ANZCTR - Registration

Registration number

ACTRN12625000028404

Ethics application status

Approved

Date submitted

29/10/2024

Date registered

15/01/2025

Date last updated

15/05/2025

Date data sharing statement initially provided

15/01/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

Evaluation of a new biomarker for tear film health

Scientific title

Evaluation of a new biomarker for tear film health in individuals with tear dysfunction

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1314-2337

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Meibomian gland dysfunction

Aqueous-deficient dry eye

Condition category

Condition code

Eye

Diseases / disorders of the eye

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention 1: Prednisolone Sodium Phosphate 0.5% 5mg/mL eye drops minims (Bausch & Lomb Australia Pty Ltd)
Mode: topical ocular.
Dose: one drop, both eyes, four times daily, self-administered by the participant.
Duration: 14 days, ± 2 days.
Treatment adherence will be monitored by the use of an at-home treatment tracking diary.

Intervention 2: LipiFlow Thermal Pulsation (Johnson & Johnson Pty Ltd)
Single dose of standard in-office standard therapy of 12 minutes duration, both eyes simultaneously.
Administered by the study optometrist at day 14 ± 2 only to participants who do not show a clinical improvement in signs of dry eye ("treatment non-responders") after 14 days of treatment with Prednisolone Sodium Phosphate 0.5% 5mg/mL or placebo (saline (sodium chloride) 0.9%).

Acoustically-driven microfluidic extensional rheometry: The novel extensional rheometry platform is a laboratory-based platform that can be used to analyse the rheological (stretching) properties of a tear sample. Tear samples collected from study participants are analysed on the platform at all study visits for all participants. The tear rheological analysis generated by the platform is a primary outcome of this study.

Eligible participants will be assessed at baseline to be classified as being in one of two subgroups (aqueous-deficient dry eye or meibomian gland dysfunction) for the purposes of endpoint analysis and treatment response. All study procedures and interventions will be the same for participants in both subgroups.

"Treatment responders" will exit the study after Day 14. "Treatment non-responders" will receive LipiFlow Thermal Pulsation at Day 14, as described above, and be re-assessed for treatment response at Day 42. Treatment ‘responders’ in the aqueous-deficient dry eye subgroup will be defined as individuals who show greater than or equal to 3 units improvement (NEI scale) in overall corneal fluorescein staining in the study eye. Treatment ‘responders’ in the meibomian gland dysfunction subgroup will be defined as those with an absolute MGYLS score of greater than or equal to 5 or a MGS of greater than or equal to 15 in the study eye.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Diagnosis / Prognosis

Intervention code [3]

Treatment: Devices

Comparator / control treatment

Saline (sodium chloride) 0.9% eye drops minims (Bausch & Lomb Pty Ltd)
Mode: topical ocular.
Dose: one drop, both eyes, four times daily, self-administered by the participant.
Duration: 14 days, ± 2 days.
Treatment adherence will be monitored by the use of an at-home treatment tracking diary.

"Treatment responders" will exit the study after Day 14. "Treatment non-responders" will receive LipiFlow Thermal Pulsation at Day 14, as described above, and be re-assessed for treatment response at Day 42. Treatment ‘responders’ in the aqueous-deficient dry eye subgroup will be defined as individuals who show greater than or equal to 3 units improvement (NEI scale) in overall corneal fluorescein staining in the study eye. Treatment ‘responders’ in the meibomian gland dysfunction subgroup will be defined as those with an absolute MGYLS score of greater than or equal to 5 or a MGS of greater than or equal to 15 in the study eye.

Intervention 2: LipiFlow Thermal Pulsation (Johnson & Johnson Pty Ltd)
Single dose of standard in-office standard therapy of 12 minutes duration, both eyes simultaneously.
Administered by the study optometrist at day 14 ± 2 only to participants who do not show a clinical improvement in signs of dry eye ("treatment non-responders") after 14 days of treatment with Prednisolone Sodium Phosphate 0.5% 5mg/mL or placebo (saline (sodium chloride) 0.9%).

Control group

Placebo

Outcomes

Primary outcome [1]

Change in tear aqueous-specific rheology attributes (all participants).

Timepoint [1]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Primary outcome [2]

Change in meibomian gland secretions (meibomian gland dysfunction group only).

Timepoint [2]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Primary outcome [3]

Change in total corneal fluorescein staining score (aqueous-deficient dry eye group only).

Timepoint [3]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [1]

The percentage of eyes with an MGYLS score of greater than or equal to 5 (meibomian gland dysfunction group only)

Timepoint [1]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [2]

Change in tear lipid layer thickness

Timepoint [2]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [3]

Change in central corneal fluorescein staining score

Timepoint [3]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [4]

The percentage of eyes with an increase of greater than or equal to 10 mm/5 min in Schirmer test score (aqueous-deficient dry eye group only)

Timepoint [4]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [5]

*Primary outcome: Change in meibomian gland secretions (meibomian gland dysfunction group only).

Timepoint [5]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (primary timepoint, all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [6]

Change in conjunctival hyperaemia

Timepoint [6]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [7]

Change in conjunctival lissamine green staining score

Timepoint [7]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [8]

The percentage of eyes with an MGS score of greater than or equal to 15 (meibomian gland dysfunction group only)

Timepoint [8]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [9]

Change in SPEED score

Timepoint [9]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [10]

Change in tear meniscus height (TMH)

Timepoint [10]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [11]

Change in OSDI score

Timepoint [11]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [12]

Change in tear MMP-9 result

Timepoint [12]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [13]

Change in meibomian gland score (MGS)

Timepoint [13]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [14]

Change in "foreign body sensation" symptom score

Timepoint [14]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [15]

Change in "eye dryness" symptom score

Timepoint [15]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [16]

Change in non-invasive tear break-up time (NITBUT)

Timepoint [16]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [17]

Change in Schirmer test score

Timepoint [17]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [18]

Change in "eye discomfort" symptom score

Timepoint [18]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [19]

Change in "pain" symptom score

Timepoint [19]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [20]

Change in "burning/stinging sensation" symptom score

Timepoint [20]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [21]

Change in meibomian glands yielding liquid secretion (MGYLS) score

Timepoint [21]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [22]

Exploratory outcome: Change in tear cytokine levels

Timepoint [22]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [23]

Change in "photophobia" symptom score

Timepoint [23]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Secondary outcome [24]

Change in "itching" symptom score

Timepoint [24]

Baseline (all participants), Day 14 ± 2 post-intervention commencement (all participants), Day 42 ± 3 post-intervention commencement (Treatment non-responder participants at Day 14)

Eligibility

Key inclusion criteria

1. Male or female, aged at least 18 years of age;
2. Provide written informed consent and documentation, in accordance with privacy requirements, obtained prior to performing any study procedures;
3. Ability to understand and follow study instruction, with the intention of completing all of the required study visits.
4. Have a stable artificial tear dosage regimen for at least 30 days prior to Visit 1.
5. Have a stable regime of non-heat based, self-administered eyelid hygiene for at least 30 days prior to Visit 1.

The following inclusion criteria apply only to the aqueous deficient-dry eye subgroup:
1. OSDI score greater than or equal to 13, AND:
In at least one eye (where if both eyes are eligible, the eye with worse (higher) corneal fluorescein staining will be deemed the ‘study eye’; if both eyes have the same fluorescein staining score, the right eye will be the study eye):
2. TMH less than or equal to 0.2mm OR Schirmer test score with anaesthesia less than or equal to 5mm/5 minutes; and
3. Overall corneal fluorescein staining score of greater than or equal to 5 using the NEI scale (Lemp 1995); and
4. Conjunctival hyperaemia (bulbar redness score (greater than or equal to 1) using the Efron scale); and
5. MGS greater than 12.

The following inclusion criteria apply only to the meibomian gland dysfunction subgroup:
1. OSDI score less than or equal to 32, AND:
In at least one eye (where if both eyes are eligible, the eye with the worse (lower) MGS score will be deemed the ‘study eye’; if both eyes have the same MGS score, the right eye will be the study eye):
2. Meibomian gland score (MGS) less than or equal to 12 (assessed using the Meibomian Gland Evaluator, Korb and Blackie 2008); and
3. Non-invasive tear break-up time (NITBUT) less than or equal to 10 seconds; and
4. Overall corneal fluorescein staining score of less than 3 using the NEI grading scale.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. Known hypersensitivity or contraindication to any of the study procedures, interventions or their components.
2. Anticipated change in habitual artificial tear use (type/frequency) over the course of the study. Note: Participants must have had a stable artificial tear dosage regimen for at least 30 days prior to Visit 1 to be eligible.
3. Anticipated change in non-heat based, self-administered eyelid hygiene regimen over the course of the study. Note: Participants must have had a stable regime for this form of therapy at least 30 days prior to Visit 1 to be eligible.
4. Within 30 days of Visit 1, or anticipated required use throughout the study period:
a. Topical ophthalmic corticosteroids;
b. Other topical ophthalmic anti-inflammatory medications, such as Restasis, Cequa or Xiidra;
c. Topical, systemic or nasal anti-histamines;
d. Topical ophthalmic IOP-lowering medications;
e. Topical investigational ophthalmic drugs or devices;
f. Contact lenses;
g. Warm compresses or other heat-based eyelid therapy;
h. Systemic or nasal corticosteroids;
i. Systemic immunomodulatory medications.
5. Within 90 days of Visit 1, have received intense pulsed light (IPL), LipiFlow, or another similar treatment for dry eye disease.
6. Ocular surgery or trauma in either eye within the past 90 days.
7. Planned ocular surgery in either eye during the study period.
8. Within 90 days of Visit 1, or anticipated throughout the study period, use of high-dose omega-3 supplements (defined as combined daily dose of greater than or equal to 3000mg EPA + DHA).
9. Current use of punctal plugs, their anticipated insertion during the study, or a history of punctal cautery in either eye at any time prior to Visit 1, or anticipated use during the study period.
10. Current active ocular infection.
11. Current use of eyelash extensions, or anticipated use throughout the study period.
12. History of herpetic eye disease.
13. History of glaucoma or ocular hypertension.
14. IOP >24mmHg in either eye at Visit 1.
15. Documented history of steroid-induced IOP responsiveness.
16. At Visit 1, experience more than two occurrences of reflex tearing during basal tear collection in a single eye.
17. In the opinion of the investigator, be unable to adhere to the trial protocol or unable to successfully instil eye drops.
18. Currently pregnant or breastfeeding, or planning to become pregnant over the course of the study.
19. History of a systemic infection known to affect eye health (e.g., positive for COVID-19, or a upper respiratory infection within 4 weeks of Visit 1), by self-report.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

20/01/2025

Actual

7/03/2025

Date of last participant enrolment

Anticipated

25/08/2025

Actual

Date of last data collection

Anticipated

18/10/2025

Actual

Sample size

Target

60

Accrual to date

8

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

University

Name [1]

The University of Melbourne

Country [1]

Australia

Primary sponsor type

University

Name

The University of Melbourne

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Melbourne Central Human Research Ethics Committee

Ethics committee address [1]

https://research.unimelb.edu.au/work-with-us/ethics-and-integrity/our-ethics-committees

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

13/10/2024

Approval date [1]

11/02/2025

Ethics approval number [1]

Summary

Brief summary

As the most common indication for seeking medical eye care in developed countries, tear dysfunction is a major public health issue. The most common form of tear dysfunction is dry eye disease. 

At present, major barriers to optimal dry eye medical care are difficulties in reliably diagnosing and assessing the severity of the condition. There is therefore a need for new, rapid, cost-effective methods for detecting and staging dry eye, and tear dysfunction more generally, in clinical practice.

This study seeks to evaluate a new method for analysing tear health, based upon quantifying biophysical attributes related to tear viscoelasticity, using a novel acoustically-driven microfluidic extensional rheometry platform.

This study seeks to assess the therapeutic responsivity of the new method by examining correlations between the changes to dry eye clinical signs and ADMiER-derived tear rheology attributes, in response to established interventions for dry eye. We hypothesise that the viscoelastic properties of the tears will correlate to changes in the clinical signs and symptoms of dry eye disease.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Laura Downie

Address

Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053

Country

Australia

Phone

+61 3 9035 3043

Email

[email protected]

Contact person for public queries

Name

Laura Downie

Address

Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053

Country

Australia

Phone

+61 3 9035 3043

Email

[email protected]

Contact person for scientific queries

Name

Laura Downie

Address

Department of Optometry and Vision Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, 200 Berkeley Street, Carlton, Victoria 3053

Country

Australia

Phone

+61 3 9035 3043

Email

[email protected]

Trial Review

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