Atropine 0.02% is the highest concentration that does not produce significant clinical symptoms from accommodation paresis or pupillary dilation. This would be an appropriate starting point in evaluating a low dosage of atropine to slow myopic progression.

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ImportanceThe global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression.ObjectiveTo assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression.Design, Setting, and ParticipantsThis was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with −0.50 diopter (D) to −6.00 D spherical equivalent refractive error (SER) and no worse than −1.50 D astigmatism.InterventionsOnce-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months.Main Outcomes and MeasuresThe primary outcome was the proportion of participants’ eyes responding to therapy (<0.50 D myopia progression at 3 years). Secondary efficacy outcomes included mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6 to 10 years of age at baseline). Safety measurements for treated participants (3 to 16 years of age) were reported.ResultsA total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (odds ratio [OR], 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (least squares mean [LSM] difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P < .001), and slowed axial elongation (LSM difference, −0.13 mm; 95% CI, −0.19 mm to −0.07 mm; P < .001). At month 36, compared with placebo, low-dose atropine, 0.02%, also showed benefit but did not significantly increase the responder proportion (OR, 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (LSM difference, 0.10 D; 95% CI, −0.02 D to 0.22 D; P = .10) but did slow mean axial elongation (LSM difference, −0.08 mm; 95% CI, −0.13 mm to −0.02 mm; P = .005). There were no serious ocular adverse events and few serious nonocular events; none were judged as associated with atropine.Conclusions and relevanceResults of this randomized clinical trial suggest efficacy for low-dose atropine, 0.01%, across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression.Trial RegistrationClinicalTrials.gov Identifier: NCT03350620

To identify ways in which the safety of childbirth might be increased, we investigated the causes of death among the 886 women who died during pregnancy or within 90 days post partum ("maternal deaths") in Massachusetts from 1954 through 1985. The maternal mortality rate declined from 50 per 100,000 live births in the early 1950s to the current rate of 10 per 100,000 live births. Between one third and one half of the maternal deaths were considered to have been preventable. The leading causes of maternal death from 1954 through 1957 were infection, cardiac disease, pregnancy-induced hypertension, and hemorrhage. In contrast, from 1982 through 1985 the leading causes of death were trauma (suicide, homicide, and motor vehicle accidents) and pulmonary embolus. We observed a rapid increase in the frequency of death among women who received little or no antenatal care. From 1980 through 1984 the maternal mortality rate for white women was 9.6 per 100,000 live births, whereas for nonwhites it was 35 per 100,000 live births (relative risk, 2.9; 95 percent confidence limits, 2.5 and 3.2). Fifty percent of the nonwhite women who died during pregnancy or within 90 days post partum received little or no antenatal care, in contrast to only 15 percent of the white women. These data show that the leading causes of maternal death have changed markedly in Massachusetts during the past 30 years. Although the overall maternal mortality rate has declined sharply, further improvement may occur with better antenatal care and specific efforts to prevent trauma and pulmonary embolus.

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