Effect of Mingmu nourishing cream on asthenopia

Purpose: To assess the therapeutic efficacy and safety of Mingmu nourishing cream in asthenopia. Methods: This study retrospectively analyzed data from 124 patients who were treated for asthenopia in the Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, China from January 2015 to January 2018. Patients were divided into control group (n = 63; received conventional eye drops) and study group (n = 61; received Mingmu nourishing cream in addition to control group treatment). The ocular symptom scores and tear secretion test (Schirmer's I test (SIT)) were compared between the two groups before and after treatment. Furthermore, the clinical efficacy of Mingmu nourishing cream in the treatment of asthenopia was evaluated. Results: The differences in SIT, conjunctival congestion classification and ocular symptoms between the two groups after treatment were statistically significant (p < 0.05). Moreover, the rate of total therapeutic efficacy in the study group was 86.9 % (53/61), which was significantly higher than the control group (p < 0.05). Conclusion: Mingmu nourishing cream significantly improves symptoms and exhibits favourable tolerability profile. Multi-center large sample study is needed for further verifications of the findings of this study.


INTRODUCTION
Asthenopia is a syndrome characterized by intertwined ocular or systemic organic factors as well as psychological factors [1].Patients usually have obvious self-conscious symptoms, which manifest as ocular pain, eye swelling, burning sensation, foreign body sensation, tearing, photophobia, blurred vision and in severe cases, systemic symptoms such as headache, nausea and vomiting [2].A previous study reported that in a survey of 260 workers who used video terminals for a long time, 247 people were found to have subjective symptoms of eye fatigue and discomfort [3].
Treatment regimens for asthenopia include medication, and changing lifestyle habits, amongst others [4].However, due to the progress of science and technology in modern society and the acceleration of the pace of life, an increasing number of patients with asthenopia show low compliance with the treatment methods above.This presents a challenge in the treatment of the disease because it cannot be cured by Western medicine alone [5].
With the continuous progress in modern pharmacology, the understanding of the mechanism of action of Mingmu nourishing cream has increased.It has been shown that the cream tonifies the liver and kidney, invigorates Qi and nourishes the blood, strengthens the spleen, resolves turbidity, brightens the eyes and removes obstacles, which have provided the medical basis for further development and clinical use of the formula [6].Traditional Chinese medicine applications have been used since ancient times and Mingmu nourishing cream (previously used as a decoction) is widely used for the treatment of eye diseases [7].However, its therapeutic efficacy and safety on asthenopia are still unclear.Therefore, this study aimed to investigate the efficacy of Mingmu nourishing cream on asthenopia.

Study design
This is a retrospective analysis that collected patients' data admitted to the Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, China from January 2015 to January 2018.The study was approved by the Ethics Committee of the same hospital (approval no.23LL-31).Subjects were divided into control group (n = 63) and study group (n = 61).All procedures were carried out in accordance with the Declaration of Helsinki [8].

Diagnostic criteria
To ascertain asthenopia in the study subjects, the following diagnostic criteria were examined: causes of asthenopia; inadequate vision, temporary blurred or blurred vision; dry and astringent eyes, itching, tears, burning sensation, swelling pain, blepharospasm; headache, dizziness, memory loss, insomnia.

Inclusion criteria
Patients who met the following criteria were included in the study viz: Patients who were 18 years or older; patients who satisfied all diagnostic criteria for asthenopia based on their medical history and visual examinations; patients who had a normal naked eye vision or corrected vision (distant vision not less than 1.0 or at least one eye not less than 0.8); those who have not used other therapies within the first three months of receiving this therapy and have no adverse reactions; patients who completed duly signed informed consent forms; and patients whose clinical data was complete.

Exclusion criteria
The following criteria were used to exclude patients from the study: Patients with uncorrected refraction, strabismus, glaucoma, and severe dry eye disease; pregnant or lactating women; patients with serious heart disease, liver disease, encephalopathy, hypertension, and other primary diseases; patients taking other medications that may interfere with the therapeutic effect; patients who had adverse reactions to asthenopia and Sturgeon eye drops; patients with severe cataracts or refractive partials; g. patients who had an eye surgery six months before the start of the study; patients with incomplete clinical data.

Schirmer's, I test (SIT)
The reflexed end of the tear secretion test strip was placed in the outer and middle third of the lower lid conjunctiva.The patient was instructed to close the eyes gently, remove the filter strip after 5 min of testing and read the results of the test strip.Length of wetting <10 mm was considered abnormal.

The duration of sustained eye use at close range [9]
The subjects were asked to read under prescribed reading conditions and the time from the start of reading to the appearance of any of the symptoms in the diagnostic criteria as well as the point at which the subject showed any discomfort and could not continue reading was recorded as the time of close eye use [9].

Statistical analysis
All data in this study were confirmed by more than two medical staff.Statistical analysis was performed using SPSS 20.0 (SPSS Inc., Chicago, IL, USA).Paired samples t-test between before and after treatment was done in each group.Fischer's exact test was carried out for qualitative data between groups while Wilcoxon's signed rank test between preand post-treatment was also conducted in each group.A significant level was set at p < 0.05.

Basic clinical characteristics
Among the 124 patients with asthenopia, the age of the patients in the study group was 32 -83 years, with an average age of (54.05 ± 6.91) years.On the other hand, the age of the patients in the control group was 32 -80 years, with an average age of (51.35 ± 7.09) years.There was no significant difference in gender, age, BMI, marital status and disease between the two groups (p > 0.05).

SIT index
As shown in Table 2, the differences in the SIT index between the groups were statistically significant (p < 0.05) when the pre-and posttreatment values were compared.This indicates that the SIT values increased to different degrees in both groups after treatment than before treatment.The increase in SIT was more prominent in the study group compared to the control group.

Grading of conjunctival congestion
There was a statistically significant difference in the conjunctival congestion between the groups after treatment (p < 0.05) indicating that the improvement of conjunctival congestion in the study group was more significant than that in the control group (Table 3).

Clinical therapeutic effect
As shown in Table 4, the total therapeutic efficacy in the study group was 86.9 %, which was significantly higher (p < 0.05) than control group (54.0 %).This indicates that the effect of Mingmu nourishing cream treatment in the study group was better than the control group.

Symptom score
Table 5 depicts the symptom scores between the control and study groups.There were significant differences (p < 0.05) in all the symptoms examined except for the dizziness and headache symptoms, which were not statistically different in both groups (p > 0.05).

Total symptom scores
The total symptom scores of the two groups before treatment were not statistically different (p > 0.05).However, the differences between the two groups after treatment were statistically significant (p < 0.001).

DISCUSSION
Asthenopia belongs to the category of "liver strain" and "eye fatigue" in Chinese medicine [10].Therefore, ancient medical practitioners considered overuse of the eyes, dark depletion of the heart and blood and loss of moistening of the eyes as important etiological mechanisms of the disease [11].Modern medical practitioners believe that the pathogenesis of this disease is due to overuse of the eyes and constriction of the tendons and veins as well as unrestrained emotions, which prevent the liver Qi from harmonizing and relaxing, resulting in Qi stagnation and blood stasis.Further reasons include overexertion (which depletes the essence and blood of the liver and kidneys, resulting in fatigue), poor diet (which impairs the transport and transformation function of the spleen and stomach) as well as dysfunction of the internal organs (which results in deficiency of Qi and blood and prevents the essence from reaching the head and eyes, resulting in this disease) [12].The liver is the main organ that facilitates the transmission of Qi and blood fluids up to the eyes, which are moistened to be able to discern colors and see objects.Asthenopia occurs as a result of prolonged strain on the eyes, which adversely affects the blood, leading to malnourishment of the eyes and thus asthenopia [13].
Mingmu nourishing cream has the effect of strengthening the spleen and benefiting the Qi, nourishing the liver and brightening the eyes.In this study, Dendrobium and Radix Achyranthis bidentata are used as the major constituents of Mingmu nourishing cream.It is believed that when Qi moves, blood moves and when Qi is strong, blood is generated.The combination of the herbs has the function of tonifying both Qi and blood, tonifying without stagnation, tonifying Qi and strengthening spleen, nourishing the liver and brightening the eyes.Dendrobium is sweet and warm and belongs to the lung and spleen meridians.It is known to tonify Qi, strengthen the spleen, raise yang and lift the spleen [14].
Modern studies have shown that Dendrobium plays a role in improving immunity and strengthening the heart [15].Angelica sinensis, pungent, sweet and warm, belongs to the heart, liver and spleen meridians, tonifies blood, regulates menstruation, activates blood circulation and relieves pain.
Radix Rehmanniae praeparata and Cassia Seeds are herbs.Radix Rehmanniae Praeparata is classified as a member of the liver and kidney meridians.It nourishes the blood, nourishes the yin, benefits the essence and fills the marrow.
Radix Rehmanniae is an important medicine for nourishing the blood and tonifying the kidneys, helping the five viscera to be full of Qi and blood and making the ears and eyes bright.Cassia Seeds nourish blood, calm liver yang, astringes yin, and stop pain [16].The combination of Radix Rehmanniae praeparata and Cassia Seeds is effective in tonifying and nourishing the blood, which circulates throughout the body and transfuses upward to the eyes so that the eyes can see clearly because of the blood [17].
Schisandra chinensis and motherwort are the adjuvants in Mingmu nourishing cream.Schisandra chinensis is pungent and warm, moves Qi to dispel wind, invigorates blood and relieves pain, and according to the Compendium of Materia Medica, it "searches liver Qi, nourishes liver blood, and increases brightness of the eyes when taken for a long time" [18].Motherwort moves the head and eyes upward, opens depression in the middle and regulates menstrual blood downward.In combination with Angelica sinensis, it moves Qi, nourishes and invigorates blood, which not only improves blood flow to the head and eyes but also enables the smooth flow of Qi and blood throughout the body [19].Motherwort is pungent, sweet, and warm and enters the liver, kidney, and spleen meridians, and has the effect of nourishing the liver and brightening the eyes, benefiting the essence and tonifying the kidney.It is good at treating two deficiencies, harmonizing yin and yang, and enriching Qi and blood.The entire formula is based on tonifying deficiency, and the combination of the herbs is used to tonify the liver and kidney, benefit the Qi and strengthen the spleen, so that both yin and yang, Qi and blood are tonified, and the eyes are moistened and the vision is clear [20].

Limitations of this study
This study also has some limitations.First, this study is retrospective.At the same time, because the research population comes from a single hospital, it is difficult to give a general conclusion on the action of the cream.Second, this study did not address the potential mechanism of action of Mingmu nourishing cream on asthenopia still needs further study.

CONCLUSION
Mingmu nourishing cream provides an effective treatment for asthenopia thereby providing a new method for the clinical treatment of asthenopia.However, a multicenter, large sample study is needed for further verifications of the findings of this study.

Table 1 :
Comparison of clinical data between groups

Table 2 :
Comparison of SIT index between groups

Table 3 :
Comparison of the grading of conjunctival congestion between groups

Table 4 :
Comparison of clinical therapeutic effect between groups

Table 5 :
Comparison of symptom scores between two groups after intervention