Traditional Chinese Medicine Ultrasonic Atomization Treatment for Dry Eye Disease

NCT06089317 | Completed

• 1 other identifier: CMDF-21B2005A_R1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 4

Brief Summary

Dry eye disease (DED) is the most prevalent ocular surface disease worldwide. Standard treatments like artificial tears show limited effect. Regarding the ultrasonic atomization, the ultrasonic nebulizer produces consistent steam from the solution with a treatment effect delivered to the ocular surface. We aim to evaluate the effectiveness and safety of traditional Chinese medicine (TCM) ultrasonic atomization as an adjuvant treatment for DED. This is a randomized double-masked, active- and placebo-controlled trial. 200 subjects will be equally assigned to the herbal compound decoction(CD) group, dendrobium caulis (DC) group, houttuynia cordata (HC) group, placebo atomization(PA) group, and artificial tear (AT) group by stratified permuted block randomization. Subjects of CD, DC, HC, and PA groups will receive TCM ultrasonic atomization treatment (6 times/week). All patients will receive hypromellose 0.3% w/v lubricant eye drops for a 1-week wash-out and a 4-month follow-up period. Outcomes included non-invasive tear break-up times, corneal and conjunctival fluorescein staining, and other dry eye-related parameter examined by LipiView II Ocular Surface Interferometer, OCULUS® Keratograph 5M, and slit lamp biomicroscope evaluated by masked clinical assessors at baseline, week 1, 2, 3, 4 and month 2, 3, 4. The other subjective questionnaires like the Ocular Surface Disease Index (OSDI) questionnaire are also selected.

Conditions

Dry Eye Syndromes

Keywords

Dry Eye Syndromes; Traditional Chinese Medicine; Ultrasonic Atomization; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (2)

• Change in the Ocular Surface Disease Index (OSDI)

  The Ocular Surface Disease Index (OSDI) is a 12-item symptom frequency-based questionnaire. It is self-administered to assess DED-related symptoms and severity. The final OSDI score is calculated by dividing the product of the total sum of the score and 25 by the total number of answered questions, with a range from 0 to 100. The score reflects the severity of DED(normal: 0-12, mild: 13-22, moderate: 23-32, severe: \>33).

  baseline to 4th week

• Change in Non-invasive Tear Break-up Times (NIBUT)

  The non-invasive tear break-up time (NIBUT) will be measured by the OCULUS Keratograph® 5M (Oculus, Wetzlar, Germany). Subjects will be instructed to keep their eyes on as much as possible during the examination. First and average NIBUT will be recorded by the machine accordingly. Shortening NIBUT(\< 10 seconds) suggests instability of the tear film.

  baseline to 4th week

Secondary Outcomes (19)

• Change in Ocular Surface Disease Index (OSDI)

  4 months

• Change in symptom Assessment iN Dry Eye (SANDE, modified)

  4 months

• Change in 36-Item Short Form Health Survey (SF-36)

  4 months

• Change in the Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI:GH)

  4 months

• Change in Non-Invasive Tear Break Up Times (NIBUT)

  4 months

Other Outcomes (13)

• Intraocular Pressure (IOP)

  4 months

• Best Corrected Visual Acuity (BCVA)

  4 months

• Change in Posterior Subcapsular of Lens

  4 months

Study Arms (5)

Compound Decoction (CD) group

ACTIVE COMPARATOR

Drug: TCM ultrasonic atomization treatment with herbal Compound Decoction (CD); Drug: Artificial Tears (AT)

Dendrobii Caulis (DC) group

ACTIVE COMPARATOR

Drug: TCM ultrasonic atomization treatment with Dendrobii Caulis (DC); Drug: Artificial Tears (AT)

Houttuynia Cordata (HC) group

ACTIVE COMPARATOR

Drug: TCM ultrasonic atomization treatment with Houttuynia Cordata (HC); Drug: Artificial Tears (AT)

Placebo Atomization (PA) group

PLACEBO COMPARATOR

Drug: Placebo TCM ultrasonic atomization treatment (PA); Drug: Artificial Tears (AT)

Artificial Tears (AT) group

OTHER

Drug: Artificial Tears (AT)

Interventions

Placebo TCM ultrasonic atomization treatment (PA) DRUG

The subjects will receive TCM ultrasonic atomization treatment with the ultrasonic nebulizer (WH-2000, YueHua, China) 6 days a week, once daily, 10 minutes per session, for 4 weeks. The solution for atomization of the PA group is low-concentration compound decoction (5%) same with the CD group. Subjects will be treated with hypromellose 0.3% w/v eye drops four times per day too.

Placebo Atomization (PA) group

TCM ultrasonic atomization treatment with herbal Compound Decoction (CD) DRUG

The subjects will receive TCM ultrasonic atomization treatment with the ultrasonic nebulizer (WH-2000, YueHua, China) 6 days a week, once daily, 10 minutes per session, for 4 weeks. The solution for atomization of the CD group is TCM compound decoction. The prescription of atomization solution in the CD group contains Honeysuckle flower (金銀花) 5g, Chrysanthemum flower (菊花) 5g, Pale betterflybush flower (密蒙花) 5g, Mild mint herb (薄荷) 5g, Barbary wolfberry fruit (枸杞子) 10g, and Ophiopogon japonicus (麥冬) 5g. Subjects will be treated with hypromellose 0.3% w/v eye drops four times per day too.

Compound Decoction (CD) group

TCM ultrasonic atomization treatment with Dendrobii Caulis (DC) DRUG

The subjects will receive TCM ultrasonic atomization treatment with the ultrasonic nebulizer (WH-2000, YueHua, China) 6 days a week, once daily, 10 minutes per session, for 4 weeks. The solution for atomization of the DC group is Dendrobii Caulis extracts. The prescription of the DC group contains Dendrobium (石斛) 35g. Subjects will be treated with hypromellose 0.3% w/v eye drops four times per day too.

Dendrobii Caulis (DC) group

TCM ultrasonic atomization treatment with Houttuynia Cordata (HC) DRUG

The subjects will receive TCM ultrasonic atomization treatment with the ultrasonic nebulizer (WH-2000, YueHua, China) 6 days a week, once daily, 10 minutes per session, for 4 weeks. The solution for atomization of the HC group is Heartleaf Houttuynia Herb extracts. The prescription of the HC group contains Heartleaf Houttuynia Herb(魚腥草) 35g. Subjects will be treated with hypromellose 0.3% w/v eye drops four times per day too.

Houttuynia Cordata (HC) group

Artificial Tears (AT) DRUG

The subjects will receive lubricant eye drop (Hypromellose 0.3% w/v Eye Drops) four times per day only.

Artificial Tears (AT) group; Compound Decoction (CD) group; Dendrobii Caulis (DC) group; Houttuynia Cordata (HC) group; Placebo Atomization (PA) group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one eye of subjects meets DED diagnostic criteria as the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS II); and
• Ocular Surface Disease Index (OSDI)≥13 and \<33; and
• The age range between years 18-80, no sex limitation; and
• Symptoms of dry eye for at least 6 months; and
• Can complete the questionnaires independently and understand Chinese or English.

You may not qualify if:

• Had or currently suffering from other concomitant ocular surface diseases, including chronic conjunctivitis, ocular rosacea, cicatricial pemphigoid, graft-versus-host disease, limbal stem cell deficiency, and severe ocular allergy;
• Received any refractive surgery and corneal surgery before, including corneal transplant; or any eye surgery in the past 6 months;
• Receiving DED-related medications, including topical steroid eyedrops, topical antibiotics, topical cyclosporin A, and topical diquafosol;
• Received intense pulsed laser (IPL) or vectored thermal pulsation (VTP) therapy in the past 12 months;
• Received topical antiglaucomatous treatment in the past 12 months
• Plans to use contact lenses during treatment and follow-up periods or used contact lenses 2 weeks before the baseline measurement and recruitment;
• Had or currently suffering from severe cardiopulmonary disease, liver and kidney dysfunction, and severe blood system diseases;
• Suffering from glucose-6-phosphate dehydrogenase deficiency (G6PD);
• Had or currently suffering from specific respiratory diseases, e.g. emphysema, bronchitis, asthma, chronic obstructive pulmonary disease, bronchial dilatation;
• Has adverse reaction history to herbs used in this study before;
• Whose TCM constitution is manifested as "yang-deficiency" or diagnosed by TCM practitioners that their TCM syndrome is not suitable for the atomization treatment;
• Pregnancy, preparation for pregnancy, or lactation;

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (4)

Hong Kong Eye Hospital

Kowloon, Hong Kong, Hong Kong

Location

The Chinese University of Hong Kong Eye Centre (CUHKEC)

Kowloon, 000000, Hong Kong

Location

The CUHK Medical Centre (CUHKMC)

Shatin, 000 000, Hong Kong

Location

Prince of Wales Hospital

Shatin, 000000, Hong Kong

Location

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

Lubricant Eye Drops

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Ophthalmic Solutions; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Lubricants; Specialty Uses of Chemicals

Study Officials

• Kelvin KL Chong, MBChB

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Ophthalmology and Visual Sciences, CUHK

Model Details: A total of 200 subjects with mild to moderate DED will be recruited. Only one eye of recruited subjects with the shorter NIBUT will be selected and analyzed as the study eye. The subjects will be randomly divided into TCM compound decoction (CD) group, dendrobium caulis (DC) group, houttuynia cordata (HC) group, placebo atomization (PA) group, and artificial tears (AT) group equally. An online-based clinical trial randomization tool with a permuted block and stratification randomization method is applied for the randomization, and block sizes are randomly chosen. Stratification variances is sex and age.

Study Record Dates

• First Submitted: October 13, 2023
• First Posted: October 18, 2023
• Study Start: July 28, 2024
• Primary Completion: June 22, 2025
• Study Completion: June 22, 2025
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

HK (4)