The Effect of Manuka Eye Drops on Tear Film Properties

• Sponsor: The University of New South Wales (Other)
• Overall Status: Completed
• CT.gov ID: NCT03622619
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 2.6
• Patients Per Site Per Month: 18

Study Details

Study Description

Brief Summary

Traditionally, Manuka honey has been used to combat against bacteria and reduce inflammation (the body's way of reacting to infection, irritation or other injury). Due to the inflammatory nature of dry eye, Manuka eye drops show promise as a treatment for dry eye disease. The aim of this research is to compare the effects of two over the counter eye drops that are used to treat dry eye conditions over a one month period.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Other: Optimel Antibacterial Manuka+ Dry Eye Drops; Other: Systane Ultra Lubricating Eye Drops	N/A

Detailed Description

The aim of the present study is to conduct a randomised clinical trial to compare the effect on tear film properties and dry eye signs and symptoms of Optimel Manuka eye drops compared to Systane Ultra, a widely available over the counter aqueous tear supplement as a control eye drop. This investigation will involve a minimum of 40 participants who have dry eye, who are randomly put into two groups receiving either Optimel Manuka drops or Systane Ultra used three times daily for one month. Both of these products are commercially available in Australia. Results from this study will inform practitioners as to the potential benefits of Manuka eye drops on tear film characteristics and signs and symptoms of dry eye.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Manuka Eye Drops on Tear Film Properties
• Actual Study Start Date: Aug 13, 2018
• Actual Primary Completion Date: Oct 30, 2018
• Actual Study Completion Date: Oct 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Manuka eye drops	Other: Optimel Antibacterial Manuka+ Dry Eye Drops; Leptospermum sp Honey 165mg/g
Active Comparator: Systane Ultra	Other: Systane Ultra Lubricating Eye Drops; Polyethylene glycol 400 0.4% and propylene glycol 0.3%

Outcome Measures

Primary Outcome Measures

1. A Measurable Difference in Tear Lipid Layer Thickness After 4 Weeks of Daily Use [28 days]

   The primary endpoint is a measurable difference in tear lipid layer thickness between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Tear film inferior lipid layer thickness (LLT; nm) is measured using the LipiView II (Johnson and Johnson Vision, USA). The participant's eye is positioned in front of an illumination source that is directed toward the tear film on the corneal surface. The camera records a 20-second video of the tear film interference and subsequently displays a value in interferometric colour units (ICU), where 1 ICU approximates 1nm of lipid layer thickness.

2. A Measurable Difference in Tear Evaporation Rate After 4 Weeks of Daily Use. [28 days]

   A measurable difference in Tear evaporation rate between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Measured using a Modified Vapometer. The Modified Vapometer is a closed chamber device which is used for measuring transepidermal water loss. Participants will be seated upright on a chair and provided with a distance fixation target. To minimize the effect of skin evaporation, petroleum jelly (Vaseline, http://www.unilever.com.au/brands-in-action/detail/Vaseline/299339/) will be applied over the upper eyelid and the surrounding areas. The VapoMeter will then be placed over the eye and a non-invasive measurement of tear evaporation will be taken within 10 s. Participants will be instructed not to blink during open eye measurement and to maintain a normal straight gaze at the fixation target. Evaporation rates with the eyes closed will also be taken, in order to account for the skin evaporation from eyelids and surrounding skin tissue.

3. A Measurable Difference in Fluorescein Tear Break-up Time After 4 Weeks of Daily Use [28 days]

   A measurable difference in fluorescein tear break-up time between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Fluorescein tear break-up time (TBUT; sec) (Opti-Strip-FL, Optimed, Lane Cove West, NSW, Australia) was measured viewed with a yellow Wratten filter (No. 12, Kodak) and cobalt light of the slit lamp biomicroscope. Three consecutive TBUT measurements for each eye were taken by a single masked investigator.

Secondary Outcome Measures

1. A Measurable Difference in Subjective Symptoms After 4 Weeks of Daily Use [28 days]

   A measurable difference in subjective symptoms between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Subjective symptoms is measured using an visual analogue scale ranging from 0 to 100, with higher scores meaning worse outcome. Participants are asked to visually represent their symptom severity by marking a dot on a line ten centimetres in length. These are then measured using a ruler to the nearest 0.5mm and given a score from zero to 100, with zero indicative of no symptoms and 100 suggesting maximum symptom severity

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to read and comprehend English and give informed consent as demonstrated by signing a record of informed consent;

• General population aged 18 years and over;

• In good general health;

• Subjectively experiencing dry eye symptoms (e.g. burning, irritation, and discomfort due to dryness of the eye or exposure to wind or sun). Participants will be selected based on a minimum OSDI score of 13 points (1).

• Willing to discontinue CL wear for 1 week before first visit and continue to do so until the conclusion of the study;

• Participant is willing to discontinue their use of any previous conventional dry eye treatment method commenced before the study throughout the study;

• Willing to comply with the dosage and study visit schedule as directed by the investigator;

• No planned changes to diet and willing not to substantially alter their usual diet for the duration of the study, including their typical intake of fish, green tea or oral supplements known to have anti-inflammatory properties;

• Willingness to notify the study investigator if instructed to alter their diet by health/medical practitioner.

Exclusion Criteria:

• Allergy to benzoic acid preservatives;

• Allergy to honey products;

• Active anterior eye disease/ infection, inflammation/allergy that requires ocular medical treatment;

• Eye injury or surgery in the past 6 months including chemical burns, penetrating injuries, traumatic iritis, orbital fractures, laser surgery, strabismus surgery, cataract or any other intraocular surgeries;

• Soft contact lens, rigid gas permeable, orthokeratology lens wearer within one week prior to the study and during the study.

• Use of any of the following medications (including steroids) up to 12 weeks prior to start of the study or during the course of the study:

• Ocular medication, category S3 and above;

• Any systemic or topical medications that will affect ocular physiology e.g. anti-acne medications such as Roaccutane and corticosteroid or immunosuppressant medications such as Hydrocortisone, Prednisolone and antihistamine medications such as Claritine;

• Any systemic disease that may affect ocular health e.g. Graves disease, and auto-immune diseases such as ankolysing spondylitis, multiple sclerosis and systemic lupus erythematosis;

• Epilepsy or history of migraines exacerbated by flashing, strobe-like lights.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	School of Optometry and Vision Science	Sydney	New South Wales	Australia	2050

Sponsors and Collaborators

• The University of New South Wales

Investigators

• Principal Investigator: Jacqueline Tan, PhD, University of New South Wales

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 21, 2018

More Information

Publications

None provided.

• Responsible Party: Jacqueline Tan-Showyin, Senior Research Fellow, The University of New South Wales
• ClinicalTrials.gov Identifier: NCT03622619
• Other Study ID Numbers: SOVS2018-501
• First Posted: Aug 9, 2018
• Last Update Posted: May 18, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Dry Eye Syndromes; Anti-Bacterial Agents; Ophthalmic Solutions; Lubricant Eye Drops

Study Results

Participant Flow

Arm/Group Title	Manuka Eye Drops	Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
Period Title: Overall Study
STARTED	23	23
COMPLETED	21	21
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Manuka Eye Drops	Systane Ultra	Total
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%	Total of all reporting groups
Overall Participants	21	21	42
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.20 (3.47)	20.56 (3.16)	21.39 (3.39)
Sex: Female, Male (Count of Participants)
Female	12 57.1%	16 76.2%	28 66.7%
Male	9 42.9%	5 23.8%	14 33.3%
Race/Ethnicity, Customized (Count of Participants)
Asian	17 81%	15 71.4%	32 76.2%
Non-Asian	4 19%	6 28.6%	10 23.8%
Region of Enrollment (participants) [Number]
Australia	21 100%	21 100%	42 100%
Ocular Surface Disease Index Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	33.65 (12.38)	28.17 (12.31)	30.91 (12.51)

Outcome Measures

1. Primary Outcome

Title	A Measurable Difference in Tear Lipid Layer Thickness After 4 Weeks of Daily Use
Description	The primary endpoint is a measurable difference in tear lipid layer thickness between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Tear film inferior lipid layer thickness (LLT; nm) is measured using the LipiView II (Johnson and Johnson Vision, USA). The participant's eye is positioned in front of an illumination source that is directed toward the tear film on the corneal surface. The camera records a 20-second video of the tear film interference and subsequently displays a value in interferometric colour units (ICU), where 1 ICU approximates 1nm of lipid layer thickness.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Manuka Eye Drops	Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
Measure Participants	21	21
Mean (Standard Deviation) [nm]	-5.1 (22.2)	-3.2 (21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	A Measurable Difference in Tear Evaporation Rate After 4 Weeks of Daily Use.
Description	A measurable difference in Tear evaporation rate between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Measured using a Modified Vapometer. The Modified Vapometer is a closed chamber device which is used for measuring transepidermal water loss. Participants will be seated upright on a chair and provided with a distance fixation target. To minimize the effect of skin evaporation, petroleum jelly (Vaseline, http://www.unilever.com.au/brands-in-action/detail/Vaseline/299339/) will be applied over the upper eyelid and the surrounding areas. The VapoMeter will then be placed over the eye and a non-invasive measurement of tear evaporation will be taken within 10 s. Participants will be instructed not to blink during open eye measurement and to maintain a normal straight gaze at the fixation target. Evaporation rates with the eyes closed will also be taken, in order to account for the skin evaporation from eyelids and surrounding skin tissue.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Manuka Eye Drops	Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
Measure Participants	21	21
Mean (Standard Deviation) [gm-2h]	-10.8 (16.7)	0.7 (10.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	A Measurable Difference in Fluorescein Tear Break-up Time After 4 Weeks of Daily Use
Description	A measurable difference in fluorescein tear break-up time between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Fluorescein tear break-up time (TBUT; sec) (Opti-Strip-FL, Optimed, Lane Cove West, NSW, Australia) was measured viewed with a yellow Wratten filter (No. 12, Kodak) and cobalt light of the slit lamp biomicroscope. Three consecutive TBUT measurements for each eye were taken by a single masked investigator.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Manuka Eye Drops	Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
Measure Participants	21	21
Mean (Standard Deviation) [seconds]	2.0 (3.0)	0.0 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	A Measurable Difference in Subjective Symptoms After 4 Weeks of Daily Use
Description	A measurable difference in subjective symptoms between Optimel Manuka eye drops and Systane Ultra eye drops after 4 weeks of daily use. Subjective symptoms is measured using an visual analogue scale ranging from 0 to 100, with higher scores meaning worse outcome. Participants are asked to visually represent their symptom severity by marking a dot on a line ten centimetres in length. These are then measured using a ruler to the nearest 0.5mm and given a score from zero to 100, with zero indicative of no symptoms and 100 suggesting maximum symptom severity
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Manuka Eye Drops	Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g	Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
Measure Participants	21	21
Burning/stinging	-10.7 (23.2)	-8.9 (18.6)
Grittiness/foreign body sensation	-20.8 (20.4)	-15.0 (17.9)
Dryness	-35.4 (22.1)	-32.2 (19.2)
Blurry vision	-13.6 (22.5)	-20.6 (29.8)
Overall discomfort	-14.7 (15.1)	-10.7 (17.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Burning/stinging

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Grittiness/foreign body sensation

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments	Dryness
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments	Blurred vision
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Manuka Eye Drops, Systane Ultra
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments	Overall discomfort
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	Manuka Eye Drops		Systane Ultra
Arm/Group Description	Optimel Antibacterial Manuka+ Dry Eye Drops: Leptospermum sp Honey 165mg/g		Systane Ultra Lubricating Eye Drops: Polyethylene glycol 400 0.4% and propylene glycol 0.3%
All Cause Mortality
	Manuka Eye Drops		Systane Ultra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Manuka Eye Drops		Systane Ultra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Manuka Eye Drops		Systane Ultra
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/21 (0%)
Eye disorders
Ocular Stinging	1/21 (4.8%)	1	0/21 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.