Dr Ann Webber
PhD MS BAppSc(Optom)(Hons) FAAO
QUT School of Optometry and Vision Science, Brisbane QLD
Dr Susan A Cotter
OD MS FAAO
Southern California College of Optometry at Marshall B Ketchum University, Fullerton CA, USA
Amblyopia is a neuro-developmental disorder resulting from abnormal visual experience early in life that affects 2-3 per cent of children.1,2 Vision development becomes compromised because of the presence of an amblyogenic factor, that is, constant unilateral strabismus, anisometropia or obstruction of the ocular media.
The first step in the treatment of amblyopia is correction of significant refractive error. When present, typical prescribing protocols, based on a cycloplegic refraction, provide the full correction of anisometropic, astigmatic and myopic refractive error, with the goal of providing equally clear retinal images. The amount of hyperopic correction is dependent on whether the child also has an esotropia, and any reduction in hyperopia (cutting the plus usually by not more than +1.50 D) is made symmetrically to both eyes.3
Wearing such an optical correction has been shown, over time, to have a bona fide treatment effect on amblyopia beyond the visual acuity (VA) improvement obtained from simply eliminating optical blur.3-5
Vision loss that is still present following a minimum of 16-18 weeks of optical treatment alone usually warrants some form of penalisation of the sound eye.
Historically, patching has been the most widely used form of penalising; however, patching can have psycho-social drawbacks and compliance can be problematic. An alternative treatment is pharmacologic penalisation of the sound eye using 1% atropine sulfate eye-drops.
This review highlights the current evidence base for pharmacologic penalisation of the sound eye with atropine to treat unilateral amblyopia. Patient selection, treatment protocols, expected treatment outcomes, treatment time course, adverse effects, follow-up considerations, and patient/parent education are discussed.
Atropine, a belladonna alkaloid, is as an anticholinergic drug. In the eye, atropine blocks the responses of the ciliary muscle and the iris sphincter to cholinergic stimulation, thereby producing cycloplegia and mydriasis, respectively. Atropine has a slower onset and more prolonged effect than cyclopentolate or tropicamide. The time to maximum cycloplegia takes several hours and can persist for 14 days or longer.
Atropine is contraindicated for eyes with shallow anterior chambers because of the risk of precipitating angle closure glaucoma. There is mild stinging associated with the instillation of the drops and local allergic (hypersensitivity) reactions are occasionally seen. Systemic side-effects include dryness, flushing of skin, fever, tachycardia, confusion, unusual behaviour and irritability.
Use of 1% atropine for amblyopia treatment
When used for amblyopia treatment, the atropine drop is administered to the sound eye with the goal of the resultant cycloplegia causing sufficient blur so that fixation switches from the sound eye to the amblyopic eye.
The extent of blur and whether it is present at near only or at both distance and near, depends on the child’s refractive error and whether the child is wearing his/her full refractive correction. A hyperopic child wearing a full correction will be blurred only at near, whereas one wearing a partial correction will be blurred at both distance and near.
Historically, atropine penalisation has been advocated for mild to moderate amblyopia (6/24 or better VA) based on the premise that the amount of blur induced by the atropine would be likely to be insufficient to cause a shift in fixation preference in amblyopic eyes with 6/30 or worse VA.
In 1997, a survey of the Pediatric Eye Disease Investigator Group (PEDIG) investigators found that three per cent prescribed atropine as the primary treatment modality for amblyopia and 41 per cent prescribed it when patching proved unsuccessful.6 Without rigorously conducted studies, treatment for amblyopia had been based mainly on observation and clinical impression, and patching was the mainstay of treatment.
Since then, the PEDIG has reported findings from numerous randomised clinical trials and prospective observational studies, the Amblyopia Treatment Studies (ATS), which clinicians can turn to for guidance in developing sound treatment protocols for their practices.7
The first PEDIG clinical trial for amblyopia that evaluated atropine compared VA outcomes in children aged from three to younger than seven years of age with moderate amblyopia (6/12 to 6/30) who had been randomised to either daily administration of 1% atropine in the sound eye or at least six hours of daily patching.6
Both treatment groups had similar improvements in amblyopic eye VA at six months and the treatment effect did not vary by age, cause of amblyopia or depth of amblyopia. Both treatments were well tolerated, with parents reporting a slightly higher degree of acceptance for atropine treatment (Table 1).8 Surprisingly, a shift in fixation preference from the atropinised sound eye to the amblyopic eye was not essential for VA improvement.9,10
Table 1. Acceptance of treatment regime by patients reported in ATS studies8,15
A subsequent randomised clinical trial compared less frequent (weekend only) administration of 1% atropine drops to daily atropine as an initial treatment for three-year-old to seven-year-old children with moderate amblyopia.11 VA improvement was 2.3 lines in both groups at the four-month outcome visit. Those who had shown VA improvement at the four-month visit continued on treatment.
At the time of study completion, approximately 50 per cent in both groups had amblyopic eye VA of either 6/8 or better, or VA within one line or equal to that of the fellow eye; 80 per cent reached their maximum VA improvement by four months; some showed continued improved for up to 10 months.
Prescribing a plano lens to the sound eye to augment the effect of atropine by creating blurred distance vision in addition to increased blur at near has also been evaluated in a randomised trial.12 Prescribing a plano lens did not substantially improve amblyopic eye VA compared with prescribing weekend atropine alone; however, more patients (40 per cent) achieved 6/7.5 or better VA in the added plano lens group than in the atropine alone group (29 per cent). Amblyopic eye VA improved at least three lines in approximately 50 per cent of the participants. Atropine has also been shown to be an effective treatment for children with severe amblyopia of 6/30 to 6/120.9
For moderate amblyopia in children 3 to < 7 years of age:
• Atropine penalisation (one drop in the non-amblyopic eye) has a similar treatment effect as two hours and six hours of prescribed patching; thus, it can be considered for first-line amblyopia treatment or for patching failures.
• Daily atropine administration is not necessary; a twice-per-week schedule is also effective; daily administration has not been shown to result in larger improvements or quicker results.
• There is no evidence that atropine needs to be administered only on weekend days or that the days need to be sequential.
• Atropine penalisation can be effective in treating both moderate and severe amblyopia, and amblyopia in children older than seven years of age.
Reverse amblyopia and measuring sound eye VA
Although some children in the aforementioned clinical trials had apparently reduced sound eye VA at follow-up visits, there were no cases of persistent reverse amblyopia, where VA measured more than one line worse than baseline, after discontinuation of atropine.9,10,12 Initially, reverse amblyopia was suspected in some children but it was then determined that in most of these cases the sound eye VA had not been assessed through the full hyperopic correction.
Atropine can uncover hyperopia additional to that found with cyclopentolate drops at the initial refraction. Therefore, it is important to determine if the atropinised sound eye has any uncorrected hyperopia, and when present, to measure sound eye VA through the full hyperopic prescription at follow-up visits. Nevertheless, it is important to monitor sound eye VA during atropine penalisation therapy because there are reported cases of reverse amblyopia in the literature.13,14
The most common ocular adverse effect associated with atropine treatment in the aforementioned studies was light sensitivity, with reports varying from seven per cent to 29 per cent, albeit rarely sufficient to lead to a change in treatment.9,12,15 Systemic reactions were rare and in most instances these children were switched to daily 5% homatropine.6,11,12 Although we are not aware of any studies substituting 1% cyclopentolate, it is possible this shorter-acting cycloplegic eye-drop could be similarly effective if administered daily.
Use in older children
There is currently no known age cut-off in terms of visual plasticity and thus the potential for successful amblyopia treatment. While amblyopia is more responsive to treatment in younger children, many older children have marked improvements in VA.16
In a clinical trial of seven-year-old to younger than 13-year-old children with moderate amblyopia, VA improvements were found to be comparable for those who were randomised to two hours of patching compared with those randomised to weekend-only atropine.17
Reading requirements during school days should be considered for older children who are being treated with atropine, particularly when their sound eye has hyperopic refractive error that is under-corrected.
Atropine penalisation for amblyopia is an alternative treatment to patching for children with moderate amblyopia and has also been shown to be effective for some patients with severe amblyopia. Two days per week is typically an effective dose. Light sensitivity can be easily managed with sunglasses and a brimmed hat when outdoors; systemic reactions are rare. Overall, parents and children generally find atropine penalisation to be an acceptable treatment method and often prefer it to patching. In addition to using atropine as a first-line treatment for amblyopia, it should be considered for patching failures.
ML, an active pre-schooler, presented at four years and nine months of age. He had been prescribed glasses to be worn full-time and patching of his right eye for five hours per day at the age of two years; however, his glasses were broken and patching had been abandoned because of an allergic reaction to adhesive patches and non-compliance with a ‘Pirate Pete’ eye patch.
Pertinent clinical findings were a cycloplegic refraction of RE +8.00 DS and LE +9.50 DS, with best-corrected VA of 6/9 and 6/45 in the right and left eyes, respectively.
In regard to patient management, the importance of full-time glasses wear was emphasised, and given the history of non-compliance with patching, twice weekly 1% atropine penalisation was prescribed.
Amblyopic eye VA improved from 6/45 to 6/30 at the three-month review and then to 6/21 at the six-month review. ML is still on treatment with the aim of his showing further improvement at the next review.
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