At the completion of this CPD activity, optometrists will have developed their knowledge of myopia management. Including:
- Identify patients best suited for combination orthokeratology/low-concentration atropine treatment for myopia
- Understand the elements of a thorough baseline assessment of myopic patients
- Gauge efficacy of combination treatment in myopia management
- Review a case study exemplifying the adoption of combination treatment
NOTE: Optometry Australia members can enter their details at the bottom of this article to have it automatically added to their Learning Plan.
As myopia rates soar globally, the search for optimal clinical interventions continues. A new avenue of research suggests there is a synergistic effect to a combined atropine and orthokeratology management approach. DR PAULINE KANG outlines when this may be an appropriate intervention.
Dr Pauline Kang
B Optom (hons) GradCertOcTher PhD FAAO
School of Optometry and Vision Science, UNSW, Sydney, Australia
Axial elongation underlying myopia development and progression predisposes the eye to various sight-threatening complications including myopic maculopathy, retinal detachments, tears and degeneration and glaucoma.1 The persistent and progressive nature of excessive axial elongation underlying myopia has prompted the investigation of various optical and pharmacological interventions to slow or stop childhood myopia progression including orthokeratology and low concentration atropine eye drops.2,3
Orthokeratology
Orthokeratology involves the overnight wear of specialised rigid contact lenses. The lenses incorporate a reverse geometry lens design that gently reshapes the anterior cornea to correct ametropia, most commonly myopia.4
Following clinical trials demonstrating the myopia control effects of orthokeratology, the lenses are increasingly prescribed to children for the treatment of progressive myopia. Meta analyses, which pool data from various clinical trials, have reported an overall 41-45% reduction in myopia progression in children treated with orthokeratology compared to the single vision correction.5-7 It has been hypothesised that changes in the retinal optical profile (induction of myopic defocus) following orthokeratology lens wear may be responsible for the myopia control effects.8
Atropine
Atropine is also becoming an increasingly popular treatment for progressive myopia, with large randomised controlled trials demonstrating myopia control effects with low concentration atropine.9-11
The recent Low-Concentration Atropine for Myopia (LAMP) study investigated three concentrations of atropine (0.01%, 0.025% and 0.05%) and monitored myopia progression in 350 children aged four to 12 years over a two-year period. Defined by both axial length and refractive error changes, a dose-dependent effect was reported with higher concentrations of atropine resulting in greater reduction of myopia progression.9
The study authors proposed 0.05% atropine concentration to be optimal, as it demonstrated the greatest myopia control effect over the two-year treatment period – approximately 64.5% reduction in myopia progression compared to a predictive myopia progression model when defined through spherical equivalent changes.
Vision-related quality of life was also found to be similar between the three concentrations.9
Atropine is hypothesised to induce myopia control effects through blocking of muscarinic receptors in the retina and/or sclera,12,13 or potentially stimulating α2-adrenoceptors involved in axial elongation.14 However, underlying treatment mechanism remains overall poorly understood.
Clinical studies on combined treatments
If orthokeratology and atropine induce myopia control effects through different mechanisms, combining treatments may result in a synergistic effect and improve overall treatment efficacy. Although limited, some studies have started to investigate the effects of combining orthokeratology and atropine monotherapy treatments.
Despite the fact that the LAMP study indicated 0.05% to be the ideal atropine concentration for myopia,9 recent studies exploring combining orthokeratology with atropine treatment have included 0.01% atropine and positive outcomes have so far been reported.
Study 1: combination treatment effective in cases with low baseline myopia
The first prospective study to investigate the efficacy of combined orthokeratology and low-concentration atropine treatment involved 73 Japanese children aged eight to 12 years who were randomised to either a combination (orthokeratology plus 0.01% atropine; n=43) or a monotherapy (orthokeratology; n=37) treatment group.15
After two years of treatment, there was a significant difference in overall axial elongation between groups with less myopia progression in the combination treatment group (combination 0.29 ± 0.20 mm, monotherapy 0.40 ± 0.23 mm; p=0.03). The greatest change in axial elongation occurred during the first year of treatment.15 As greater differences in treatment groups were found in children with lower baseline myopia (-1.00 to -3.00 D), the study authors suggested combination treatment may be effective in children with low baseline myopia.15
Study 2: increased treatment efficacy – in first six months
The Atropine with Orthokeratology (AOK) study also investigated the additive effect of combining orthokeratology with 0.01% atropine over two years. The study involved six to 11-year-old children in Hong Kong who were randomly allocated to a combination (orthokeratology plus 0.01% atropine; n=29) or a monotherapy (orthokeratology; n=30) treatment group.16
Preliminary one-year results were published with similar outcomes; combination treatment resulted in better myopia control (combination 0.07 ± 0.16 mm, monotherapy 0.16 ± 0.15 mm; p=0.03).16 The efficacy of myopia control increased from 57% to 81% reduction in myopia progression when atropine was added to orthokeratology treatment when compared to the historical control group from the previous Reduction in Myopia in Orthokeratology (ROMIO) clinical trial. However, the difference in myopia progression was evident during the first six months of treatment only.16
Study 3: significantly-reduced progression with combination treatment
A retrospective study investigated the impact of adding 0.01% atropine treatment in 60 Chinese children under the age of 12 who had experienced myopia progression of greater than 0.25 mm/year while undergoing orthokeratology treatment for one year. Treatment efficacy was compared to a historical control group (n=29).17
In agreement with previous studies, authors reported significantly-reduced myopia progression during the second year with combination treatment compared to the first year with orthokeratology monotherapy and to the control group.17
Study 4: OK with different concentrations of atropine
Another retrospective study investigated combining orthokeratology with different concentrations of atropine: 0.025% and 0.125%. Patients were stratified as having myopia <6 D or ≥6 D and self-selected to either be treated with orthokeratology lenses alone, or in combination with atropine, and treatment over two years was evaluated.18Adding either concentration of atropine to orthokeratology treatment was found to have a positive effect although differences in treatment effect between the lower and higher concentrations of atropine were not assessed.18
A clinical trial underway
Currently, there is a randomised controlled multicentre clinical trial under way involving a group of children treated with orthokeratology and 0.01% atropine and another treatment group of orthokeratology and placebo eye drops which will be investigated over a two-year treatment period.19
Selecting patients for combination treatment
Based on the outcomes of recent clinical trials, myopic children who are continuing to demonstrate significant myopia progression while on orthokeratology treatment17 or myopic children who have low baseline myopia may be best suited to orthokeratology and low concentration atropine combination treatment.15
Myopic children who have multiple risk factors20 for myopia – including family history of myopia, longer baseline axial lengths, young age of myopia onset, spend little time outdoors and conduct significant periods of near work – may also be suited for combination treatment.
Assessment of patients undergoing combination treatment
A thorough baseline assessment of patients is imperative in myopia management. As recommended by the International Myopia Institute Clinical Guidelines,21 assessment should include:
• History taking
• Refraction (non-cycloplegic and/or cycloplegic as indicated) and visual acuity
• Accommodation and vergence functions
• Ocular health including intraocular pressure and pupil responses
• Corneal topography
• Axial length (ocular biometer, if available)
To monitor treatment safety and efficacy of combination treatment and fit of orthokeratology lenses, regular review schedules should be arranged according to the following schedule:21
• One day
• Four to seven days
• One month
• Three months
• Then six monthly
Review consultations will typically include part of the assessment conducted at baseline including refraction, ocular health, corneal topography and axial length measurements.
Assessing efficacy of treatment
To assess the efficacy of treatment, clinicians need to compare the patient’s eye growth rate to that expected from an emmetropic child of comparable age.22 There have been large population-based studies reporting axial length growth curves which can be used in assisting clinical decision making.23-25
Overall, axial length growth is faster in younger (approximately less than 10 years) compared to older children. Emmetropic axial length growth of approximately 0.1-0.2 mm/year have been reported in younger children and approximately 0.1 mm/year in older children.23-25 Axial eye growth greater than these values may indicate myopia progression and poor treatment response. However, these are simplified average values and clinicians must take into factors such as baseline axial lengths, gender and ethnicity, which will also influence axial eye growth.
Other clinical considerations
Current studies have mainly investigated 0.01% atropine concentration for combination treatment. With the recent Therapeutic Goods Administration (TGA) approval of EIKANCE 0.01%, Australia’s first low-concentration atropine eye drop for myopia control, this may be an ideal concentration to initially prescribe.
If patients continue to demonstrate significant myopia progression while on combination orthokeratology and atropine treatment, clinicians may consider increasing atropine concentration although future studies to determine the ideal concentration of atropine are required, as well as the longer term treatment effects. Current studies suggest that treatment effects may only occur during the initial six to 12 months of treatment.15,16
Currently, the only orthokeratology lens approved by TGA ‘to control myopia’ is the Menicon Night Bloom. If prescribing other orthokeratology lens designs or concentrations of atropine other than 0.01%, clinicians may consider creating patient information and consent forms highlighting the off-label nature of myopia control treatment, and to highlight potential treatment sides effects and risks.
Patients should be informed of appropriate orthokeratology lens wear and atropine use including instillation of drops at least five to 10 minutes prior to wearing orthokeratology lenses at night.15,16 Multiple modes of instruction including verbal, written or visual (video) are recommended.
Case study
A 9-year-old boy presented to the UNSW Myopia clinic in November 2018 with a history of myopia progression as determine by refractive error changes as shown in Table 1.
Both parents are moderately myopic (positive family history) and the patient is an avid reader (two to three hours per day). Cycloplegic subjective refraction and axial lengths (ZEISS IOLMaster 700) were found to be RE -4.50/-0.50 x 100 and 24.62mm, and LE -4.50/-0.50 x 155 and 24.59 mm.
After discussion of various myopia control treatment options including atropine, orthokeratology and multifocal contact lenses, orthokeratology treatment was selected, and lens fitting was initiated two weeks later.
The patient was seen for several follow up visits to finalise orthokeratology lens fit after which myopia progression was regularly monitored as shown in Figure 1.
During 2019, axial length measurements in both eyes were overall stable and demonstrated little myopia progression.
The patient was unable to seen at the UNSW Myopia Clinic throughout the first half of 2020 due to the first NSW COVID-19 lockdown during which he experienced myopia progression (axial length increase RE 0.17 mm and LE 0.16 mm in approximately seven months).
He was then monitored closely during the second half of 2020 where he demonstrated further progression (axial length change RE 0.12 mm and LE 0.16 mm in approximately 5 months). This prompted discussion of adding low concentration atropine treatment to his myopia management.
The patient did not opt for atropine treatment and was unable to seen again during the first few months of 2021 due to the second NSW COVID-19 lockdown. Adjunct 0.025% atropine treatment was then initiated in May 2021 (red arrow in Figure 1) after which axial length was stable for the remainder of the year. The higher 0.025% atropine concentration was selected as the patient had several myopia risk factors including positive family history, longer baseline axial lengths and regular long periods of near work.
References
1. Haarman AEG et al. The complications of myopia: A review and meta-analysis. Invest Ophthalmol Vis Sci 2020;61:49.
2. Jonas JB et al. IMI – Prevention of myopia and its progression. Invest Ophthalmol Vis Sci 2021;62:6.
3. Wildsoet CF et al. IMI – Interventions for controlling myopia onset and oprogression report. Invest Ophthalmol Vis Sci 2019;60:M106-M131.
4. Swarbrick HA. Orthokeratology review and update. Clin Exp Optom 2006;89:124-143.
5. Si JK et al. Orthokeratology for myopia control: a metaanalysis. Optom Vis Sci 2015;92:252-257.
6. Sun Y et al. Orthokeratology to control myopia progression: a meta-analysis. PLoS One 2015;10:e0124535.
7. Wen D et al. Efficacy and acceptability of orthokeratology for slowing myopic progression in children: A systematic review and meta-analysis. J Ophthalmol 2015;2015:360806.
8. Kang P, Swarbrick H. New perspective on myopia control with orthokeratology. Optom Vis Sci 2016.
9. Yam JC et al. Two-year clinical trial of the Low-Concentration Atropine for Myopia Progression (LAMP) study: Phase 2 report. Ophthalmology 2020;127:910-919.
10. Chia A et al. 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;119:347-354.
11. Chia A et al. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia control with atropine 0.01% Eyedrops. Ophthalmology 2016;123:391-399.
12. McBrien NA et al. The M4 muscarinic antagonist MT-3 inhibits myopia in chick: evidence for site of action. Ophthalmic Physiol Opt 2011;31:529-539.
13. Arumugam B et al. 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;53:5827-5837.
14. Carr BJ et al. Alpha2 -adrenoceptor agonists inhibit form-deprivation myopia in the chick. Clin Exp Optom 2019;102:418-425.
15. Kinoshita N et al. 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;10:12750.
16. Tan Q et al. Combined atropine with orthokeratology for myopia control: Study design and preliminary results. Curr Eye Res 2019;1-8.
17. Chen Z et al. Adjunctive effect of orthokeratology and low dose atropine on axial elongation in fast-progressing myopic children-A preliminary retrospective study. Cont Lens Anterior Eye 2019;42:439-442.
18. Wan L et al. The synergistic effects of orthokeratology and atropine in slowing the progression of myopia. J Clin Med 2018;7.
19. Yuan Y et al. Efficacy of combined orthokeratology and 0.01% atropine for myopia control: the study protocol for a randomized, controlled, double-blind, and multicenter trial. Trials 2021;22:863.
20. Morgan IG et al. IMI – Risk factors for myopia. Invest Ophthalmol Vis Sci 2021;62:3.
21. Gifford KL et al. IMI – Clinical management guidelines report. Invest Ophthalmol Vis Sci 2019;60:M184-M203.
22. Chamberlain P et al. Axial length targets for myopia control. Ophthalmic Physiol Opt 2021;41:523-531.
23. Tideman JWL et al. Axial length growth and the risk of developing myopia in European children. Acta Ophthalmol 2018;96:301-309.
24. Rozema J et al. Axial growth and lens power loss at myopia onset in Singaporean children. Invest Ophthalmol Vis Sci 2019;60:3091-3099.
25. Sanz Diez P et al. Growth curves of myopia-related parameters to clinically monitor the refractive development in Chinese schoolchildren. Graefes Arch Clin Exp Ophthalmol 2019;257:1045-1053
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