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Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years

2023; American Medical Association; Volume: 141; Issue: 10 Linguagem: Inglês

10.1001/jamaophthalmol.2023.2097

2168-6173

Karla Zadnik, Erica Schulman, Ian Flitcroft, Jennifer Swingle Fogt, Louis C. Blumenfeld, Tung M. Fong, Eric J. Lang, Houman D. Hemmati, Simon Chandler, Carol Aune, Isabel Ayet, Darren Bell, Marie I. Bodack, Jeffrey Colburn, Sue Cotter, Annegret Dahlmann‐Noor, Stephen R. Glaser, James Hoekel, Daniel Iacono, Erin C. Jenewein, Caroline C. W. Klaver, Stephen Lichtenstein, Chunming Liu, James Loughman, Zoltán Zsolt Nagy, Matthew Paul, Melanie A. Schmitt, David I. Silbert, Sarah Singh, Daniel J. Twelker, Fuensanta A. Vera‐Díaz, Dorothy Wang, Colin E. Willoughby, Nikki Buck, Michelle Bailey, Wayne Schuck, Leo Ballering, Robert J. Spiegel, Tuyen Ong, M.aC. Figueras Nadal, Michelle Novello, John Kappelhof, Nestor R. Gonzalez, Gregory Luke Larkin, Kenneth A. Somberg, Ann Killian, J. V. Castellana, Stephen Crockett,

Retinal Diseases and Treatments

The 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.To 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.This 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.Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months.The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported.A 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, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P = .37) or slow mean SER progression (least squares mean [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); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P = .03), slowed mean SER progression (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). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine.This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine 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.ClinicalTrials.gov Identifier: NCT03350620.