Effect of Behavioral Intervention (Baduanjin Alone or Laughter Exercise Plus Artificial Tears) Versus Artificial Tear on Dry Eye Disease: a Randomised Controlled Trial

The goal of this clinical trial is to compare the effect of behavioral intervention (Baduanjin alone or laughter exercise plus artificial tears) versus artificial tears in patients with dry eye disease.

The main questions it aims to answer are:

• Does the Baduanjin improve the Ocular Surface Disease Index score of patients with dry eye disease?
• Does the laughter exercise plus artificial tears improve the Ocular Surface Disease Index score of patients with dry eye disease?

Researchers will compare behavioral intervention (Baduanjin alone or laughter exercise plus artificial tears) versus artificial tears to see if behavioral intervention works to treat dry eye disease.

Participants will：

• Do the Baduanjin 5 times per week, or do laughter exercise plus artifical tears 4 times per day, or use artificial tears alone 4 times per day for 12 weeks
• Visit the clinic once right before the intervention and the 4, 8, 12, 16, 24, 36, and 48 weeks after starting the intervention for checkups and tests
• Use the app developed by our study to record the behavioral intervention and/or use of eye drops.

Study Overview

• Status: Not yet recruiting
• Conditions: Dry Eye Disease (DED)
• Intervention / Treatment: Behavioral: Baduanjin; Behavioral: Laughter exercise; Drug: Artificial tears

• Study Type: Interventional
• Enrollment (Estimated): 540
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lingyi Liang; Phone Number: 13829738319; Email: lianglingyi@gzzoc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 TO ≤45 years of age, any sex.
• Meet the dry eye diagnostic criteria of the DEWS international consensus, and show both of the following two conditions: OSDI score between 18 and 80; NIBUT (Non-invasive tear break-up time) < 8 seconds
• Best corrected visual acuity ≥ 0.5(10/20) (in each eye).
• Intraocular pressure between 5 and 21 mmHg (in each eye).
• Women of childbearing potential must agree to use safe contraception during the study.
• Willingness/ability to return for all study visits and to follow instructions from the study investigator and their staff.
• Voluntary participation and signing of the informed consent form approved by the Ethics Committee.

Exclusion Criteria:

• NEI corneal fluorescein staining score > 5 (in either eye).
• Wore contact lenses within the past 14 days and cannot commit to not wearing them during the study period (3 months) (in either eye).
• Received refractive surgery (LASIK, SMILE) or other ocular surgery, or had ocular trauma within the past 12 months (in either eye).
• Had acute allergic conjunctivitis, infection, or ocular surface inflammation within the past 3 months (in either eye).
• Eyelid abnormalities that affect eyelid function, such as nystagmus, blepharospasm, ectropion, entropion, or severe trichiasis (in either eye).
• Previously diagnosed with glaucoma and received medical or surgical treatment (in either eye).
• Currently receiving other ophthalmic or systemic treatments that may affect the tear film.
• Allergy to fluorescein sodium.
• Have a serious health condition that may limit their ability to participate.
• Pregnant, breastfeeding, or planning to become pregnant.
• Diagnosed with neurological or psychiatric disorders (e.g., severe anxiety, depression, or severe sleep disorder).
• Have difficulty with physical movement.
• Previous experience with traditional exercise such as Baduanjin.
• Previous experience with laughter exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baduanjin alone; Perform Baduanjin 5 times per week for 12 weeks. During the first 4 weeks, participants will practice with a coach in person once per week. The remaining sessions will be done by following a video or live online class. Each session lasts 24 minutes.	Behavioral: Baduanjin; Participants perform Baduanjin 5 times per week for 12 weeks. The standardized version, endorsed by the General Administration of Sport of China, includes 8 movements performed for 10 to 15 minutes.
Experimental: Laughter exercise plus artificial tears; Perform laughter exercise 4 times per day and use 0.1% sodium hyaluronate eye drops in both eyes 4 times per day.	Behavioral: Laughter exercise; Launch the "smile face recognition" APP on smart phone, after user guidance and pretest, a smile exercise will display on the phone, while facing the front camera on the phone, participant will do an exercise emphasizing facial movements, as exaggerated as possible. The exercise last for 12 weeks and 4 times a day; Drug: Artificial tears; Participants use 0.1% sodium hyaluronate eye drops 4 times per day in both eyes.
Active Comparator: Artificial tears; Use 0.1% sodium hyaluronate eye drops in both eyes 4 times per day for 12 weeks.	Drug: Artificial tears; Participants use 0.1% sodium hyaluronate eye drops 4 times per day in both eyes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of OSDI scores at week 12	The OSDI is a 12-item patient-reported outcomes questionnaire designed by a staff of a pharmaceutical company (Allergan, Inc.) to provide a rapid assessment of the range of ocular surface symptoms, including symptoms related to chronic dry eye, their severity, and their impact on the patient's ability to function. In addition to an overall score, there are three subscales of the OSDI: ocular symptoms, vision-related function, and environmental triggers. The OSDI score is calculated as: (total points from all answers × 100) / (number of answered questions × 4). A higher score indicates worse symptoms.	From baseline to weeks 1, 2, 4, 6, 8, 10, and 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with 10 points or more decreased in OSDI at week 12	The proportion of patients with a decrease from baseline in the ocular surface disease index score (OSDI) of 10 points or more (the minimal clinically meaningful cut-off)	From baseline to the end of interventions at week 12
Change in OSDI score at week 48	OSDI scores change from baseline to week 48.	From baseline to weeks 16, 24, 36, and 48.
Change in non-invasive tear film break up time at week 12	Non-invasive tear break-up time (NIBUT), measured using a keratograph (Keratograph 5M). Participants blink twice, then the time to first dry spot on the cornea is recorded using Placido disk principle. The average of three measurements is used.	From baseline to weeks 4, 8, and 12
Change in non-invasive tear film break up time at week 48	Non-invasive tear break-up time (NIBUT), measured using a keratograph (Keratograph 5M). Participants blink twice, then the time to first dry spot on the cornea is recorded using Placido disk principle. The average of three measurements is used.	From baseline to weeks 16, 24, 36, and 48
Change in tear meniscus height at week 12	Tear meniscus height, measured using a keratograph (Keratograph 5M) as the vertical height of the tear fluid just below the pupil margin, reflecting tear secretion volume.	From baseline to weeks 4, 8, and 12
Change in tear meniscus height at week 48	Tear meniscus height, measured using a keratograph (Keratograph 5M) as the vertical height of the tear fluid just below the pupil margin, reflecting tear secretion volume.	From enrollment to the weeks 16, 24, 36, and 48
Change in corneal fluorescein staining score at week 12	Corneal fluorescein staining score (NIH scale, 0-15). The cornea is divided into 5 regions, each scored 0-3 based on the number of staining dots, for a total score of 0 to 15.	From baseline to weeks 4, 8, and 12
Change in corneal fluorescein staining score at week 48	Corneal fluorescein staining score (NIH scale, 0-15). The cornea is divided into 5 regions, each scored 0-3 based on the number of staining dots, for a total score of 0 to 15.	From baseline to weeks 16, 24, 36, and 48
Change in lipid layer thickness at week 12	Lipid layer thickness, measured automatically using a Lipiview interferometer.	From baseline to weeks 4, 8, and 12
Change in lipid layer thickness at week 48	Lipid layer thickness, measured automatically using a Lipiview interferometer.	From baseline to weeks 16, 24, 36, and 48
Change in Self-Rating Anxiety Scale at week 12	The Self-Rating Anxiety Scale consists of 20 items related to anxiety symptoms. It assesses the severity of anxiety over the past week across dimensions such as subjective anxiety feelings, autonomic nervous system disturbances, and motor tension. The raw score is the sum of all item scores, which is then converted to a standardized score ranging from 0 to 100. Higher scores indicate more severe anxiety.	From baseline to weeks 4, 8, and 12
Change in Self-Rating Anxiety Scale at week 48	The Self-Rating Anxiety Scale consists of 20 items related to anxiety symptoms. It assesses the severity of anxiety over the past week across dimensions such as subjective anxiety feelings, autonomic nervous system disturbances, and motor tension. The raw score is the sum of all item scores, which is then converted to a standardized score ranging from 0 to 100. Higher scores indicate more severe anxiety.	From baseline to weeks 16, 24, 36, and 48
Change in Self-Rating Depression Scale at week 12	The Self-Rating Depression Scale consists of 20 items related to depressive symptoms. It assesses the severity of depression over the past week across core dimensions including low mood, slowed thinking, somatic symptoms (e.g., sleep disturbances, loss of appetite), and reduced volitional activity. The raw score is the sum of all item scores, which is then converted to a standardized score ranging from 0 to 100. Higher scores indicate more severe depression.	From baseline to weeks 4, 8, and 12
Change in Self-Rating Depression Scale at week 48	The Self-Rating Depression Scale consists of 20 items related to depressive symptoms. It assesses the severity of depression over the past week across core dimensions including low mood, slowed thinking, somatic symptoms (e.g., sleep disturbances, loss of appetite), and reduced volitional activity. The raw score is the sum of all item scores, which is then converted to a standardized score ranging from 0 to 100. Higher scores indicate more severe depression.	From baseline to weeks 16, 24, 36, and 48
Change in Subjective Happiness Scale at week 12	The Subjective Happiness Scale consists of 4 items measuring subjective well-being, covering life satisfaction, positive emotional experiences, and frequency of negative emotions. The total score is the average of the item scores, ranging from 0 to 7. Higher scores indicate a higher level of subjective happiness.	From baseline to weeks 4, 8, and 12
Change in Subjective Happiness Scale at week 48	The Subjective Happiness Scale consists of 4 items measuring subjective well-being, covering life satisfaction, positive emotional experiences, and frequency of negative emotions. The total score is the average of the item scores, ranging from 0 to 7. Higher scores indicate a higher level of subjective happiness.	From baseline to weeks 16, 24, 36, and 48
Change in Pittsburgh Sleep Quality Index at week 12	The Pittsburgh Sleep Quality Index consists of 15 items assessing sleep quality over the past month across 7 dimensions: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The component scores are summed to give a global score ranging from 0 to 21. Higher scores indicate worse sleep quality.	From baseline to weeks 4, 8, and 12
Change in Pittsburgh Sleep Quality Index at week 48	The Pittsburgh Sleep Quality Index consists of 15 items assessing sleep quality over the past month across 7 dimensions: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The component scores are summed to give a global score ranging from 0 to 21. Higher scores indicate worse sleep quality.	From baseline to weeks 16, 24, 36, and 48
Change in SF-36 Scale at week 12	The 36-Item Short Form Health Survey (SF-36) consists of 36 items measuring health-related quality of life across 8 dimensions: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each dimension score is standardized to a range of 0 to 100. Higher scores indicate better health status in that dimension.	From baseline to weeks 4, 8, and 12
Change in SF-36 Scale at week 48	The 36-Item Short Form Health Survey (SF-36) consists of 36 items measuring health-related quality of life across 8 dimensions: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each dimension score is standardized to a range of 0 to 100. Higher scores indicate better health status in that dimension.	From baseline to weeks 16, 24, 36, and 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure at week 12	Participants rest quietly for at least 5 minutes. Blood pressure is then measured using an electronic or mercury sphygmomanometer. Two measurements are taken, 1-2 minutes apart, and the average of the two readings is recorded for systolic and diastolic pressure (mmHg). If the two measurements differ by more than 5 mmHg, a third measurement is taken, and the average of all three is used.	From baseline to weeks 4, 8, and 12
Change in blood pressure at week 48	Participants rest quietly for at least 5 minutes. Blood pressure is then measured using an electronic or mercury sphygmomanometer. Two measurements are taken, 1-2 minutes apart, and the average of the two readings is recorded for systolic and diastolic pressure (mmHg). If the two measurements differ by more than 5 mmHg, a third measurement is taken, and the average of all three is used.	From baseline to weeks 16, 24, 36, and 48
Change in heart rate at week 12	While the participant is at rest, heart rate (beats per minute) is measured by palpating the radial artery or using the heart rate monitor function of an electronic blood pressure device.	From baseline to weeks 4, 8, and 12
Change in heart rate at week 48	While the participant is at rest, heart rate (beats per minute) is measured by palpating the radial artery or using the heart rate monitor function of an electronic blood pressure device.	From baseline to weeks 16, 24, 36, and 48
Change in respiratory rate at week 12	While the participant is resting quietly and unaware of being observed, the number of breaths per minute is counted by watching the rise and fall of the chest or abdomen. The measurement lasts at least 60 seconds. To avoid voluntary breath control, the participant's attention is diverted before the measurement.	From baseline to weeks 4, 8, and 12
Change in respiratory rate at week 48	While the participant is resting quietly and unaware of being observed, the number of breaths per minute is counted by watching the rise and fall of the chest or abdomen. The measurement lasts at least 60 seconds. To avoid voluntary breath control, the participant's attention is diverted before the measurement.	From baseline to weeks 16, 24, 36, and 48
Change in visual acuity at week 12	Visual acuity measured with habitual correction, i.e., participants wear their usual glasses or none. If it is below 0.5, corrected (pinhole) visual acuity is also measured.	From baseline to weeks 4, 8, and 12
Change in visual acuity at week 48	Visual acuity measured with habitual correction, i.e., participants wear their usual glasses or none. If it is below 0.5, corrected (pinhole) visual acuity is also measured.	From baseline to weeks 16, 24, 36, and 48
Change in introcular pressure at week 12	Intraocular pressure is measured using a non-contact tonometer. Three measurements are taken, and the average is recorded (mmHg).	From baseline to weeks 4, 8, and 12
Change in introcular pressure at week 48	Intraocular pressure is measured using a non-contact tonometer. Three measurements are taken, and the average is recorded (mmHg).	From baseline to weeks 16, 24, 36, and 48
Adherence to intervention at week 12	Adherence is defined as the ratio of the number of completed training sessions to the number of planned sessions, expressed as a percentage.	From baseline to week 12
Adherence to intervention at week 48	Adherence is defined as the ratio of the number of completed training sessions to the number of planned sessions, expressed as a percentage.	From baseline to weeks 24 and 48
Change in blood glucose at week 12	A fasting venous blood sample (approximately 5 mL) is collected from the participant in the morning after an overnight fast. The blood is placed in a vacuum tube containing a coagulant or gel separator and centrifuged to separate serum. Fasting blood glucose is measured using an automated biochemical analyzer. If postprandial glucose or glucose tolerance-related measures are needed, the blood collection time should be specified separately. Results are recorded in mmol/L.	From baseline to week 12
Change in blood glucose at week 48	A fasting venous blood sample (approximately 5 mL) is collected from the participant in the morning after an overnight fast. The blood is placed in a vacuum tube containing a coagulant or gel separator and centrifuged to separate serum. Fasting blood glucose is measured using an automated biochemical analyzer. If postprandial glucose or glucose tolerance-related measures are needed, the blood collection time should be specified separately. Results are recorded in mmol/L.	From baseline to weeks 16, 24, 36, and 48
Change in blood lipids at week 12	A fasting venous blood sample (approximately 5 mL) is collected from the participant in the morning after an overnight fast. The blood is placed in a vacuum tube containing a coagulant or gel separator and centrifuged to separate serum. Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose are measured using an automated biochemical analyzer. Results are recorded in mmol/L.	From baseline to week 12
Change in blood lipids at week 48	A fasting venous blood sample (approximately 5 mL) is collected from the participant in the morning after an overnight fast. The blood is placed in a vacuum tube containing a coagulant or gel separator and centrifuged to separate serum. Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose are measured using an automated biochemical analyzer. Results are recorded in mmol/L.	From baseline to weeks 16, 24, 36, and 48
Change in tear inflammatory cytokine levels at week 12	MMP-9, IL-6 are inflammatory markers measured in tear samples. Levels are assessed using a laboratory method with a tear test kit. Higher levels indicate greater inflammation.	From baseline to weeks 4, 8, and 12
Change in tear inflammatory cytokine levels at week 48	MMP-9, IL-6 are inflammatory markers measured in tear samples. Levels are assessed using a laboratory method with a tear test kit. Higher levels indicate greater inflammation.	From baseline to weeks 16, 24, 36, and 48
Change in meibum expressibility at week 12	On the lower eyelid, pressure is applied over the central 5 meibomian gland openings along the lash line. The number of glands that secrete any meibum is counted. Scoring (0-3 per eye): 0 (normal) = all 5 glands express meibum; 1 (mild) = 3 or 4 glands express; 2 (moderate) = 1 or 2 glands express; 3 (severe) = no glands express	From baseline to weeks 4, 8, and 12
Change in meibum expressibility at week 48	On the lower eyelid, pressure is applied over the central 5 meibomian gland openings along the lash line. The number of glands that secrete any meibum is counted. Scoring (0-3 per eye): 0 (normal) = all 5 glands express meibum; 1 (mild) = 3 or 4 glands express; 2 (moderate) = 1 or 2 glands express; 3 (severe) = no glands express	From baseline to weeks 16, 24, 36, and 48
Change in meibum quality at week 12	The upper eyelid meibomian glands are pressed, and the consistency of the expressed meibum is graded using the highest grade observed. Scoring (0-3 per eye): 0 (normal) = clear, fluid secretion; 1 (mild) = cloudy, fluid secretion; 2 (moderate) = cloudy, granular secretion; 3 (severe) = thick, toothpaste-like secretion	From baseline to weeks 4, 8, and 12
Change in meibum quality at week 48	The upper eyelid meibomian glands are pressed, and the consistency of the expressed meibum is graded using the highest grade observed. Scoring (0-3 per eye): 0 (normal) = clear, fluid secretion; 1 (mild) = cloudy, fluid secretion; 2 (moderate) = cloudy, granular secretion; 3 (severe) = thick, toothpaste-like secretion	From baseline to weeks 16, 24, 36, and 48
Change in meibomian gland dropout grading at week 12	Images of the meibomian glands are taken with a Keratograph 5M and graded by the same experienced ophthalmologist. The grade of gland dropout in the eyelid is scored (0-3 for upper and lower lids separately): 0 (normal) = no gland loss; 1 (mild) = loss of less than one-third of the gland area; 2 (moderate) = loss between one-third and two-thirds; 3 (severe) = loss of more than two-thirds	From baseline to weeks 4, 8, and 12
Change in meibomian gland dropout grading at week 48	Images of the meibomian glands are taken with a Keratograph 5M and graded by the same experienced ophthalmologist. The grade of gland dropout in the eyelid is scored (0-3 for upper and lower lids separately): 0 (normal) = no gland loss; 1 (mild) = loss of less than one-third of the gland area; 2 (moderate) = loss between one-third and two-thirds; 3 (severe) = loss of more than two-thirds	From baseline to weeks 16, 24, 36, and 48

Collaborators and Investigators

• Sponsor: Zhongshan Ophthalmic Center, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: April 5, 2026
• First Submitted That Met QC Criteria: April 5, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Dry Eye Syndromes; Ophthalmic Solutions; Pharmaceutical Solutions; Pharmaceutical Preparations; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Solutions; Specialty Uses of Chemicals; Lubricants; Lubricant Eye Drops
• Other Study ID Numbers: 2026LSPJ089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No