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Does instilling proxymetacaine before cyclopentolate significantly reduce stinging? The implications for paediatric cycloplegia
  2. J D H YOUNG
  1. Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
  1. Dr Shona Sutherland

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Editor,—Cyclopentolate 1% is the drug most commonly used to obtain paediatric pupil dilatation and cycloplegia. It is widely disliked by children and ophthalmic staff because of the severe stinging instillation may produce. As a result many children develop a negative association with the clinic, and become distressed and uncooperative before drop instillation and during subsequent examinations. To try to reduce this discomfort, previous instillation of the local anaesthetic proxymetacaine has been advocated in a single study,1 which reported significant benefit. However, this was a retrospective study, with the particular limitation of using parental recall of their child's distress a year previously, as the measure of the pain experienced with the use of cyclopentolate alone. We therefore considered that more data were required before the use of proxymetacaine is included in routine cycloplegia.

Because cyclopentolate is unstable at neutral pH, preparations are acidified with dilute hydrochloric acid to around pH 4 so that stinging on instillation might be expected.

However, although proxymetacaine has been shown to sting less than other local anaesthetic drops, it is also acidified with hydrochloric acid to a similar pH and can cause discomfort

It could be that stinging is not the sole reason for children's unhappy memories of their clinic visit. Factors not yet evaluated include lack of understanding, a dislike of eye examination, and a recollection of the prolonged blurring produced by the cycloplegia in hypermetropes.

We designed a study to quantify the pain experienced by patients specifically attributable to cyclopentolate minims 1%, with and without previous instillation of proxymetacaine minims.

We enrolled only adult subjects to allow for accurate numerical pain scoring and to exclude the confounding factors mentioned above. Subjects were adult patients attending the ophthalmology clinic for the first time. Exclusions were pre-existing corneal disease, eye surgery, eye drop use, or an inability to understand the pain scoring system. Informed consent was obtained including the use of an information sheet approved by Tayside ethics committee.

Participating subjects had either proxymetacaine 0.5% or saline instilled in their first eye (either left or right was chosen randomly). Using a standard numerical pain scoring system of 0 to 10, the subjects were asked to record the pain score after all stinging pain has stopped. They were encouraged to record the score of the stinging at its peak. The score was re-recorded after instilling the second, remaining drop in the fellow eye. The process was repeated with the instillation of cyclopentolate 1%, sequentially, in each eye approximately 45 seconds later.

We used a standard numerical pain scoring system 0 to 10. The saline and proxymetacaine labels were covered so that the tests were double blind. All the tests were carried out by one investigator (MS).

In all, 29 subjects completed the study. The age range was 29–84 years, with an average age of 66 years. The mean pain score for proxymetacaine was 0.79 (SD 0.86). This compares with a mean pain score of 0.16 (SD 0.27) with saline. The difference between these is statistically significant (p <0.001). The mean pain score for cyclopentolate instilled after proxymetacaine was 0.36 (SD 0.60). This compares with a mean pain score of 4.19 in the patients who received cyclopentolate after the placebo saline (SD 2.43). This result was highly significant (p <0.001). Taking the total pain scores for each eye and using a parametric test the difference between the total pain scores was found to be highly significant (p <0.001) (Whitney U test). These results are summarised in Tables 1 and2.

Table 1

Results ranked in order of increasing pain score

Table 2

Combined pain score


In this study we found a highly statistically significant reduction in total discomfort with cyclopentolate instilled after premedication with proxymetacaine compared with the use of cyclopentolate instilled after a placebo. We also demonstrated that proxymetacaine does cause some discomfort although this is minor compared with cyclopentolate alone. Most of the pain from the combined medication came from the initial proxymetacaine drop. It has been demonstrated elsewhere that diluting proxymetacaine 0.5% can reduce this stinging substantially without compromising efficacy.2 In practice, however, only the 0.5% preparation is currently commercially available.

This study provides support for the hypothesis that previous instillation of local anaesthetic should reduce discomfort in paediatric cycloplegia. However, as other factors may contribute to the discomfort experienced by children, further studies are required to determine if this benefit is realised in practice. Even if pretreatment with proxymetacaine does prove to be advantageous, it remains an unsatisfactory compromise. Ultimately the best solution to this important issue will be the development of a short acting, non-stinging cycloplegic which is stable at a neutral pH and iso-osmolar with tears.


The authors would like to thank Dr Ruoling Chen for his help preparing the statistics in this study


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