Clinical

Low-dose Atropine and OrthoK: What Does the Evidence Say?

April 1, 2024

By Eman Ali Alzghoul, PhD candidate at the School of Optometry and Vision Science, University of New South Wales

orthokeratology

Photo Credit: AMR Images, Getty Images

Myopia is one of the most prevalent eye conditions worldwide, and by 2050, it is expected to affect half of the world’s population.1,2  While there are numerous interventions aimed at controlling the progression of myopia, a standardized approach to managing this condition is yet to be established in clinical practice.3 According to a global survey of myopia management attitudes and strategies among eye care practitioners, combination treatment was perceived to be the most effective method for controlling myopia, followed by orthokeratology and pharmaceutical approaches.4 

How Do Atropine and OrthoK Control the Progression of Myopia?
The exact mechanisms by which atropine and OrthoK slow myopia progression are not yet fully understood. For atropine, the mechanisms of action are believed to involve both accommodative and non-accommodative pathways. Atropine is known to paralyze the ciliary muscles, causing a reduction in the eye’s ability to change focus (accommodation). This change in accommodation may lead to a reduction in accommodative lag, a factor linked to myopia progression in children.3,5,6 Additionally, atropine has been shown to increase choroidal thickness, interfere with scleral remodeling, and modulate retinal dopamine release, which has been associated with a decrease in the rate of axial eye growth.7-9

OrthoK lenses are specially designed rigid gas preamble lenses worn overnight to temporarily reshape the cornea and correct low to moderate myopia during the day.10-12 OrthoK works by flattening the central cornea while simultaneously steepening the mid-peripheral cornea. These modifications in the corneal shape are accompanied by alterations in epithelial thickness,13-15 creating peripheral myopic defocus,16 inducing positive spherical aberration, and altering choroidal thickness.17 These combined changes are thought to slow the progression of myopia in OrthoK patients.

Several studies have reported a significantly slower axial elongation among patients who were assigned a combination therapy of 0.01% atropine and OrthoK compared to those who used OrthoK alone.18-20 The mechanism underlying this effect is still debated. It is assumed that atropine-induced pupil dilation may expose a larger portion of the peripheral retina to relative myopic defocus induced by OrthoK.21 Additionally, atropine slightly reduces the amplitude of accommodation, potentially decreasing hyperopic defocus during near work in myopic children.22-24 Moreover, a larger pupil diameter may increase total higher-order aberrations, which have been strongly linked to reduced axial elongation in OrthoK-treated groups.25-27 

Atropine or OrthoK: What Does the Current Literature Say?
Atropine has been shown to inhibit myopia progression compared to placebo by 88.7% with high atropine doses (0.5% and 1%)  and 49- 60% using lower doses (0.01% and 0.05%).7,22,28-30 A 2020 meta-analysis by Zhao et al.31 suggested that 0.05% atropine might be the optimal dose to slow myopia progression while minimizing adverse effects and rebound after discontinuation. Currently, 0.01% atropine is widely used for myopia control in East Asian countries, particularly Taiwan and Singapore.22 However, atropine treatment must be accompanied by corrective spectacles or contact lenses so that myopic children can see clearly. 

OrthoK lenses have been shown to reduce axial elongation by 30–60% compared to single-vision placebo groups.32-35 However, the effectiveness varies among individuals.36,37 Factors associated with enhanced myopia control include higher baseline myopia, older age, later onset of myopia, larger pupil size, and smaller treatment zone.10-12 

While a limited number of studies have directly compared the efficacy of OrthoK and low-dose atropine in controlling myopia progression, the available evidence remains controversial. According to Tasi et al.’s38 meta-analysis, OrthoK was similar to 0.01%−0.025% atropine in inhibiting axial elongation over a one-year follow-up period.38 Similarly, a recent meta-analysis by Wang et al.39 reported that the axial growth rate in children wearing OrthoK lenses alone was comparable to that of children wearing single-vision spectacle lenses during the day and using 0.01% atropine drops nightly. 

However, not all studies agree on the relative effectiveness of OrthoK and atropine. Lyu et al.40 suggested that OrthoK was superior to 0.02% atropine in controlling axial length elongation in children with higher myopia over a two-year treatment period.39 In contrast, Zhao et al.5 found that 0.01% atropine eye drops were more effective than OK lenses in young children under 10 years of age over a one-year treatment period.

Combined Treatment
Three two-year clinical trials have demonstrated that the combination of OrthoK and 0.01% atropine is more effective than OrthoK alone in children aged 6-18,6,43,44  with an additional slowing of axial elongation ranging from 0.11 to 0.18 mm. In a recent review, Sánchez-González et al.43 confirmed the efficacy of utilizing a combination approach of 0.01% atropine and OrthoK compared to OrthoK alone. This finding has been further supported by Tsai et al.,38 who observed a synergistic effect when combining 0.01% atropine with OrthoK lenses comparable to that of high-dose atropine, suggesting that this approach may provide a viable alternative for managing the condition while potentially reducing the risk of side effects associated with high-dose atropine treatment.

However, the efficacy of the combination treatment may not be consistent across all children and could be influenced by factors such as age. For example, Tang et al.44 conducted a retrospective study comparing OrthoK lenses alone and in combination with 0.01% atropine (OKA) for myopia control. The study found that the combination treatment was the most effective in controlling myopia, with axial elongation being less than 0.15 mm over a one-year follow-up in older children aged 10–14. Another study performed by Xu et al. revealed that the efficacy of OKA was similar to that of OrthoK lenses in children aged 8–10 years, while in those aged 10–12 years, the efficacy of OKA was similar to that of atropine.6  

Summary and Future Direction
Taken together, both 0.01% atropine and OrthoK have been shown to effectively reduce myopia progression when used as individual treatments. When 0.01% atropine is combined with OrthoK, it appears to be more effective than OrthoK alone. Furthermore, while these treatments have shown promise, none have demonstrated 100% efficacy in controlling myopia progression.45 A personalized myopia control strategy based on age, initial myopic refractive error, and the rate of myopia progression may be able to better control myopia in children and adolescents. Further research is necessary to determine the best patient characteristics and atropine dosage for maximizing the benefits of this combined treatment strategy.

 

Eman Ali Alzghoul is an alumnus of UNSW Sydney who graduated with a master’s degree in Optometry from the School of Optometry and Vision Science. After earning her Bachelor of Optometry in 2008, she worked as a teaching assistant and a registered clinical optometrist at Jordan University of Science and Technology (JUST). Eman is a keen educator and clinical supervisor for optometry and research students. Her research focused on contact lens compliance, visual impairment, patient care, and myopia control treatments. With her past teaching and clinical experience and her own research interests, she now hopes to contribute to the vision research field by investigating the visual functions and myopic control strategies as a part of her PhD. Eman values sharing research, effective science communication, and teamwork.

 

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