In the treatment of strabismic, anisometropic, or mixed strabismic/anisometropic amblyopia, published literature suggests atropine penalization is as effective as occlusion for mild and moderate amblyopia and can be promoted as a first-line treatment for such severities.1–5 It has also been shown to be a viable treatment for severe amblyopia1,5–8 and can be used in older children to avoid the associated social stigma of occlusion.9
Despite these findings, evidence suggests atropine penalization is rarely used as first-line treatment in the United Kingdom.10,11 A recent survey examined reasons why atropine penalization was not used by head orthoptists.10 However, opinions were not evaluated in those who would consider atropine penalization (but only as second-line treatment). Possible explanations for avoiding use of atropine penalization as first-line treatment could include severe side effect risk (eg, flushing, irritability, headache, heart problems, and death),12 photosensitivity,4,6,9 perceived inefficacy compared to occlusion,7,10 reverse amblyopia risk,6,13,14 atropine supply problems,5 or the logistics of needing an ophthalmologist to prescribe atropine.15
Another reason for avoidance of atropine penalization as first-line treatment could be lack of a consistent evidence base to guide clinical practice. The literature on logistical aspects of atropine penalization is diverse. For example, the prescribed dosage has varied from daily1,3–7,16,17 to just weekend8,9,18 administration, although twice-weekly and weekend atropine have now been shown to be as effective as daily atropine for mild and moderate amblyopia.2,6,19,20 Treatment duration varies from 1 month1 to 6.9 years6 and the duration of treatment required to obtain maximal visual acuity improvement is conflicting (3.6 to 6 months).3,5,7 It has also not been established whether weaning off atropine when stopping treatment would help reduce incidence of visual acuity regression in the amblyopic eye.16,17,21 Finally, efficacy of atropine penalization has not been evaluated in treating stimulus deprivation and ametropic amblyopia, and it is not known whether these amblyopia types are treated with atropine penalization in practice.
Although briefly examined in a previous amblyopia treatment survey,10 the specific use of atropine penalization in UK clinical practice has not been previously studied. The current study aimed to determine the current clinical practice of atropine penalization in the United Kingdom, identify perceived barriers limiting use of atropine penalization as first-line treatment, and ascertain whether any of the barriers could be resolved, thereby giving patients a wider treatment choice.
Responses were obtained from 151 orthoptists throughout the United Kingdom. As a proportion of the entire orthoptic workforce, this only equated to 13% (n = 1,123 [963 of whom were BIOS members]), but most (71%) indicated that they had departmental protocols regarding the use of atropine. The sample obtained was therefore likely to give a fair representation of clinical practice in the United Kingdom. Most respondents were from England (12% of total from region, n = 111), although percentage coverage in other regions was higher due to lower headcounts (Scotland = 19%, n = 19; Northern Ireland = 26%, n = 8; Wales = 24%, n = 11; Islands = 67%, n = 2).
Patient Selection and Logistical Aspects of Using Atropine Penalization in Clinical Practice
Of respondents using atropine penalization within clinical practice (93% of sample; non-users = 5.5%, no answer = 1.5%), only 25% used it as first-line treatment. All respondents were asked about age groups and amblyopia types and severities they would hypothetically target with first-line atropine penalization treatment (Figures 1–2). Children younger than 7 years were most commonly targeted; 93% of respondents would use atropine penalization in children ages 4 to 7 years (Figure 1). Although 65% of respondents would use atropine penalization in those younger than 4 years, only 3 respondents (2%) would consider using atropine penalization only in this age group. Twenty-three percent of respondents would consider using atropine penalization in those older than 7 years, with just 1 respondent (< 1%) who would consider using atropine solely in this age group. In terms of the depth of amblyopia that would be considered for treatment with atropine, a wide range of interocular acuity differences were identified (Figure 2) and tended to be skewed toward moderate and dense amblyopia (> 0.300 logMAR). The most common amblyopia types that respondents would consider treating with atropine penalization were strabismic (92%), anisometropic (74%), and mixed strabismic/anisometropic (91%), although some would consider atropine penalization when treating stimulus deprivation (40%) and ametropic (11%) amblyopia.
Patient selection criteria for hypothetical use of atropine penalization as indicated by respondents (n = 151) with regard to patient age. Respondents were asked to assume atropine penalization was being used as first-line treatment (no previous occlusion).
Patient selection criteria for hypothetical use of atropine penalization as indicated by respondents (n = 151) with regard to level of interocular acuity difference. Respondents were asked to assume atropine penalization was being used as first-line treatment (no previous occlusion).
Eighty-nine percent of respondents said they would stop treatment in successful cases after there was no visual acuity improvement on three consecutive visits. Some also said they stopped when visual acuity was equal (63%), fixation began to alternate or completely swapped (36%), or after treatment for a certain period of time (28%, 1.5 to 6 months). On terminating treatment, 28% of respondents would decrease atropine dosage over time (weaning), with the remainder choosing to stop that visit.
Current Use of Atropine Penalization in Clinical Practice
Favored atropine penalization dosage was daily administration (48%), followed by alternate day (41%) and weekend (29%), with a small proportion who preferred weekly doses (9%). Seventeen percent of respondents used more than one dosage frequency. Between July 2010 and July 2011, respondents administered atropine penalization to a median of 5 patients (range: 0 to 350 and 0 to 40 [excluding outliers], respectively; interquartile range: 7 [unchanged, excluding outliers]). Of those using atropine as first-line treatment (n = 37), the median duration of use in practice was 4 years (range: 0.3 to 30 years; interquartile range: 4).
Adverse Effects of Using Atropine Penalization
Respondents using atropine penalization in their department (n = 141) were asked to report side effects in patients receiving atropine penalization between July 2010 and July 2011. Of systemic side effects associated with atropine, those most commonly reported by respondents were skin rash/flushing (19% of respondents), mood changes (13%), and eye irritation/pain (11%). Occurrence of other systemic side effects was low (eg, dry mouth [4%], swelling of facial region/tongue or dizziness [1.5%], and fainting, constipation, or breathing problems [1%]). Sixteen percent of respondents were unable to recall whether any of their patients receiving atropine penalization had experienced side effects.
Side effects were of concern to many respondents (n = 151), with 71% feeling there was a significant risk of side effects when using atropine at all (13%), on a long-term basis (18%), or at high dosages (40%). Only 28% felt there was no significant risk of side effects (no answer = 1%). When asked if they avoided atropine penalization due to risk of side effects, 18% of respondents answered yes (no = 81%; no answer = 1%).
Between July 2010 and July 2011, survey respondents reported an estimated 39 cases of reverse amblyopia following atropine penalization treatment alone or with optical penalization/occlusion. However, many respondents stated their cases were more than 12 months ago or they were unsure how many they had seen, making it impossible to determine actual incidence. All reported cases of reverse amblyopia were successfully treated and resolved.
Barriers to Use of Atropine Penalization
For department-specific problems limiting ability to use atropine penalization, inability to prescribe and obtain prescription for atropine was most frequently cited (32%) (Table 1). Survey data also indicated that 60% of respondents (n = 91) had trouble obtaining atropine (37% = no, 3% = no answer), inhibiting use of the treatment. Thirty-two percent of this group had to change to Minims atropine 1% (Bausch & Lomb, Surrey, United Kingdom) that consisted of single-use 0.05-mL droppers given in a box of 20, which 4 respondents (4%) considered to be either not cost effective or to have too great of a risk to be given to the parents to use.
Barriers to Use of Atropine Penalization Reported by Respondents (n = 105 of 151)
Respondents were asked for their opinion of atropine penalization regarding promotion of compliance, level and speed of visual acuity improvement in the amblyopic eye, and stability of visual acuity after treatment (Figure 3). Atropine penalization was considered more likely to gain compliance compared to occlusion, but occlusion was considered to give a better treatment effect and a faster rate of improvement and stability after treatment cessation (Figure 3). The rationale given by respondents for these views is summarized in Table 2.
Respondent opinions (n = 151) on atropine penalization in comparison to occlusion with regard to most effective treatment for promotion of compliance, speed and level of visual acuity (VA) improvement in the amblyopic eye, and maintenance of stable VA in the amblyopic eye after treatment. Dependencies included parental attitude and motivation; the individual patient; compliance; density, etiology, and type of amblyopia; and patient age. Free text answers include those provided by respondents as supplementary information to other options selected.
Summary of Thoughts and Opinions Reported by Respondents Regarding Atropine Penalization (n = 52)
Based on survey responses, percentages of orthoptists offering atropine as first-line treatment and at lower dosages have increased from previous figures.10 Current evidence may have facilitated this, as reflected by the skewed median duration that respondents used atropine penalization as first-line treatment in clinical practice (4 years). Where the evidence base was limited, recommended practice for occlusion was sometimes applied (eg, terminating treatment after three consecutive visits with no visual acuity improvement).23
Amblyopia types and severities targeted with atropine penalization follow current evidence that found it a viable treatment for all severities of strabismic, anisometropic, and mixed strabismic/anisometropic amblyopia.1–9,18 Some aspects of practice do not follow current evidence, but explanations can be identified. For example, fewer respondents targeted older children (> 7 years) using atropine penalization (Figure 1), which contradicts current evidence.3,8,9 However, 2 respondents mentioned they avoided atropine penalization use in patients with intractable diplopia risk. Some respondents also expressed concerns about the systemic retention and potency of atropine once instilled (Table 2). This may correlate with reluctance to use atropine penalization in older children at a higher risk of developing intractable diplopia,24,25 although current evidence indicates that systemic retention of atropine reduces with increasing age.26
Although more orthoptists are using atropine penalization, concerns regarding side effects and reverse amblyopia are still identified as off-putting (Table 2) despite low occurrence of reverse amblyopia4,9,13,14,16–18,20 and side effects3,4,7,9,17–20 in the literature. It was not possible to quantify the number of reverse amblyopia cases occurring in a year using current survey data, but a prospective survey in the future may help monitor this.
There may be other barriers contributing to lack of atropine penalization use as first-line treatment. The most commonly referenced barrier was obtaining atropine prescriptions (Table 1), but power to prescribe would not address supply problems. Difficulties obtaining atropine drops and ointment, which delayed and prevented treatment, were described by 60% of the sample. Some respondents also expressed concerns regarding the efficacy and cost of substitute Minims atropine, which is more expensive than occlusion patches in the United Kingdom (based on UK prices from April 2014, a box of 20 Minims atropine costs £21.79 in comparison to £6.29 for a box of 20 Opticlude occlusion patches [3M, St. Paul, MN]).
Even if such barriers were surmounted, atropine penalization is perceived to lack efficacy compared to occlusion in many aspects of amblyopia treatment (Figure 3). Some respondents (23%) considered atropine penalization better for promoting compliance (Figure 3), which is supported by opinions in Table 2, but is countered by those feeling occlusion compliance was sufficient enough to not require atropine penalization. More respondents (30%) considered compliance dependent on parental attitude and motivation and the individual patient. The evidence base was also divided on this matter,4,27 correlating with lack of consensus among respondents.
Only 1% of respondents considered atropine penalization more effective in improving amblyopic eye visual acuity (Figure 3). The low median number of patients receiving atropine per year by the sample indicates a tendency to use atropine more as second-line treatment, supported by free text answers frequently stating atropine was used as a last resort. Prognosis may be more limited in such cases and may have affected overall opinions of atropine efficacy in improving visual acuity.
Occlusion was also considered to give the fastest visual acuity improvement (Figure 3). One study4 demonstrated that occlusion produces a faster visual acuity improvement than atropine penalization, although no statistical comparison was made between the two treatment groups. There are no other supporting studies for this. In many cases, respondents were unsure which treatment they preferred or whether they were similar, indicating further research is required in this area.
When asked to indicate which treatment provided best stability of visual acuity after treatment, 37% selected occlusion (Figure 3), but a comparable percentage considered the two treatments similar. This agrees with current evidence showing similar regression/stability rates between the two treatments.5,21
Overall, bias toward second-line use of atropine penalization treatment could originate from perceived inefficacy of atropine penalization compared to occlusion, atropine supply and prescribing issues, wariness of side effects and reverse amblyopia, and other opinions described in Table 2. Monitoring occurrence of side effects and reverse amblyopia with a national database could help alleviate certain concerns and facilitate evidence-based decisions about whether to use atropine penalization, and this study is currently being undertaken by one of the authors.
Other avenues for further research were also highlighted by this survey. A proportion of respondents (28%) reduced atropine dosage over time when stopping treatment, similar to weaning off occlusion.16,17,21 Determining the effect of atropine penalization weaning on visual acuity regression may help practitioners evaluate efficacy of atropine penalization in maintaining visual acuity stability after treatment. No literature could be identified that examined treatment of stimulus deprivation amblyopia with atropine penalization, yet 40% of respondents considered this an option. Research is needed to determine best practice for the use of atropine penalization in this group.
Some limitations of the study findings exist. The response rate was lower than anticipated; however, some departments notified one of the authors (MP) that they had returned one response representative of departmental working practices and 71% of respondents were working to a departmental atropine protocol. Therefore, the survey responses were likely to give a reasonable representation of actual clinical practice. Another caveat to consider is the possibility that orthoptists not currently practicing or not practicing within the United Kingdom or Islands may have answered the survey, although it was stated in the invitation and attached information sheet that respondents needed to be qualified and currently practicing with the United Kingdom or Islands to be eligible to participate. An e-mail address was provided for queries about survey eligibility and orthoptists who were practicing outside of the United Kingdom and Islands who enquired via this address were instructed not to participate. We made every effort to ensure that the likelihood of respondents not meeting these eligibility criteria was very small, although we cannot absolutely guarantee it with an anonymous survey.
Finally, a responder bias toward using atropine penalization as second-line treatment exists. This may reflect current practice patterns because regular atropine penalization users are more likely to respond in comparison to the previous survey, which additionally examined other aspects of practice (eg, occlusion) and therefore may have garnered more general interest from clinicians. An effect of this is opinions of orthoptists using atropine penalization as first-line treatment may have been relatively masked by those using it as a last resort.
The data reported here demonstrate that more orthoptists in the United Kingdom are using atropine penalization as first-line treatment since 2010. Practice patterns are changing to follow published literature. It is not certain whether this translation into evidence-based practice is happening in other countries because a recent study in North America found Pediatric Eye Disease Investigator Group recommendations for evidence-based amblyopia management had not been widely translated into clinical practice28 and only looked at occlusion treatment, excluding children having atropine penalization. However, despite this change in practice patterns, many clinicians still raise concerns regarding general efficacy, side effects, and reverse amblyopia. The evidence base for these areas may not have filtered into clinical practice, or is not sufficient to convince clinicians that atropine penalization can be used safely and effectively to produce good clinical outcomes. Common barriers against use of atropine penalization relate to obtaining prescriptions and atropine supplies.
Even with addressing these issues, first-line atropine penalization use may still remain low in the United Kingdom. This is due to a reluctance to use atropine penalization compared to alternatives without additional risk of systemic side effects (eg, occlusion). However, when considering some of the negative psychosocial consequences of occlusion and the increasing importance of patient choice, there is a strong argument for offering atropine penalization as first-line treatment of moderate amblyopia. Yearly incidence data on side effects/reverse amblyopia through atropine penalization use will also help to guide orthoptists and patients on the relative advantages and disadvantages, and choosing between the two similarly effective treatments.