Both orthokeratology (OK) lenses and low-concentration atropine are effective forms of myopia control.1,2 Could we expect a greater efficacy to control myopia if we combine the treatments? In this post, LH is considering whether to start a young patient on a monotherapy or go straight to combination treatment. Here is the original post.
To combine or not to combine treatments?
This case was presented prior to scientific publications on combining atropine and orthokeratology, hence some commenters expressed concern about the evidence base. This is still a fair comment as we only have a handful of studies now indicating an additive effect by combining orthokeratology and atropine. Thus far, the ideal concentration and ideal targets for dual therapy are yet to be determined - early indication is that 0.01% and lower myopes of 1-3D may be the answers, respectively.3,4
There is also merit to the commenters’ opinions to start one treatment first to determine its myopia control efficacy, before adding an adjunct. This indicates consideration to safety, as additive treatments could also increase the risk of complications, for example irritation from preservatives in atropine increasing risk of a contact lens adverse event.
What do we know about combination treatment efficacy?
Recently published studies do suggest that combination treatments control myopic progression better. Here is a brief outline of the handful of studies with data over 12 months or longer.
- Tan et al showed 0.09mm slower axial elongation in their 0.01% atropine + OK lens group (0.07mm) than the OK lens group (0.16mm) in 1 year.5 The effect was significant in the first six months only, with no difference in growth between groups in the second six months.
- Kinoshita et al found a 0.18mm additional control effect after two years, although only significant in 1-3D myopes: 0.01% atropine + OK grew 0.30mm whilst OK lens only group grew 0.48mm.6
- In a three year study, Chen et al fit children with OK monotherapy for the first year (Phase 1) and if they progressed by more than 0.30mm in a year they were allocated to either 0.01% atropine + OK group or OK only group for a further two years. There was no significant difference in cumulative axial elongation over 3 years, and no effect of baseline age or refractive error on the response to dual therapy.7
- Two meta-analyses concurred that adding atropine will reduce axial elongation by an additional 0.09mm over one year. One meta-analysis evaluated 4 studies which only included 0.01%,8 while the other evaluated 5 studies which included a variety of concentrations.3 None of the studies reported serious adverse events. Given the small number of studies currently published, these meta-analyses don't add a lot of information compared to viewing the studies in isolation.
- There is only one study currently underway on the combination of 0.01% and a multifocal soft contact lens: the CooperVision Biofinity D lens +2.50 Add. Early results show good tolerance of the combination but no longitudinal results are available yet.9
What time of day should atropine be used?
There was also discussion around the appropriate time and method to instill atropine drops, especially within the context of utilizing OK lenses. Currently, there are no guidelines for using low-concentration atropine drops with myopia controlling contact lenses.
Side effects appear to be minimal
Ocular surface exposure to preservatives in the atropine drop, such as BAK, is more likely the larger concern of combination treatment than the cycloplegic and mydriatic side effects of atropine interacting with OK treatment. Kinoshita et al6 (diluted atropine with BAK) found SPK in 2/43 of the combination group and 1/37 of the OK only group which worsened over time and required discontinuation of OK and switching to spectacles. Tan et al5 (preservative free single use atropine) reported 1 case of bacterial conjunctivitis in each group which recovered with a week out of OK lenses and topical antibiotics. Neither group reported other adverse events or allergies related to atropine or OK use.
When to instill atropine
The peak mydriatic effect of atropine starts within an hour after instillation and the peak cycloplegic action of atropine starts after approximately 3 hours, then phases off.10 In an attempt to reduce the impact of atropine side effects on near vision and pupil size, it is typically instilled at night time, before sleep. This has been followed in subsequent studies of atropine + OK, where atropine has been used 5-10 minutes before applying the OK lenses.4-7
Interestingly, in a study by Kothari et al investigating the efficacy of 1% atropine as monotherapy, 17 subjects who instilled drops at bedtime progressed more than 0.50D a year. 13 of these subjects subsequently progressed less than 0.50D a year after they were switched to instill atropine in the morning (7am).11 There were no baseline age or refraction predictors of the faster progressors. Hence, it seems that time of atropine instillation may potentially influence efficacy, but further study is required.
Take home messages:
- Combination treatment of atropine 0.01% and orthokeratology appears to provide increased myopia control efficacy than orthokeratology alone, although studies indicate this may work best for 1-3D myopes and/or in the first 6-12 months of treatment. Should you try monotherapy first and then add atropine? The data doesn't indicate a greater effect with younger age, although younger children progress more quickly overall so if you and/or the parents are concerned about fast progression, a combination treatment could be helpful.
- There are no studies yet that indicate how time of day of atropine use may influence efficacy. Using both atropine and OK at night time could increase risk to the ocular surface, but this appears to be of minimal impact in studies and especially if preservative free atropine is used.
Further reading on atropine and combination treatment
- Sun Y, Xu F, Zhang T, Liu M, Wang D, Chen Y, Liu Q. Orthokeratology to control myopia progression: a meta-analysis. PloS one. 2015 Apr 9;10(4):e0124535. (link)
- Gong Q, Janowski M, Luo M, Wei H, Chen B, Yang G, Liu L. Efficacy and adverse effects of atropine in childhood myopia: a meta-analysis. JAMA ophthalmology. 2017 Jun 1;135(6):624-30. (link)
- Gao C, Wan S, Zhang Y, Han J. The efficacy of atropine combined with orthokeratology in slowing axial elongation of myopia children: a meta-analysis. Eye & Contact Lens. 2021 Feb 1;47(2):98-103. (link)
- Kinoshita N, Konno Y, Hamada N, Kanda Y, Shimmura-Tomita M, Kaburaki T, Kakehashi A. Efficacy of combined orthokeratology and 0.01% atropine solution for slowing axial elongation in children with myopia: a 2-year randomised trial. Sci Rep. 2020 Jul 29;10(1):12750. (link)
- Tan Q, Ng AL, Choy BN, Cheng GP, Woo VC, Cho P. One‐year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial. Ophthalmic and Physiological Optics. 2020 Sep;40(5):557-66. (link)
- Kinoshita N, Konno Y, Hamada N, Kanda Y, Shimmura-Tomita M, Kakehashi A. Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia: first year results. Japanese journal of ophthalmology. 2018 Sep;62(5):544-53. (link)
- Chen Z, Zhou J, Xue F, Qu X, Zhou X. Two-year add-on effect of using low concentration atropine in poor responders of orthokeratology in myopic children. British Journal of Ophthalmology. 2021 Mar 11. (link)
- Wang S, Wang J, Wang N. Combined orthokeratology with atropine for children with myopia: a meta-analysis. Ophthalmic Research. 2020 Aug 11. (link)
- Huang J, Mutti DO, Jones-Jordan LA, Walline JJ. Bifocal & Atropine in Myopia (BAM) Study: Baseline Data and Methods. Optometry and vision science: official publication of the American Academy of Optometry. 2019 May;96(5):335. (link)
- Webber AL, Sharwood P. Practical use and prescription of ocular medications in children and infants. Clinical and Experimental Optometry. 2021 Apr 3;104(3):385-95. (link)
- Kothari M, Rathod V. Efficacy of 1% atropine eye drops in retarding progressive axial myopia in Indian eyes. Indian journal of ophthalmology. 2017 Nov;65(11):1178. (link)