Myopia
Conditions
Brief summary
Myopia (nearsightedness) is increasing in prevalence throughout the world. It is associated with a risk of potentially blinding complications such as retinal detachment and myopic maculopathy. There is a direct association between the degree of myopia and the risk of complications. Myopia develops in childhood and during adolescence. To prevent higher degrees of myopia, we need to halt disease progression in children and teenagers. Low-dose atropine eye drops have been shown to reduce myopia progression by 50% in Asian populations but its effect in non-Asian populations is unknown. The aim of this study is to investigate if low-dose atropine can reduce myopia progression in Danish children and teenagers. The study is an investigator initiated randomized clinical trial conducted as a collaboration between three Danish Eye Departments covering all of Denmark.
Detailed description
The main hypotheses tested in this study are: * 0.01% atropine one drop nightly reduces the progression of childhood myopia in Danish children. * 0.01% atropine one drop nightly is safe and with no significant side effects. * A 6-month loading dose of 0.1% atropine followed by a 0.01% atropine maintenance dose is superior to single 0.01% atropine. * 0.1% atropine one drop nightly is safe and has tolerable side effects. * The rebound effect after stopping both atropine regimens is limited. * Choroidal thickness is a predictor for the progression of childhood myopia.
Interventions
DRUG0.1% atropine and 0.01% atropine
0.1% atropine loading dose for 6 months followed by 0.01% atropine for 18 months
DRUG0.01% atropine
0.01% atropine for 24 months
Placebo for 24 months
Sponsors
Aarhus University Hospital
Vejle Hospital
Line Kessel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Children aged ≥6-\<9 years: myopia ≤-1 (spherical power) in at least one eye * Children aged ≥9-≤12 years: myopia ≤-2 (spherical power) in at least one eye * Cylinder less than 1.5 diopters
Exclusion criteria
* Myopia related to retinal dystrophies * Collagen syndroms (Ehlers-Danlos syndrome, Marfan syndrome and Stickler syndrome) * Other ocular pathology (e.g., amblyopia, strabismus) * Previous eye surgery * Previous use of agents thought to affect myopia progression, e.g. atropine, pirenzepine or 7-methylxanthine (metabolite of caffeine and theobromine) and orthokeratology contact lenses * Known allergy to atropine or any of the contents of the trial medication (active and in-active ingredients) used in the study * Non-compliance to eye examinations * Serious systemic health troubles (e.g., cardiac or respiratory illness) and developmental disorders and delays
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Axial Length at 36 Months | 36 months | Treatment group comparison of axial length at 36 months, as measured using IOLMaster 700 |
| Spherical Equivalent at 36 Months | 36 months | Treatment group comparison of spherical equivalent at 36 months, as measured using cycloplegic autorefraction |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 36 months | Total individual adverse events per interventional arm |
| Change in Choroidal Thickness From Baseline to 36 Months | 36 months | Treatment group comparison of change in choroidal thickness from baseline to 36 months, as measured using optical coherence tomography (OCT) |
Countries
Denmark
Participant flow
Recruitment details
Danish children with myopia were referred from optometrists and ophthalmologists across Denmark. Recruitment and follow-up took place between May 2019 and April 2024 (Last patient last visit = 23 of April 2024)
Participants by arm
| Arm | Count |
|---|---|
| Loading Dose In phase 1 (treatment phase), the participants (n=33) will receive 0.1% atropine loading dose for 6 months followed by 0.01 % atropine for 18 months. The eye drops are administered as one eye drop daily in each eye at bedtime.
In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | 33 |
| Low Dose In phase 1 (treatment phase), the participants (n=32) will receive 0.01 % atropine for 24 months. The eye drops are administered as one eye drop daily in each eye at bedtime.
In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | 32 |
| Placebo In phase 1 (treatment phase), the participants (n=32) will receive placebo eye drops for 24 months. The eye drops are administered as one eye drop daily in each eye at bedtime.
In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | 32 |
| Total | 97 |
Baseline characteristics
| Characteristic | Loading Dose | Low Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 9.5 Years | 9.4 Years | 9.2 Years | 9.4 Years |
| Axial length | 24.5 mm STANDARD_DEVIATION 0.86 | 24.6 mm STANDARD_DEVIATION 0.78 | 24.4 mm STANDARD_DEVIATION 0.9 | 24.6 mm STANDARD_DEVIATION 0.84 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 32 Participants | 32 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 18 Participants | 18 Participants | 55 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Spherical equivalent refraction | -3.00 Diopters STANDARD_DEVIATION 1.59 | -2.97 Diopters STANDARD_DEVIATION 1.13 | -3.07 Diopters STANDARD_DEVIATION 1.04 | -2.99 Diopters STANDARD_DEVIATION 1.27 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 33 / 33 | 10 / 32 | 17 / 32 |
| serious Total, serious adverse events | 0 / 33 | 0 / 32 | 3 / 32 |
Outcome results
Primary
Axial Length at 36 Months
Treatment group comparison of axial length at 36 months, as measured using IOLMaster 700
Time frame: 36 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Loading Dose | Axial Length at 36 Months | 25.28 mm |
| Low Dose | Axial Length at 36 Months | 25.25 mm |
| Placebo | Axial Length at 36 Months | 25.33 mm |
Primary
Spherical Equivalent at 36 Months
Treatment group comparison of spherical equivalent at 36 months, as measured using cycloplegic autorefraction
Time frame: 36 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Loading Dose | Spherical Equivalent at 36 Months | -4.45 Diopters |
| Low Dose | Spherical Equivalent at 36 Months | -4.26 Diopters |
| Placebo | Spherical Equivalent at 36 Months | -4.43 Diopters |
Secondary
Adverse Events
Total individual adverse events per interventional arm
Time frame: 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Loading Dose | Adverse Events | 104 Number of adverse events reported |
| Low Dose | Adverse Events | 22 Number of adverse events reported |
| Placebo | Adverse Events | 18 Number of adverse events reported |
Secondary
Change in Choroidal Thickness From Baseline to 36 Months
Treatment group comparison of change in choroidal thickness from baseline to 36 months, as measured using optical coherence tomography (OCT)
Time frame: 36 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Loading Dose | Change in Choroidal Thickness From Baseline to 36 Months | 2 microns |
| Low Dose | Change in Choroidal Thickness From Baseline to 36 Months | 7 microns |
| Placebo | Change in Choroidal Thickness From Baseline to 36 Months | 3 microns |