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Traditional Chinese Medicine Ultrasonic Atomization Treatment for Dry Eye Disease

Not Applicable
Recruiting
Conditions
Dry Eye Syndromes
Interventions
Drug: TCM ultrasonic atomization treatment with herbal Compound Decoction (CD)
Drug: TCM ultrasonic atomization treatment with Houttuynia Cordata (HC)
Drug: Placebo TCM ultrasonic atomization treatment (PA)
Drug: TCM ultrasonic atomization treatment with Dendrobii Caulis (DC)
Drug: Artificial Tears (AT)
Registration Number
NCT06089317
Lead Sponsor
Chinese University of Hong Kong
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Compound Decoction (CD) groupTCM ultrasonic atomization treatment with herbal Compound Decoction (CD)-
Compound Decoction (CD) groupArtificial Tears (AT)-
Placebo Atomization (PA) groupArtificial Tears (AT)-
Houttuynia Cordata (HC) groupTCM ultrasonic atomization treatment with Houttuynia Cordata (HC)-
Placebo Atomization (PA) groupPlacebo TCM ultrasonic atomization treatment (PA)-
Artificial Tears (AT) groupArtificial Tears (AT)-
Dendrobii Caulis (DC) groupArtificial Tears (AT)-
Houttuynia Cordata (HC) groupArtificial Tears (AT)-
Dendrobii Caulis (DC) groupTCM ultrasonic atomization treatment with Dendrobii Caulis (DC)-
Primary Outcome Measures
NameTimeMethod
Change in the Ocular Surface Disease Index (OSDI)baseline to 4th week

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).

Change in Non-invasive Tear Break-up Times (NIBUT)baseline to 4th week

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.

Secondary Outcome Measures
NameTimeMethod
Change in Ocular Surface Disease Index (OSDI)4 months

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).

Change in symptom Assessment iN Dry Eye (SANDE, modified)4 months

Symptom Assessment iN Dry Eye (SANDE) questionnaire is a 2-item frequency- and severity-based visual analog scale. It is self-administered to evaluate the frequency and severity of dry eye symptoms.

The final SANDE score is calculated by obtaining the square root of the product of the frequency of symptoms score and the severity of symptoms score, with a range from 0 (minimal degree of dry eye symptoms) to 100 (maximal degree of dry eye symptoms)

Change in 36-Item Short Form Health Survey (SF-36)4 months

The 36-Item Short Form Health Survey (SF-36) is a 36-item self-administered questionnaire, with 8 domains included: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). The physical health sub-scale and Mental health sub-scale will be graded respectively.

Change in the Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI:GH)4 months

The Work Productivity and Activity Impairment Questionnaire: General Health V2.0 (WPAI: GH) is a 6-item questionnaire that measures impairments in work and activities.

Change in Quality of Expressed Meibum4 months

The meibomian gland evaluator will be applied to the central aspects of the inferior eyelid margin. The result will be graded by a masked assessor.

Each gland in each area will be assessed for expressibility and graded according to a 4-point scale: grade 0, no secretion; grade 1, inspissated/ toothpaste-like expression; grade 2, cloudy fluid secretion; and grade 3, clear fluid/normal secretion. The sum scores of 5 glands will be between 0 and 15.

Change in Lid Margin and Eyelash Abnormalities4 months

Lid margin and eyelash abnormalities will be accessed by a slit lamp, including telangiectasia, meibomian gland capping, Demodex lash cylindrical collarettes, staphylococcal lash crusting, and seborrheic lash crusting.

All items will be graded based on a four-point scale: grade 0, absent; grade 1, mild; grade 2, moderate; grade 3, severe.

Changes in Schirmer I test4 months

The Schirmer I test (ST) will be performed by sterile standard filter paper strips without anesthesia. The filter paper strips will be gently put on the temporal side of both lower eyelids for 5 minutes. The wetting length by tears in each strip will be recorded in nanometers (mm) by a masked assessor.

The strips will be collected in sterile centrifuge tubes respectively for further laboratory tests.

Change in Non-Invasive Tear Break Up Times (NIBUT)4 months

Non-Invasive tear break up time (NIBUT) will be measured by the OCULUS Keratograph® 5M (Oculus, Wetzlar, Germany) in both eyes. Participants were instructed to keep their eyes on as much as possible during the examination. First and average NIKBUTs will be recorded by the machine.

Shortening NIBUT(\< 10 seconds) suggests instability of the tear film.

Changes in Tear Meniscus Height (TMH)4 months

The tear meniscus height (TMH) will be measured by the OCULUS Keratograph® 5M (Oculus, Wetzlar, Germany).

Changes in Bulbar Redness4 months

Bulbar conjunctival hyperaemia is automatically evaluated the Keratograph 5M (OCULUS, Wetzlar, Germany) according to the JENVIS grading scale from 0 to 4.

Changes in Lipid Layer Thickness4 months

The lipid layer thickness (LLT) of the tear film will be determined with the LipiView ® II Ocular Surface Interferometer (TearScience, Morrisville, NC). Minimum, Maximum, and Average thickness in nanometers (nm) will be measured.

Changes in Partial Blinking Rate4 months

The partial blinking rate will be reported as the percentage of incomplete blinks. The total and partial blinking times will be automatically recorded by the LipiView ® II Ocular Surface Interferometer (TearScience, Morrisville, NC).

Changes in Meiboscore4 months

The meiboscore grading will be based on the infrared meibography captured by the LipiView ® II Ocular Surface Interferometer (TearScience, Morrisville, NC). Both superior and inferior eyelids will be recorded. The result will be graded by a masked assessor.

The grading scheme is a 3-point scale (grade 0, no meibomian gland atrophy; grade 1, less than 1/3 area of glands lost; grade 2, 1/3-2/3 area of glands lost; grade 3, more than 2/3 area of glands lost)

Change in Tear Film Breakup Time (TBUT)4 months

The tear film breakup time (TBUT) is the time of the initial breakup of the tear film after a full blink. 2% Sodium fluorescein will be instilled in both eyes of the subjects. A masked follow-up assessor will do the examination via the slit lamp with a blue cobalt light. The TBUT will be measured three times with a stopwatch and taken on average.

Change in Corneal and Conjunctival Fluorescein Staining4 months

Fluorescein sodium liquid will be instilled on the ocular surface. After 3 minutes, the corneal and conjunctival punctate epithelial erosions will be observed and graded via the slit lamp biomicroscope with a blue cobalt light.

The Oxford Grading System is selected for grading. The severity will be divided into 6 grades (Grade 0, absent; Grade 1, minimal; Grade 2, mild; Grade 3, moderate; Grade 4, marked; Grade 5, severe)

Change in Expressibility of Meibomian Glands in the Meibomian Glands Yielding Liquid Secretion (MGYLS) (the inferior eyelid)4 months

Expressibility of the inferior eyelid meibomian glands is assessed with the Meibomian Gland Evaluator (TearScience, North Carolina, USA) applied inferior to central aspects of the inferior eyelid margin. The result is graded by a masked assessor.

The meibomian glands yielding liquid secretion (MGYLS) is the total number of glands that yield lipid secretions at the central aspects of the eyelid margin.

Change in Tear Film Osmolarity (TFO)4 months

The tear film osmolarity (TFO) is measured by the ScoutPro™ Osmolarity System (TearLab , San Diego, CA) via the disposable test card in both eyes.

The normal osmolarity was considered as lower than 308 mOsm/L in both eyes. A difference more than 8 mOsm/L between two eyes reflects the stability of the tear film.

Changes in Matrix metallopeptidase 9 (MMP-9)4 months

The MMP-9 enzyme-linked immunosorbent assay (ELISA) development kit (Invitrogen, Carlsbad, CA)) will be applied for measurement of the concentration of MMP-9 in participants' tears.

Adverse events (AEs)4 months

The adverse events (AEs) will be the number of incidents based on a checklist of symptoms, signs, and diseases by patients' reporting, slit-lamp examination, or doctor's diagnosis.

Trial Locations

Locations (4)

The CUHK Medical Centre (CUHKMC)

🇭🇰

Shatin, Hong Kong

Hong Kong Eye Hospital

🇭🇰

Kowloon, Hong Kong

The Chinese University of Hong Kong Eye Centre (CUHKEC)

🇭🇰

Kowloon, Hong Kong

Prince of Wales Hospital

🇭🇰

Shatin, Hong Kong

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