Solving the myopia mystery

There are more randomized clinical studies on atropine eye drops for myopia control, but this time did it work in U.S. children?

On July 13, the National Institutes of Health (NIH) reported on the results of a two-year NIH-funded trial, which found that low-dose atropine eye drops (concentration 0.01%) worked no better than a placebo in slowing the progression of myopia in school-age children in the U.S., according to the study published in JAMA Ophthalmology.

As the NIH noted, the findings in the July trial “contradict” historical results in East Asia where nightly use of low-dose atropine eye drops slowed myopia progression. The contradictory results raised more questions than answers about atropine as a treatment for myopia. In February, news broke in JAMA online of another randomized trial from The Chinese University of Hong Kong that suggested nightly doses of atropine may have the potential to delay or prevent the onset of myopia in children. “The difference between 0.05% atropine and placebo was statistically significant,” but 0.01% atropine was not, wrote that study’s authors.

And on June 1, JAMA Ophthalmology published results of another study suggesting low-dose atropine (0.01%) was effective and safe and “may provide a treatment option for childhood myopia progression.” Karla Zadnik, O.D., Ph.D., dean of The Ohio State University College of Optometry, is the lead author. The treatment effect of atropine 0.01% was slightly less than 0.25 D over three years. There was no significant difference in refractive error with atropine 0.02% compared with placebo.

Although effective, stronger concentrations of atropine (0.5% to 1.0%) have more side effects, including light sensitivity and blurry near vision, the NIH says.

“The overall mixed results on low-dose atropine show us we need more research,” reacted Michael Chiang, M.D., director of the National Eye Institute, part of the NIH. “Would a different dose be more effective in a U.S. population? Would combining atropine with other strategies have a synergistic effect? Could we develop other approaches to treatment or prevention based on a better understanding of what causes myopia progression?”

The NIH article expressed some urgency about getting the dosage correct given that by 2050 an estimated 44 million people in the U.S. are expected to have myopia.

“The new study means we need to study atropine more!” says study co-author Katherine Weise, O.D., MBA, University of Alabama at Birmingham School of Optometry. “More optometrists need to be thinking about what we can do to solve the myopia mystery. It may be higher concentrations of atropine. It may be special glasses or contact lenses. It may be environmental interventions. The more people we can get thinking about myopia, the better. 

“It will take a real convergence of eye research to solve the environmental, genetic, and structural mystery of myopia,” Dr. Weise adds. “Any time we can provide our patients with treatment outcomes from gold standard research, we are helping in so many ways. Parents can be armed with knowledge to make the best decisions for their children.”

Latest study results on children’s myopia

In the study released in July, 187 children ages 5 to 12 years were given either nightly atropine or placebo. The eye drops did not slow myopia progression or axial elongation, write that study’s authors. The trial’s children were from diverse races/ethnicities including white, Black, East Asian, Hispanic or Latino, multiracial and West/South Asian.

“These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in U.S. children,” say the study authors, members of the Pediatric Eye Disease Investigator Group, a collaboration of optometrists and ophthalmologists that conducted the study. Among their findings:

• No significant differences between the groups (atropine vs. placebo) in degree of myopia compared with baseline.
• No significant differences in axial length within the two groups when compared with baseline measurements.

“The latest NIH study from Repka et al. did not find that 0.01% atropine slows myopia progression or eye growth,” says David Berntsen, O.D., Ph.D. Dr. Berntsen is the clinical sciences department chair at the University of Houston College of Optometry. He and Jeffrey Walline, O.D., Ph.D., associate dean for research at The Ohio State University, co-authored an editorial, “Delaying the Onset of Nearsightedness,” that accompanied the study (in China) released in February.

Continues Dr. Berntsen: “This finding adds to the growing number of studies finding variable results with 0.01% atropine. Results in primarily Asian children in Asia using 0.01% atropine show a little more consistency (though not always) in slowing myopia progression and eye growth than in primarily Caucasian samples. Speculation about why this may be true includes improved compliance in Asian children, longer drug activity in children with dark irides, and faster myopia progression among children in Asia.”

Weise notes that in the NIH study there was a 94% retention rate at 2.5 years and more than 90% of the children documented “excellent” (76% to 100% of the time compliance).

Optometry has a part to play in myopia control

As they did earlier, Drs. Berntsen and Walline continue to support more research to solve the contradiction, so effective and safe treatment options can be provided to patients.

“Research continues to monitor myopia progression and eye growth with a variety of low concentrations, generally ranging from 0.01% to 0.05% atropine, and should include a direct comparison of children of various races to determine whether one group is more likely to benefit from myopia control than another,” Dr. Walline says.

Yet myopia has proven a tough nut to crack.

“We aren't exactly sure how myopia affects the growth of the eye,” Dr. Weise says. “It was initially thought to be related to accommodation. We don't think that's true anymore. Then, we learned that atropine made it all the way back to the retina, where it might have an effect. We think maybe it also affects the choroid. So, if we don't really know how it works, it's hard to determine treatment regimens that work. There is also variability in how the atropine drops are manufactured. There are also more side effects and more rebound effects in concentrations that are more effective. Then, adding cost for the families and even getting a child to use a drop nightly for a treatment that provides no immediate visual benefit (such as special contact lenses or special glasses, e.g.), atropine becomes a spider web of question marks.

“Optometrists should dig into the myopia literature,” she says. “Optometry has been studying myopia for decades. But now, we are welcoming more pediatricians, researchers and eye care providers to the conversation. The more questions we get asked, the more answers we'll seek. With the right collaborations and care, optometry can play a major role in our myopia understandings.” 

Drs. Walline and Berntsen note that no one treatment may work for all patients. Doctors of optometry might consider low-dose atropine in combination with other treatment options. Perhaps a secondary treatment?

Atropine can be a better fit than contact lenses for patients with high astigmatism or children not ready for contacts, says Dr. Walline, adding, “We also do not currently have access to promising novel spectacle designs for myopia control in the U.S.

“In addition to considering atropine as a primary myopia control treatment, optometrists should consider low-concentration atropine as a secondary treatment to be used when the parent or doctor don’t feel that an optical treatment provides enough myopia control,” he says. “Most studies indicate better myopia control for children who are provided both an optical treatment (glasses or contact lenses) and atropine when compared to optical treatment alone. Therefore, atropine may be considered as an adjunctive treatment when myopia seems to progress too quickly when already on an optical myopia control treatment regimen.”

Like Dr. Weise, they also sound a cautionary note about compounding or the manufacturing of atropine.

Recent studies have raised concerns about the lack of standardization of compounded low concentrations of atropine for myopia control. One study looked at compounding pharmacies and concluded that “an inconsistent and wide variety of formulation and labeling practices exist for compounding 0.01% atropine prescribed to slow pediatric myopia progression.”

“At this time, low-concentration atropine must be formulated by a compounding pharmacy,” Dr. Berntsen says. “Unfortunately, compounding pharmacies don’t use a standard protocol to formulate low-concentration atropine, which may affect the consistency, stability, effectivity and comfort of the drops. A company that receives Food and Drug Administration approval for myopia control with low-concentration atropine will likely provide us with a consistent and stable formulation that we can trust to prescribe to our patients.”

Children’s vision resources from the AOA

View AOA resources for children’s vision.

Read the Clinical Report: Myopia Management produced by the AOA’s Evidence-based Optometry Committee.