Re: Chia et al.: Five-year clinical trial on atropine for the treatment of myopia 2: myopia control with atropine 0.01% eyedrops (Ophthalmology 2016;123:391-9)

We read with interest the article by Chia et al1Chia A. Lu Q.S. Tan D. Five-year clinical trial on atropine for the treatment of myopia 2: myopia control with atropine 0.01% eyedrops.Ophthalmology. 2016; 123: 319-399Abstract Full Text Full Text PDF Scopus (304) Google Scholar on low-dose atropine treatment for controlling myopia progression in 400 children (the majority of whom were of ethnic Chinese origin). In the initial phase of the Atropine in the Treatment of Myopia (ATOM) 2 study, they were randomized to receive atropine 0.01%, 0.1%, and 0.5% once nightly in both eyes for 2 years. We performed calculations taking into account all children reported in Table 3 that received atropine 0.01% (n = 70) compared with those who received atropine 0.5% (n = 136) and differences in progression during the first year reached statistical significance (P = 0.0013). Similarly, we compared all children who received atropine 0.1% (n = 139) versus those who received atropine 0.5% (n = 136) and the difference in the progression during the first year was also statistically significant (P = 0.0102). As expected, this trend continued when we grouped together and compared all children who received atropine 0.01% or 0.1% (n = 209) versus those who received atropine 0.5% (n = 136; P = 0.0011). In addition, we did not find a difference among all children who received atropine 0.01% (n = 70) and atropine 0.1% (n = 139; P = 0.3538). However, in terms of the progression during the second year, when comparing all children who received atropine 0.01% (n = 70) versus those who received atropine 0.5% (n = 136) the difference was not significant (P = 0.1760), nor was it either in the second year among those who received atropine 0.1% (n = 139) versus those who received 0.5% (n = 136; P = 0.1482). Clearly, during the first year of treatment the effect of more concentrated atropine 0.5% was significantly greater than that of the lesser concentrations and such differences were minimized during the second year of treatment. Therefore, we believe that a promising approach would be to start the first year of treatment in myopic children with this type of more concentrated atropine (0.5%), and beginning the lower concentration (0.01%) the second year. To avoid the rebound effect, therapy with 0.01% atropine should be maintained continuously for ≥3 or 4 years, when children reach the age at which myopia tends to stabilize, approximately between 16 and 17 years of age.2COMET GroupMyopia stabilization and associated factors among participants in the Correction of Myopia Evaluation Trial (COMET).Invest Ophthalmol Vis Sci. 2013; 54: 7871-7884Crossref PubMed Scopus (89) Google Scholar Prescribing higher doses of atropine (i.e., 0.5% nightly) undoubtedly will cause more visual symptoms and children will be more likely to require photochromatic progressive glasses (around 70% according to ATOM 2). We believe that, despite the additional need for these glasses, it is worth the initial use of the highest concentration of atropine, for the benefit to be gained in the lower progression of myopia, which can lead to a lower final refractive error after stabilization. Additionally, the effect on accommodation tends to decrease during the first months of use.3Chia A. Chua W.H. Cheung Y.B. 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: 347-354Abstract Full Text Full Text PDF PubMed Scopus (414) Google Scholar We have had some experience with a different approach: the use of atropine 1% once a week along with multifocal photochromic glasses, however, some patients complain of symptoms (mainly photophobia) 24 to 48 hours following the application.4Galvis V. Tello A. Rodriguez C.J. Rey J.J. Atropine dose to treat myopia.Ophthalmology. 2012; 119: 1718-1719Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Therefore, lower concentration dose is undoubtedly a very appealing option. Another issue is that, as the authors highlighted, the subgroup of children who did not require retreatment had lower rates of myopia progression not only during the first 24 months (phase 1) and in the washout phase (phase 2) compared with those who required retreatment, but also during phase 3, even though they did not receive atropine during the last 2 years of the study. Why did these children respond so well to the initial treatment? Certainly, as the authors pointed out, questions remain on which children would best benefit from topical atropine (e.g., in terms of age, magnitude of myopia, axial length, rate of progression, and family history), when treatment should be started and discontinued, and for how long it should be used. Finally, we wonder why for >7 years there have been no new studies on the safety and efficacy of the relatively selective M(1)-antagonist, pirenzepine, in slowing the progression of myopia in humans.5Tan D.T. Lam D.S. Chua W.H. et al.Asian Pirenzepine Study GroupOne-year multicenter, double-masked, placebo-controlled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia.Ophthalmology. 2005; 112: 84-91Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar Because pirenzepine is less likely than atropine to cause mydriasis and cycloplegia, it seemed to be a very promising alternative. Five-Year Clinical Trial on Atropine for the Treatment of Myopia 2: Myopia Control with Atropine 0.01% EyedropsOphthalmologyVol. 123Issue 2PreviewTo compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years. Full-Text PDF ReplyOphthalmologyVol. 123Issue 6PreviewI read with interest the correspondence by Galvis et al, regarding our article1 and thank the authors for sharing their data and interpretations. Full-Text PDF