Myopia is an irreversible visual impairment whose therapeutic goal is to prevent it from developing into high myopia. In recent years, the age of onset of myopia has become younger and younger, with an average age of onset of about 8 years. Although the exact mode of action of atropine to inhibit the development of myopia has not been fully elucidated. But it has been established that the use of low concentrations of atropine in the early stages can slow the development of myopia. Eikance (atropine 0.01%) eye drops were first approved in Australia in September 2021 for slowing the development of myopia in children.
Australia approves Eikance eye drops for slowing the development of myopia
Aspen announced on March 17 that the Australian Therapeutic Supplies Authority (TGA) has approved Eikance (Atropine sulfate monohydrate) 0.01% eye drops, or 0.01% atropine sulfate eye drops, for slowing the development of myopia in children and adolescents. Eikance is available as a treatment option to slow the progression of myopia in children aged 4 to 14 years whose myopia progresses ≥ -1.0 D diopter per year.
It is worth noting that this is not only the first low-dose atropine eye drops in Australia to slow the progression of myopia in children and adolescents, but also the first eye drops in the world to be explicitly used to alleviate myopia.
The TGA registration of EIKANCE 0.01% eye drops is based on multiple trials, including two key randomized, double-blind clinical trials in children with myopia aged 4-12 years and 6-12 years who received atropine 0.01% eye drops and were followed up for 2 to 5 years to evaluate the effectiveness and safety of atropine 0.01% eye drops in the treatment of myopia in children. Most of its studies were conducted in Asian children.
ATOM 2 study: Myopia in children aged 6 to 12 years
Chia 2012 (ATOM 2) was a randomized, double-blind, three-arm, active-controlled, parallel-group study that compared 400 myopia progression rates of 400 myopia aged 6 to 12 years (mean refractive error -4.5 to -4.8 D) who received 0.5%, 0.1%, or 0.01% atropine eye drops for 2 years. Initially, the 0.01% concentration is used as an inactive control, as its effect is assumed to be minimal.
Follow-up studies from Chia 2014 reported on the effect of treatment discontinuation on myopia rebound, while Chia 2016 assessed the effects of reintroduction of aggressive treatment with very low doses of atropine (0.01% eye drops). The total treatment period for the ATOM 2 series of studies was 5 years.
The final mean myopia progression over a 2-year period in the atropine 0.01%, 0.1%, and 0.5% groups were -0.49±0.60, -0.38±0.60, and -0.30±0.63D (p = 0.07), with significant differences between only 0.01% and 0.5% (p<0.05). The percentage of children who developed mild progression of myopia at the age of 2 years was 50% in the 0.01% group, 58% in the 0.1% group, and 63% in the group treated with 0.5% atropine eye drops. The average change in AL over two years was 0.41± 0.32 mm (0.01%), 0.28± 0.27 mm (0.1%) and 0.27± 0.25 mm (0.5%).
After discontinuation of atropine treatment, Chia 2014 observed a rebound in myopia in all 3 groups, but the rebound in the 0.5% group (-0.87±0.52D) was significantly greater than that in the 0.1% (-0.68±0.45D) and 0.01% (-0.28±0.33D). The increase was greatest in the first 8 months, followed by a slowdown in the following 4 months. Similarly, the AL of the 0.5% group (0.35 mm) and the 0.1% group (0.33 mm) was significantly higher (p<0.0001) compared to the 0.01% group (0.19 mm).
Chia 2016 showed that fewer children in the 0.01% group (24%) required re-treatment compared to those in the 0.1% (59%) and 0.5% (68%) groups. By year 5, the overall progression of myopia in the 0.01% group (-1.38±0.98D) was less than 0.1% (-1.83±1.16D, p = 0.003) and 0.5% (-1.98±1.10D, p< 0.001). This is mainly due to the fact that fewer children in the 0.01% group progressed after treatment was stopped, and patients who needed re-treatment also had lower rates of progression in famine years compared to the 0.1% and 0.5% groups (-0.63, -0.94 and -1.09 D, respectively) (Figure 1).
LAMP study: Myopia in children aged 4 to 12 years
Yam 2018 (LAMP Study) was a randomized, double-blind, four-arm, placebo-controlled, parallel-group study that compared the progression of myopia in 438 myopic children aged 4 to 12 years (with an average refractive error -3.71 to -3.98 D) who received 0.05%, 0.025%, or 0.01% atropine eye drops and placebo eye drops over a 12-month treatment period. Ocular adverse events were also reported. The overall design is very similar to the one used in the ATOM study series.
The final mean myopia progression at the end of 12 months of treatment in the atropine 0.05%, 0.025%, and 0.01% groups, and placebo group was -0.27±0.61, -0.46±0.45, and -0.59±0.61D, and -0.81±0.53D (p<0.001, respectively. For each pair of comparisons, the differences between the groups are also significant. At the 12th month, 69.6%, 51.6%, and 43.8% of subjects in the 0.05%, 0.025%, and 0.01% treatment groups progressed < 0.5 D, compared with 24.2% in the placebo group.
Similarly, the AL changes in the placebo group (0.41±0.22 mm) were greater than in the atropine group (0.05% (0.20±0.25 mm), 0.025% (0.29±0.20 mm), and 0.01% (0.36±0.29 mm) (p< 0.001). The difference between the placebo group and the 0.01% group was not significant, but for all other pairwise comparisons between the active treatment group, the difference was statistically significant (p < 0.001).
Yam 2019 (Phase 2 Report) is a randomized, double-blind trial expanded from the LAMP study, which included 483 children aged 4 to 12 years with at least -1.0 (D) degrees of myopia. Children in the initial placebo group switched to 0.05% atropine starting with follow-up in the second year, while children in the 0.05%, 0.025%, and 0.01% atropine groups continued to use the same regimen. Changes in ball equivalents (SE) and AL and their group-to-group differences are the primary outcome measures.
Over a two-year period, the mean SE progress of the 0.05%, 0.025% and 0.01% atropine groups was 0.55_0.86 D, 0.85_0.73 D and 1.12_0.85 D (p=0.015, p<0.001 and p=0.02, respectively), and the mean AL changes over the two years were 0.39±0.35 mm, 0.50±0.33 mm and 0.59±0.38 mm (p=0.04, p<0.001 and p=0.10, respectively).
The second-year efficacy of the 0.05% and 0.025% atropine groups remained similar compared to the first year (p> 0.1), but there was a slight improvement in the 0.01% atropine group (p = 0.04). For the stage 1 placebo group, myopia progression was significantly reduced after switching to atropine (SE change, 0.18 D in the second year vs. 0.82 D in the first year [p< 0.001]; AL extended by 0.15 mm in the second year versus 0.43 mm in the first year [p< 0.001]). At all concentrations, loss of modulation and pupil size changes were similar to the results of the first year and were well tolerated. Vision and vision-related quality of life were not affected.
Summary of the safety of eye drops
All medications have side effects. Most of the side effects of 0.01% EIKANCE eye drops are mild and temporary. The most common side effects of 0.01% EIKANCE eye drops are blurred vision, photophobia, allergies, eye pain, swelling, redness, itching, headache, fatigue.
EIKANCE 0.01% eye drops should not be used if children are allergic to atropine or any of the listed ingredients, or have angle-closure glaucoma or have a family history of glaucoma.
Certain medications may interfere with EIKANCE 0.01% eye drops and affect how they work. These include medications for glaucoma, medications for depression, antihistamines, medications for Parkinson's disease, medications for psychiatric disorders, medications for muscle weakness, and potassium citrate and potassium supplements. Consult your eye care professional or pharmacist about the medications, vitamins or supplements you are taking and whether these medications, vitamins or supplements affect EIKANCE 0.01% eye drops.
Atropine 0.01% eye drops
In recent years, successive clinical studies have shown that indigestion of low-dose atropine may be an effective therapy to combat the rapid deterioration of visual acuity in children with myopia or myopia. In China, 0.01% of atropine with the same ingredient, such as ytomin, shanto, anto, etc., is approved for mydriasis.
参考来源：First eye drops registered on the Australian Register of Therapeutic Goods (ARTG) to slow the progression of short-sightedness now available for children aged from 4 to 14 years old. 新闻，CISION；SOURCE Aspen Australia；2022年3月17日。 2022年5月13日访问。
Note: The above information is compiled from the network, designed to help patients understand the international new drug dynamics, without any basis for medication, please consult the attending physician for specific medication guidelines.