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Atropin Eye Drops may Slow Myopia Progresivity in Children

Myopia or nearsightedness is difficulty in seeing objects clearly at a long distance. Myopia is a global health problem that causes not only vision problems but also the risk of blindness, especially in children. The use of atropine eye drops is thought to slow the progression of myopia.

Atropin Eye Drops may Slow Myopia Progresivity in Children


Uncorrected myopia can have a serious impact on the quality of life. Individuals with high myopia (≤ −5 D) have a lower quality of life than individuals with mild myopia. Currently, refractive surgery (for example, LASIK), wearing glasses, and contact lenses are the therapeutic options.

One method being studied to arrest myopia progression is applying topical atropine eye drops. The progress of refractive abnormalities due to myopia is thought to be slowed by the use of atropine. However, the growth of the eyeball is a potential factor causing refractive abnormalities to reappear when stopping the use of atropine eye drops.

The Action Mechanism of Atropine to Slow Myopia Progressivity

Although the action mechanism of atropine to slow the progression of myopia refractive disorders is still not known with certainty, several theories have been put forward. Atropine is a nonselective muscarinic receptor antagonist that has long been studied for its effects on experimental animals for decades.

Applying atropine eye drops in slowing the progression of myopia is based on the assumption that lens accommodation affects the severity of myopia, and cycloplegic drugs can prevent this. However, further evidence reveals that atropine prevents the progression of myopia in animals with nicotinic receptors rather than muscarinic receptors.

Meanwhile, nonpharmacological modalities that function in decreasing eye lens accommodation (for example, glasses), do not have a significant effect in preventing the worsening of myopia. As a result, the accommodation function is no longer considered as a major factor in the progression of myopia.

One theory states that amacrine cells play a role in expressing muscarinic receptors in the cell membrane. Atropine binding muscarinic receptors in amacrine cells is thought to increase the release of dopamine. Dopamine is a chemical mediator that inhibits eye growth.

Decreased levels of gamma-aminobutyric acid (GABA) are also considered as one mechanism that explains the role of atropine, considering that the neurotransmitter attenuates after atropine therapy in mice with myopia.

The sclera is also thought to be a target of atropine action. Why? Because the sclera fibroblast cells have five kinds of muscarinic receptors on their cell membrane. Also, atropin binding receptor has the potential to inhibit scleral remodeling.

Benefits of Atropine in the treatment of myopia

The ATOM (Atropine for the Treatment of Childhood Myopia) 1 and ATOM 2 studies form the initial scientific basis of the benefits of atropine in the treatment of myopia.
ATOM 1 is a randomized, controlled, double-blind clinical trial recruiting 400 participants of school-age children who experience myopia with varying degrees of severity (-1.00 to -6.00 D) and mild astigmatism (≤ 1.5 D). Participants were randomized and divided into two groups with equal amounts to get 1% atropine eye drops in one eye each night while the other side-eye received a placebo.

After undergoing therapy for 2 years, the mean value of myopia progression was lower in participants who received 1% topical atropine compared to participants in the control group. The use of atropine lasted for 2 years and then stopped, and participants were monitored for 12 months after therapy. During the period without therapy, the phenomenon of myopia rebound was more significant in the group receiving atropine (-1.14 ± 0.80 D) than the placebo (-0.38 ± 0.39 D).

Following up on ATOM 1 research results, the ATOM 2 study recruited and randomized 400 other participants in 3 groups at a ratio of 2: 2: 1 to get atropine 0.5%; 0.1%; and 0.01% to test the hypothesis whether the administration of low-dose atropine is as effective in preventing the progression of myopia compared to atropine 1%.

From testing the use of atropine lasted for 2 years and then stopped and patients monitored further for 1 year, ATOM 2 results showed that the average progression of myopia in the first 24 months in the group of participants who received 0.5% atropine was -0.30 ± 0, 60 D. In the atropine group 0.1% is -0.38 ± 0.60 D. And atropine 0.01% is -0.49 ± 0.63 D.

In the following 12 months, the phenomenon of myopia rebound was more evident in patients who received atropine 0.5% compared to those who received atropine 0.1% and 0.01%. The progression of total myopia during the 3 years of the lowest study period, was shown in the atropine group of 0.01%, followed by atropine participants of 0.1% and 0.5%. This result indicated that at lower doses, atropine is more effective in suppressing myopia progression and has a smaller level of myopia rebound.

Although the results of the ATOM 1 and ATOM 2 studies have shown effectiveness in myopia, the practice of giving atropine is still not widely practiced. This is partly influenced by concerns about ideal dosages, drug safety, and the extent to which clinical trial results can be applied to different ethnic groups.

A systematic review and meta-analysis were carried out by Gong et al. to assess the benefits and risks of giving various topical atropine doses as myopia therapy in children. The results of the systematic review showed that there were significant mean differences between the intervention groups receiving atropine compared to the control group related to myopia progression of 0.50 D per year for low-dose atropine (atropine 0.01%); 0.57 D per year for moderate-dose atropine (atropine 0.01% -0.5%), and 0.62 D per year for high-dose atropine (0.5% -1.0%).

High doses of atropine are associated with higher side effects. The incidence of photophobia in applying high-dose atropine occurred in 43.1% of cases. Only 6.3% in the group receiving low-dose and 17.8% in the group receiving moderate doses of atropine. The difference in the level of side effects affected by this dose is also seen in other side effects, such as a lack of sharp near vision and allergic reactions.

Gong et al.'s study had several limitations.
1. The level of heterogeneity between studies that became the sample of the analysis was quite high because various types of study designs were included in the meta-analysis to be able to calculate the magnitude of the effect to be assessed.
2. in-depth analysis of the side effects of atropine administration, limited by a system of reports of side effects that are not yet comprehensive as well as differences in the incidence of symptoms of side effects reported in each study.
3. the incidence of myopia rebound is not widely reported in various study samples. 

Clinical Implications

The clinical implication of the various literature discussed in the previous section is that atropine eye drops can be considered in pediatric patients with myopia to slow the progression of myopia.

Education and evaluation of parents 'and patients' perceptions about the goals, procedures, potential side effects, success rate of therapy need to be applied before starting therapy. Parents and patients need to understand that applying atropine eye drops is aimed at slowing the myopia progressivity, not improving vision, as well as refraction therapy using orthokeratology techniques.

In addition, a long-term commitment to therapy for at least 2 years should be given by the patients and their parents accompanied by monitoring during and after therapy. The monitoring is aimed at keeping the status of mild myopia from increasing to be high myopia before the children growing up. The use of low-dose atropine, for example, at a dose of 0.1%, is recommended because it has the same efficacy as a higher dose while the level of side effects is low. The recommended dose frequency is once a day before bedtime.



References
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