the potential value of acupuncture for dry eyes.[41] Studies have found that acupuncture can increase tear lactoferrin content and promote tear film mucin expression.[42] One study indicated that acupuncture at points around the eye of a rabbit dry eye model could inhibit the pro-inflammatory activity of IL-6, thereby inhibiting the inflammatory response of the ocular surface.[43] Another study showed that acupuncture could inhibit the expression of Bax and Fas proteins associated with the apoptosis of lacrimal gland epithelial cells in a rabbit with dry eye.[44] Further, the rabbits dry eye model showed that acupuncture might promote tear secretion by increasing the lacrimal reflex pathway.[45] Clinical study found that acupuncture BL1(Jing Ming) only could promote tear secretion and improve OSDI assessment in patients with DES.[46] These evidences revealed the acupuncture for DES by affects the hormonal, nervous, and immunological systems and can increase tear production.[47] Our results found that the changes in the BUT, SIT, CFL, OSDI, IL-6, and TNF-α values were significantly different between the AC + AT and AT groups, which indicated the acupuncture could significantly increase tear secretion, maintain membrane stability, inhibit the inflammation, and decrease the injury of ocular tissues.
Based on the results of 15 studies, it was found that using acupuncture in combination with artificial tears resulted in better clinical outcomes for patients with DES compared to using artificial tears alone. Our study found varying effects in patients with DES who underwent successful acupuncture treatment. However, there were several limitations to this study. Firstly, all the studies included had a small number of participants. Secondly, not all the studies were well-designed or of high-quality, and the funnel plot indicated heterogeneity amongst the studies included. Thirdly, all the included studies had a short follow-up duration. Long-term high-quality studies are needed to demonstrate the effects of TCM treatment.
In conclusion, we conducted an analysis of the main outcomes and inflammatory indicators of patients with DES who received a combination of acupuncture and artificial tears versus those who received only artificial tears. Our findings suggest that the use of acupuncture with artificial tears would be favors to inhibit the inflammation, stimulate the eye nerve and promote the secretion of lacrimal gland. Acupuncture treatment was acceptable to patients with DES and there were no serious AEs, and its potential as a promising treatment option for DES.
Author contributions
Conceptualization: Qing-Hua Peng, Ying Wang.
Data curation: Qing-Hua Peng, Ying Wang, Li Xiao.
Formal analysis: Ying Wang.
Funding acquisition: Qing-Hua Peng, Yi-Jing Yang.
Investigation: Ying Wang.
Methodology: Ying Wang, Ying Deng, Yasha Zhou.
Project administration: Qing-Hua Peng, Yi-Jing Yang.
Resources: Ying Wang.
Software: Ying Wang, Jing Lu, Jun Peng.
Supervision: Qing-Hua Peng, Yi-Jing Yang.
Validation: Qing-Hua Peng.
Visualization: Qing-Hua Peng.
Writing – original draft: Yi-Jing Yang, Ying Wang.
Writing – review & editing: Ying Wang.
Abbreviations:
- AC
- acupuncture
- AT
- artificial tears
- BUT
- tears breakup time
- CFL
- corneal fluorescein staining
- CI
- confidential interval
- DES
- dry eye syndrome,
- OR
- odds ratio
- OSDI
- ocular surface disease index,
- SIT
- Schimer I test
- SMD
- Std. Mean difference
YW and Y-JY contributed equally to this work.
This work were supported by the National Natural Science Foundation of China (82274341 and 82274588), the Scientific Research Project of Traditional Chinese Medicine of Hunan Province (B2023041), the Qihuang Scholars Support Project of Peng Qinghua, the Scientific research project of Hunan Provincial Department of Education (21B0391), the Natural Science Foundation of Hunan Province (2023JJ40475 and 2023JJ50307), Postgraduate scientific research and innovation project of Hunan Province(CX20210691), and the Academician Liu Liang Workstation Guidance Project (22YS003).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Wang Y, Peng J, Xiao L, Deng Y, Lu J, Zhou Y-S, Yang Y-J, Peng Q-H. Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis. Medicine 2024;103:1(e36374).
Contributor Information
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Ying Deng, Email: 104473746@qq.com.
Jing Lu, Email: 153547680@qq.com.
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