Combined Atropine With Orthokeratology in Childhood Myopia Control (AOK) -A Randomized Controlled Trial

Myopia Clinical Trial

Official title:

Combined Atropine With Orthokeratology in Childhood Myopia Control (AOK) -A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02955927
• Other study ID #: HSEARS20160406005/UW 16-404
• Status: Completed
• Phase: N/A
• Start date: November 2016
• Est. completion date: May 8, 2021

Study information

• Verified date: August 2021
• Source: The Hong Kong Polytechnic University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: May 8, 2021
• Est. primary completion date: May 8, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

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

Related Conditions & MeSH terms

• Myopia

Intervention

Drug:
• 0.01% atropine eye drops

Device:
• ortho-k

Locations

Country	Name	City	State
Hong Kong	School of Optometry, The Hong Kong Polytechnic University	Kowloon

Sponsors (2)

Lead Sponsor	Collaborator
The Hong Kong Polytechnic University	The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (16)

Arumugam B, McBrien NA. Muscarinic antagonist control of myopia: evidence for M4 and M1 receptor-based pathways in the inhibition of experimentally-induced axial myopia in the tree shrew. Invest Ophthalmol Vis Sci. 2012 Aug 24;53(9):5827-37. doi: 10.1167/iovs.12-9943. — View Citation

Berntsen DA, Sinnott LT, Mutti DO, Zadnik K. A randomized trial using progressive addition lenses to evaluate theories of myopia progression in children with a high lag of accommodation. Invest Ophthalmol Vis Sci. 2012 Feb 13;53(2):640-9. doi: 10.1167/iovs.11-7769. Print 2012 Feb. — View Citation

Brodstein RS, Brodstein DE, Olson RJ, Hunt SC, Williams RR. The treatment of myopia with atropine and bifocals. A long-term prospective study. Ophthalmology. 1984 Nov;91(11):1373-9. — View Citation

Chen C, Cheung SW, Cho P. Myopia control using toric orthokeratology (TO-SEE study). Invest Ophthalmol Vis Sci. 2013 Oct 3;54(10):6510-7. doi: 10.1167/iovs.13-12527. — View Citation

Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, Tan D. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2). Ophthalmology. 2012 Feb;119(2):347-54. doi: 10.1016/j.ophtha.2011.07.031. Epub 2011 Oct 2. — View Citation

Chia A, Lu QS, Tan D. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% Eyedrops. Ophthalmology. 2016 Feb;123(2):391-399. doi: 10.1016/j.ophtha.2015.07.004. Epub 2015 Aug 11. — View Citation

Cho P, Cheung SW, Edwards M. The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control. Curr Eye Res. 2005 Jan;30(1):71-80. — View Citation

Cho P, Cheung SW. Retardation of myopia in Orthokeratology (ROMIO) study: a 2-year randomized clinical trial. Invest Ophthalmol Vis Sci. 2012 Oct 11;53(11):7077-85. doi: 10.1167/iovs.12-10565. — View Citation

Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, Tan D. Atropine for the treatment of childhood myopia. Ophthalmology. 2006 Dec;113(12):2285-91. Epub 2006 Sep 25. — View Citation

Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group. Progressive-addition lenses versus single-vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria. Invest Ophthalmol Vis Sci. 2011 Apr 25;52(5):2749-57. doi: 10.1167/iovs.10-6631. — View Citation

Fan DS, Lai C, Lau HH, Cheung EY, Lam DS. Change in vision disorders among Hong Kong preschoolers in 10 years. Clin Exp Ophthalmol. 2011 Jul;39(5):398-403. doi: 10.1111/j.1442-9071.2010.02470.x. Epub 2011 Feb 1. — View Citation

Lam CS, Lam CH, Cheng SC, Chan LY. Prevalence of myopia among Hong Kong Chinese schoolchildren: changes over two decades. Ophthalmic Physiol Opt. 2012 Jan;32(1):17-24. doi: 10.1111/j.1475-1313.2011.00886.x. — View Citation

Liu Y, Wildsoet C. The effective add inherent in 2-zone negative lenses inhibits eye growth in myopic young chicks. Invest Ophthalmol Vis Sci. 2012 Jul 31;53(8):5085-93. doi: 10.1167/iovs.12-9628. — View Citation

Morgan IG, Ohno-Matsui K, Saw SM. Myopia. Lancet. 2012 May 5;379(9827):1739-48. doi: 10.1016/S0140-6736(12)60272-4. Review. — View Citation

Pan CW, Ramamurthy D, Saw SM. Worldwide prevalence and risk factors for myopia. Ophthalmic Physiol Opt. 2012 Jan;32(1):3-16. doi: 10.1111/j.1475-1313.2011.00884.x. Review. — View Citation

Pauné J, Morales H, Armengol J, Quevedo L, Faria-Ribeiro M, González-Méijome JM. Myopia Control with a Novel Peripheral Gradient Soft Lens and Orthokeratology: A 2-Year Clinical Trial. Biomed Res Int. 2015;2015:507572. doi: 10.1155/2015/507572. Epub 2015 Oct 28. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in axial length in 2 years		Every 6 months for a period of 2 years