The results of a recent three-year clinical trial suggest that the first drug therapy to slow the progression of near-sightedness in children could be on the horizon, hopefully reducing future risk of retinal detachment, cataracts, macular degeneration and glaucoma.
The study found that a daily drop in each eye of a low dose of atropine, a drug used to dilate pupils, was better than a placebo at limiting eye-glass prescription changes and inhibiting elongation of the eye in near-sighted children aged between six and 10, reports MedicalXPress.
Elongation leads to myopia, or near-sightedness, which starts in children and worsens into the teen years before levelling off in most people. Apart from needing lifelong vision correction, near-sightedness increases the risk for retinal detachment, macular degeneration, cataracts and glaucoma later in life – and most corrective lenses don’t do anything to stop myopia progression.
“The idea of keeping eyeballs smaller isn’t just so people’s glasses are thinner. It would also be so that in their 70s they don’t suffer visual impairment,” said lead study author Karla Zadnik, professor and dean of the College of Optometry at Ohio State University.
“This is exciting work for the myopia research community, of which I’ve been part for 35 years. We’ve talked about treatment and control for decades,” she said, “and it’s exciting to think there could be options in the future for millions of children we know are going to be myopic.”
The results of the CHAMP (Childhood Atropine for Myopia Progression) trial were published in JAMA Ophthalmology.
About one in three adults worldwide is near-sighted, and the global prevalence of myopia is predicted to increase to 50% by 2050.
Animal studies years ago hinted at atropine’s ability to slow the growth of the eye, but the full-strength drug’s interference with near vision and concerns about pupil dilation hindered early considerations of its potential as a human therapy for myopia. More recent research has suggested a low dose of atropine might be the ticket.
This new double-masked, randomised phase three trial assessed the safety and effectiveness of two low-dose solutions, with atropine concentrations of either .01% or .02%, versus placebo. Treatment for each of the 489 children aged six to 10 assessed for the drug’s effectiveness consisted of one daily drop per eye at bedtime, which minimised the disruption of any blurring effects atropine might have on vision.
Researchers were a bit surprised to find that the most significant improvements at all time points compared to placebo resulted from the solution containing .01% of atropine. Though the .02% atropine formulation was also better at slowing progression of myopia than placebo, the results were less consistent.
“The .01% story is clearer and more obvious in terms of significantly slowing both the growth of the eye as well as then resulting in a lower glasses prescription,” Zadnik said.
Including a measure of the eye’s growth was a key component of the study because “the field is actually moving toward axial elongation being as important as or more important than the glasses prescription for the most meaningful outcome”, she said. “If we’re trying to slow eye growth to prevent bad outcomes for people in their 80s, measuring the eye growth directly is really important.”
The drug’s safety was assessed in a larger sample of 573 participants which also included children as young as three and up to 16. Both low-dose formulations were safe and well tolerated. The most common side effects were sensitivity to light, allergic conjunctivitis, eye irritation, dilated pupils and blurred vision, although reports of all of them were few.
The CHAMP trial was the first study of low-dose atropine to include placebo controls for three years and to involve a large, diverse population recruited from 26 clinical sites in North America and five countries in Europe. In a second section of the trial, researchers are evaluating how the eyes respond when the treatment is over.
The experimental drug is made without preservatives, and if federally approved as a therapy, would be distributed in single-use packaging for convenience and to prevent contamination.
Off-label low-dose atropine that can currently be obtained at compounding pharmacies may contain preservatives that can lead to dry eye and corneal irritation, researchers noted.
Study details
Efficacy and safety of 0.01% and 0.02% atropine for the treatment of paediatric myopia progression over three years: a randomised clinical trial
Karla Zadnik, Erica Schulman, Ian Flitcroft, Jennifer Fogt, Louis C. Blumenfeld, Tung M. Fong, Eric Lang, Houman Hemmati, Simon Chandler.
Published in JAMA Ophthalmology on 1 June 2023.
Abstract
Importance
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.
Objective
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.
Design, Setting, and Participants
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 three 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.
Interventions
Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months.
Main Outcomes and Measures
The primary outcome was the proportion of participants’ eyes responding to therapy (<0.50 D myopia progression at three 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.
Results
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 randomised 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 randomisation 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 relevance
Results 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.
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