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Atropine as part of treatment protocols for amblyopia

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Tim Fricke
BOptom MSc FAAO
Minne-Merri Consultants, Melbourne VIC

 

Management of amblyopia has progressed from largely conventional thinking to evidence-based practice in the past 15 years. Prior to this century, the vast majority of books, opinion pieces and guidelines from learned bodies included the conventional wisdom that amblyopia should be treated with all-day patching of the good eye from the time of diagnosis, and treatment should cease when a child turned six years of age because after that, it would not work.

Although long-standing principles of individualising and connecting with patient needs remain, new evidence should change the way we manage patients who have amblyopia.

Even the reasons for treating amblyopia have been better defined over the past 15 years. As eye-care practitioners, we have always been comfortable with the idea that improving vision is a reason unto itself, along with the positive reinforcement of individual patient anecdotes. More recently, there is evidence that treating amblyopia is important to the patients themselves, as well as economists, actuaries and policy-makers, among others. For example, treating amblyopia has been shown to measurably improve quality of life for patients,1 and it provides a good return on health dollar investment.2

As practitioners, our primary aim in amblyopia therapy is to improve monocular function—to achieve normal visual acuity (VA) and fixation in each eye separately. This provides a ‘spare tyre’ for life, or ‘vision insurance’, along with a better quality of life and better health economics outcomes. Our secondary aim is to improve binocular function—to achieve normal fusion (all levels) and binocular correspondence measured with both eyes open. This provides insurance against or part treatment of uncosmetic strabismus, along with a better quality of life.

 

Amblyopia treatment protocols

 

The Monitored Occlusion Treatment of Amblyopia (MOTAS) group in the United Kingdom and the Paediatric Eye Disease Investigator Group (PEDIG) in the United States have been instrumental to the accumulation of new evidence for the treatment of amblyopia. For the first time, we can base amblyopia treatment protocols on solid evidence with flexible details. My interpretation of best evidence-based practice divides treatment into four stages, which will be elaborated on but can be summarised as:

Stage 1. Prescribe glasses only for three months or until vision of the amblyopic eye stops improving, whichever is longer.

Stage 2. Prescribe glasses and all-day patching of the non-amblyopic eye for preschool children, or glasses and two hour/day patching of the non-amblyopic eye for school children.

Stage 2. Modification 1: when compliance/resolve for patching wanes or if patching is unsuccessful, change to glasses with atropine penalisation of the non-amblyopic eye.

Stage 2. Modification 2: when approaching equal visual acuity between eyes, consider translucent or refractive penalisation, for example Bangerter Filter, or over-correcting hyperopia.

Stage 3. Use glasses, prisms, vision therapy and/or surgery to treat any strabismus.

Stage 4. Use vision therapy and/or glasses modifications to treat accommodation-vergence issues, particularly high lag of accommodation in the previously amblyopic eye.

Atropine penalisation has an important evidence-based role in treatment of amblyopia, within a framework such as this, with safe protocols such as those described below and with defined discharge criteria as described below.

 

First step

 

As a first step after amblyopia diagnosis, MOTAS and PEDIG have independently established that it is worthwhile to start with up to three months of treatment with glasses alone.3-5 This stage in treatment provides equally clear retinal images by correcting anisometropia, with a bias towards fusion and supporting the impaired accommodation of the amblyopic eye.

It is also the practitioner’s opportunity to set up a trusting relationship with the child, building rapport and understanding without doing anything that the child will strongly dislike. In this time, around 75 per cent of children with either anisometropic or strabismic amblyopia will gain approximately two lines of improvement in visual acuity.3-5

 

Occlusion and/or penalisation ­therapies

 

After refractive-only treatment for up to three months, MOTAS and PEDIG have shown that a variety of occlusion and/or penalisation therapies can be used to decrease the strength of the neural signals from the non-amblyopic eye. Practitioners can devise suitable treatments for individual patients within the following bounds:

  • Opaque patching of the non-amblyopic eye achieves a faster initial treatment response (visual acuity improvement of the amblyopic eye) than penalisation.6-9
  • More patching hours probably gains faster and sometimes fuller treatment response, but part-time patching works.10-12
  • Weekend atropine penalisation of the non-amblyopic eye achieves results (visual acuity improvement in the amblyopic eye) similar to those of daily atropine.13
  • Prescribing specific activities (concentrated, interactive near activities) to be done during part-time patching might not matter.14,15
  • Atropine penalisation and opaque patching have different impacts (social, physical comfort, effort required) on children and families.16
  • The younger that treatment can be started, the better, but there is no age limit to amblyopia treatment.17-20
  • Amblyopia recurrence is always a risk as you finish active phases of treatment but tapering the treatment helps.21-23

Consider translucent penalisation (a Bangerter Filter applied to the spectacle lens of the non-amblyopic eye) if visual acuity is better than 6/30 in the amblyopic eye and compliance seems likely.24

Extra practitioner effort significantly improves compliance with amblyopia therapy.25 For example, take the time to explain amblyopia to parents and children, and provide reward stickers, a log book and an information sheet.

The MOTAS group has done the most thorough work to model amblyopia treatment dose (hours of patching) versus therapeutic response (VA improvement).19 The results provide evidence-based support for the concept of ‘amblyopia treatment cycles’, where one cycle = one week for every year of life. A four-year-old can achieve a two line improvement in VA in four weeks, while this takes six weeks for a six-year-old to achieve the same.19

 

Atropine penalisation

 

Atropine is a non-selective muscarinic antagonist, long known to cause mydriasis and cycloplegia by disrupting parasympathetic innervation to the pupillary sphincter and ciliary body muscles. Both of these mechanisms and outcomes of ophthalmic atropine use degrade the retinal image for the duration of effect, particularly in a hyperopic eye. This degradation of retinal image means it can be used to penalise a non-amblyopic eye, giving some competitive advantage in cortical image processing to information coming from the amblyopic eye.

If a practitioner decides that atropine penalisation of the non-amblyopic eye is the most appropriate way to treat amblyopia at some stage, they should:

  • Note contra-indications for atropine—Down Syndrome, spastic paralysis, brain damage, narrow anterior chamber angles, hypersensitivity to any of the ingredients.
  • Prescribe 1% Atropt for somewhere between once daily and twice weekly use in the non-amblyopic eye.
  • Provide a patient information hand-out including critical information about complications.
  • Advise wearing sunglasses and a hat when outside.
  • Reiterate that the family should contact you or a hospital emergency department immediately if the child shows signs of adverse reactions—local allergic reactions, dry mouth, facial flushing, headaches, ataxia, tachycardia, fever, irritability, low blood pressure or difficulty breathing.
  • In a very small minority of cases (I have never encountered reactions requiring these responses), adverse reactions might need to be controlled in the short term via supportive treatments for high fevers and dehydration or intramuscular physostigmine to counteract the muscarinic antagonist effect of atropine, in severe or life-threatening toxicity.
  • In a small minority of cases, adverse reactions need to be controlled in the longer term by decreasing the dosage, for example, to ‘weekend only’, changing drug therapy to homatropine or ceasing drug therapy entirely.
  • It is sensible to review after one week of atropine penalisation to assess distance visual acuity (although noting that treatment effect does not require reduced distance visual acuity in the atropined eye, and that we do not expect improved visual acuity in amblyopic eye at this stage), complications from atropine use, efficacy of atropine use (little to no pupil response to light, or accommodative response, in the non-amblyopic eye), and accommodation in the amblyopic eye (systemic absorption of atropine can lead to decreased accommodation in the eye that does not receive drops—consider a bifocal correction if this occurs).

It is then sensible to review after each amblyopia treatment cycle, in other words, one week for every year of the patient’s life. The practitioner should have clear criteria for discharging from atropine penalisation. For example, no improvement over two cycles, or continuous compliance for six months, or another therapy becomes indicated.

 

What to do after atropine penalisation—the final stages of amblyopia therapy

 

The third stage of amblyopia therapy involves treating any strabismus. The motor aspects of strabismus may require surgery, prism, an altered refractive correction, vision therapy and/or a near addition. The sensory aspects of strabismus may require anti-suppression vision therapy.26

The fourth and final stage of amblyopia therapy involves the removal of any other impediments to efficient binocular vision. This may require further alterations of refractive correction, a near addition, prism or vision therapy. Particularly, accommodative dysfunction in a previously amblyopic eye can lead to treatment regression. Note that active vision therapy to improve accommodation vergence skills is only likely to be useful once visual acuities are equal or almost equal—it will not replace the other amblyopia therapy stages.

 

  1.  van de Graaf ES, van der Sterre GW, van Kempen-du Saar H, Simonsz B, Looman CW, Simonsz HJ. Amblyopia and Strabismus Questionnaire (A&SQ): clinical validation in a historic cohort. Graefe’s Arch Clin Exp Ophthalmol 2007; 245: 1589-1595.
  2. Membreno JH, Brown MM, Brown GC, Sharma S, Beauchamp GR. A cost-utility analysis of therapy for amblyopia. Ophthalmology 2002; 109: 2265-2271.
  3. Stewart CE, Moseley MJ, Fielder AR, Stephens DA, MOTAS. Refractive adaptation in amblyopia: quantification of effect and implications for practice. Brit J Ophthalmol 2004; 88: 1552-1556.
  4. Cotter SA et al including PEDIG. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology 2006; 113: 895-903.
  5. Cotter SA et al including PEDIG. Treatment of strabismic amblyopia with refractive correction. Am J Ophthalmol 2007; 143: 1060-1063.
  6. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002; 120: 268-278.
  7. Repka MX et al including PEDIG. Two-year follow-up of a 6-month randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2005; 123: 149-157.
  8. Pediatric Eye Disease Investigator Group, Repka MX et al. A randomized trial of atropine vs patching for treatment of moderate amblyopia: follow-up at age 10 years. Arch Ophthalmol 2008; 126: 1039-1044.
  9. Scheiman MM et al including PEDIG. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol 2008; 126: 1634-1642.
  10. Stewart CE, Moseley MJ, Stephens DA, Fielder AR. Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS). Invest Ophth Vis Sci 2004; 45: 3048-3054.
  11. Pediatric Eye Disease Investigator Group, Wallace DK et al. A randomized trial of increasing patching for amblyopia. Ophthalmology 2013; 120: 2270-2277.
  12. Pediatric Eye Disease Investigator Group. A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology 2003; 110: 1632-1637.
  13. Repka MX et al including PEDIG. A randomized trial of atropine regimens for treatment of moderate amblyopia in children. Ophthalmology 2004; 111: 2076-2085.
  14. Pediatric Eye Disease Investigator Group. A randomized trial of near versus distance activities while patching for amblyopia in children aged 3 to less than 7 years. Ophthalmology 2008; 115: 2071-2078.
  15. Christoff A et al including PEDIG. Distance versus near visual acuity in amblyopia. J AAPOS 2011; 15: 342-344.
  16. Holmes JM et al including PEDIG. Impact of patching and atropine treatment on the child and family in the amblyopia treatment study. Arch Ophthalmol 2003; 121: 1625-1632.
  17. Stewart CE, Fielder AR, Stephens DA, Moseley MJ. Treatment of unilateral amblyopia: factors influencing visual outcome. Invest Ophth Vis Sci 2005; 46: 3152-3160.
  18. Scheiman MM et al including PEDIG. Randomized trial of treatment of amblyopia in children aged 7 to 17 years. Arch Ophthalmol 2005; 123: 437-447.
  19. Stewart CE, Stephens DA, Fielder AR, Moseley MJ, Cooperative M. Modeling dose-response in amblyopia: toward a child-specific treatment plan. Invest Ophth Vis Sci 2007; 48: 2589-2594.
  20. Holmes JM et al including PEDIG. Effect of age on response to amblyopia treatment in children. Arch Ophthalmol 2011; 129: 1451-1457.
  21. Holmes JM et al including PEDIG. Risk of amblyopia recurrence after cessation of treatment. J AAPOS 2004; 8: 420-428.
  22. Holmes JM et al including PEDIG. Factors associated with recurrence of amblyopia on cessation of patching. Ophthalmology 2007; 114: 1427-1432.
  23. Tacagni DJ, Stewart CE, Moseley MJ, Fielder AR. Factors affecting the stability of visual function following cessation of occlusion therapy for amblyopia. Graefe’s Arch Clin Exp Ophth = Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie 2007; 245: 811-816.
  24. Pediatric Eye Disease Investigator Group, Rutstein RP et al. A randomized trial comparing Bangerter filters and patching for the treatment of moderate amblyopia in children. Ophthalmology 2010; 117: 998-1004 e1006.
  25. Loudon SE, Fronius M, Looman CW, Awan M, Simonsz B, van der Maas PJ, Simonsz HJ. Predictors and a remedy for noncompliance with amblyopia therapy in children measured with the occlusion dose monitor. Invest Ophth Vis Sci 2006; 47: 4393-4400.
  26. Birch EE, Stager DR Sr, Berry P, Leffler J. Stereopsis and long-term stability of alignment in esotropia. J AAPOS 2004; 8: 146-150.


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