March 2014




ATOM trials find atropine eye drops reduce myopia progression

by Erin L. Boyle EyeWorld Senior Staff Writer

Donald T.H. Tan

Donald T.H. Tan, FRCOphth, speaking at the 2013 ESCRS Congress in Amsterdam Source: Erin L. Boyle

Two studies approach the treatment of myopia in children in one Asian country

The Atropine in the Treatment of Myopia (ATOM) study found that atropine eye drops reduced myopia progression and axial elongation in children in a dose-related way. The study also found a rebound phenomenon with higher doses of the eye drop, said Donald T.H. Tan, FRCOphth, head and senior consultant, Singapore National Eye Centre.

"We think that atropine eye drops are safe with no serious adverse or systemic effects, but in the higher doses, the side effects of pupil dilation, loss of accommodation, and near vision limit practical use," he said. In his talk "New strategies for the prevention of myopia," presented at the 2013 European Society of Cataract & Refractive Surgeons (ESCRS) Congress, he outlined traditional methods for reducing myopia progression, including spectacle undercorrection or overcorrection; contact lens use, including soft, rigid, dual focus, and peripheral defocus lenses; and pharmacological methods, including muscarinic antagonists. Dr. Tan said there are more than 180 interventional studies in the literature on the topic, one that is of vital importance around the world, especially in Eastern Asia. The trials were conducted at the Singapore Eye Research Institute. Singapore is the "myopia capital of the world," Dr. Tan said, with approximately 80% of teenagers myopic by 18 years of age and 13% with high myopia.

"This is really very high," he said. "The myopia rates in East Asia are the highest in the world, but this is a global phenomenon that started in the '70s." In the last 14 years of clinical trials, the two ATOM studies have shown that atropine eye drops can reduce myopia progression in a dose-related manner. However, a rebound affect can happen with higher doses. The lower dose of 0.01% atropine "appears to have the best therapeutic index with clinically few, relatively insignificant amounts of pupil dilatation, near vision, and accommodation loss, and yet appears to be fairly similar in efficacy to higher doses," Dr. Tan said.

"That means, overall, 0.01% [atropine eye drops] seem to slow myopic progression by 60% in our Asian population, and without any of the side-effects associated with higher doses," he said.


The ATOM1 was a randomized, double-masked, placebo-controlled clinical trial. It was designed to determine the safety and efficacy of atropine eye drops on myopia progression in children.

ATOM1 was conducted from 1999 to 2004 with 400 children, 6 to 12 years old. One eye was administered 1% atropine once at night and the other eye was untreated. There was a second control group with placebo vehicle eye drop application in one eye. Photochromic glasses were given to all study subjects. The three-year study had two years of treatment and one year of washout observation without medication.

For the first two years, there was a 77% reduction in the mean progression of myopia, Dr. Tan said. No serious adverse effects were found, but cases of allergic conjunctivitis and dermatitis were reported.

The washout year subsequently showed a "quite significant" rebound phenomenon in both refractive and axial length data, Dr. Tan said.

"The atropine eyes rapidly tried to become myopic again, although they didn't quite go back," he said.


ATOM2 was started at the time of the ATOM1 washout period, with three lower doses of atropine0.5%, 0.1%, 0.01%to see if the side effects seen in the first trial could be mitigated. The study had the same amount of children and similar methodology, but slightly older patients and slightly higher myopia. The study was also increased to bilateral treatment over five years, with two years on treatment, one washout year, and restarting on the appropriate concentration for those who continued to progress for another two years.

The first results at two years showed that the efficacy in retarding myopia progression in the three concentrations was "remarkably similar, and not statistically different," he said. A dose-related response at that time existed, but with only a small clinical difference. The main differences were in the side effects, with the two higher concentrations still causing significant pupil dilatation, accommodation loss, and loss of near vision. In contrast, these problems were almost totally obviated with the lowest 0.01% dose.

After the washout year, in which no treatment was prescribed for a year, "everything flipped," showing a dose-related rebound phenomenon inversely related, with the 0.01% demonstrating minimal rebound, while significant rebounds were seen in the higher concentrations.

"At the one-year washout at three years, the 0.01% [cases] had the lowest prevalence of myopia," he said. "By three years, the 0.01% [group] had almost no rebound phenomenon and had the lowest axial elongation." The lowest concentration, 0.01%, was chosen as the appropriate concentration to treat those who had progressed, and after the washout year, this concentration was offered to all children in the study for an additional two years (up to year 5), for those who were still continuing to exhibit myopia progression. "At the end of five years of treatment, the 0.01% [group] had the least myopic progression. This was statistically significant compared to the other two higher doses," he said.

Future In the future, Dr. Tan said a more varied clinical treatment strategy for use of atropine 0.01% would need to be developed. Questions remain about the use of atropine. They include: "Will atropine continue to be effective if it is used for longer periods of time, and how long?" and "What is the optimal age to start and stop atropine?" and "Could there still be undiscovered longer-term effects?"

In addition, the question of whether atropine 0.01% can be brought to the market and into ophthalmic practices is still unanswered, he said. Those questions might be a good foundation for an ATOM3 study.

"We're developing a clinical strategy for Singapore in myopic clinics across several hospitals, and we're working at various clinical algorithms, and perhaps this could be ATOM3," Dr. Tan said.

Editors' note: Dr. Tan has no financial interests related to this article.

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