Trial Review

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
ACTRN12625000100493
Ethics application status
Approved
Date submitted
16/01/2025
Date registered
30/01/2025
Date last updated
30/01/2025
Date data sharing statement initially provided
30/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the impact of external factors on diurnal changes to corneal immune cells
Scientific title
Investigating the impact of light filtering lenses on diurnal changes to corneal immune cells in healthy adults aged 18 to 45 years
Secondary ID [1] 313440 0
IVCM_Diurnal25
Universal Trial Number (UTN)
U1111-1314-4025
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy 335825 0
Condition category
Condition code
Eye 332397 332397 0 0
Normal eye development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The eye exposed to the intervention will be randomly allocated. Each intervention will be worn once only, as described for each intervention (below).

• Nexcare Opticlude Orthoptic Eyepatch
The Nexcare Opticlude Eyepatch will be worn overnight over one eye until the next morning visit (08:00-10:00).
On a separate testing day, about one week later, the Nexcare Opticlude Eyepatch will be worn overnight over one eye until the next late afternoon visit (16:00-18:00).

• NOIR Frame style #46 Laser Safety Eyewear for 180-532nm, Filter colour: orange, Visible Light Transmission: 48%, CE rating/EN207 180-315, D LB7 + IR LB4, >315-532 DIRM LB6 (Blue + UV filter)
On a separate week, the NOIR safety glasses with Blue + UV filter over one eye (control eye exposed to natural light) will be worn from awakening until a visit in the late afternoon (16:00-18:00).

• NOIR Frame style #46 Laser Safety Eyewear for 190-398nm and 10,600nm, Filter colour: clear, Visible Light Transmission: 93%, CE rating 190-315 D LB7 + IR LB4, >315-398 DIRM LB5, 9000-11000 DI LB3 (UV only filter)
On a separate week, the NOIR safety glasses with UV- only filter will be worn over one eye (with the control eye exposed to natural light) from awakening in the morning, until late in the late afternoon (16:00-18:00).

A reminder notification to use the intervention, as indicated, will be sent out to participants the day prior to the study visit. Adherence to the intervention will be assessed by participant self-report at the study visit.
Intervention code [1] 330013 0
Treatment: Devices
Comparator / control treatment
The control will be the same participants but the contralateral eye that is exposed to natural light and environmental conditions (i.e. not exposed to the intervention).
Baseline levels will also be measured prior to the administration of any interventions.
Control group
Active

Outcomes
Primary outcome [1] 340149 0
Physiological diurnal change in the dynamic characteristics of corneal epithelial dendritic cells
Timepoint [1] 340149 0
Baseline AM vs Baseline PM
Primary outcome [2] 339956 0
Physiological diurnal change in the dynamic characteristics of corneal epithelial T cells
Timepoint [2] 339956 0
Baseline AM vs Baseline PM
Primary outcome [3] 340169 0
Physiological diurnal change in the dynamic characteristics of corneal stromal immune cells
Timepoint [3] 340169 0
Baseline AM vs Baseline PM
Secondary outcome [1] 443137 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the morphology of corneal stromal immune cells
Timepoint [1] 443137 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [2] 443136 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the morphology of corneal epithelial dendritic cells
Timepoint [2] 443136 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [3] 443130 0
Difference between Baseline AM (morning) and intervention A eyepatch AM in the dynamic characteristics of corneal epithelial T cells
Timepoint [3] 443130 0
Baseline AM vs intervention A eyepatch AM
Secondary outcome [4] 443164 0
Difference between control eye and eyepatch intervention eye in the neuroimmune interactions of corneal epithelial T cells before and after apparent contact of a corneal nerve
Timepoint [4] 443164 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [5] 443109 0
Physiological diurnal change in the morphology of corneal epithelial dendritic cells
Timepoint [5] 443109 0
Baseline AM vs Baseline PM
Secondary outcome [6] 443132 0
Difference between Baseline AM (morning) and the eyepatch intervention AM in the dynamic characteristics of corneal stromal immune cells
Timepoint [6] 443132 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [7] 443106 0
Physiological diurnal change in the morphology of corneal epithelial T cells
Timepoint [7] 443106 0
Baseline AM vs Baseline PM
Secondary outcome [8] 443138 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the neuroimmune interactions of corneal epithelial T cells before and after apparent contact of a corneal nerve
Timepoint [8] 443138 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [9] 443141 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the density of corneal epithelial T cells
Timepoint [9] 443141 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [10] 443116 0
Physiological diurnal change in the neuroimmune interactions of corneal epithelial dendritic cells before and after apparent contact of a corneal nerve
Timepoint [10] 443116 0
Baseline AM vs Baseline PM
Secondary outcome [11] 443112 0
Physiological diurnal change in the neuroimmune interactions of corneal epithelial T cells before and after apparent contact of a corneal nerve
Timepoint [11] 443112 0
Baseline AM vs Baseline PM
Secondary outcome [12] 443111 0
Physiological diurnal change in the morphology of corneal stromal immune cells
Timepoint [12] 443111 0
Baseline AM vs Baseline PM
Secondary outcome [13] 443143 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the dynamic characteristics of corneal epithelial T cells
Timepoint [13] 443143 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [14] 443131 0
Difference between Baseline AM (morning) and the eyepatch intervention AM in the dynamic characteristics of corneal epithelial dendritic cells
Timepoint [14] 443131 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [15] 443148 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the dynamic characteristics of corneal stromal immune cells
Timepoint [15] 443148 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [16] 443129 0
Physiological diurnal change in the density of corneal stromal immune cells
Timepoint [16] 443129 0
Baseline AM vs Baseline PM
Secondary outcome [17] 443156 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the density of corneal stromal immune cells
Timepoint [17] 443156 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [18] 443140 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the density of corneal epithelial dendritic cells
Timepoint [18] 443140 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [19] 443139 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the neuroimmune interactions of corneal epithelial dendritic cells before and after apparent contact of a corneal nerve
Timepoint [19] 443139 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [20] 443128 0
Physiological diurnal change in the density of corneal epithelial T cells
Timepoint [20] 443128 0
Baseline AM vs Baseline PM
Secondary outcome [21] 443161 0
Difference between the control eye and eyepatch intervention eye for the morphology of corneal epithelial T cells
Timepoint [21] 443161 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [22] 443163 0
Difference between the control eye and eyepatch intervention eye for the morphology of corneal stromal immune cells
Timepoint [22] 443163 0
Control eye AM vs intervention A eyepatch eye AM
Secondary outcome [23] 443149 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the morphology of corneal epithelial T cells
Timepoint [23] 443149 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [24] 443142 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the density of corneal stromal immune cells
Timepoint [24] 443142 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [25] 443127 0
Physiological diurnal change in the density of corneal epithelial dendritic cells
Timepoint [25] 443127 0
Baseline AM vs Baseline PM
Secondary outcome [26] 443133 0
Difference between Baseline AM (morning) and eyepatch intervention AM in the morphology of corneal epithelial T cells
Timepoint [26] 443133 0
Baseline AM vs eyepatch intervention AM
Secondary outcome [27] 443150 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the morphology of corneal epithelial dendritic cells
Timepoint [27] 443150 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [28] 443153 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the neuroimmune interactions of corneal epithelial dendritic cells before and after apparent contact of a corneal nerve
Timepoint [28] 443153 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [29] 443158 0
Difference between the control eye and eyepatch intervention eye for the morphology of corneal epithelial dendritic cells
Timepoint [29] 443158 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [30] 443152 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the neuroimmune interactions of corneal epithelial T cells before and after apparent contact of a corneal nerve
Timepoint [30] 443152 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [31] 443151 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the morphology of corneal stromal immune cells
Timepoint [31] 443151 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [32] 443147 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the dynamic characteristics of corneal epithelial dendritic cells
Timepoint [32] 443147 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [33] 443166 0
Difference between the control eye and eyepatch intervention eye in the density of corneal epithelial dendritic cells
Timepoint [33] 443166 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [34] 443154 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the density of corneal epithelial dendritic cells
Timepoint [34] 443154 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [35] 443159 0
Difference between the control eye and eyepatch intervention eye for the dynamic characteristics of corneal stromal immune cells
Timepoint [35] 443159 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [36] 443155 0
Difference between Baseline PM, eyepatch intervention PM, blue+UV blocking lens intervention PM, and UV-only blocking lens intervention PM in the density of corneal epithelial T cells
Timepoint [36] 443155 0
Baseline PM vs eyepatch intervention PM vs blue+UV blocking lens intervention PM vs UV only blocking lens intervention PM
Secondary outcome [37] 443160 0
Difference between the control eye and eyepatch intervention eye for the morphology of corneal stromal immune cells
Timepoint [37] 443160 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [38] 443157 0
Difference between the control eye and eyepatch intervention eye for the dynamic characteristics of corneal epithelial T cells at the corneal whorl and periphery at AM and PM
Timepoint [38] 443157 0
Control eye AM vs eyepatch intervention eye AM
Secondary outcome [39] 443165 0
Difference between the control eye and eyepatch intervention eye for the neuroimmune interactions of corneal epithelial dendritic cells before and after apparent contact of a corneal nerve
Timepoint [39] 443165 0
Control eye AM vs eyepatch intervention eye AM

Eligibility
Key inclusion criteria
• Male or female aged 18 to 45 years, with full legal capacity to volunteer;
• Provide written informed consent to participate;
• In good general health;
• Have the ability to understand and follow study instructions, with the intention of completing all required study visits;
• Have not worn contact lenses consistently (i.e., less than once per week) over the three months prior to baseline;
• Habitual unaided monocular distance vision (uncorrected distance visual acuity) of at least 6/15 or binocular 6/12, and unaided binocular near vision of N12 or better at 40cm;
• Have typical sleeping patterns, defined as obtaining at least six hours of sleep per night, with sleep onset time between 21:00 PM and 2:00 AM, and waking up between 05:00 AM and 09:00 AM;
• Have at least 3 T cells in either the corneal whorl or periphery within the field of view on IVCM at baseline.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Any known active ocular disease and/or infection (including dry eye disease).
• Presence of any of the following conditions: active ocular inflammation, active ocular allergy, a corneal disorder or abnormality that could affect corneal sensitivity or normal spreading of the tear film (except superficial punctate keratitis), severe blepharitis or obvious inflammation of the eyelid margin, which in the judgment investigator may interfere with the interpretation of the study results.
• An injury to either eye in the 12 weeks prior to enrolment.
• Ocular surgery within the past six months at baseline, or has ocular surgery planned over the course of participation in the study.
• Prior history of laser refractive eye surgery.
• A known allergy to, or previous reaction to, any eye drops required for the study.
• The presence of significant corneal scarring or a physical factor that impairs the ability to perform corneal imaging.
• Clinically significant dry eye disease, as specified in the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) definition, defined by dry eye symptoms (i.e., an Ocular Surface Disease Index (OSDI) score greater than or equal to 13, out of 100 (Schiffman et al. 2000)) AND one or more of the following clinical signs (Wolffsohn et al. 2017):
o Tear osmolarity of greater than or equal to 308 mOsm/L in either eye or interocular differences greater than 8mOsm/L;
o Tear break up time (TBUT) < 10 sec in either eye;
o Ocular surface staining: > 5 corneal spots, > 9 conjunctival spots, or lid margin (greater than or equal to 2 mm length and greater than or equal to 25% width)
• Current use of any topical medications other than artificial lubricant eye drops (e.g., anti-glaucoma medications, corticosteroids);
• Have a history of a systemic infection known to affect corneal immune status (e.g., positive for COVID-19 or upper respiratory infection within 4 weeks of baseline), by self-report;
• Have received a vaccination within 2 weeks of baseline, by self-report;
• Any condition that would contraindicate the drawing of blood, or a significant history of vasovagal syncope during blood draws;
• Any blood-borne illnesses such as hepatitis and Human Immunodeficiency Virus (HIV) that may affect the eyes
• Females who are pregnant or breastfeeding at the time of study enrolment or who plan to become pregnant during the study (as reported by the participant);
• Unable or unwilling to wear the study interventions (eye patch, blue + UV light-filtering glasses, and UV only light-filtering glasses) or an actigraphy watch and MiEye light meter ‘pin’, as assessed during the Baseline visit;
• Unable or unwilling to keep a sleep diary;
• Requires a habitual spectacle or contact lens correction for daily activity;
• Unable to sit/lie supine comfortably during the examination procedures.
• Participation in an interventional clinical trial within the previous 30 days, or currently enrolled in an interventional clinical trial;
• Current shift-work and/or recent cross-time zone travel in the last month, or such anticipated travel during the study period;
• A condition or situation that, in the opinion of the study investigator, will limit the potential participant’s ability to comply with the study protocol, might adversely affect their safety or substantially confound the study outcomes.

References:
1. Schiffman, R.M., et al., Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol, 2000. 118(5): p. 615-21.
2. Wolffsohn, J.S., et al., TFOS DEWS II Diagnostic Methodology report. Ocul Surf, 2017. 15(3): p. 539-574.

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)
Sealed opaque envelops
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation). The randomisation will be stratified so that each participant has equal chance of receiving the intervention in a cross-over study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
This will be, to our knowledge, the first study to evaluate the diurnal variations in corneal immune cells in response to localised environmental factors. As a novel exploratory study, it is not possible to accurately calculate a required sample size using conventional statistical methods (which requires a reliable estimate of effect size and variability).

The nominated sample size of 18 completed participants is anticipated to provide sufficient power to detect significant inter-group differences.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/01/2025
Actual
Date of last participant enrolment
Anticipated
30/09/2025
Actual
Date of last data collection
Anticipated
30/11/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317879 0
University
Name [1] 317879 0
The University of Melbourne
Country [1] 317879 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 320216 0
None
Name [1] 320216 0
Address [1] 320216 0
Country [1] 320216 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316564 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316564 0
Ethics committee country [1] 316564 0
Australia
Date submitted for ethics approval [1] 316564 0
15/11/2024
Approval date [1] 316564 0
10/01/2025
Ethics approval number [1] 316564 0
29193

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

Contacts
Principal investigator
Name 138258 0
Prof Laura Downie
Address 138258 0
Department of Optometry and Vision Sciences, The University of Melbourne, 200 Berkeley St, Carlton, VIC, 3053
Country 138258 0
Australia
Phone 138258 0
+6139035 3043
Fax 138258 0
Email 138258 0
[email protected]
Contact person for public queries
Name 138259 0
Laura Downie
Address 138259 0
Department of Optometry and Vision Sciences, The University of Melbourne, 200 Berkeley St, Carlton, VIC, 3053
Country 138259 0
Australia
Phone 138259 0
+6139035 3043
Fax 138259 0
Email 138259 0
[email protected]
Contact person for scientific queries
Name 138260 0
Laura Downie
Address 138260 0
Department of Optometry and Vision Sciences, The University of Melbourne, 200 Berkeley St, Carlton, VIC, 3053
Country 138260 0
Australia
Phone 138260 0
+6139035 3043
Fax 138260 0
Email 138260 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Data sharing is not currently part of our ethics approval.



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
No additional documents have been identified.