Higher Dose of Atropine Eye Drops Slowed Myopia Progression in Kids

Children with myopia using 0.05% atropine eye drops had less myopia progression and/or less axial elongation compared with those using placebo or 0.01% atropine, though they had higher rates of adverse events, a secondary analysis of the randomized MOSAIC trial showed.

Compared with the group who switched from placebo to 0.05% atropine drops at year 3, the group who used 0.01% atropine drops then switched to placebo or tapering of placebo had more spherical equivalent progression (adjusted difference -0.13 diopters [D], 95% CI -0.22 to -0.04, P=0.01) and axial elongation (adjusted difference 0.06 mm, 95% CI 0.02-0.09, P=0.008), and the group taking 0.01% atropine then tapering this dose had more axial elongation (adjusted difference 0.04 mm, 95% CI 0.009-0.07, P=0.04), reported James Loughman, PhD, of the Centre for Eye Research Ireland in Dublin, and colleagues.

No patients discontinued treatment in the 0.05% atropine group due to adverse events, although they were more common in this group, with 15% of patients experiencing blurred near vision and 8% experiencing photophobia during year 3, compared with 3% and 0%, respectively, in the group taking 0.01% atropine then tapering, and no reports in both placebo groups, they noted in JAMA Ophthalmology.

“The findings support the use of 0.05% atropine as an effective and safe option for myopia control, particularly in children or populations less responsive to 0.01%,” Loughman told MedPage Today, noting that atropine — a muscarinic receptor antagonist — “is a well-established treatment for slowing myopia progression.” However, the ideal dose has been unclear.

“Most studies on atropine have been carried out in Asian populations, which consistently show strong efficacy of low-dose atropine, particularly 0.05%, in controlling myopia progression​​,” he explained. “Results in European populations are less consistent, partly due to genetic, environmental, and lifestyle differences, and potentially due to the lower concentration used.”

The initial MOSAIC trial was a 2-year trial that examined daily 0.01% atropine eye drops in European kids with myopia, showing that they slowed axial elongation, but the “refractive effect was less pronounced compared to Asian cohorts,” Loughman said.

The current trial, MOSAIC2, “aimed to evaluate the safety and efficacy of increasing the atropine concentration to 0.05% in this population and to assess treatment discontinuation effects and tapering protocols for 0.01% atropine,” he added. “No clinical trial has previously examined the effect of 0.05% atropine in a European population.”

The findings were surprising because myopia progression slowed significantly in the 0.05% group “despite an effective treatment delay of 2 years compared to the group initially treated with 0.01% atropine,” Loughman noted. “Typically, treatment efficacy is greater in younger children, and with earlier intervention, so achieving such results after a significantly delayed start is an encouraging sign.”

As for the impact of the results, Loughman said “the 0.13 D reduction in myopia progression and 0.06 mm reduction in eye growth are both small in clinical terms.”

However, he added, “it must be recognized that these effects were observed in children over a short 1-year period and following a treatment delay of at least 2 years since the trial commenced. Additionally, all of these children were older and more myopic than is ideal at the time of treatment initiation. These all suggest that the observed effect could translate to much more significant treatment benefits in younger, less myopic children, potentially leading to reduced long-term risks of high myopia and associated complications, such as retinal detachment or myopic maculopathy​​.”

“Even small reductions in axial elongation can have significant public health benefits by decreasing the prevalence of sight-threatening conditions,” he noted.

Loughman said the side effects were “mild and manageable, even in fair-skinned, blue-eyed children.”

“Notably, these effects did not lead to increased treatment discontinuation, suggesting they were tolerable,” he pointed out. “Varifocal and photochromic lenses were offered to children experiencing symptoms, but very few required additional management.”

Moving forward, clinicians “should consider patient-specific factors such as age, baseline myopia, and risk tolerance when choosing atropine concentrations,” Loughman said. “Regular monitoring for axial elongation and myopia progression is key.”

Douglas Fredrick, MD, of the University of California San Francisco and Kaiser Permanente in South San Francisco, told MedPage Today that “this study greatly adds to our knowledge on the topic of myopia prevention, and it will guide therapeutic decisions. The fact that the 0.05% treatment group still had efficacy despite a 2-year lag in initiation of treatment is an encouraging finding suggesting that earlier initiation of treatment may have an even more profound effect.”

He agreed that the 1-year improvement is small, but “it is important to understand that treatment with low-dose atropine will become significant not after 1 or 2 years but after many years of treatment.”

“The hope is that after 5 or 10 years of treatment, thousands of young adults will be -4.00 myopes instead of -6.00 or greater myopes, and 20 or 30 years later, hundreds of patients will be spared retinal detachment or macular degeneration,” he added.

Vittorio Mena Jr., OD, an optometrist in Clifton, New Jersey, told MedPage Today that it’s best to start with 0.05% atropine doses. “If a child has an adverse event, they can either use the drops every other day or switch to a lower dosage such as 0.025% or 0.01%.”

The drug is not approved for myopia in the U.S., he said, and insurance doesn’t cover it. “A monthly supply of 0.05% in the U.S. can range anywhere from $50-$95 a bottle, but they are easily available when prescribed by an eye care professional and can even be shipped to the patient’s home.”

Study participants in MOSAIC2, which took place at a single center in Ireland, included 199 of 250 children in the initial study. Mean age was 13.9, 60.8% were girls, and 83.4% were white. All had spherical equivalent ≤ -0.50 D, no myopia treatment, and no significant comorbidities.

In one group, patients were switched from placebo taken during the initial 2 years to 0.05% atropine drops for 1 year, and in the other group, patients were switched from 0.01% atropine drops taken during the initial 2 years to placebo, tapering of placebo, or tapering of 0.01% atropine drops for 1 year.

Study limitations included the smaller sample sizes in year 3 and complications due to the COVID-19 pandemic.