Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000542493
Ethics application status
Approved
Date submitted
22/05/2025
Date registered
28/05/2025
Date last updated
28/05/2025
Date data sharing statement initially provided
28/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Can eye drops safely replace reading glasses in older adults? A short-term study.
Scientific title
Investigating the physiological effects of acute pilocarpine use for presbyopia treatment on posterior ocular structures
Secondary ID [1] 314505 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
Sub-study of ACTRN12624000383561.

Health condition
Health condition(s) or problem(s) studied:
Presbyopia 337572 0
Retinal ischemia 337573 0
Condition category
Condition code
Eye 333917 333917 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an interventional study that will investigate Vuity eye drops' (pilocarpine 1.25%) mechanism of action on the choroid and retina, as the first step towards ensuring this treatment is safe for long-term use. The aim of this study is to understand whether acute pilocarpine administration can change choroidal thickness, choroidal blood flow, or retinal function. We hypothesise that this occurs via 3 mechanisms: 1/ by failing to correct retinal defocus, 2/ by constricting the pupil, or 3/ by directly stimulating muscarinic receptors within the choroid and retina.

Each participant will participate in 3 controlled experiments to understand whether acute administration of Vuity eye drops (pilocarpine 1.25%) can act directly or indirectly on the choroid and retina. Participants will receive 1 drop of Vuity in the experimental eye during each of the 3 study visits.

- Experiment 1 will examine whether pilocarpine changes the physiology of the choroid and retina, independently from hyperopic defocus. In this experiment, participants will first undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a far viewing distance (6 m) to allow pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated.

- Experiment 2 will examine whether pilocarpine changes the physiology of the choroid and retina independently from both hyperopic defocus AND retinal illuminance (determined by pupil size). In this experiment, 1 drop of tropicamide (1%) will first be instilled by a study researcher to both eyes of the participant to control for pupil size and therefore retinal illuminance. Participants will then undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a far viewing distance (6 m) to allow pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated.

- Experiment 3 will examine whether pilocarpine changes the physiology of the choroid and retina by subjecting the eye to sustained periods of hyperopic retinal defocus, independently of retinal illuminance (determined by pupil size). In this experiment, 1 drop of tropicamide (1%) will first be instilled by a study researcher to both eyes of the participant to control for pupil size and therefore retinal illuminance. Participants will then undergo a 20-minute stabilisation period by watching a movie at a far viewing distance (6 m). After stabilisation, baseline measures of retinal and choroidal thickness and blood flow (using optical coherence tomography, OCT) and retinal function (using global flash multifocal electroretinography, gmfERG) will be acquired, with participants' eyes fully corrected for any hyperopic defocus. After baseline measures are completed, 1 drop of Vuity (pilocarpine 1.25%) is administered by a study researcher to the participants' experimental eye. Participants will then undergo 60-min stabilisation period by watching a movie at a near viewing distance (30 cm) to subject the eyes to hyperopic defocus while allowing pilocarpine to reach maximal effect in the eye, before measures of retinal and choroidal thickness and blood flow are repeated.

Each experiment is anticipated to take 2 hours (total ~6 hours for the study). The 3 experiments will be conducted across 3 separate study visits, spaced at least 24 hours apart to ensure no carryover effects from the previous visit. Each experiment will be performed at the same time of day (±1 hour) to control for known diurnal variations in choroidal thickness. A random number generator will be used to randomise the experimental eye and the order of experiments for each participant.
Intervention code [1] 331126 0
Treatment: Drugs
Intervention code [2] 331127 0
Diagnosis / Prognosis
Comparator / control treatment
Three experiments will be conducted to assess Vuity’s possible mechanisms of action. One drop of Vuity is administered to the experimental eye, and the outcome measures will be compared between experimental and fellow eyes, and before vs after treatment, within each participant.

- For experiment 1, hyperopic defocus will be controlled by correcting retinal defocus.

- For experiment 2, pupil size will be controlled by maximally dilating the pupil with tropicamide, and hyperopic defocus will be controlled by correcting near vision with lenses.

- For experiment 3, pupil size will be controlled by maximally dilating the pupil with tropicamide, and hyperopic defocus will be controlled by subjecting the retina to equal amount of hyperopic defocus.
Control group
Active

Outcomes
Primary outcome [1] 341562 0
Change in choroidal thickness. Measurements of subfoveal choroidal thickness
Timepoint [1] 341562 0
Baseline and 60 minutes after administration of the treatment.
Secondary outcome [1] 447940 0
Change in chorioretinal vascular and perfusion density. Vascular density can be divided into several components: superficial capillary plexus (SCPs), deep capillary plexus (DCP), and choriocapillaris (CC), but will be assessed together as a composite outcome.
Timepoint [1] 447940 0
Baseline and 60 minutes after administration of the treatment.
Secondary outcome [2] 447941 0
Change in retinal thickness. The standardised Early Treatment Diabetic Retinopathy Study (ETDRS) grid allows for the measurement of the thicknesses of all individual retinal layers at different retinal eccentricities.
Timepoint [2] 447941 0
Baseline and 60 minutes after administration of the treatment.
Secondary outcome [3] 447942 0
Change in amplitude and latency of the global flash multifocal electroretinogram (gmfERG) waveform components, measured at each retinal eccentricity, for both direct and induced retinal responses.
Timepoint [3] 447942 0
Baseline and 60 minutes after administration of the treatment.
Secondary outcome [4] 448087 0
Change in choroidal thickness. Measurements of peripheral choroidal thickness
Timepoint [4] 448087 0
Baseline and 60 minutes after administration of the treatment.

Eligibility
Key inclusion criteria
Adults in good general and eye health who only wear optical correction (glasses and/or contact lenses) for presbyopia correction, and are willing and able to provide written informed consent for study participation.
Minimum age
40 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical conditions
- Uncontrolled systemic disease or clinically significant disease state in any body system that, in the opinion of the investigator, could have affected the safety of the individual or interpretation of endpoint measures
- History of ocular pathology or intraocular surgery that, in the opinion of the investigator, could have affected the safety of the individual or interpretation of endpoint measures

Contraindications for Vuity eye drops
- Known allergy or sensitivity to pilocarpine, other components in Vuity eye drops, or other cholinergic agonist medications
- Narrow iridocorneal angles that are at risk of angle-closure and physiological anisocoria of >1 mm between pupils, as these conditions could affect the safety of the individual or interpretation of endpoint measures

Prior/Concomitant therapy
- Use of any topical prescription or over-the-counter ophthalmic medications that, in the opinion of the investigator, could have a substantial effect on visual function and affect interpretation of endpoint measures
- Use of systemic medications with potential ocular side effects, including topiramate, hydroxychloroquine, ethambutol, phosphodiesterase 5 inhibitors (sildenafil, vardenafil, tadalafil), or tamoxifen, that could have a substantial effect on visual function and affect interpretation of endpoint measures
- Use of systemic or intranasal anticholinergics and alpha-adrenergic receptor agonists with potential pupillary or accommodative effects, including oxymetazoline, tetrahydrozoline, phenylephrine, naphazoline, atropine, pilocarpine, beta-blockers, or antihistamines, that could have a substantial effect on visual function and affect interpretation of endpoint measures
- Use of systemic maprotiline, tricyclic antidepressants, or monoamine oxidase inhibitors, that could have a substantial effect on visual function and affect interpretation of endpoint measures

Diagnostic assessments
- Ametropia, defined as refractive error based on non-cycloplegic subjective refraction with a spherical equivalent of less than 0.50 Dioptres in absolute value (that is, regardless of whether it is myopia or hyperopia). Additionally, it must have a maximum magnitude of astigmatism of 1.00 Dioptres. This way, clinically significant mixed astigmatisms, which could have a spherical equivalent within the range ± 0.50 Dioptres, are excluded. This is to exclude individuals who wear bifocal or multifocal glasses or contact lenses for habitual correction, as this may affect interpretation of endpoint measures
- Monocular best-corrected distance visual acuities poorer than 0.00 logMAR (Snellen 6/6) in both eyes, as this may be indicative of an underlying ocular condition or abnormality that may affect the safety of the individual or interpretation of endpoint measures

Other
- Females who are not pregnant or breastfeeding, and are not considering becoming pregnant or donating eggs during the study or for ~30 days after the last dose of study intervention, as safety of Vuity eye drops has not been established for use in pregnancy and lactation.

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)
Allocation is not concealed.
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)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Interventional before vs after design - outcome measures will be collected before and after the interventional treatment.
Split person design - each participant will receive interventional treatment in one eye and control treatment in the other eye.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
GraphPad Prism (GraphPad Software, San Diego, CA) and/or SPSS Statistics (IBM, Armonk, NY) will be used for conducting statistical analyses. All statistical tests will be two-tailed and at 5% significance level throughout the analyses. Summaries of continuous variables which are normally distributed will be presented as means and standard deviations or medians and inter-quartiles for skewed data, while categorical variables will be presented as frequencies and percentages. Paired t-test will be used to test for differences in endpoint measures between presbyopia correction with optical correction vs. pilocarpine eye drops. The assumption of normality of data will be assessed by visual inspection of Normal Q-Q plots and/or Shapiro-Wilk test of normality. Upon violation of the assumption of normality, a nonparametric Wilcoxon signed-rank test will be conducted instead of a paired t-test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2025
Actual
Date of last participant enrolment
Anticipated
1/07/2027
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 27077 0
New Zealand
State/province [1] 27077 0
Auckland

Funding & Sponsors
Funding source category [1] 319043 0
Charities/Societies/Foundations
Name [1] 319043 0
The Association for Research in Vision and Ophthalmology
Country [1] 319043 0
United States of America
Funding source category [2] 319044 0
Charities/Societies/Foundations
Name [2] 319044 0
Freemasons Foundation
Country [2] 319044 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Country
New Zealand
Secondary sponsor category [1] 321510 0
None
Name [1] 321510 0
Address [1] 321510 0
Country [1] 321510 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317650 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 317650 0
Ethics committee country [1] 317650 0
New Zealand
Date submitted for ethics approval [1] 317650 0
11/04/2024
Approval date [1] 317650 0
18/12/2024
Ethics approval number [1] 317650 0

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

Contacts
Principal investigator
Name 141698 0
Dr Alyssa Lie
Address 141698 0
School of Optometry and Vision Science The University of Auckland 85 Park Road, Grafton Auckland 1023
Country 141698 0
New Zealand
Phone 141698 0
+64 21 0266 4662
Fax 141698 0
Email 141698 0
[email protected]
Contact person for public queries
Name 141699 0
Alyssa Lie
Address 141699 0
School of Optometry and Vision Science The University of Auckland 85 Park Road, Grafton Auckland 1023
Country 141699 0
New Zealand
Phone 141699 0
+64 21 0266 4662
Fax 141699 0
Email 141699 0
[email protected]
Contact person for scientific queries
Name 141700 0
Alyssa Lie
Address 141700 0
School of Optometry and Vision Science The University of Auckland 85 Park Road, Grafton Auckland 1023
Country 141700 0
New Zealand
Phone 141700 0
+64 21 0266 4662
Fax 141700 0
Email 141700 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.