Clinical trial NCT02955927: Combined Atropine With Orthokeratology in Childhood Myopia Control (AOK) -A Randomized Controlled Trial
Official title: Combined Atropine With Orthokeratology in Childhood Myopia Control (AOK) -A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myopia
Keywords: Myopia control,ortho-k, atropine eye drops, children
Lead sponsor: The Hong Kong Polytechnic University
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong
First posted: 2016-11-04
Enrollment: 89
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to compare effects in retardation of myopia progression of combined ortho-k and 0.01% atropine therapy with those of ortho-k alone.Myopia control methods mainly focus on optical and pharmaceutical interventions . Currently, overnight-wear orthokeratology (ortho-k), is used extensively in Hong Kong with approximately 50% retardation effect. Pharmaceutical methods have focused on the use of atropine eye drops to slow myopic progression.The use of 1% atropine was limited by the manifestation of side effects and rebound effect.However, both side effect and rebound effect was minimal with 0.01% atropine.It was suggested that 0.01% was the optimum concentration for controlling myopia.The mechanisms of neither ortho-k nor atropine in myopia control are fully understood.It is believed that ortho-k and atropine act via different mechanisms.It is possible that by combining these two methods, additional retardation of myopia progression could be achieved.

Detailed description: Although it is believed that myopia is the result of an interplay between genetic and environmental factors and its progression has been attributed to the lack of outdoor activities and intensive school work, myopia control methods mainly focus on optical and pharmaceutical interventions. Use of bifocal and multifocal lenses have been shown to be ineffective in myopia control. Specially designed soft contact lenses for myopia control have recently been launched, but their effectiveness has yet to be confirmed. Currently, overnight-wear orthokeratology (ortho-k), which involves reshaping the cornea by overnight wear allowing for improved, frequently unaided, vision during the day, is used extensively in Hong Kong. Approximately 50% retardation in axial length elongation was observed in studies of patients receiving ortho-k (LORIC study, 46%, ROMIO study,43%, and TO-SEE study, 52%).

Pharmaceutical methods have focused on the use of atropine eye drops to slow myopic progression. The use of 1% atropine was first suggested in the 1990's, but its application was limited by the manifestation of side effects such as pupil dilatation and loss of accommodation. The effectiveness of lower concentrations (0.5%, 0.1% and 0.01%) have been evaluated in a recent five-year randomized clinical trial, where the authors reported that 0.01% atropine once daily was effective resulting in about 50% of spherical equivalent reduction. However, this was as a result of one year (3rd year) discontinuation of atropine in the five-year study. Rebound effect was minimal with 0.01% atropine and higher dosages were associated with more manifest rebound effects, which appeared to negate former myopia retardation effects. Only 24% of those receiving 0.01% progressed 0.50D or more after discontinuation for one year. By contrast, proportion of children progressed 0.50D or more in 0.5% and 0.1% groups were 59% and 68% respectively. Moreover, use of 0.01% atropine showed sustained myopia reduction with clinically negligible effects on pupil dilatation and loss of accommodation. The authors suggested the use of 0.01% as the optimum concentration for controlling myopia.

The mechanisms of neither ortho-k nor atropine in myopia control are fully understood. It is believed that ortho-k and atropine act via different mechanisms, with ortho-k slowing myopia progression by reducing peripheral hyperopic defocus, while atropine exerts effects on anti-muscarinic receptors of the retina and sclera. However, some subjects respond poorly to either atropine or ortho-k, as demonstrated in clinical trials, suggesting that a single treatment may be not enough. It is possible that by combining these two methods, additional retardation of myopia progression could be achieved. In this randomized trial, we will explore the effectiveness of combination of ortho-k and atropine therapy, and evaluate additional effects by comparing the combination with ortho-k treatment alone.

Eligibility criteria: Inclusion Criteria:

* Manifest myopia between 1.00-4.00D in both eyes at screening visit
* Manifest astigmatism ≤2.50D; with-the-rule astigmatism (axes 180 ± 30) ≤2.50D; astigmatism with other axes ≤0.50D in both eyes at screening visit
* \<1.00D difference in manifest spherical equivalent (SE) between the two eyes at screening visit
* Baseline cycloplegic objective refraction between 1.00-4.00D in sphere; astigmatism ≤2.50D; \<1.00D difference in manifest SE between the two eyes
* Best-corrected logMAR visual acuity 0.10 or better in both eyes
* Symmetrical corneal topography with corneal toricity \<2.00D in either eye
* Normal ocular health other than myopia
* Agree to be randomized and to attend the scheduled visits and aftercare

Exclusion Criteria:

* Contraindications to atropine: known allergies or cardiovascular disease, epilepsy
* Contraindications to contact lens wear and ortho-k: corneal scar, history of ocular inflammation/infection, limbus-to-limbus corneal cylinder and dislocated corneal apex
* Strabismus or amblyopia
* History of myopia control treatment (e.g. soft contact lenses, progressive add spectacles, atropine eye drops)
* Rigid contact lens (including ortho-k) wear experience
* Systemic condition which might affect refractive development (for example, Down syndrome, Marfan's syndrome)
* Ocular conditions which might affect refractive error (for example, cataract, ptosis)
* Poor response to lens wear including poor lens handling, poor vision and/ocular response after lens modifications
* Poor compliance with schedule visits

Primary outcomes:
measure: Changes in axial length in 2 years
timeFrame: Every 6 months for a period of 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Kowloon
country: Hong Kong
facility: School of Optometry, The Hong Kong Polytechnic University
Study officials:
affiliation: The Hong Kong Polytechnic University
name: Pauline Pauline, PhD
role: PRINCIPAL_INVESTIGATOR
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