Article

COUNTERPOINT: ATROPINE

The clinical use of atropine to slow the progression of myopia

Atropine has been used for more than 100 years to slow the progression of myopia. Early studies demonstrated that it was effective, but side effects, such as photophobia secondary to pupillary dilation and paralysis of accommodation causing blur, resulted in termination of its use to control the progression of myopia.1-3

In the mid-1970s, atropine’s use was resumed with the development of photochromic lenses to reduce photophobia and use of progressive lenses to handle the accommodative issues. In 1971, Bedrossian4 prescribed atropine 1% in one eye. After one year, the atropine-treated eye had a mean progression of myopia of 0.02D while the other eye increased its myopia by 0.8D.4,5 Similar findings have been reported in many other studies.6-13

Chiang and colleagues14 followed more than 700 Caucasian myopes who used atropine 1% weekly and reported that the annual progression was 0.08D/year in atropine-treated patients as compared to 0.5D/year in untreated patients. Atropine 1% has also been shown to work equally well for high myopia.15

The first Atropine for the Treatment of Myopia (ATOM1) study treated one eye with atropine 1% while the other eye was used as a control. The children wore photochromic, progressive glasses.16 After two years, the mean progression of myopia in the placebo-treated control eyes was –0.6D/year, with an axial length (AL) change of 0.19mm/year. The atropine-treated eyes demonstrated only –0.14D/year of progression, and the axial length remained essentially unchanged (–0.02mm). More importantly, 86% completed the study.

In summary, numerous studies have demonstrated that atropine 1% slows the progression of myopia by approximately 80% without serious complaints of blur and photophobia. Our office has been using atropine 1% for more than 15 years with similar findings.

Because of the perceived problems with atropine 1%, a number of researchers investigated the use of lower concentrations of atropine. Shih et al17 investigated various percentages and reported the following: with atropine 0.5%, 61% did not progress; with atropine 0.25%, 49% did not progress; and with atropine 0.1%, 42% did not progress. In this study, the control group had only 8% who did not progress. Others have shown that low dosages such as atropine 0.025% could prevent the development of myopia in emmetropic patients who had myopic tendencies.18 Another study reduced atropine’s side effects by varying its concentration seasonally.19 This is an effective method for maintaining higher dosage during the myogenic seasons (i.e., winter).

What has changed the utilization of atropine to slow myopia progression is the ATOM2 study.20-22 This study compared atropine 0.01%, 0.1%, and 0.5% against a historical control. There were three phases: treatment (two years), cessation (one year); and resumption for those patients who continued to progress (two years). As expected in phase one, the stronger concentrations had a greater effect on slowing elongation of the eyes and on reducing the progression of refractive error.

However, after phase two (the cessation period) those on the higher percentage seemed to have rebounded more. If only the refractive error findings are reviewed, the data might be incorrectly interpreted to mean that lower concentrations of atropine (e.g., 0.01%) are more effective in slowing the progression. However, if the axial length data is reviewed, the opposite is true (Figure 1); the most effective agent to slow the progression of myopia is atropine 1%, and the ability of atropine to slow myopia is concentration-related.

Figure 1. This figure summarizes axial length (AL) data for the ATOM1 and ATOM2 studies in the first two of three phases: treatment, cessation, and resumption over a three-year period. It is readily apparent that AL data in these two studies demonstrate a reduction in progression of myopia being dosage dependent, with the greatest effect occurring with atropine 1% even after cessation. The AL findings are in conflict with the refractive change data in the ATOM1 and ATOM2 studies.

The cessation data also needs to be viewed in perspective. No one advocates going cold turkey with atropine. Abrupt stopping of atropine is like stopping patients from taking steroid drops. The lesson from the cessation phase is that you cannot stop the drop abruptly; the treatment must be tapered.

The second outcome from the cessation phase is that 50% of the patients treated for two years stopped progressing after cessation. The older the child and the lower the concentration initially used, the greater the likelihood that atropine treatment can be stopped. After the third phase, resumption of atropine in a lower concentration was able to slow the progression again.

More recently, the Low-Concentration Atropine for Myopia Progression (LAMP) study evaluated the results of atropine 0.05%, 0.25%, and 0.01%.23 The results were more consistent with previous studies; the higher the percentage, the better the ability to control progression of myopia and AL. The researchers did not find a statistical difference between atropine 0.01% and placebo in slowing the progression of myopia when using AL as the standard for progression.

Recently, researchers have been asking the question: Is atropine synergistic with other modalities of treatment, e.g., contact lenses? Kinoshita et al24 reported that after one year, the orthokeratology alone group progressed 0.19mm while the orthokeratology plus atropine group only progressed 0.09mm. We might ask which is more effective in slowing the progression of myopia, orthokeratology or atropine. There is one study that attempted to answer that question; the authors reported that atropine 0.125% and ortho-k are equivalent.25 It is important to note that atropine 0.01% was not used in that study.

A RECOMMENDED ATROPINE TREATMENT PROTOCOL

In 2000, we began to use atropine 1% once a day with photochromic, progressive lenses. In the majority of cases, this treatment stopped the progression of myopia. More than 80% of our patients accepted this regimen. Most of the patients electing to have this treatment were young (under 6 years of age), had parents whose myopia was greater than 6.0D, and were of Asian descent. We advised our myopic patients of this option along with orthokeratology. Around 2008, we added orthokeratology, which was preferred by older patients who had a refractive error less than 6.0D. Our dropout rate has been around 20%, and there have been minimal complaints of blur and photosensitivity because of the use of progressive, transitional lenses.

The ATOM1 and ATOM2 studies, the original work of Shih, and the LAMP study have caused us to modify our treatment protocol. Prior to ATOM2, we used atropine 0.02% as our low-dosage treatment. After the ATOM2 study, we decided to switch to atropine 0.01%; however, we have not found it effective enough. Thus, initially we prescribe atropine 0.02%, but we still use atropine 0.01% to prevent the development of myopia or add it for those patients who are still progressing on a mild-to-moderate basis with orthokeratology or soft multifocal lenses.

We measure their ALs at three months. If there is no progression, we increase the duration between visits to four months and then to six months. However, if there is progression, the dosage is increased stepwise from atropine 0.01% to 0.02% to 0.05% to 0.1%, and, finally, atropine 1%. Our criterion of progression is 0.06mm within three months. It should be noted that the eye continues to grow as part of normal development until approximately age 14 years. We use group data to guide our treatment, but realize that each patient’s progression is independent. Our goal is to find the minimum concentration to stop or severely retard the progression of myopia.

WHICH OPTION TO INITIALLY USE

Children who love their glasses are going to fail with any contact lens treatments (Figure 2). Conversely, a child or parent who wants to eliminate glasses is best served by a contact lens option. Also, contact lens options may not be appropriate for young children (younger than 6 years of age). Generally, they are progressing quickly and are in need of more aggressive treatment (e.g., atropine 1% q.h.s. in both eyes). At approximately 14 to 16 years of age, patients using atropine should be tapered in percentage and eventually discontinued.

Figure 2. This figure is a meta-analysis of all treatment regimens for myopia control. It is apparent that atropine 1% is the gold standard, with under-correction being the least effective. Again, there is a dosage-dependent relationship between atropine and myopia control.
Reprinted with permission Huang J, Wen D, Wang Q, et al. Efficacy comparison of 16 interventions for myopia control in children: A network meta-analysis. Ophthalmology. 2016 Apr;123:697-708.

Low dosage, in my experience, can be used even in presbyopic patients who are still showing progression. However, instruct them to use the medication for about one week before prescribing an add based on either cross-cylinder techniques or balancing positive relative accommodation/negative relative accommodation (PRA/NRA), because even low doses affect accommodative function in this population.

SUMMARY

In summary, atropine is a strong suppressant of myopia. It may be used as a standalone treatment or in combination with contact lenses to slow the progression of myopia. Dosage is dependent upon myopia progression rate and age of onset. Myopia progression should be monitored by frequent measurement of AL. Higher dosages of atropine need to be tapered to prevent rebound. CLS

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