Safety and Efficacy Study of 0.5%, 0.1% & 0.01% Atropine Treatment to Both Eyes In Treatment of Myopia In Children

The purpose of this study is to find an optimal dose of atropine for preventing the rapid progression of myopia in children by comparing the efficacy, safety and functional impact of binocular treatment with 0.5%, 0.1% and 0.01% atropine and to develop a treatment regimen for the routine management of childhood myopia.

A Randomised, Double-Masked Study to Compare The Safety and Efficacy of Bilateral 0.5%, 0.1% \& 0.01% Atropine Treatment In Controlling Progression of Myopia In Children

Study Duration and Visit Schedule Total of 5 years with 15 scheduled visits.

1. Phase I: 2 years with 8 scheduled visits
2. Phase II: 3 years with 7 scheduled visits

STUDY DESIGN This study consists of 2 phases, each with a different design. Phase I is a double-masked single-centre clinical trial wherein 400 children aged 6-12 years, with myopia of -2.00 D or worse in each eye, and from whom assent and parental/guardian consent have been obtained, will be randomised to receive 0.5% atropine, 0.1% atropine or 0.01% atropine once nightly in both eyes. Participants will be assigned to treatment in the ratio of 2:2:1, respectively. Each child will receive treatment for a period of 2 years during which they will be reviewed every 4 months.

Phase II is an open-label study wherein all children will continue to be followed-up regularly for changes in their refractive error after stopping atropine treatment. Those children who demonstrate myopia progression of -0.5 D or more, at least on one eye after a minimum of 8 months washout period will restart atropine treatment in both eyes. The appropriate dose will be determined by analysis of the data from Phase I of the study. Treatment will be for a further 2 years and all children, including those not receiving treatment, will be reviewed every 6 months.

Eligibility Criteria:
Inclusion Criteria:

1. Written Informed Consent from parent and assent from child has been obtained
2. Children aged 6 to 12 years
3. Refractive error of spherical equivalent -2.00 D or worse in each eye as measured by cycloplegic autorefraction
4. Active myopia progression of at least spherical equivalent -0.50 D over the last 12 months as determined or suggested by refractive records or change in lens power
5. Astigmatism of less than or equal to -1.50 D as measured by cycloplegic or non-cycloplegic autorefraction
6. Distance vision correctable to logMAR 0.2 or better in both eyes
7. A difference between non-cycloplegic subjective spherical refraction and cycloplegic subjective spherical refraction of not greater than -1.00 D
8. Normal intraocular pressure of not greater than 21 mmHg
9. Normal ocular health other than myopia
10. In good general health with no history of cardiac or significant respiratory diseases
11. No asthma-requiring medications in the past one year
12. No allergy to atropine, cyclopentolate, proparacaine and benzalkonium chloride
13. Willing and able to comply with scheduled visits and other study procedures

Exclusion Criteria:

1. Ocular or systemic diseases which may affect vision or refractive error
2. Any ocular condition wherein topical atropine is contraindicated
3. Defective binocular function or stereopsis
4. Amblyopia or manifest strabismus including intermittent tropia
5. Previous or current use of atropine or pirenzepine
6. Any other conditions precluding adherence to the protocol including unwillingness to refrain from contact lens wear for the duration of the study