Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000667415
Ethics application status
Approved
Date submitted
16/05/2016
Date registered
23/05/2016
Date last updated
24/10/2019
Date data sharing statement initially provided
24/10/2019
Date results provided
24/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of intense pulsed light therapy for dry eye relief
Scientific title
Evaluation of the efficacy and mechanism of action of intense pulsed light for the treatment of meibomian gland dysfunction
Secondary ID [1] 289230 0
None
Universal Trial Number (UTN)
U1111-1181-5488
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Meibomian gland dysfunction 298795 0
Evaporative dry eye 298796 0
Condition category
Condition code
Eye 298846 298846 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: Treatment of meibomian gland dysfunction (MGD) with intense pulsed light (IPL)
Description: Eligible participants with various severities of symptomatic MGD will be recruited for the interventional study, and provided with a Participant Information Sheet. Volunteers have the opportunity to discuss any concerns with the researchers prior to signing a written consent form. Eligible participants will be required to attend at least five visits over 105 days. All products involved in the study are commercially available, and all tests performed are standard clinical procedures and will be carried out by New Zealand registered therapeutic optometrists. Research procedures will be performed at the Ocular Surface Laboratory, Department of Ophthalmology, University of Auckland, New Zealand.
In this prospective, double-masked, placebo-controlled trial, four or five adjacent, but overlapping IPL pulses (E-Eye IPL device, E-Swin, France) will be administered to the skin area immediately below the lower eyelid at an intensity level related to the individual’s Fitzpatrick Skin Type (ranging from 9 - 13 J/cm2). IPL therapy will be administered on Day 1, Day 15, Day 45 and Day 75 as per manufacturer’s recommendations. The treatment duration is approximately 20 seconds per eye and this is followed by 40 minutes of standard clinical ophthalmic testing. A fifth ‘follow-up’ visit is arranged on Day 105 to measure clinical outcomes only (no IPL treatment at this visit). Visits on Day 15, 45 and 75 will each take up to 45 minutes; the remaining two visits will each take approximately 80-90 minutes. The IPL therapy will be applied to both eyes of each participant, however, half the participants will be randomly assigned to receive a ‘mock’ treatment. Neither the researcher collecting clinical data, nor the participant will be privy to the treatment group assignment.
Intervention code [1] 294765 0
Treatment: Devices
Comparator / control treatment
Placebo treatment (neither the participant, nor the researcher collecting clinical data will have knowledge of participant’s assigned treatment group until study completion). For the placebo treatment, the E-Eye IPL device will be administered to the skin area immediately below the lower eyelid but no pulses will be directly applied to the area.
Control group
Placebo

Outcomes
Primary outcome [1] 298317 0
Change in non-invasive tear breakup time as measured by the Oculus Keratograph 5M.
Timepoint [1] 298317 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement
Primary outcome [2] 298318 0
Change in lipid layer thickness as graded from interference patterns observed on imaging by the Oculus Keratograph 5M.
Timepoint [2] 298318 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Primary outcome [3] 298319 0
Change in Symptom Assessment in Dry Eye (SANDE) questionnaire score, which comprises of two questions that use a 100 mm horizontal linear visual analogue scale to quantify both severity and frequency of dry eye symptoms.
Timepoint [3] 298319 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [1] 323835 0
Change in best spectacle corrected visual acuity (logMAR).
Timepoint [1] 323835 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [2] 323836 0
Change in Ocular Surface Disease Index (OSDI) questionnaire score.
Timepoint [2] 323836 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [3] 323837 0
Change in tear meniscus height (tear fluid adjacent to the lower eyelid) will be digitally analysed to determine the exact tear meniscus height by the Oculus Keratograph 5M.
Timepoint [3] 323837 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [4] 323838 0
Change in bulbar conjunctival redness (redness of the white part of the eye) will be digitally analysed using a coloured image of the eye taken by the Oculus Keratograph 5M.
Timepoint [4] 323838 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [5] 323839 0
Change in non-contact meibography, which involves recording an image of the patient’s everted upper and lower eyelid using the Oculus Keratograph 5M.
Timepoint [5] 323839 0
Baseline, and Day 105 after intervention commencement.
Secondary outcome [6] 323859 0
Change in central corneal nerve density as determined by imaging with in-vivo confocal microscopy.
Timepoint [6] 323859 0
Baseline, and Day 105 after intervention commencement.
Secondary outcome [7] 323860 0
Change in lid margin Demodex mite population as determined by lash epilation with slit lamp biomicroscopy.
Timepoint [7] 323860 0
Baseline, and Day 105 after intervention commencement.
Secondary outcome [8] 323861 0
Change in ocular bacterial species determined by culturing eyelid margin swabs.
Timepoint [8] 323861 0
Baseline, and Day 105 after intervention commencement.
Secondary outcome [9] 323862 0
Change in lipid composition within whole tear samples, analysed by mass spectrometry.
Timepoint [9] 323862 0
Baseline, and Day 105 after intervention commencement.
Secondary outcome [10] 323863 0
Tear osmolarity (saltiness of tear film) as measured non-invasively with the Tearlab System (Tearlab, USA).
Timepoint [10] 323863 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement
Secondary outcome [11] 323864 0
Ocular surface staining with lissamine green dye, observed by slit lamp biomicroscopy and graded according to the Oxford scheme.
Timepoint [11] 323864 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement.
Secondary outcome [12] 323865 0
Ocular surface staining with fluorescein sodium dye, observed by slit lamp biomicroscopy and graded according to the Oxford scheme.
Timepoint [12] 323865 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement
Secondary outcome [13] 323866 0
Tear evaporation rate, assessed non-invasively with the VapoMeter (Delfin, Finland).
Timepoint [13] 323866 0
Baseline, then on Day 15, Day 45, Day 75 and Day 105 after intervention commencement
Secondary outcome [14] 323867 0
Change in central corneal sensitivity is assessed using validated non-contact aesthesiometer
Timepoint [14] 323867 0
Baseline, and Day 105 after intervention commencement.

Eligibility
Key inclusion criteria
Participants with symptomatic dry eye caused by meibomian gland dysfunction.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Contraindications to light therapy e.g. clinical skin treatments within last two months, implants beneath the lower eyelid area, tattoos, semi-permanent make-up, or pigmented lesions in the treatment area will also be excluded from the study. Contact lens wearers must refrain from wearing contacts within one week of commencing the study, and during the study. Individuals taking prescribed photosensitising medications such as doxycycline within 3 months of study commencement.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This study is a randomised, double-masked, placebo-controlled clinical trial. Therefore the researcher determining the participant’s eligibility, and collecting clinical outcomes will be unaware as to the treatment group allocation. The interventional treatment (IPL or placebo) will be carried out by a third party not involved in the collection of research data..
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised random number generation to create a randomisation table onto which consecutive participant numbers will be applied.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Sham treatment in the control group will be matched as closely as possible to actual treatment, but without applying the device to the skin beneath the eyes.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Up to 100 participants will be recruited to achieve a completed sample of at least 72 (allowing for drop out). The sample size is based on results collected from previous pilot study (Craig et al, 2015). Power calculations show that a minimum of 36 subjects is required, to detect a clinically significant difference of 1 lipid layer grade, in pairwise comparisons, with 80% power (beta = 0.2), and at a two-sided statistical significance level of 5% (a = 0.05). The SD of normal values was estimated at 1 lipid layer grade. Sample size estimates were determined using a uniform non-parametric adjustment, with PASS 2002 (NCSS Statistical Software LLC, Utah, USA).. Post IPL scores at Day 1, 15, 45, and 75 will be compared to pre-IPL scores at baseline. Repeated measures analysis will be utilised to compare data across the various time points and paired analyses to compare pre- and post-IPL data at individual time points. Variables will be tested for normality using the Kolmogarav-Smirnoff test. Ordinal variables and those with non-normal distributions will be analysed with Friedman two-way analysis of variance, with pairwise Wilcoxon (paired) or Mann-Whitney (non-paired) post-hoc testing as required. Normally distributed continuous data will be assessed with a repeated measures two-way ANOVA with Tukey’s HSD post-hoc testing. Differences between treated and non-treated participant data will be compared with the paired samples t-test and the Wilcoxon signed-rank test for parametric and nonparametric data, respectively. Correlations between parametric and nonparametric data will be assessed with Pearson’s product-moment correlation or Spearman’s rank order correction, respectively. Outcomes will be considered significant if p<0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/05/2016
Actual
3/10/2016
Date of last participant enrolment
Anticipated
Actual
4/09/2017
Date of last data collection
Anticipated
Actual
21/12/2017
Sample size
Target
100
Accrual to date
Final
87
Recruitment outside Australia
Country [1] 7880 0
New Zealand
State/province [1] 7880 0
Auckland

Funding & Sponsors
Funding source category [1] 293609 0
University
Name [1] 293609 0
The University of Auckland
Country [1] 293609 0
New Zealand
Funding source category [2] 293610 0
Commercial sector/Industry
Name [2] 293610 0
E-Swin
Country [2] 293610 0
France
Funding source category [3] 304110 0
Charities/Societies/Foundations
Name [3] 304110 0
NZAO Education and Research Fund (NERF) Committee
Country [3] 304110 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 292429 0
None
Name [1] 292429 0
Address [1] 292429 0
Country [1] 292429 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295052 0
University of Auckland Human Participants Ethics Committee
Ethics committee address [1] 295052 0
Ethics committee country [1] 295052 0
New Zealand
Date submitted for ethics approval [1] 295052 0
03/04/2016
Approval date [1] 295052 0
16/05/2016
Ethics approval number [1] 295052 0
017173

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65898 0
A/Prof Jennifer P Craig
Address 65898 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 65898 0
New Zealand
Phone 65898 0
+6499238173
Fax 65898 0
+6493677173
Email 65898 0
[email protected]
Contact person for public queries
Name 65899 0
Jennifer P Craig
Address 65899 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 65899 0
New Zealand
Phone 65899 0
+6499238173
Fax 65899 0
+6493677173
Email 65899 0
[email protected]
Contact person for scientific queries
Name 65900 0
Jennifer P Craig
Address 65900 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 65900 0
New Zealand
Phone 65900 0
+6499238173
Fax 65900 0
+6493677173
Email 65900 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseRandomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction: Intense pulsed light therapy for meibomian gland dysfunction.2020https://dx.doi.org/10.1016/j.jtos.2020.01.003
N.B. These documents automatically identified may not have been verified by the study sponsor.