At the completion of this article, the reader should be able to improve their management of progressive myopia with atropine, including:
- Review the evidence in support of atropine (0.01%-0.05%) for myopia management
- Understand the place for alternative regimens like step treatment, loading dose, or modified schedules for optimal myopia control
- Consider myopia risk factors when deciding atropine concentration, weighing benefits against side effects
- Acknowledge diverse responses from global trials, considering ethnic and regional variations.
Dr Pauline Kang
B Optom (hons) GradCertOcTher PhD FAAO
School of Optometry and Vision Science, UNSW, Sydney, Australia
When it comes to myopia, Dr Pauline Kang says optometrists should consider prescribing atropine for management, and tailor the choices about concentration to individual requirements. Ultimately, a nuanced approach, informed by the latest evidence, will be the one that is most effective.
Progressive myopia can be managed through pharmacological, optical, behavioural and, more recently, light-based therapies.1,2 Topical atropine is currently the most widely prescribed pharmacological treatment for childhood myopia with numerous clinical trials establishing its efficacy in controlling myopia progression.2
Although early studies explored higher concentrations of atropine (0.1-1%),3,4 due to significant side effects – including photophobia and cycloplegia – lower concentrations ranging from 0.01% to 0.05% have been investigated and have been found to have positive treatment outcomes.5-7 More recently, trials of atropine have been expanded to include investigation of its efficacy in children at risk of developing myopia.8
What is the ideal concentration of atropine for myopia control?
Various concentrations of atropine for myopia control have been explored and clinical trials have provided suggestions of ideal concentrations to prescribe to myopic children.
The seminal Atropine for the Treatment Of Myopia 2 (ATOM2) study prompted investigations of low-concentration atropine for myopia control after it reported that 0.01% atropine effectively slowed myopia progression, when defined by refractive changes, at rates comparable to higher 0.1% and 0.5% concentrations, particularly during the first year of treatment.
Further, children undergoing 0.01% atropine were found to experience minimal side effects, impact on visual function and rebound effects on cessation of treatment, which additionally supported its use.5 Positive study outcomes led to the prescription of 0.01% atropine in clinical practices for the management of progressive myopia.
The subsequent Low concentration Atropine for Myopia Progression (LAMP) randomised controlled trial explored 0.01%, 0.025% and 0.05% atropine to determine the optimal low concentration of atropine for controlling myopia and whether a concentration dependent response existed.7
Although all three concentrations caused minimal side effects and rebound effects on treatment cessation, the authors found a concentration-dependent response and proposed 0.05% atropine to be the best concentration to prescribe to myopic children.6,7 (The LAMP trial recruited only Chinese children and the authors have acknowledged that 0.05% atropine may not be ideal for other ethnic populations).
Findings from other studies
There have since been numerous clinical trials from around the globe exploring low-concentration atropine for myopia in children, typically aged six to 12 years, with mixed results.
For example, in Australia, 0.01% atropine was found to reduce myopia progression in a multi-racial cohort only during the first 18 out of 24 months of treatment (0.25 D and -0.10mm difference between atropine and control groups at 18 months).9 Another randomised controlled trial in India reported that 0.01% atropine significantly reduced myopia progression through refractive changes (0.19 D) only over a one year treatment period.10 The Myopia Outcome Study of Atropine In Children (MOSAIC), which included predominantly White Irish children, reported a modest treatment effect over two years with children undergoing 0.01% atropine experiencing less axial length elongation (-0.07 mm) compared to the control placebo group. However, this effect was not reflected in refractive changes where no significant difference was found.11
Another large trial, ChildHood Atropine for Myopia Progression (CHAMP) study, investigated 0.01% and 0.02% atropine across multiple clinical sites in the US and Europe and found 0.25 D and -0.13 mm less myopia progression in the 0.01% atropine compared to placebo group, and, interestingly, no significant difference between the 0.02% and placebo group over three years of treatment. A higher atropine concentration of 0.02% did not result in greater treatment outcomes or proportion of treatment responders.12
What atropine concentration do I prescribe a myopic child?
Concentrations between 0.01% to 0.05% atropine are widely accepted as being appropriate for myopia management. Eye health care practitioners also need to consider myopia risk factors when selecting atropine concentration.
The LAMP study found an age-dependent effect on treatment responses with younger children experiencing poorer responses to atropine treatment compared to older children. The authors suggested that a higher concentration of 0.05% atropine may be required for younger children to be able to experience similar treatment outcomes to older children.13 Considering faster myopia progression is associated with younger age of onset, selecting a higher concentration of atropine and being more ‘aggressive’ with treatment may be appropriate.
The impact of baseline refractive error on treatment response is unclear. Some studies have found an association with higher baseline myopia and better treatment outcomes while others have reported no effect.11,13,14 Positive parental history of myopia is also another risk factor that may be associated with poorer treatment outcomes,14 although the LAMP study found no impact of parental history.13
Considering side effects
Side effects with atropine is another important consideration when selecting atropine concentration. The main side effects of atropine include photophobia due to pupil size increase and reduced accommodation amplitude causing near vision blur.
Although concentration-dependent side effects have been noted with greater increase in pupil size and reduction of accommodation amplitude with higher concentrations of atropine,6 studies have found low concentrations of atropine (between 0.01% to 0.05%) to be overall well tolerated.7,9-12
Eye health care practitioners also need to note that different levels of pigmentation within the iris – thus sensitivity to atropine side effects – will exist which may impact treatment acceptance. Side effects of atropine can be easily monitored during treatment follow-up consultations through history and symptoms, and pupil and accommodative function assessment. If the child is experiencing significant side effects, atropine concentration can be reduced, or treatment type changed.
Is step treatment or loading dose an option?
Step treatment involves a stepwise increase in atropine concentration when treatment responses are suboptimal. This approach stems from clinical trials that have demonstrated concentration dependent responses to atropine, with higher concentrations resulting in greater myopia control.5,6
A retrospective study conducted in Taiwan included myopic children undergoing 0.05% atropine. If myopia progression of greater than -0.50 D was evident at any six-month follow-up visit over a minimum three-year treatment period, the concentration of atropine was increased to 0.1%. Forty-four out of the 97 enrolled children treated with 0.05% atropine were switched over 0.1% atropine. Although details of change in myopia progression after increasing atropine concentration was not discussed, the authors supported a step treatment approach.15
More recently, a Danish study investigated the impact of loading dose where participants were treated with 0.1% atropine for the first six months of treatment, followed by 0.01% atropine for the remaining 18 months. Treatment outcomes were compared to another treatment group undergoing 0.01% atropine only for the entire 24 months, and a placebo control group.16 Preliminary one-year results indicated modest treatment effects with atropine which was not statistically different from the control group. Loading dose did not have a significant impact with minimal differences in myopia progression in children who received a loading dose of 0.1% atropine during the first six months compared to children who were consistently treated with 0.01% atropine.16 Two-year treatment outcomes will confirm whether loading dose of a higher concentration atropine has any longer term benefits.
Modified treatment schedules
Most clinical trials have explored daily atropine treatment on myopia progression. A handful of studies have explored modified treatment schedules where atropine, typically at higher concentrations, were prescribed at reduced frequencies to decrease side effects.
A retrospective study reviewed clinical records of children using 0.125% atropine either once every night or once every two nights. Six-months of atropine treatment was considered baseline myopia progression and was measured one year after this baseline date. No significant difference in myopia progression was found between the two groups and the authors proposed that 0.125% atropine every second night may be an appropriate treatment option for children who cannot tolerate side effects related to daily use of 0.125% atropine.17
Another recent study explored the impact of reducing the frequency of 1% atropine eye drops in Chinese children.18 During the first two years, children administered 1% atropine eye drops once a month at night (one eye at day one and the other eye at day 16). During the following year, the frequency of atropine treatment was reduced to once every two months and, in the final year, children ceased atropine treatment. Myopia progression during the four years of treatment were compared to a control group.
During first two years, children treated with once a month 1% atropine had significantly less myopia progression compared to the control group (axial length change: 0.12 ± 0.10 vs 0.39 ± 0.19 mm; refraction change: -0.21 ± 0.22 vs -0.89 ± 0.23 D), and significant differences maintained during the following year with once every two month 1% atropine treatment (axial length change: 0.14 ± 0.09 vs 0.39 ± 0.14mm; refraction change: -0.31 ± 0.29 vs -0.80 ± 0.66 D), and during the last year of no treatment (axial length change 0.19 ± 0.13 vs 0.40 ± 0.16 mm; refraction change: -0.41 ± 0.23 vs -0.75 ± 0.64 D). The authors concluded that increasing atropine concentration with a reduced dosage regimen is another potential management option.
Patient compliance and treatment outcomes
The impact of patient compliance to low concentration atropine treatment and myopia control outcomes is not well understood as compliance rates have generally been high in clinical trials.5,6 However, based on optical treatments which have shown full-time wear to result in best myopia control outcomes, it could be assumed that a similar effect will be experienced with atropine and high treatment compliance is recommended.19 Minimal side effects with low concentration atropine is likely to aid in greater treatment compliance which further supports its use. Further research into the impact of treatment compliance on treatment outcomes is required.
Summary – current evidence-based management
Atropine is an effective and established treatment for progressive myopia. Clinical studies support the use of low concentration atropine ranging in concentration between 0.01% to 0.05% in myopic children. The ideal concentration is likely to vary between individuals, but understanding the child’s risk profile can aid in selecting the optimal concentration.
Based on current evidence, younger age and positive family history of myopia may indicate a higher atropine concentration but clinicians must weigh benefits of higher atropine concentrations with side effects.
Although concentration-dependent side effects have been noted, 0.01% to 0.05% atropine is generally well accepted in myopic children and eye health care practitioners should continue to monitor ocular health and function at follow-up consultations to determine if atropine treatment is causing any significant adverse effects.
If starting treatment on a lower 0.01% atropine yields poor results, eye health care practitioners may use a step approach and increase atropine concentration. Loading dose, or increasing atropine concentration, but reducing frequency of administration are other treatment regimens that are being explored and may offer a strategy to improve treatment efficacy with atropine. With commercial and compounded low concentration atropine formulations available for prescribing, atropine is an effective and readily-available treatment option for myopic children.
More reading
Atropine for myopia control: science and practice
Aussie myopia study reveals who benefits the most from low-dose atropine
Low-dose atropine EIKANCE secures first myopia TGA approval
Reference
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