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Trial registered on ANZCTR


Registration number
ACTRN12621000075886
Ethics application status
Approved
Date submitted
30/11/2020
Date registered
29/01/2021
Date last updated
17/09/2023
Date data sharing statement initially provided
29/01/2021
Date results information initially provided
5/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of low dose atropine eye drops on coordinated aiming and focusing in young adult eyes
Scientific title
The effect of 0.05% atropine sulfate eye drops on the binocular vision characteristics of young adult myopes' eyes
Secondary ID [1] 302897 0
Nil known
Universal Trial Number (UTN)
U1111-1262-0141
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressing myopia 319903 0
Condition category
Condition code
Eye 317840 317840 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
0.05% atropine sulfate (0.1% BAK) eye drops, 1 drop in each eye at night before bed, for 9 nights
To monitor adherence to the intervention, eye drop bottles will be weighed before dispensing, and after conclusion of the clinical trial. Participants will also receive nightly text message reminders at 9pm to encourage compliance.
Intervention code [1] 319181 0
Treatment: Drugs
Comparator / control treatment
0.9% sodium chloride (0.1% BAK) eye drops, 1 drop in each eye at night before bed, for 9 nights.
To monitor adherence to the intervention, eye drop bottles will be weighed before dispensing, and after conclusion of the clinical trial. Participants will also receive nightly text message reminders at 9pm to encourage compliance.
Control group
Placebo

Outcomes
Primary outcome [1] 325854 0
Change in near heterophoria, as measured with participant wearing their habitual correction with a Howell-Dwyer near card at 33cm, dissociated with 6 base-down prism in front of the right eye.
Timepoint [1] 325854 0
2 days and 10 days post-commencement of intervention
Primary outcome [2] 325855 0
Change in near fusional reserves (positive and negative), as measured with participant wearing their habitual correction and fixating on a 6/9 equivalent near target in primary gaze, 40cm from the participants eyes. A 50 prism dioptre prism bar will be placed with 1 prism dioptre in front of the participant's right eye with the prism base-in (negative fusional reserves) to be tested first. Participants will be instructed to report when the letters "become blurred or doubled" but to try to keep the target single as long as possible as the magnitude of base-in prism is increased. The participant's blur, break, and recovery values for negative fusional reserves will be recorded, before the procedure is then repeated again using base-out prism to test positive fusional reserves.
Timepoint [2] 325855 0
2 days and 10 days post-commencement of intervention
Primary outcome [3] 325856 0
Change in near point of convergence, as measured with the participant wearing their habitual correction, and with a 6/9 equivalent near target held in front of the participant's eyes in primary gaze at a distance of initially 40cm. The target will then be moved slowly towards the participant, and the participant will be instructed to report when the letters on the target "double". The distance at which the participant first reports sustained doubling is reported in cm as the near point of convergence.
Timepoint [3] 325856 0
2 days and 10 days post-commencement of intervention
Secondary outcome [1] 389349 0
Change in accommodative posture, which will be measured monocularly on both eyes of each participant using the Grand Seiko WAM-5500 open-field autorefractor. Participants will be required to wear their habitual distance correction with their fellow eye patched, while the eye to be measured fixates through the instrument’s open-field beam splitter on a distance target (6/9 letter on ETDRS chart viewed at a distance of 6 m) followed by a near target (6/9 equivalent letter target suspended from a near-point rod which will be mounted on the instrument. The distance will be measured once in each eye, and then 3 consecutive measurements will be taken at near for each eye, and averaged.
Timepoint [1] 389349 0
2 days and 10 days post-commencement of intervention
Secondary outcome [2] 389350 0
Change in relative accommodation (positive/negative), measured with the participant behind the phoropter with their habitual spectacle correction in place, with eyepieces converged and participant's fixation of a target of 6/9 equivalent vertical letters at 40cm. Positive lenses will be added first in +0.25 D steps until the participant reports sustained blur of the letters (negative relative accommodation). Negative lenses will then be added in -0.25 D steps until the participant reports sustained blur (positive relative accommodation).
Timepoint [2] 389350 0
2 days and 10 days post-commencement of intervention
Secondary outcome [3] 389351 0
Change in binocular accommodative facility (+/- 2 D), as measured with participants wearing their habitual spectacle correction and fixating on a near letter target of 6/9 equivalent at a distance of 40cm. Using a +/- 2D binocular lens flipper, the plus lenses will first be placed in front of the participant's eyes and the participant will be instructed to say "clear" as soon as the target letters appear clear. The binocular lens flipper will then quickly be flipped to the -2.00 D lenses and the participant will once again be instructed to say "clear" when the target appears clear. This will constitute one "cycle". The cycles will continue for 1 minute. The accommodative facility will be recorded as the number of cycles per minute that the participant was able to perform.
Timepoint [3] 389351 0
2 days and 10 days post-commencement of intervention
Secondary outcome [4] 389352 0
Change in accommodative amplitude, as measured monocularly and binocularly with the push up method. Accommodative amplitude will be measured monocularly in each of the participant's eyes (right, and then left) while wearing their habitual spectacle correction and fixating on a near target of 6/9 equivalent. The fellow eye will be occluded for the monocular measurements, and the target will be held 40 cm in front of the participant’s eyes in primary gaze. The participant will be instructed to “keep the target clear and single for as long as possible” and report when letters “first start to blur”. The target will slowly be moved towards the participant at a rate of 1-2 cm per second, until the participant first reports blur. The participant will then be asked if the letters remain blurred, or whether they become clear. If they are cleared, the target is moved closer until the first sustained blur. This distance from target to participant is measured in centimetres (to the nearest half centimetre). If the participant is wearing spectacles, the distance will be measured to the spectacle plane. If the participant is wearing contact lenses, the distance will be measured to the corneal plane. The amplitude of accommodation is then recorded as the inverse of this distance. The procedure will then be repeated for the left eye (with the right eye occluded), and then with both eyes together (no occlusion).
Timepoint [4] 389352 0
2 days and 10 days post-commencement of intervention
Secondary outcome [5] 389353 0
Change in score on the 5-item Dry Eye Questionnaire, as measured by the participant's subjective symptoms of dry eye, assessed using the 5-item Dry Eye Questionnaire (e.g. eye discomfort frequency and intensity, eye dryness frequency and intensity, watery eyes frequency). The DEQ-5 gives a composite score reflective of the different ways dry eye symptoms can manifest. The DEQ-5 was not intended to be used as multiple separate outcomes of eye discomfort.
Timepoint [5] 389353 0
2 days and 10 days post-commencement of intervention
Secondary outcome [6] 389354 0
Change in score on the Convergence Insufficiency Symptom Survey, as measured by any subjective participant symptoms which may be attributed to convergence insufficiency, as specified in the Convergence Insufficiency Symptom Survey (e.g. tiredness, headaches, discomfort, sleepiness in eyes associated with near work; double vision, loss of concentration, losing place when reading).
Timepoint [6] 389354 0
2 days and 10 days post-commencement of intervention

Eligibility
Key inclusion criteria
Healthy, young adult myopes with a myopic refractive error between -0.75 and -6.00 DS, with no more than 1.50 DC of astigmatism or 2 D of anisometropia, whose refractive error is currently corrected with single vision distance spectacles or contact lenses, and who have stereoacuity of 200 seconds of arc or greater.
Minimum age
18 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• No current or previous myopia control (atropine, OrthoK, peripheral defocus soft CLs)
• No amblyopia or strabismus
• Best corrected visual acuity (BCVA) greater than or equal to 0.1 logMAR, with no more than 1 line difference in VA between eyes
• Habitual correction (either single vision distance spectacles or contact lenses) within 0.50D of cycloplegic refraction result
• No pregnancy or breastfeeding
• No history of ocular surgery
• No history of significant ocular infection or injury
• No allergy to atropine, tropicamide, or benzalkonium chloride (BAK)
• No known angle closure glaucoma, or temporal VH ratio less than 0.3:1 in either eye
• Intraocular pressure of less than 21 mmHg in each eye
• No current use of: anticholinergics, antiglaucoma medications, antimyasthenics, potassium drugs, carbachol/physostigmine/pilocarpine, no CNS depressants (such as antiemetics, phenothiazines, or barbiturates).

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 performed by "off-site" research team member in possession of the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple block randomisation (block size of 6) using a randomisation table from a
statistic book
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
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
To calculate sample size, the normative mean and standard deviation, and clinically meaningful difference were obtained for all outcome measures. Mean, standard deviation and clinically meaningful differences were obtained from Scheiman and Wick (2014). Given that the effect size is smallest for binocular accommodative facility (BAF) at 0.4, the data must be adequately powered to find statistically significant differences in BAF between the test and control groups if they exist. Using this effect size, to detect a difference with 95% confidence using two-sided type I error, a minimum power of 80%, and accounting for a potential attrition rate of 20%, 24 participants will be enrolled in this study.

Demographic data such as age, sex, and ethnicity; and baseline parameters such as cycloplegic spherical equivalent refraction, distance and near visual acuity, CI Symptom Survey score, pupil diameter, iris colour, and intraocular pressure will be analysed using descriptive statistics. For parameters which have been collected using both eyes (cycloplegic spherical equivalent refraction, pupil size, intraocular pressure, amplitude of accommodation, visual acuity), the eye chosen to be included in analysis will be randomised during the data analysis for each participant.
The mean of each parameter at each time point will be calculated for each participant prior to statistical analysis. The Kolmogorov-Smirnov test will then be performed to ensure the data does not significantly depart from a normal distribution. A linear regression model (repeated measures analysis of variance – RM-ANOVA) will be performed to examine the changes in the primary outcome measures of: distance and near heterophoria, positive and negative fusional vergence, near point of convergence, amplitude of accommodation, binocular accommodative facility, and positive and negative relative accommodation; with within-subject factors of time (Day 1, 3 and 10), and between-subject factors of treatment group (test, control). If Mauchly’s test of sphericity indicates significant violation of the sphericity assumption, the Greenhouse-Geisser correction to the degrees of freedom will be applied.
If significant differences are identified in the main ANOVA (p < 0.05), post-hoc testing with Bonferroni correction for multiple comparisons will be performed.
RM-ANOVA will also be performed for secondary outcome measures such as IOP, pupil diameter, distance and near visual acuity, CISS and DEQ-5 scores, to observe their changes over time, and in response to treatments.
Analysis of covariance (ANCOVA) will also be performed to find any associations between changes in outcome measures, using the methods of Bland and Altman for the analysis of repeated measures.13 Prior to performing the ANCOVA, the data will be checked to ensure homogeneity of regression slopes between the dependent variable and covariate.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2021
Actual
8/07/2021
Date of last participant enrolment
Anticipated
30/04/2021
Actual
13/11/2022
Date of last data collection
Anticipated
1/06/2021
Actual
12/12/2022
Sample size
Target
24
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 32110 0
4059 - Kelvin Grove

Funding & Sponsors
Funding source category [1] 307319 0
University
Name [1] 307319 0
Queensland University of Technology
Country [1] 307319 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
2 George Street, Brisbane City, Queensland 4000
Country
Australia
Secondary sponsor category [1] 307956 0
None
Name [1] 307956 0
Address [1] 307956 0
Country [1] 307956 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307409 0
Queensland University of Technology (QUT) Human Research Ethics Committee
Ethics committee address [1] 307409 0
Office of Research Ethics and Integrity
Level 4, 88 Musk Avenue
Kelvin Grove QLD 4059
Ethics committee country [1] 307409 0
Australia
Date submitted for ethics approval [1] 307409 0
Approval date [1] 307409 0
08/09/2020
Ethics approval number [1] 307409 0
2000000508

Summary
Brief summary
Low dose atropine eye drops of various concentrations are used to slow the rate of myopic refractive error (short-sightedness) progression in children and adolescents. Atropine is an anticholinergic agent (inhibits the parasympathetic nervous system) which when used as an eye drop, leads to pupil dilation and cycloplegia (reduction or temporary elimination of focusing ability). While these side effects are desirable when treating certain ocular conditions like uveitis or amblyopia, when atropine is used in treating myopia progression, only very low concentrations are used to minimise these side effects.
While the effect of low dose atropine on pupil dilation and cycloplegia are widely documented, the implications for single and clear binocular vision when taking this medication have not specifically been studied.
The objective of this research project is to examine the effect of nightly dosing of 0.05% atropine sulfate eye drops for 10 days with respect to the binocular vision characteristics of young adult myopes. Outcome measures will include: distance and near heterophoria (measures the coordination of the aiming between the two eyes at distance and near), positive and negative relative accommodation (measures the range of the focusing system over which clear focus is maintained when performing near tasks), accommodative posture (accuracy of focusing when reading), positive and negative fusional vergence (measures the range of the focusing system over which single vision is maintained when performing near tasks), binocular accommodative facility (a measure of the flexibility of the focusing system), and near point of convergence (a measure of the degree to which the two eyes can focus inwards while still maintaining single vision).
The outcomes of this research would be expected to inform the development of clinical protocols for assessing patient suitability for low dose atropine treatment, through determination of effects on binocular vision, and identification of patients who would be most impacted by these side effects. This will help to identify potentially unsuitable candidates for treatment and any contraindications to treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107134 0
Dr Emily Pieterse
Address 107134 0
School of Optometry and Vision Science
Queensland University of Technology
Victoria Park Road, Kelvin Grove, Queensland 4059
Country 107134 0
Australia
Phone 107134 0
+61 731385712
Fax 107134 0
Email 107134 0
e.pieterse@qut.edu.au
Contact person for public queries
Name 107135 0
Emily Pieterse
Address 107135 0
School of Optometry and Vision Science
Queensland University of Technology
Victoria Park Road, Kelvin Grove, Queensland 4059
Country 107135 0
Australia
Phone 107135 0
+61 731385712
Fax 107135 0
Email 107135 0
e.pieterse@qut.edu.au
Contact person for scientific queries
Name 107136 0
Emily Pieterse
Address 107136 0
School of Optometry and Vision Science
Queensland University of Technology
Victoria Park Road, Kelvin Grove, Queensland 4059
Country 107136 0
Australia
Phone 107136 0
+61 731385712
Fax 107136 0
Email 107136 0
e.pieterse@qut.edu.au

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
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 381019-(Uploaded-21-08-2023-17-52-17)-Basic results summary.docx
Plain language summaryNo Short-sightedness (myopia) is associated with unst... [More Details]

Documents added automatically
No additional documents have been identified.