To investigate variables associated with myopic progression despite treatment in the Atropine in the Treatment of Myopia Study.
Retrospective cohort study.
Two hundred of 400 children were randomized to receive atropine 1% in 1 eye only in this institutional study. Children were followed up with cycloplegic autorefraction every 4 months over 2 years. Children whose myopia progressed by more than 0.5 diopter (D) in the atropine-treated eye at 1 year were classified as being progressors.
Among the 182 children still in the study at 1 year, 22 (12.1%) were classified as progressors. Univariate analysis suggested these children tended to be younger (8.5 ± 1.4 years vs 9.3 ± 1.5 years; P = .023), to have higher myopic spherical equivalent (SE) at baseline (−3.6 ± 1.3 D vs −2.8 ± 1.4 D; P = .015), and to have 2 myopic parents (77.3% vs 48.1%; P = .012). In nonprogressors, the myopia progression at 1 year was less in the atropine-treated eyes compared with the untreated fellow eye (+0.16 ± 0.37 D vs −0.73 ± 0.48 D; P < .001), but in progressors, progression was more similar between eyes (−0.92 ± 0.31 D vs −1.06 ± 0.44 D; P = .363). Regression analysis showed that the risk of being a progressor was 40% lower with each year of increased age, 43% lower for every 1.0 D less in myopia at baseline, and 59% lower for every 1.0 D less in myopic change in the untreated eyes over the first year.
Doctors and parents need to be aware that there is a small group of children (younger, with higher myopia, and greater tendency of myopic progression) who may still progress while receiving atropine treatment.
The increasing prevalence of myopia worldwide, and particularly in East Asia, has spurred the research and clinical interest in the control of myopic progression. The impetus included the wish to decrease the myopic burden to individuals and society and also to reduce the risk of potentially blinding complications associated with high myopia. Atropine has been shown to be quite effective in slowing myopia progression in many studies. In the Atropine for the Treatment of Childhood Myopia (ATOM) 1 study, topical atropine 1% therapy was shown to slow myopic progression by 80% at 2 years compared with control eyes (−0.28 ± 0.92 diopters [D] vs −1.20 ± 0.68 D; P ≤ .001). Similar findings have been described in other studies. However, in previous studies, as well as clinically, there are some children who showed progressive myopia despite treatment with atropine. The aim of this study was to investigate the risk factors in children who recorded myopia progression despite treatment with atropine 1% in the ATOM 1 study.
The study protocol was in accordance with the principles of the Declaration of Helsinki and was approved by the Singapore Eye Research Institute Review Board. Written informed consent was given by parents or legal guardians of the children before enrolment. This was a retrospective cohort study based on the data from the ATOM 1 study. The ATOM 1 study was a prospective, randomized, double-masked, placebo-controlled trial of 400 children between 6 and 12 years of age with low to moderate myopia.
Participants were randomized into 2 groups: an atropine-treatment group and a placebo-treatment group. Only data from children in the atropine group were used for analysis in this study. In this group, children received atropine 1% in 1 randomly assigned eye and vehicle agent (0.5% hydroxypropyl methylcellulose and 1:10 000 benzalkonium chloride) in the other eye. Children were reviewed at a pretreatment visit, then 2 weeks after treatment was started (baseline), and then every 4 months for 2 years. Cycloplegic autorefraction and axial length were measured at each visit.
Cycloplegic autorefraction was performed by investigators who were trained in study protocols and was performed to assess refractive errors at baseline and then every 4 months in the first year of the study. The cycloplegic regimen used included 1 drop of proparacaine hydrochloride (Alcaine; Alcon-Couvreur, Puurs, Belgium) followed by 3 drops of 1% cyclopentolate hydrochloride (Cyclogyl; Alcon-Couvreur) timed 5 minutes apart. Cycloplegic autorefraction measurements were obtained 30 minutes after the last drop using a Canon RK5 autorefractor-autokeratometer (Canon, Inc, Ltd, Tochigiken, Japan); 5 readings with a maximum difference of 0.25 D were recorded and averaged. Spherical equivalent was calculated as sphere plus half cylinder power. Axial length measures were assessed by A-scan ultrasonography with Nidek US-800 EchoScan (Nidek, Co, Ltd, Tokyo, Japan): 6 readings were recorded and averaged (with standard deviation of 0.12 mm).
Parents also completed a questionnaire at baseline visit that contained questions on patients’ social history such as housing type, number of hours spent on homework, type of homework, outdoor activities and hobbies. Parental myopia data also were collected, but this was based on parent self-report.
Children with myopia progression of more than 0.50 D at 1 year in the atropine-treated eye were classified as being progressors because this value was clinically significant. The progressors and nonprogressors were compared with regard to baseline characteristics (such as age, gender, and spherical equivalent [SE]), change in SE at 1 year from baseline, as well as the socioeconomic and myopia status of their parents. Potential risk factors, that is, those with a P value of less than .10 in the comparison between progressors and nonprogressors, were included in the log-binomial model to assess their association with the risk of progressive myopia.
One hundred eighty-two (91.0%) of the initial 200 participants in the atropine-treated group were still in the study at 1 year. Twenty-two children (12.1%) had myopic progression of more than 0.5 D in the first year and were classified as progressors. In these children, there was a mean myopic progression of −0.92 ± 0.31 D in the atropine-treated eye compared with −1.06 ± 0.44 D in the untreated eye ( P = .363; Figure 1 ). In contrast, nonprogressors had a mean hyperopic shift of +0.16 ± 0.37 D at 1 year in the atropine-treated eye, compared with −0.73 ± 0.48 D in the untreated eye ( P < .001). Over 2 years, there was a mean myopic progression of −1.25 ± 0.68 D in the treated eyes of the progressors versus −0.15 ± 0.84 D in those of the nonprogressors.
Only 2% (n = 1) of children who progressed by less than 0.50 D in untreated eye were progressors, compared with 9% (8), 24% (8) and 31% (5) in those who progressed 0.50 to 1.00 D, 1.01 to 1.50 D, and more than 1.50 D in the untreated eyes, respectively ( Figure 2 ). Compared with nonprogressors, progressors were younger (8.5 ± 1.4 years vs 9.3 ± 1.5 years; P = .023; Table 1 ), started to wear spectacles at a younger age (6.7 ± 1.2 years vs 7.3 ± 1.5 years; P = .066), and were more myopic at baseline (−3.6 ± 1.3 D vs −2.8 ± 1.4 D; P = .015). The mean change of SE in the first year was greater in the progressor group than in the nonprogressor group in both the treated eyes (−0.92 ± 0.31 D vs +0.16 ± 0.37 D; P < .001) and the untreated eyes (−1.06 ± 0.44 D vs −0.73 ± 0.48 D; P = .003). The 2 groups of children were comparable with regard to age at first spectacle prescription and in the distribution of gender and ethnicity ( Table 1 ). No significant differences were found between the progressors and the nonprogressors regarding time spent on outdoor activities (6.1 ± 4.1 hours per week vs 5.9 ± 4.9 hours per week; P = .877) and various near-work activities, such as time spent reading or writing, watching TV, or playing video games.
|Nonprogressors (n = 160)||Progressors (n = 22)||P Value|
|Change in SE (D) over 1 y, mean (SD) a|
|Atropine-treated eye||0.16 (0.37)||–0.92 (0.31)||<.001|
|Fellow untreated eye||–0.73 (0.48)||–1.06 (0.44)||.003|
|Change in SE (D) over 2 y, mean (SD) b|
|Atropine-treated eye||–0.15 (0.84)||–1.25 (0.68)||<.001|
|Fellow untreated eye||–1.17 (0.66)||–1.53 (0.65)||.049|
|Male gender, no. (%)||89 (55.6)||13 (59.1)||.822|
|Chinese ethnicity, no. (%)||155 (96.9)||20 (90.9)||.201|
|Age at baseline (y), mean (SD)||9.3 (1.5)||8.5 (1.4)||.023|
|Age spectacle wear began (y), mean (SD)||7.3 (1.5)||6.7 (1.2)||.066|
|SE at baseline (D), mean (SD)||–2.8 (1.4)||–3.6 (1.3)||.015|
|First spectacle prescription (D), mean (SD)||1.46 (0.83)||1.50 (0.57)||.881|
|Parental myopia status, no. (%)|
|Mother with myopia||118 (73.8)||20 (90.9)||.111|
|Father with myopia||104 (65.0)||19 (86.4)||.055|
|Both parents with myopia||77 (48.1)||17 (77.3)||.012|
|Mother’s education level, no. (%)|
|Primary/secondary education||75 (46.7)||9 (40.9)||.234|
|Preuniversity or diploma||40 (25.0)||7 (31.8)|
|Tertiary||44 (27.5)||6 (27.3)|
|Father’s education level, no. (%)|
|Primary/secondary education||52 (32.5)||6 (27.3)||.978|
|Preuniversity or diploma||38 (23.8)||6 (27.3)|
|Tertiary||67 (41.9)||10 (45.5)|
|Housing type, no. (%)|
|3- or 4-room HDB flat||28 (17.5)||2 (9.1)||.657|
|5-room flat/HDB maisonette||63 (39.4)||9 (40.9)|
|Private housing||67 (41.9)||11 (50.0)|