Dual therapy may slow the progression of condition.
Myopia management options and knowledge have proliferated over the past decade. This pursuit of knowledge has been fueled by the understanding that the worldwide prevalence of myopia is increasing and that this spike in myopia cases may increase the population’s ocular pathology burden.1,2
With this dynamic landscape and urgent need to curb the onset and progression of myopia, it is imperative that clinicians explore every avenue for improving myopic progression treatment outcomes. Although most studies have focused on evaluating monotherapy options, there is growing evidence suggesting that dual therapy may further slow myopic progression. Thus, the purpose of this literature review is to explore the current state of knowledge related to using a low-dose atropine as an adjunct therapy in patients who are also being treated with optical-based myopia management strategies.
Low-concentration atropine (0.1%-0.05%) has been demonstrated to be effective while having minimal adverse effects.3 Although atropine was once thought to exert its antimyopigenic effects as an antimuscarinic, its full mechanism is unknown.4 Orthokeratology and other optical-based clinically proven myopia management strategies are thought to reduce myopic progression by decreasing retinal peripheral hyperopic defocus.5 Thus, if a myopic patient were prescribed both atropine and orthokeratology, which appear to operate under different mechanisms, the atropine and orthokeratology might produce an additive treatment effect.
Kinoshita et al were some of the first investigators to report on this topic with their 2-year, parallel-group, randomized trial, which compared participants receiving combination orthokeratology with atropine (n = 43) with participants who were being treated with only orthokeratology (n = 37).6,7 The authors found that the combination group had a significant slowing of axial length elongation compared with atropine alone over the duration of the study. Kinoshita et al interestingly found that most of the added benefit detected with the combination occurred during the first 6 months of treatment.6 This result has since been corroborated by Yu et al and Tan et al.8,9
Xu et al completed a 2-year, randomized trial comparing the efficacy of standard spectacles (n = 40), standard spectacles plus atropine (n = 42), orthokeratology (n = 40), and combined atropine and orthokeratology (n = 42) treatments.10 The authors found a significant treatment difference among groups with their pairwise comparison determining that the combined treatment was superior to atropine or orthokeratology treatment alone. Tan et al later conducted a 2-year, randomized trial comparing the combination of orthokeratology plus atropine (n = 45) to orthokeratology alone (n = 44) with the authors determining a similar conclusion.9
Chen et al conducted a 3-year trial evaluating the effect of adding atropine for patients who were poorly responding to orthokeratology (≥ 0.30 mm of axial elongation after 1 year of treatment).11 The patients in this study were given the option to use atropine (n = 37) or not (n = 36) while continuing to use orthokeratology after 1 year of monotherapy. Chen et al determined after 2 years of combination treatment there were no additional benefits to adding atropine.
Multifocal, soft contact lenses (CLs) have demonstrated the ability to slow myopic progression,12-14 and there are emerging data regarding their usefulness in combination with atropine. Jones et al were among the first to evaluate atropine in combination with soft CLs with the authors performing an ancillary study to the Bifocal Lenses in Nearsighted Kids study (BLINK; NCT02255474).13,15 The BLINK study compared monthly, center-distance soft CLs with +2.50 D or +1.50 D adds to single vision CLs of the same brand. The authors found that the +2.50 add CLs but not the +1.50 D add CLs were able to significantly slow myopic progression compared with single vision CLs.
Jones et al compared a group of 46 patients being treated with atropine and +2.50 add soft CLs with age-matched +2.50 D add and single vision CL wearers from the BLINK study. The authors found that combination atropine and +2.50 D add CLs did not provide an additional treatment benefit. Erdinest et al has since implemented a 3-year, retrospective review, which compared patients who were treated with a daily disposable CL plus atropine (n = 26), atropine (n = 29), or with single vision spectacles (n = 30). Patients taking atropine were treated for 2 years with the drop. They then were tapered off the drop for 6 months and followed for an additional 6 months. Erdinest et al determined that there was no significant benefit to combination treatment over atropine treatment alone.
Although different spectacles designs have been evaluated as a means for slowing the progression of myopia for many years, these early investigations have failed to find a clinically meaningful effect.16 Nevertheless, more recent designs that promote the reduction of peripheral retinal hyperopic defocus across the full peripheral retina have been shown to significantly reduce myopic progression.17 Nucci et al were among the first investigators to tackle this topic. The authors completed a 1-year, unmasked study that compared patients treated with defocus incorporated multiple segments (DIMS) spectacles (n = 30), atropine (n = 53), DIMS plus atropine (n = 31), and single-vision spectacles (control; n = 32). The authors determined that all 3 treatments provided a significant reduction in myopic progression; the combination group also obtained a significantly better treatment effect than monotherapy for refractive error, but not for axial length.18
Huang et al have completed a retrospective study, which compared the treatment effect between patients treated with DIMS plus atropine (n = 40), DIMS (n = 49), or single-vision spectacles (control; n = 47). The authors found a difference between the treatment groups and the control group and a greater treatment effect with the combination group.19 Between-study differences could be attributed to Huang et al enrolling Asian patients and Nucci et al enrolling European patients.
Although the literature is still emerging, most studies suggest that 0.01% atropine in combination with optical interventions provides an additional treatment benefit, though this additional reduction in ocular growth may be limited to the first 6 months of treatment. More work is needed to understand whether slightly higher concentrations of low-dose atropine (0.05%/0.025 vs 0.01%) will provide a better treatment effect when combined with optical interventions and to understand whether subsets of patients may have better results.