Childhood treatment to slow myopia progression is critical in preventing high myopia and associated sequelae, including retinal and vitreous detachment, myopic macular degeneration and increased risk of glaucoma and cataract. In the U.S.-based Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study of almost 5,000 children, 16% developed myopia during their school age years.
Management approaches for myopia have had varying success, including bifocal and progressive lenses, contact lenses, and pharmacological agents. Now, researchers at Vanderbilt Eye Institute are participating in two multi-center trials to test low-dose atropine for slowing myopia progression in children.
“The typical course of myopia is that it worsens as a child ages, causing the need for stronger eyeglass lenses,” said Lori Ann Kehler, O.D., division chief of optometry at Vanderbilt Eye Institute. “While various treatments have been proposed, nothing has been very effective in stopping the progression. We hope these trials will result in better treatment options.”
Early Evidence for Atropine
Atropine, an antimuscarinic, is approved by the FDA to treat amblyopia, but at 1 percent solution is not without adverse effects. Kehler says the Atropine for the Treatment of Myopia (ATOM) studies, conducted in Asian populations where the incidence of childhood myopia can be as high as 80 percent, provided early evidence that lower doses of atropine could be effective for controlling myopia progression.
“In the ATOM studies, investigators tested atropine drops of dosages as low as 0.01% for myopia,” said Kehler. “They demonstrated that lower-dose atropine slows myopia progression and causes few to no side effects. It was an unexpected result that gave us a lot of enthusiasm for its success as an option for treatment.”
“In the LAMP trial (Low-concentration Atropine for Myopia Progression), Chinese investigators proposed a stronger dose of 0.05% as the optimal concentration for treatment. While the full results of this study are not yet available, early data open the possibility of using slightly stronger doses of atropine.”
Evaluating Long-term Efficacy
The 2½-year PEDIG trial is testing the efficacy of daily low-dose atropine drops (0.01%) in children aged five to 12 years with myopia. Participants will be randomly assigned to daily atropine drops or placebo (vehicle solution) for 24 months, followed by 6 months off treatment. Two in three children will receive atropine; one in three will receive the placebo drops. Follow-up visits will be required at 6, 12, 18, 24 and 30 months.
The primary outcome will be retardation of myopia progression on the low-dose regimen at the end of the 24-month treatment. Continued efficacy following six months off treatment will be the secondary outcome. “In addition to determining the efficacy of atropine on myopia progression,” Kehler said, “we hope to establish the optimal dose for meaningful treatment and to evaluate the lasting effects of treatment.”
Testing Alternative Delivery Mechanism
Another study, the recently launched CHAPERONE trial, will test two different strengths of MicroPineTM, a proprietary microdose formulation of atropine delivered as an eye mist. The study will evaluate the progression of myopia in children using microdosed atropine 0.01% mist, atropine 0.1% mist, or a placebo ophthalmic solution mist. Each mist of the atropine medication is about one-fourth the volume of an eye drop.
Participants in the CHAPERONE Study will administer study medication daily in each eye for 48 months. Efficacy and safety assessments will be performed at visits scheduled for 1, 6, 12, 18, 24, 30 and 36 months after initiation of medication use. Subjects will be re-randomized at the 36-month visit, then followed at six-month intervals for an additional year.
One Tool in the Toolbox
While the use of atropine for myopia shows promise, it is just one component in the ongoing effort to advance myopia treatment. “This is not a cure for myopia,” Kehler cautioned. “Children are still going to be nearsighted, but the ultimate goal is to provide a therapy to control or slow the progression of the disease.”