麻豆传媒

Treating U.S. children with an investigational low-dose (0.01%) formulation of atropine eye drops didn't delay worsening of nearsightedness, a randomized clinical trial found.

Over 24 months, kids using the once-nightly drops and those using placebo saw mean changes in spherical equivalent refractive error (SER) of -0.82 D (95% CI -0.96 to -0.68 D) and -0.80 D (95% CI -0.98 to -0.62 D), respectively, reported Michael Repka, MD, MBA, of the Jaeb Center for Health Research in Tampa, Florida, and colleagues.

There still wasn't a significant difference in average SER change between the medicated drops and placebo by month 30, which included the on-treatment period plus 6-months post-treatment (adjusted difference -0.04 D, 95% CI -0.25 to +0.17 D).

As a result, the findings "do not support the nightly use of low-dose atropine, 0.01%, eye drops to slow myopia progression in U.S. children," they wrote in .

At both the 24-month and 30-month marks, there were no significant differences between the atropine and placebo drops in regards to axial length changes (adjusted change of 0.44 mm at 24 mo. and 0.51 mm at 30 mo. for atropine versus 0.45 mm and 0.49 mm for placebo, respectively).

Of note, the findings were consistent across all study sub-groups when stratified by age, sex, race and ethnicity, eye color, and baseline SER.

"Physicians prescribing myopia control should not overstate the value of the treatment, as well as consider other concentrations," Repka told 麻豆传媒 in an email. "The problem with changing drop strength is there is no adequately powered [data] here in the U.S."

Atropine eye drops at higher strengths (0.5%-1.0%) have been used for decades to slow myopia progression, the researchers explained. While effective, these higher strengths have been associated with side effects including photophobia and blurred near vision.

These results contrast with those of several previous trials, which have shown that different doses of atropine eye drops in kids -- including at 0.01% -- may be effective at slowing myopia progression. Even the voiced its support for the use of low-dose atropine. But Repka said that when it comes to explaining the different results of this trial -- the first to test the low-dose atropine drops in children in the U.S. -- "the most likely reason is chance."

"In addition, it is important to recognize that even the published with a treatment benefit has been less effective than we all hoped for from this treatment approach," he added. "Also, there may be impacts on the outcome from differing follow up rates in the studies that cannot be determined."

Considering the different results seen in prior studies, Jeffrey Walline, OD, PhD, of The Ohio State University in Columbus, Ohio, and David Berntsen, OD, PhD, of the University of Houston College of Optometry in Texas, pointed out that "low-concentration atropine eye drops may work better for Asian children than white children."

"Four studies conducted in Asia reported significant slowing of myopia progression, although only half of them reported significant slowing of eye growth," Walline and Berntsen wrote in an . "None of the 3 studies conducted on primarily white children reported significant slowing of myopia progression, and only one of them reported significant slowing of eye growth."

"The difference between findings in Asian and white children may include differences in pigmentation of the iris, length of study, age of children studied, and rate of myopia progression," they added. "Atropine binds to melanin, so darker irises may result in slower release and longer active time for the drug, which may yield higher effectivity in Asian children, who generally have darker irises."

They said that the trial results "indicate that stronger concentrations of atropine should be considered for first-line treatment of myopia progression, especially when considering eye growth outcomes in white children."

This condition is typically first managed with glasses or contact lenses, and there are currently no FDA-approved pharmaceuticals specifically for pediatric myopia. In 2019, the MiSight contact lens was the indicated to slow the progression of myopia in kids 8 to 12. Last month, developer Vyluma, which provided the atropine drops for this trial and the CHAMP study, its new drug application for investigational 0.01% atropine eye drops for pediatric myopia was accepted by the FDA for review.

The double-blind study included a total of 187 children (54% female), ranging in age from 5.1 to 12.9 years (mean 10.1). The participants were 46% white, 18% Black, 11% East Asian, 16% Hispanic or Latino, 6% multiracial, and 3% West or South Asian. Two-thirds of participants had brown eyes.

All participants had myopia between -1.00 and -6.00 D SER (mean baseline -2.83 D SER and 24.4 mm axial length), astigmatism of 1.50 D and below, and anisometropia less than 1.00 D and below. The children were assigned 2:1 to one drop per eye each night of either 0.01% atropine or placebo.

Treatment adherence and participant retention were high in both study groups; and the 0.01% atropine eye drops were well tolerated, according to patient questionnaires. The study groups reported similar rates of adverse ocular events, with a majority being mild in severity. Eye irritation was most common, affecting 72% of participants on atropine and 82% on placebo, followed by photophobia (26% vs 27%) and blurred vision (14% vs 16%).

"Future study of myopia control needs to evaluate stronger concentrations of atropine, consider alternative agents, as well as expand the work done with contact lenses and novel spectacle lenses, along with combination therapy," Repka suggested.

One limitation was that there was no objective measure of eye drop use. Also, the onset of the COVID-19 pandemic limited the amount of refraction examination some participants received.

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