Deep dive into the CHAMP study - Q&A with Dr Robert Clark

Both my wife and I are highly myopic, with all of the health risks that condition creates, so I have always been very motivated to understand the science behind myopia control. I used atropine 1% in children to treat myopia progression for many years with great success, but reserved that treatment for more severe cases of high myopia because of adverse side effects like blurred near vision and light sensitivity. The 2012 ATOM2 study was a game-changer for me. It demonstrated that much lower concentrations of atropine, 0.01% to 0.5%, retained most of the anti-myopia effect of atropine 1% with minimal side effects. Atropine 0.01%, in particular, had an exceptionally good safety profile and also had no rebound after treatment cessation. It immediately became my treatment of choice for most children with myopia progression. My clinical experience, published in two retrospective studies in 2015 and 2019, mirrored the results of the ATOM2 study, but in a multi-ethnic, mostly non-Asian population. We found that atropine 0.01% was very effective at slowing myopia progression in most children and was exceptionally well tolerated, with minimal light sensitivity and no impaired near vision.

The CHAMP study was designed to provide the data to support government agency approval of low-dose atropine to treat myopia in children. Prior to the CHAMP study, all of the large, prospective clinical trials using low-dose atropine to treat myopia progression were conducted in Asian populations. The CHAMP study was an important contribution to the atropine literature, the largest and longest placebo-controlled clinical trial of low-dose atropine conducted in a majority non-Asian, ethnically diverse population. It was conducted in six countries spanning two continents, North America and Europe. Its results confirmed the excellent safety profile of atropine 0.01%, with no serious ocular or non-ocular adverse events attributed to atropine across hundreds of patient-years of observation, and confirmed its efficacy in slowing myopia progression. The results for all three study measures, change in spherical equivalent refractive error, change in axial length, and percentage of children who would not require even one change in spectacle correction over three years, defined as < 0.50 diopters total myopia progression, were significantly better in the atropine 0.01% group than the placebo group.

The existing literature evaluating atropine to control myopia progression contains a major flaw – it emphasizes the average treatment response. In my clinical experience treating hundreds of children over many years, few children have the average response of slowed myopia progression. Instead, in many children, the “atropine responders”, there is a profound effect with atropine eye drops essentially halting myopia progression, while in other children, the “non-responders”, there is minimal effect with continued myopia progression. Combining the results between these two groups, responders and non-responders, yields a smaller average treatment benefit for atropine eye drops that masks a much larger treatment benefit in responsive children. The CHAMP results provide a clear criterion to separate atropine 0.01% responders from non-responders – myopia progression after one year of treatment. In children who progressed ≤ 0.25 diopters during the first year of treatment, 64% progressed < 0.50 diopters total over three years. In children who progressed > 0.25 diopters over one year, only 9% achieved <0.50 diopters total progression. The important point to emphasize is that children with myopia progression > 0.25 diopters during the first 12 months of treatment are likely non-responders who will require more aggressive treatment to control their myopia.

A sub-group analysis of the CHAMP data divided the subjects into two groups, children who enrolled into the study with < -3 diopters of myopia compared with children with ≥ -3 diopters of myopia. This data demonstrated that the lower myopia group had 75% less progression on treatment with atropine 0.01% compared with the higher myopia group. Further refining the data to include only those subjects who followed the study protocol, i.e. good adherence to taking the eye drops, showed an almost doubling of the treatment effect in the lower myopes. The take home message is that initiating treatment with atropine 0.01% early, at lower levels of myopia without waiting for progression, will result in the best control of myopia.

There are two major advantages of the NVK002 formulation of atropine 0.01% compared with compounded atropine drops. First, it is preservative free, so it will be much gentler on the ocular surface over the duration of the treatment. Second, it is shelf-stable at room temperature, eliminating the need for refrigeration.  Both of those factors are critical to maintaining adherence to treatment. The drops can be stored at the bedside to be administered before sleep and transported easily to maintain treatment on extended vacations and summer camps.

As a clinician who has prescribed concentrations of atropine ranging from 1% to 0.005%, the CHAMP data provides strong reassurance that my current clinical practice, starting with atropine 0.01% for all children with progressive myopia, is the best choice. There is evidence to support higher concentrations of atropine as having a stronger effect at suppressing myopia, but many children will have a great response to atropine 0.01% and will not need to be exposed to any higher concentrations of atropine. The important new finding is the criterion to quickly identify atropine responders versus non-responders. Atropine 0.01% creates such a profound reduction in myopia progression in responsive children that any myopia progression over the first year of treatment should prompt consideration of an escalation of myopia control therapy.