Atropine explored as treatment for childhood myopia

Take-home message: Atropine slowed childhood myopia progression by 50% to 60% in two large trials in Asia.

Reviewed by Donald Tan, MBBS, FRCSE

Singapore-Atropine appears to be an effective treatment for childhood myopia, said Donald Tan, MBBS, FRCSE.

Although myopia in children is a global problem, it is especially prevalent in Asia.

For example, in Singapore, 80% of 18 year olds have myopia, with 13% of them having high myopia, explained Dr. Tan, Arthur Lim Professor in Ophthalmology, ophthalmology and visual sciences academic clinical program, Duke-NUS Graduate Medical School, Singapore National Eye Centre, and Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Previous randomized controlled trials that tried to halt myopia progression in children did not find much effect from rigid gas-permeable lenses or progressive addition spectacles, he noted.

However, research at the Singapore Eye Centre has focused on and found success with atropine. Atropine is a nonspecific muscarinic acetylcholine receptor antagonist that is the most effective treatment to inhibit myopia progression to date, Dr. Tan said.

Since the 1970s, atropine 1% eye drops have been used for pupil dilation in inflammatory conditions, accommodative loss in amblyopia therapy, and for myopia control in Asia.

Despite its effectiveness, it is still not completely clear how or why atropine works, Dr. Tan said.

A previous study from Valley Forge Pharmaceuticals tested an atropine gel in children in the United States, but the study was abandoned after the company was acquired by Novartis, Dr. Tan noted. Pediatric trials in the United States often require long-term study, he said.

The ATOM Trials

The ATOM Trials

The Atropine for the Treatment of Myopia (ATOM) trials in Singapore have found effective results with atropine, Dr. Tan said.^1,2

The first ATOM trial began in 1999 and included 400 children from six to 12 years old with myopia ranging from –1 to –6 D. For 2 years, the children received 1% atropine at night in one eye, while the second eye served as a control. A second group of patients received vehicle eye drops in one eye and control drops in the other eye.

“There was a 77% reduction in the mean progression of myopia, with a strong correlation with axial length,” Dr. Tan said.

There were no serious adverse effects.

One surprise was the rebound effect in year 3.

“The moment we stopped treatment-bang-we could see a sharp descent,” Dr. Tan said. “That was a bit disappointing.”

ATOM2 study

That led to the development of the ATOM2 trial. ATOM2 was a double-masked controlled trial over 5.5 years. There were 400 children between six and 12 years old who were randomly assigned to receive 0.5%, 0.1%, or 0.01% atropine as bilateral treatment for 2 years. Year 3 was a washout year; treatment commenced if necessary in years 4 and 5.

The study found that the dosing effects were similar among all potencies, suggesting that lower concentrations could be used. Side effects included allergic conjunctivitis (4%), loss of more than one line of best-corrected visual acuity (13%, but it recovered on the cessation of drops), and glare (1%). There was no change in IOP and no cataract formation. Researchers found the treatment had no effect on retinal function.

Effective at lower concentrations

Effective at lower concentrations

“Atropine eye drops reduce myopia progression and axial elongation in children in a dose-related manner, but appear to be still highly effective even at lower concentrations,” Dr. Tan said.

“The drops are safe, and there are no serious adverse effects, and at the lowest concentrations, the clinical side-effects of pupil dilation and loss of accommodation are greatly minimized,” he said.

The ATOM2 study showed that atropine 0.01% has the best therapeutic index and slows myopia progression by 50% to 60%, Dr. Tan noted.

The main clinical advantage of the 0.01% dose lies in the fact the pupil dilation is only about 1 mm, and the minimal loss of accommodation of only about 4 D (which means children still have about 12 D of remaining accommodation) results in no loss in near vision, he added.

There also appears to be no rebound effect upon cessation of 0.01% atropine, unlike the higher doses, he said.

Going forward, researchers must look further at appropriation treatment duration, when to start and stop dosing, and whether any newer alternative anti-muscarinic agents have an improved therapeutic index, Dr. Tan said.

A new ATOM study in Japan, led by Shigeru Kinoshita, MD, of Kyoto Prefectural University, is now under way, Dr. Tan said. There is also a formulation of atropine (Myopine) that is compounded by Dr. Tan’s hospital pharmacy. It has been used in about 1,000 children since 2014.

The basic treatment pattern that clinicians are recommending is use of atropine for 2 years and if there is no myopia progression, then stop and observe for 2 years.

The child can start atropine if myopia progresses again. If there were moderate response over the 2 years, the child would likely continue atropine for a third year. If myopia progresses more, the child may need a higher dose, Dr. Tan said.

The use of treatment may be combined with behavioral modifications, such as encouraging children to play outside more, Dr. Tan said.

References

1. Chua WH, Balakrishnan V, Chan YH, et al. Atropine for the treatment of childhood myopia. Ophthalmology. 2006;113:2285-2291.

2. Chia A, Chua WH, Cheung YB, et al. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2). Ophthalmology. 2012;119:347-354.

Donald Tan, MBBS, FRCSE

E: [email protected]

This article was adapted from Dr. Tan’s delivery of the Richard L. Lindstrom, MD Lecture during the 2015 meeting of the American Society of Cataract and Refractive Surgery meeting. Dr. Tan did not indicate any proprietary interest.