Traditional Chinese Medicine in Dry Eye Syndrome
Pat Lim,1, Wanwen Lan,4,6 Wei Qi Ping,2 Louis Tong.3,4,5,6
- Singapore Chung Hwa Medical Institution, Singapore
- Beijing University of Chinese Medicine, China
- Singapore National Eye Center, Singapore
- Singapore Eye Research Institute, Singapore
- Duke-National University of Singapore(NUS) Graduate Medical School, Singapore
- Yong Loo Lin School of Medicine, NUS, Singapore
1. Pat Lim
Singapore Chung Hwa Medical Institution
Head, TCM Ophthalmology Department
640 Lorong 4 Toa Payoh
2. Wei Qi Ping
Professor of Ophthalmology
Beijing University of Chinese Medicine
Beijing, PR China
Email: email@example.com | Commercial interests: Nil
Grant Acknowledgements: National Medical Research Council NMRC/045/2012 (List other funding)
In recent years, the prevalence of dry eye has been on the rise due to an ageing global population, increased usage of medication and environment irritants.
Current available treatments for dry eye include artificial eye drops, artificial tear ointment, vitamin A ointment, special eyewear, anti-autoimmunity drugs and lacrimal punctum occlusion. However, these treatments have limited effects. The development of dry eye treatments has been hampered by a limited understanding of the underlying pathophysiological processes.
Based on the clinical research trial data from recent years, there is strong evidence suggesting that Traditional Chinese Medicine (TCM) would provide an alternative treatment modality for the patients with dry eye syndrome and have its advantage measurements over the standard western clinical measurements when compare the treatments.
In this chapter, we aim to explore common TCM treatments available for dry eye syndrome, comprising herbal medicine, acupuncture or a combination of both methods.
Clinical trial data also strongly suggest that TCM provides an alternative mode of treatment for dry eye syndrome and is safer, more economical, and provides longer lasting effects.
Keywords: Clinical trial, Complementary medicine, Alternative medicine, Chinese medicine, dry eye, Acupuncture
Dry eye syndrome is a lacrimal film abnormality caused by decreased lacrimal secretions, or hyperactive lacrimal evaporation.1 The condition is presented with symptoms of discomfort in the eye which may accompany ocular surface diseases. If patients have isolated symptoms of dry eyes, they may recover with rest or short-term use of artificial tears.2 If there no ocular surface damage and/or any other local or systemic causes are present, it is termed ‘simple dry eye’. If patients present both symptoms and clinical signs of dry eyes, it is termed ‘dry eye syndrome’. With the increased usage of the computer and other IT gadgets in modern lifestyle, the incidence of dry eyes has gradually increased while the average age of onset is much lower than before. Dry eye disease imposes a significant direct health care burden and even more so indirectly.3 Dry eye disease affects millions of people around the world with prevalence rates estimated to be as high as 35% in the general population.4
Traditional Chinese Medicine (TCM) is a holistic system of healthcare developed by the Chinese and has been practiced for thousands of years. The first record of TCM is dated back to 2000 years ago in the Yellow Emperor’s Cannon of Internal Medicine (Huang-di Nei Jing). Over the years, Chinese medicine is developed from the foundations laid in the Yellow Emperor’s Cannon of Internal Medicine, however the core values of TCM never deviated from it, that is, (1) holistic treatment: to look at a disease holistically and treat from the disease roots, while addressing the symptoms; (2) strengthening the body’s resistance (zheng qi 正气) and dispelling pathogenic factors (xie qi 邪气), and (3) personalization of treatment based on environmental factors and individual constitution.
There are various modalities of treatment in TCM, including acupuncture, herbal remedies, massage (tui na 推拿), cupping, moxibustion, ear acupuncture and scraping (guasha 刮痧). The most commonly employed methods today are acupuncture, herbal remedies and massage, although massage is mostly used for relaxation than its healing functions today. Acupuncture is the insertion of needles into the skin or even the tongues and mucosal layer, based on the system of meridians and its connectivity to the various organs deep in the human body. A modification to the ancient technique of acupuncture is the development of electro stimulation, where needles are connected to weak pulses of electricity for increased stimulation of the acupoints. Herbal remedies are usually prescribed in the form of decoctions, although pills, pastes and baths are also available. Herbal remedies could be based on a single herb or a combination of a few or many, depending on the individual constitution, and modification of the remedies is commonly done. The principle of all modalities of treatment would be to eliminate pathogenic forces, while restoring the body’s balance and strengthening it.
In Chinese medicine, the disease pertains to bai se zheng (白涩症，white dry eyes), or shen shui jiang ku (神水将枯，impending desiccation of spirit water), belonging to the category of zao zheng (燥症，dryness pattern).5 The causes are mostly attributed to lung yin insufficiency or liver and kidney yin deficiency, which lead to nutritional deficiency of the eyes.
2. Clininal Manifestation of Dry Eye Syndrome
Common ocular symptoms include asthenopia (eye strain), sensation of foreign bodies in the eyes, dryness, burning sensation, swelling, ophthalmalgia (pain in eye), photophobia, redness, etc. If these symptoms are presented, patients should be asked in detail on their history of dry eyes sensation in order to find the underlying causes. For patients who present with severe dry eyes, the clinician should check if their condition is accompanied by dry mouth or joint pain, as the dry eye symptoms could be an indication of Sjörgren’s Syndrome and require prompt treatment. Clinical signs of dry eye include vasodilatation, oedema, folding of bulbar conjunctiva, shortened tear meniscus height (TMH), and occasional mucopurulent discharge in the lower fornix and punctuate staining in corneal epithelium in the palpebral fissure area. When dry eye syndrome is suspected, relevant objective tests may be considered, including Schirmer’s test and tear break up time (TBUT) test.6 Dry eyes may affect visual acuity in early stages, andfurther develop into filamentary keratitis. At later stages, if left untreated, dry eye syndrome may lead to corneal thinning, ulcers, and perforation, or, in some cases, a secondary bacterial infection.
3. Types of dry eye patterns in TCM
In most patients presenting with dry eye, their disease condition could be attributed to one or a combination of five main categories of ‘disease pattern’. These disease patterns are identified as pathologies stemming from the ‘organs’, or the root of the disease, and usually present overlapping symptoms apart from dry eye. These patterns include insufficiency of lung yin, insufficiency of liver and kidney yin, and dry eye initiated by heat in various organs. These will be described in the sections below:
1. Insufficiency of Lung Yin
Patients in this category often present with the following characteristics: Dry eyes that result in inability to see clearly over a long period, mild conjunctiva hyperemia, point lesions of the superficial corneal layer, relapses with poor recovery, dry cough with little phlegm, dry pharynx, constipation, reddish tongue with dry mouth and a thready rapid pulse.
The treatment in this case is to enrich yin and moisten the lung meridian. A representative formula is the Yang Yin Qing Fei Tang (Yin-Nourishing Lung-Clearing Decoction, 养阴清肺汤).7 Refer to Table 1 for the prescription. Please note that this prescription is often modified in 3 scenarios:
- For cases with pronounced dry throat and mouth, add bei sha shen (北沙参，Radix Glehniae) 15g, Shi Hu (石斛，Caulis Dendrobii) 10g to boost the qi and nourish the yin.
- For cases with constipation, add jue ming zi (决明子，Semen Cassiae) 15g to moisten the intestines and allow the stool to move down the rectum
- For cases with point lesions of the cornea, add chan tui (蝉蜕，Periostracum Cicadue) 6g, ju hua (菊花， Flos Chrysanthemi)12g, mi meng hua (密蒙花，Flos Buddlejae)10g to clear the heat, and brighten the eyes
|牡丹皮||mu dan pi||10g||Cortex Moutan|
|白芍||bai shao||10g||Radix Paeoniae Alba|
|生甘草||sheng gan cao||10g||Radix et Rhizoma Glycyrrhizae|
|生地||sheng di||10g||Radix Rehmanniae|
|薄荷||bo he||6g||Herba Menthae|
|玄参||xuan shen||10g||Herba Scrophulariae|
|麦冬||mai dong||15g||Radix Ophiopogonis|
|贝母||bei mu||10g||Bulbus Fritillaria|
|太子参||tai zi shen||15g||Radix Pseudostellariae|
|五味子||wu wei zi||10g||Fractus Schisandrae Chinensis|
Table 1. Prescription for Yang Yin Qing Fei Tang.
2. Liver and Kidney Yin Deficiency
In this syndrome, dry eye is accompanied with symptoms of discomfort, photophobia, symptoms increased after prolonged use, dry mouth with scant saliva, lumbago, weak and/or painful knees, dizziness, tinnitus, insomnia with profuse dreams, red tongue with thin coating and a thready pulse.
The treatment principle is to nourish the liver and kidney meridians, and a representative formula is the Modified Qi Ju Di Huang Wan (Lycium Berry, Chrysanthemum and Rehmannia Pill, 杞菊地黄丸) (Table 2). In certain scenarios, this formulation can be modified:
- For cases with dry mouth, with scanty saliva, add mai dong (麦冬，Radix Ophiopogonis) 10g, xuan shen (玄参，Radix Seroophulariae) 10g to nourish the yin and engender the fluid.
- For cases with obvious conjunctival hyperaemia, add sang bai pi (桑白皮，Cortex Mori) 9g, di gu pi (地骨皮，Cortex Lycii) 10g to clear the heat and reduce congestion.
|枸杞子||gou qi zi||15g||Fructus Lycii|
|菊花||ju hua||10g||Flos Chrysanthemi|
|熟地||shu di||10g||Radix Rehmanniae Praeparata|
|山茱萸||shan zhu yu||10g||Fructus Corni|
|山药||shan yao||10g||Rhizoma Dioscroreae|
|泽泻||ze xue||10g||Rhizoma Alismatis|
|牡丹皮||mu dan pi||10g||Cortex Moutan|
Table 2. Prescription for Modified Qi Ju Di Huang Wan.
3.Dry eye initiated by wind and heat
This type of dry eye is caused by wind and heat, including xerosis conjunctiva, fulminant red eye with actute mebula and conjunctival edema. The principle of treatment is to ‘scatter’ the wind and clear the heat. The representative formula is Sang Ju Yin桑菊饮, or Mulberry Leaf and Chrysanthemum Beverage (Table 3).
|桑叶||sang ye||9g||Folium Mori|
|菊花||ju hua||9g||Flos Chrysanthemi|
|连翘||lian qiao||9g||Fructus Forsythiae|
|桔梗||jie geng||9g||Rhizoma Phragmitis|
|杏仁||xing ren||9g||Semen Armeniacae Amarum|
|泽泻||bo he||6g||Herba Menthae|
|甘草||gan cao||3g||Radix et Rhizoma Glycyrrhizae|
|芦根||lu gen||15g||Rhizoma Phragmitis|
Table 3. Formulation for Mulberry Leaf and Chrysanthemum Bevarage.
4.Dry eye initiated by heart–heat
This is dry eye initiated by overwork from prolonged use of computers, insufficient sleep or stress-induced insomnia, and usually presents with photophobia, eye strain, eye sore or pain, with red tongue tip and rapid pulse. In this scenario, the treatment principle is to clear the heart-heat from the heart meridian by promoting urination. A representative formulation to address this is Dao Chi San 导赤散found in Table 4.
|生地||sheng di||18g||Radix Rehmanniae|
|木通||mu tong||9g||Caulis Akebiae|
|淡竹叶||dan zhu ye||12g||Herba Lophatheri|
|山栀子||zhi Zi||12g||Fructus Gardeniae|
|黄柏||huang bai||9g||Cortex Phellodendri Chinensis|
|知母||zhi mu||9g||Rhizoma Anemarhenae|
|灯芯草||deng xin cao||6g||Medulla Junci|
|甘草||gan cao||6g||Herba Schizonepetae|
Table 4. Treatment to reduce heat in the heart.
5.Dry eye initiated by liver – heat
Heat can also be initiated by the liver. In this syndrome, dry eye is initiated by prolonged visual tasks, and the patients in this category are stressed and easily agitated or frustrated with dry eye with headache. He also suffers from pain in the side abdomens at times, has red tongue with white coat and a rapid thready pulse.
Here, the physician aims to clear the liver heat and dampness from the lower part of the body meridians. A formulation such as Long Dan Xie Gan Tang 龙胆泻肝汤that in Table 5 can be employed.
|龙胆草||long dan cao||12g||Radix et Rhizoma Gentianae|
|生地||sheng di||18g||Radix Rehmanniae|
|当归||dang gui||6g||Radix Angelicae Sinensis|
|柴胡||chai hu||6g||Radix Bupleuri|
|木通||mu tong||9g||Caulis Akebiae|
|泽泻||ze xie||9g||Rhizoma Alismatis|
|车前子||che qian zi||9g||Semen Plantaginis|
|山栀子||zhi Zi||9g||Fructus Gardeniae|
|黄芩||huang qin||9g||Radix Scuttellariae|
|甘草||gan cao||5g||Herba Schizonepetae|
Table 5. Formulation for treatment of liver heat.
4. Acupuncture Treatment for dry eye
The history of using acupuncture treatment for dry eye is dated back to the Ancient Times – Northern and Southern Dynasties (581A.D). The Yellow Emperor’s Inner Classic (Huang Di Nei Jing, 黄帝内经) had records of the anatomy and physiology of the eyes, as well as the etiology, pathology, clinical manifestation, and acupuncture strategies for eye disorders.7 More than 30 eye diseases were recorded in this book. In each typical treatment session, 4-6 acupoints were selected, needles retained for 20-30 minutes, and treatment was performed once every day. Ten treatments constitute one course of treatment7 (Table 6). Most studies conducted previously did not have proper control groups. Recently, investigators in Korea have conducted randomized controlled studies in acupuncture compared to sham acupuncture.8
|ST1 (cheng qi) 承泣||太阳（tai yang）||GB20(feng chi) 风池|
|BL2 (cuan zhu) 攒竹||鱼腰 (yu yao)||SJ 23(si zhu kong)丝竹空|
|ST2 (si bai) 四白||LV3 (tai chong)太冲||GB37(guang ming)光明|
|SP6 (san yin jiao)三阴交||LI4 (he gu)合谷||DU23(shang xing)上星|
|DU20 (bai hui) 百会|
Table 6. Acupuncture points for treatment of dry eye
5. Chinese Patent Medicines
In western or clinical medicine, patients with dry eye may be given lubricants such as 1% sodium hyaluronate or carboxymethylcellulose eye drops used frequently daily. Patients with more severe or uncontrolled symptoms, may seek advice or treatment from an Ophthalmologist, who may initiate immunosuppressive, anti-inflammatory treatment, or punctum occlusion methods.
In contrast, TCM advocates the use of simple remedies comprising core herbs such asju hua (菊花，Flos Chrysanthemi), mai dong（麦冬，Radix Ophiopogonis）, gou qi zi (构杞子，Fructus Lycii), mu hu die (木蝴蝶，Semen Oroxyli) which possess yin-nourishing properties. Depending on the condition and constitution of the patients, a selection of herbs are added (10g each) into a prescription and wrapped as a tea drink. Alternatively, they are brewed in a teapot with boiling water, and consumed 6-9 times in small amounts daily Alternatively, Chinese physicians may choose one of these more standard therapies:
- (1) Qi Ju Di Huang Wan (Lycium Berry, Chrysanthemum and Rehmannia Pill, 杞菊地黄丸) 6 pills, twice daily; applicable to liver-kidney yin deficiency
- (2) Zhi Bai Di Huang Wan (Lycium Berry, Chrysanthemum and Redmannia Pill 知柏地黄丸) 6 pills, twice daily; applicable to liver-kidney yin defiency or effulgent yin-deficiency
- Yang Yin Qing Fei Kou Fu Ye (Yin-Nourishing Lung-Clearing Oral Liquid 养阴清肺口服液)10ml, twice daily, applicable to insufficiency of lung yin deficiency
6. Dietary Therapy and Preventive Measurements
Like in all types of medicine, Chinese medicine recognizes that environmental and dietary factors contribute to disease. Therefore, preventive measures and ways to adjust the environment that one is exposed to maybe just as helpful as therapeutic medications. Some of these measures include:
- Avoiding prolonged and excessive visual tasks. Patients are counseled that TV, computers and other IT gadgets should be placed in a position below eye level.
- Avoidance of air conditioning and dust, and measures to maintain a certain degree of humidity in the room
- Adopting a positive attitude to life and have a happy outlook, paying particular attention to balanced and sufficient dietary components and maintaining a healthy eating habit including the consumption of fresh vegetables and fruits, while increasing vitamins A, B, C and E intake. The patients should be advised against over-consumption of spicy, greasy-fried, or fatty and processed foods.
- Regulation of the internal emotions and working on cultivating an optimistic mood; maintaining a proper balance between work and relaxation.
7. Clinical Trial in dry eye
Sometimes, Tradition Chinese Medicine physicians employ a mixture of acupuncture and oral therapies. Recently, randomized controlled studies in the use of TCM in dry eye have been published, with data that suggest TCM is useful in improving the disease condition.9-15 In a randomized placebo-controlled study, the group receiving Chi-Ju-Di-Huang-Wan medication had a significantly improved Rose-Bengal and fluorescein TBUT compared to placebo group at 2 and 4 weeks respectively.16 A Korean study showed that in TBUT in acupuncture group had improved TBUT (p not statistically significant) after 3 weeks.14, 17 Finally, in one meta-analysis of 6 randomized controlled trials, the authors found that acupuncture significantly improved TBUT (p<0.0001), Schirmer test (p<0.00001) and cornea fluorescein staining (p=0.0001).11
We have recently conducted clinical research involving qi ju gan lu yin and qi ju gan lu yin with acupuncture on the treatment of lung and kidney yin deficiency type of dry eye.18
In the study, we aimed to evaluate the efficacy of TCM herbal medicine “qi ju gan lu yin” in treating dry eye, compared to the same“qi ju gan lu yin with acupuncture” and a total of 89 age- and gender-matched subjects were recruited. This included 44 in Group 1, the TCM Herbal Medicine Group, and 45 in Group 2, the TCM Combined Methods Group. All participants had dry eyes as their main complaint and were aged 40-70 years old. All subjects had good general health, no ocular disease, non-smoking and were non-contact lens wearer. The inclusion criteria of dry eye subjects were a positive score in the SPEED Questionnaire (Standard Patient Evaluation for Eye Dryness Questionnaire). The study group (Group 1, TCM Herbal Medicine Group) of 44 patients were given qi ju gan lu yin orally and the control group (Group 2, TCM Combined Methods Group) of 45 patients were given qi ju gan lu yin combined with acupuncture twice a week. Both groups were treated for 30 days. Pre- and post-treatment measurements of Schirmer’s and TBUT test were obtained for the TCM Herbal Medicine Group (Group 1) and TCM Combined Methods Group (Group 2). For Schirmer’s I test (mm/5 min) result in Group 1, Z=-2.050, p=0.04 (right eye); Z=-0.030, p=0.976 (left eye). In Group 2, the corresponding values in the right eye were Z=-0.429, p=0.668, and Z=-1.526, p=0.127 for left eye. For Tear Break-Up Time (TBUT), the values were Z=-7.013, p<0.001 (right eye) and Z=-2.043, p<0.001 (left eye) in Group 1 and Z=-1.650, p=0.099 (right eye), Z=-1.985 p=0.047(left eye) in Group 2.
No significant differences were found in Schirmer’s test readings between the two groups (Right eye Z=-1.441, p=0.150 and Left eye Z=-1.072, p=0.284). Significant differences were obtained for the TBUT between Group 1 and Group 2 at the post treatment visit: Right eye Z=-4.290, p<0.001 and Left eye Z=-2.594, p=0.009. Group 1 performed better than Group 2, where Z=-7.013 p<0.001 (right eye) and Z=-2.043 p<0.001 (left eye) for Group 1; was and Z=-1.650, p=0.099 (right eye) and Z=-1.985, p=0.047 (left eye) in Group 2.The total efficacy or % in improvement in SPEED was 54.4% for Group 1 and similar in Group 2 (53.3% ). The SPEED improvement in group 1 was 3.58 ± 5.40 and Group 2 was 4.40 ± 7.82. There was no significant difference between the two groups (t=0.520, p=0.604). The percentage improvement in the SANDE19 or Visual Analogue Score (VAS) in Group 1 and 2 was 61% and 55.5% respectively. VAS (Visual Analogue Score) improvement for Group 1 was 24.01±23.99 and Group 2 was 22.70±24.33. The improvement between the 2 groups was not significantly different (t=－0.252, p=0.802).
In addition we found that the TCM lung and kidney yin deficiency score aggregates for Group 1 was 68.18% and for Group 2 was 71.11%.The TCM lung and kidney yin deficiency improvement in Group 1 was 3.76±6.04 and Group 2 was 4.50 ± 5.81. These were not significantly different between the two groups (t=-0.205, p=0.838).
The findings demonstrate the usefulness of TCM treatment in treating the commonly seen dry eye syndrome in Singapore. In this study, acupuncture does not demonstrate any additional therapeutic effect over and above herbal medication alone. In fact, for TBUT, Group 1 (TCM Herbal Medicine alone) has in fact shown a better result than the combined TCM methods. The result findings suggest that TCM herbal medicine may be used as an alternative medicine to treat dry eyes in Singapore.
8. General Conclusions
A previous study in Singapore has evaluated the knowledge, attitude and practice of TCM practitioners in treatment of dry eye.20 This study shows that at least in institutional practice, the registered Chinese physicians were keen to participate in the treatment of dry eye. Although there has been randomized controlled studies in TCM in dry eye, the results are often controversial,17 and much larger studies are being planned and conducted.21, 22 Use of combined modalities of TCM may not necessarily be advantageous over a single modality, although the specific nature of the modality used may determine the outcome.
It seems that in Asian countries, the use of TCM is widespread and prevalent. Increasingly, health care workers have realized the holistic nature of dry eye. As TCM deals holistically with patients’ conditions, many dry eye patients are willing to be treated with TCM. In any case, the coordination of care of dry eye between TCM and western practitioners may be advantageous for many patients. We eagerly await the outcome of the major trials being conducted in this area.
- The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007), The ocular surface 2007, 5:75-92
- Johnson ME, Murphy PJ: Changes in the tear film and ocular surface from dry eye syndrome, Progress in retinal and eye research 2004, 23:449-474
- Waduthantri S, Yong SS, Tan CH, Shen L, Lee MX, Nagarajan S, Hla MH, Tong L: Cost of dry eye treatment in an Asian clinic setting, PloS one 2012, 7:e37711
- McCarty CA, Bansal AK, Livingston PM, Stanislavsky YL, Taylor HR: The epidemiology of dry eye in Melbourne, Australia, Ophthalmology 1998, 105:1114-1119
- Impending Dessication of Spirit Water (Shen Shui Jiang Ku Zheng). Edited by p.
- Tong L, Tan J, Thumboo J, Seow G: Dry eye, BMJ 2012, 345:e7533
- Wei Q-P, Rosenfarb A, Liang L-n: Ophthalmology in Chinese Medicine. Edited by People’s Medical Publishing House Co, LTD, 2011, p.pp. 345
- Kim TH, Kang JW, Kim KH, Kang KW, Shin MS, Jung SY, Kim AR, Jung HJ, Choi JB, Hong KE, Lee SD, Choi SM: Acupuncture for the treatment of dry eye: a multicenter randomised controlled trial with active comparison intervention (artificial teardrops), PloS one 2012, 7:e36638
- Chang YH, Lin HJ, Li WC: Clinical evaluation of the traditional chinese prescription Chi-Ju-Di-Huang-Wan for dry eye, Phytotherapy research : PTR 2005, 19:349-354
- Gronlund MA, Stenevi U, Lundeberg T: Acupuncture treatment in patients with keratoconjunctivitis sicca: a pilot study, Acta ophthalmologica Scandinavica 2004, 82:283-290
- Lee MS, Shin BC, Choi TY, Ernst E: Acupuncture for treating dry eye: a systematic review, Acta ophthalmologica 2011, 89:101-106
- Nepp J: Acupuncture in dry eye syndromes, Archivos de la Sociedad Espanola de Oftalmologia 2005, 80:267-270
- Nepp J, Wedrich A, Akramian J, Derbolav A, Mudrich C, Ries E, Schauersberger J: Dry eye treatment with acupuncture. A prospective, randomized, double-masked study, Advances in experimental medicine and biology 1998, 438:1011-1016
- Shin MS, Kim JI, Lee MS, Kim KH, Choi JY, Kang KW, Jung SY, Kim AR, Kim TH: Acupuncture for treating dry eye: a randomized placebo-controlled trial, Acta ophthalmologica 2010, 88:e328-333
- Tseng KL, Liu HJ, Tso KY, Woung LC, Su YC, Lin JG: A clinical study of acupuncture and SSP (silver spike point) electro-therapy for dry eye syndrome, The American journal of Chinese medicine 2006, 34:197-206
- Chang Y-H, Lin H-J, Li W-C: Clinical evaluation of the traditional chinese prescription Chi-Ju-Di-Huang-Wan for Dry Eye, 2005,
- Lan W, Tong L: Comments: acupuncture for treating dry eye: a randomized placebo-controlled trial, Acta ophthalmologica 2011, 89:e371-372; author reply e372
- Lim P: Unpublished data. Edited by TCM Ophthalmology Conference, Beijing, PRC, p.
- Schaumberg DA, Gulati A, Mathers WD, Clinch T, Lemp MA, Nelson JD, Foulks GN, Dana R: Development and validation of a short global dry eye symptom index, The ocular surface 2007, 5:50-57
- Lan W, Lee SY, Lee MX, Tong L: Knowledge, attitude, and practice of dry eye treatment by institutional Chinese physicians in Singapore, TheScientificWorldJournal 2012, 2012:923059
- Kim TH, Kang JW, Kim KH, Kang KW, Shin MS, Jung SY, Kim AR, Jung HJ, Lee SD, Choi JB, Choi SM: Acupuncture for dry eye: a multicentre randomised controlled trial with active comparison intervention (artificial tear drop) using a mixed method approach protocol, Trials 2010, 11:107
- Kim TH, Kim JI, Shin MS, Lee MS, Choi JY, Jung SY, Kim AR, Seol JU, Choi SM: Acupuncture for dry eye: a randomised controlled trial protocol, Trials 2009, 10:112