What to do when a patient doesn't respond to atropine

Low-concentration atropine of at least 0.025% has been shown in current studies to be effective in controlling myopia progression in children. However, TN is left stumped a 11-year-old child who has not been responding to atropine 0.025%, showing very fast progression in under a year, and shared the case with the Myopia Profile community.

Low-dose atropine is useful for slowing myopia progression and axial elongation. Unfortunately, not all children will respond well. The ATOM2 study showed that around 18% of participants responded poorly to 0.01%, 0.1% and 0.5% atropine, regardless of concentration, by showing more than 1D of progression over two years.¹  In the concentration used here, 0.025%, the LAMP study found 13% progressed by more than 1D in a year - by comparison, it was 15%, 28% and 37% in the 0.05%, 0.01% and control groups respectively.² 

Which children are likely to be poor responders? Loh et al showed that a small group of children with fast myopia progression while having atropine treatment. This group of children tend to be younger, are highly myopic and have two myopic parents.³ You can read more about the frequency and factors involved in Non-responders to Myopia Control Treatments in this blog.

Some of the commenters questioned the necessity of an ophthalmology referral as there is no abnormal pathology suspected. Optometrists as primary eye care practitioners are also well-positioned in terms of time and access to optical interventions to administer myopia control.

Therefore, it is worthwhile to considering referring to other optometrists who have the capacity to provide the services to control myopia progression if you are unable to do so.

In some countries whereby optometrists are unable to prescribe atropine, then referral to ophthalmology may be necessary if this is to be considered as part of the treatment plan. Even if atropine wasn't to be considered, ophthalmology involvement is important in cases of high childhood myopia - in a study of 112 children under age 10 with myopia of more than 6D, only 8% had 'simple high myopia' with no other associated ocular or systemic associations. 54% had an underlying systemic condition (eg. developmental delays, Marfan, Stickler, Downs syndrome) and the remaining 38% had further ocular problems associated with high myopia such as lens subluxation, coloboma, retinal dystrophy).⁴  

This case doesn't quite fit the criteria as the child is 11, but this child is young with high myopia - hence it wouldn't be inappropriate for a careful practitioner to consider even a single referral to rule out pathology. However there may be more to determine in this case first, from the optical side of things.

This patient appears to have exhibited a -3.25D jump in the right eye and a -2.25D jump in the left eye in less than a year. This is enormous progression, outside the expected of around -0.50D per year for his age (in a single vision correction)⁵ so it's crucial to evaluate the true progression - a cycloplegic refraction will help with this, especially where axial length measurements aren't available.

The binocular vision (BV) status of the patient could also play a role in driving myopia progression. An example, as KG suggested, is that the atropine might affect his accommodation which could then induce esophoria, leading to hastened myopia progression. Therefore, BV issues that are worthwhile investigating are:

• Accommodative lag and phorias– high lag of accommodation with combination of esophoria at near is associated increased rates of myopia progression.⁶
• AC/A ratio – high AC/A ratio was associated with myopia progression.⁷
• Presence of accommodative spasm – cycloplegic refraction will avoid a subjective refraction result influenced by possible spasm.

A thorough assessment of a child’s BV status will allow us to identify and manage potential BV issues that may hasten myopia progression. This can also allow us to decide on the best form of optical intervention.

Instead of single vision lenses which do not contribute to slowing progression - as this child has been wearing - it is best to prescribe some form of optical treatment which corrects as well as controls his myopia. When it comes to spectacles, the options are as follows.

• Progressive addition lenses (PALs): These work well with children who have high accommodative lag and esophoria.⁶
• Bifocal spectacle lenses: These appear to work better than PALs, on average⁸
• Defocus Incorporated Multi-Segment (DIMS) lenses: These appear to slow myopia progression and axial elongation much more effectively than PALs and slightly more effectively than bifocals. It's important to note, though, that DIMS lenses will likely not influence any binocular vision disorder - they don't provide an orthoptic 'add' as PALs or bifocals do.⁹ If binocular vision is normal and DIMS lenses are available, these are the clear spectacle lens of choice.

If parent and child are willing, contact lenses options for myopia control appear to work more effectively than PAL and bifocal spectacles, and similarly to DIMS spectacle lenses. These also have the advantage of near-worldwide availability for at least one of the following options, all of which have been specifically investigated for their myopia control efficacy.

• Orthokeratology (OK): In this particular case, if the cycloplegic refraction gives the same result, the degree of refractive error is close to the upper limit of typical OK correction ability. Depending on the patient’s corneal curvature and the practitioner's experience, OK at this degree of myopia may or may not be feasible. OK slows progression by around half on average.¹⁰
• MiSight contact lenses: These daily disposable contact lenses show similar efficacy to OK for myopia control,¹¹ however if the right eye refraction is confirmed at -6.75 spherical equivalent, the patient will be just outside the availability range of up to -6.00D.
• NaturalVue contact lenses: These daily disposable lenses are available up to -12.00D. There is no available data on refractive or axial length efficacy in a randomized controlled study for NaturalVue, but a case series report on pre- and post-fitting showed good results.¹²
• Mylo EDOF (extended depth of focus) contact lenses: These custom made monthly lenses show similar efficacy to multifocal (presbyopic) contact lenses¹³ and are availabe up to -15.00D with a variety of base curves and diameters.
• Multifocal (presbyopic) soft contact lenses: The CooperVision Biofinity centre distance lens with a +2.50 Add has shown moderate myopia control efficacy,¹⁴ similar to Mylo but perhaps not quite as good as MiSight and OK. These lenses, though, have the advantage of being available to a majority of eye care practitioners throughout the world.

As monotherapy, on the basis of the one year LAMP study² of 0.01%, 0.025% and 0.05% atropine, which are those typically prescribed to balance efficacy and side effects - 0.05% atropine likely works as well as DIMS spectacle lenses, orthokeratology or MiSight contact lenses when each are used individually as a single treatment.

Regarding combination treatments, There are early studies showing a potential synergistic effect of atropine 0.01% and orthokeratology.¹⁵ Baseline data has been presented on atropine 0.01% plus multifocal contact lenses (Biofinity centre distance +2.50 Add) indicating good short-term tolerance of combination treatment, with data on efficacy to follow.¹⁶

1. While low-dose atropine may be a good myopia control treatment option, it may not work effectively in around 15-20% of patients. This appears to be a similar observation across atropine concentration, when considering multiple studies.
2. Fast shifts in refraction to high childhood myopia (over 5-6D, especially if under 10 years of age) may warrant involvement of ophthalmology, to a level dependent on your scope of practice; but keep in mind that noone is better placed to manage vision and refraction than primary eye care.
3. This child's enormous apparent myopia progression requires confirmation with a cycloplegic refraction, especially where axial length measurement is not available to confirm the progression. Binocular vision status could also have factored into faster-than-average progression.
4. Don't forget that optical corrections can work as well as, or even in combination, with atropine.

• Why isn't the myopia control strategy working?

• Non-responders to myopia control treatments

• Case study: When a patient doesn't respond to orthokeratology