The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001428358
Ethics application status
Approved
Date submitted
5/10/2017
Date registered
9/10/2017
Date last updated
9/10/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Diagnostic ability of the breakup time measurements in detecting dry eye disease
Scientific title
Diagnostic ability of the breakup time measurements with and without sodium fluorescein instillation in detecting dry eye disease
Secondary ID [1] 293065 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry eye disease 304998 0
Condition category
Condition code
Eye 304320 304320 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In this investigator-masked randomised crossover study, the tear film breakup time of participants will be assessed in triplicate, with and without sodium fluorescein instillation, in a randomised order, by two independent observers. A 30-minute interval between measurements will ensure subsidence of reflex tearing.

In the intervention arm, sodium fluorescein was applied to the bulbar conjunctiva from a fluorescein impregnated strip (Haag-Streit) wetted with 1 drop (10-20µl) of saline and shaken to remove excess fluid. Following fluorescein instillation, participants were then instructed to blink naturally over a 1 minute period to facilitate even distribution over the ocular surface. Tear film breakup time was then assessed in triplicate under blue light with a Wratten yellow filter.
Intervention code [1] 299308 0
Diagnosis / Prognosis
Comparator / control treatment
In the control arm, tear film breakup time was measured using non-invasive automated Keratograph 5M (Oculus, Wetzlar, Germany) without sodium fluroescein instillation.
Control group
Active

Outcomes
Primary outcome [1] 303586 0
Fluorescein breakup time measured under blue light with a Wratten yellow filter. Non-invasive tear film breakup time measured using automated Keratograph 5M readings (Oculus, Wetzlar, Germany).
Timepoint [1] 303586 0
1 minute following fluorescein instillation in the intervention arm.
Secondary outcome [1] 339495 0
Discriminative ability (area under receiver operator characteristic curve) and diagnostic accuracy (Youden optimal cut-off sensitivity and specificity) of fluorescein and non-invasive tear film breakup time in detecting dry eye disease (Ocular Surface Disease Index score greater than or equal to 13).
Timepoint [1] 339495 0
Ocular Surface Disease Index questionnaire administered during study enrolment, and completed within 2 hours prior to assessment of clinical tear film parameters.

Eligibility
Key inclusion criteria
Participants will be enrolled into two age and gender matched groups, with and without symptomatic dry eye (Ocular Surface.Disease Index score greater than or equal to 13).
Age of 18 years or older
No history of major systemic disease.
No history of ocular surgery.
No use of topical or systemic medications known to affect the eye.
Able to provide written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Under 18 years of age.
History of major systemic or ocular disease.
History of ocular surgery.
Current use of topical or systemic medications known to affect the eye.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The order in which tear film breakup time measurements are conducted, with and without fluorescein instillation, will be randomised centrally by computer. The two types of tear film breakup time measurements will be conducted by two independent observers, and a third investigator will conduct study enrolment and administer the OSDI questionnaire to ensure investigator masking.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The order in which first tear film breakup time measurements are conducted will be determined via random number generation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The distributions of tear film breakup time measurements will be assessed using the D’Agostino-Pearson omnibus normality test, and then undergo logarithmic transformation before further parametric analysis if necessary. Intra-group and inter-group comparisons of medians will be conducted with paired and unpaired t-tests, respectively, and variances analysed by F-tests. Pearson's correlation anlaysis between breakup time measurements and Ocular Surface Disease Index will be peformed and Bland-Altman analysis will be conducted between breakup time measurements. A receiver operative characteristic curve will be constructed to assess the diagnostic ability of the breakup time measurements in detecting whether subjects has dry eye disease. The area under the curve (C-statistic) and diagnostic accuracy values at the Youden’s optimal diagnostic cut-off were then calculated. All tests will be two-tailed and p < 0.05 considered significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 9266 0
New Zealand
State/province [1] 9266 0
Auckland

Funding & Sponsors
Funding source category [1] 297688 0
University
Name [1] 297688 0
The University of Auckland
Address [1] 297688 0
Private Bag 92019
Auckland 1142
Country [1] 297688 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] 296710 0
None
Name [1] 296710 0
Address [1] 296710 0
Country [1] 296710 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298760 0
University of Auckland Human Participants Ethics Committee
Ethics committee address [1] 298760 0
Private Bag 92019
Auckland 1142
Ethics committee country [1] 298760 0
New Zealand
Date submitted for ethics approval [1] 298760 0
23/02/2014
Approval date [1] 298760 0
08/05/2014
Ethics approval number [1] 298760 0
UAHPEC 011368

Summary
Brief summary
This study compares two commonly used clinical methods of tear film breakup time measurement. Participants from two age and gender matched groups, with and without dry eye disease, will be enrolled into a prospective, randomised, investigator-masked, crossover study. Two independent observers measured tear film breakup time in triplicate, respectively, in a randomised order, following fluorescein instillation under blue light, and using non-invasive automated Keratograph 5M readings. A 30-minute interval between measurements ensured subsidence of reflex tearing. The median and distribution of breakup time measurements will be compared, and Bland-Altman and Pearson correlation analysis will be conducted. A receiver operative characteristic curve will then be constructed to assess the diagnostic ability of the breakup time measurements in detecting whether subjects has dry eye disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78142 0
A/Prof Jennifer P Craig
Address 78142 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 78142 0
New Zealand
Phone 78142 0
+6499238173
Fax 78142 0
+6493677173
Email 78142 0
jp.craig@auckland.ac.nz
Contact person for public queries
Name 78143 0
A/Prof Jennifer P Craig
Address 78143 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 78143 0
New Zealand
Phone 78143 0
+6499238173
Fax 78143 0
+6493677173
Email 78143 0
jp.craig@auckland.ac.nz
Contact person for scientific queries
Name 78144 0
A/Prof Jennifer P Craig
Address 78144 0
Department of Ophthalmology
The University of Auckland
Private Bag 92019
Auckland 1142
Country 78144 0
New Zealand
Phone 78144 0
+6499238173
Fax 78144 0
+6493677173
Email 78144 0
jp.craig@auckland.ac.nz

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary