Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Efficacy of a Cycloplegic Agent Administered as a Spray in the Pediatric Population

Aldo Vagge, MD, PhD; Chiara Del Noce, MD; Marco Pellegrini; Francesca Cappelli, MD; Maria Musolino, BSc; Federico Bernabei, MD; Giuseppe Giannaccare, MD, PhD; Carlo E. Traverso, MD

Abstract

Purpose:

To evaluate the efficacy and tolerability of cyclopentolate 1% administered as a spray in pediatric patients between 3 and 6 years old.

Methods:

In this prospective, randomized, parallel group study, healthy volunteers were randomly assigned to receive cyclopentolate 1% as a single drop or a single puff into closed eyes.

Results:

There were 61 patients included in the study; 31 received cyclopentolate 1% as drops and 30 received cyclopentolate 1% as spray. The mean age at presentation was 4.5 ± 1.07 years (range: 3 to 6 years) and 4.2 ± 1.06 years (range: 3 to 6 years) in the drops and spray groups, respectively. The distress level was significantly lower at the time of receiving cyclopentolate as a spray (P < .0001), with the exception of patients aged 6 years. There were no significant differences in pupil diameter between the two groups (P = .51), whereas 5 of 30 patients (16.6%) with dark irises who received cyclopentolate spray did not have adequate cycloplegia to allow for accurate refraction.

Conclusions:

Cycloplegia achieved with cyclopentolate 1% administered as a spray may be an option in uncooperative children because it is less distressing compared to cyclopentolate 1% drops. However, physicians should be aware that cycloplegia obtained is only partially effective in children with dark irises.

[J Pediatr Ophthalmol Strabismus. 2020;57(5):301–304.]

Abstract

Purpose:

To evaluate the efficacy and tolerability of cyclopentolate 1% administered as a spray in pediatric patients between 3 and 6 years old.

Methods:

In this prospective, randomized, parallel group study, healthy volunteers were randomly assigned to receive cyclopentolate 1% as a single drop or a single puff into closed eyes.

Results:

There were 61 patients included in the study; 31 received cyclopentolate 1% as drops and 30 received cyclopentolate 1% as spray. The mean age at presentation was 4.5 ± 1.07 years (range: 3 to 6 years) and 4.2 ± 1.06 years (range: 3 to 6 years) in the drops and spray groups, respectively. The distress level was significantly lower at the time of receiving cyclopentolate as a spray (P < .0001), with the exception of patients aged 6 years. There were no significant differences in pupil diameter between the two groups (P = .51), whereas 5 of 30 patients (16.6%) with dark irises who received cyclopentolate spray did not have adequate cycloplegia to allow for accurate refraction.

Conclusions:

Cycloplegia achieved with cyclopentolate 1% administered as a spray may be an option in uncooperative children because it is less distressing compared to cyclopentolate 1% drops. However, physicians should be aware that cycloplegia obtained is only partially effective in children with dark irises.

[J Pediatr Ophthalmol Strabismus. 2020;57(5):301–304.]

Introduction

In young patients, refractive assessment is usually influenced by the accommodative spasm with a possibly myopic shift in the results. Cycloplegic refraction using cycloplegic drugs is an effective way to reduce fluctuation in accommodation or spasm of ciliary muscle.1 Tropicamide and cyclopentolate are two of the most commonly used agents for cycloplegia in children.2 Instillation of cycloplegic eye drops often represents a stressful event for children due to the associated stinging and burning sensation, and it can lead to a subsequent negative effect on the relationship between physicians and patients and poor cooperation during the examination.3 Several methods of administration of cycloplegic agents have been developed to reduce children's distress.4,5

The aim of this study was to evaluate the efficacy and tolerability of cyclopentolate 1% spray in patients aged 3 to 6 years.

Patients and Methods

This was a cross-sectional, parallel group study. All participants gave their informed consent and the study followed the principles of the Declaration of Helsinki. The study involved children between 3 and 6 years of age who required cycloplegic refraction at the pediatric ophthalmology service. All healthy volunteers attending the clinic were eligible for the study. Exclusion criteria were allergy to cyclopentolate and uncooperative patients.

Participants were assigned to receive cyclopentolate 1% as either a spray or drops according to a pseudo-random numbers table (RAND function, Microsoft Excel; Microsoft Corporation).

Before introducing the cyclopentolate 1% into the spray bottle, the container was sanitized with 3% hydrogen peroxide soak for 10 minutes, rinsed several times using sterile saline, and then air dried.6 Finally, the spray bottle was labelled “cyclopentolate 1%.”

Cyclopentolate 1% spray was administered with the bottle being held 5 to 10 cm in front of the closed eye and the child sitting upright. One drop was instilled in the inferior fornix using the conventional method, with the child's head tilted back. Cyclopentolate 1% was administered twice at 15-minute intervals and the cycloplegic evaluation was performed between 30 and 40 minutes following the last instillation.

Distress on receiving cyclopentolate was evaluated by the parent/guardian using a numerical rating scale7 on which 0 means no distress and 10 means severe distress.

A second investigator masked to the drug delivery method assessed cycloplegic and mydriatic response based on measuring pupil diameter and autorefractometry before and after drug administration. Adequacy of cycloplegia was assessed before autorefraction, by pupil dilation greater than 6 mm, absence of pupil reaction to light, and accommodative stimulus. Cycloplegia was assessed by absence of the pupillary light reflex and accommodative amplitude less than 2.00 diopters (D).8 Refraction measurement was performed using the TOPCON AR RM-8000B autorefractometer (Topcon). Accommodative effort was computed as the average of three readings. The mean difference between noncycloplegic and cycloplegic refraction was compared between the two regimens using the spherical equivalent change. At the end of the visit, patients' parents/guardians were told to report any adverse reactions that may arise following the examination.

All data were expressed as means and standard error of the mean. The Shapiro-Wilk test was used to assess the normality of data. Parameters of two treatments were compared using the t test for continuous variables and the chi-squared or Fisher's exact test for categorical variables. The correlations were evaluated by Spearman's correlation coefficients. A P value less than .05 was considered significant. Prism 5.0 software (GraphPad Software) was used to analyze the data.

Results

Demographic and clinical features of the study population are reported in Table 1. Sixty-one consecutive children comprised our study group, with 31 (50.8%) receiving cyclopentolate 1% drops and 30 (49.2%) receiving cyclopentolate 1% spray. Eighteen of 31 (58%) in the drops group and 17 of 30 (56.6%) patients in the spray group were male. Mean patient age was 4.5 ± 1.07 (range: 3 to 6 years) and 4.2 ± 1.06 years (range: 3 to 6 years) in children treated with drops and spray, respectively. There were no significant differences in age (t test, P = .69) and gender (chi-square test, P = .16) between the two groups. Fifty-four (88.5%) patients were White, 4 (6.5%) were Hispanic or Latino, and 3 (5%) were Black. No significant differences were found in iris color and race between the drops and spray groups (P = 47 and .44, respectively).

Demographic and Clinical Characteristics of the Cyclopentolate 1% Drops and Spray Groups

Table 1:

Demographic and Clinical Characteristics of the Cyclopentolate 1% Drops and Spray Groups

Clinical parameters related to cyclopentolate administration in the two groups are reported in Table 2. The mean numerical rating scale score to evaluate distress levels on receiving drops or spray was 6.4 ± 1.20 and 4 ± 1.44, respectively. The difference between the two groups was statistically significant (P < .0001). The difference was not significant in children aged 6 years (P = .45). There were no significant differences regarding pupil diameter (6.2 vs 5.9 mm, drops vs spray, respectively, P = .28) and spherical equivalent change (1.50 vs 1.30 D, drops vs spray, respectively, P = .07). Five of 30 (16.6%) patients who received cyclopentolate spray did not have adequate cycloplegia to allow for accurate refraction and these children had dark iris. No complications were reported immediately after the examination or during the follow-up period.

Clinical Parameters After Cyclopentolate Administration

Table 2:

Clinical Parameters After Cyclopentolate Administration

Discussion

Cycloplegia allows physicians to obtain the most accurate and reliable data about refraction by blocking the accommodation and represents the gold standard method to evaluate refractive errors in children.9–11 Incomplete cycloplegia may lead to latent refractive errors that have been described to be associated with high hyperopia.12 Because uncorrected refractive errors in newborns and children increase the risk of amblyopia, it is mandatory to perform a careful refractive examination under cycloplegia.13

Cycloplegia is commonly achieved by the instillation of cyclopentolate 1% eye drops instilled in the inferior cul-de-sac. Cyclopentolate is a synthetic antimuscarinic cycloplegic agent that provides rapid onset of the cycloplegic effect, 25 to 75 minutes after administration, and recovery 6 to 24 hours later.14 The main side effect associated with cyclopentolate eye drop instillation is the stinging and burning sensation due to the low pH of the drug.4 This may result in loss of cooperation of the child during the subsequent examination. Spray administration of the cycloplegic agent may be useful to avoid the fear of getting something instilled in the eye and the necessity of forcefully opening the eyelids in uncooperative children.

In the current study, we evaluated the efficacy and tolerability of spray administration of cyclopentolate 1% in pediatric patients aged 3 to 6 years. The patients randomly assigned to the spray group reported a lower level of distress, with a significantly lower numerical rating scale score. This result is consistent with a previous study by Syrimi et al,5 which reported lower distress in children aged 1 to 7 years receiving cyclopentolate 1% spray, thus confirming the higher tolerability of this administration route. The administration of cycloplegic eye drops in un-cooperative children often requires the physician to force the opening of the eyelids. Conversely, spray administration on the closed eye considerably decreases the distress related to cycloplegic administration and does not compromise the subsequent steps of the ophthalmologic examination.

In our study, the numerical rating scale score was not significantly different in children aged 6 years. In agreement with this, Syrimi et al5 also noted that the difference in distress level was not significant in children older than 7 years. This may reflect a better understanding of the physician's explanation, less fear, and better cooperation due to the greater cognitive maturity of older children.15 Thus, spray administration of cycloplegic agents may be particularly indicated in younger patients.

No difference in pupil diameter between the two groups was observed. However, some patients with dark irises who received cyclopentolate spray did not achieve adequate cycloplegia. A higher failure rate in achieving cycloplegia with cyclopentolate 1% spray in dark irises was previously reported by Syrimi et al5 and Zurevinsky et al.16 These patients might require a higher concentration of cyclopentolate that may not be achieved by spray administration. Further studies are required to address this issue. Nevertheless, as reported by a previous study, some of the children may not achieve adequate cycloplegia even with the conventional use of cyclopentolate 1% drops.17

No adverse effects were observed after administration of cyclopentolate 1% spray. To ensure the sterility of the spray container, a 3% hydrogen peroxide–based treatment must be performed. Kim et al6 showed how this process guarantees the absence of microbial growth on the spray bottle during a 12-week period.

Although it can be assumed that the use of sprays may determine the spread of the eyelid bacterial flora in the conjunctival fornix, none of the patients presented inflammatory or infectious complications in the days following the examination. In agreement with previous studies,5 our results reveal a good safety profile of cyclopentolate 1% administered as a spray.

The main limitation of this study is related to the relatively small sample size. In particular, Black and Hispanic patients were poorly represented in the sample evaluated, not allowing a stratification according to patients' race. Moreover, although it has been shown that autorefractometry is able to provide reliable results in an independent operator fashion, retinoscopy could detect residual accommodation more easily.

Cyclopentolate 1% spray is effective in reducing the stress due to the administration of cycloplegic agents in young children. However, this administration system is only partially effective in children with dark irises. Thus, the traditional method of administration should be preferred in this subtype of patient.

References

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Demographic and Clinical Characteristics of the Cyclopentolate 1% Drops and Spray Groups

CharacteristicCyclopentolate Drops (n = 31)Cyclopentolate Spray (n = 30)P
Age (y), mean ± SD4.5 ± 1.074.2 ± 1.06.69a
Male gender, n (%)18 (58.0)17 (56.6).16b
Iris color, n (%).47b
  Dark/brown19 (61.3)21 (70)
  Blue/green12 (38.7)9 (30)
Race, n (%).44b
  Black1 (3.2)2 (6.7)b
  Hispanic or Latino1 (3.2)3 (10.0)
  White29 (93.5)25 (83.3)

Clinical Parameters After Cyclopentolate Administration

ParameterCyclopentolate DropsCyclopentolate SprayP
Distress on receiving cyclopentolate (NRS scale), mean ± SD6.4 ± 1.204.0 ± 1.44< .0001a
Pupil diameter (mm), mean ± SD6.2 ± 0.635.9 ± 1.37.28a
Change in spherical equivalent (D), mean ± SD1.50 ± 0.311.30 ± 0.56.07a
Rate of adequate cycloplegia (%)10083.4
Authors

From the Eye Clinic of Genoa, San Martino Polyclinic, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, IRCCS San Martino Polyclinic Hospital, Genoa, Italy (AV, CD, FC, MM, CET); Ophthalmology Unit, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy (MP, FB); and the Department of Ophthalmology, University Magna Graecia of Catanzaro, Catanzaro, Italy (GG).

The authors have no financial or proprietary interest in the materials presented herein.

The authors thank Dr. Alessia Maria Jenny Morlacchi for his help in preparing this manuscript.

Correspondence: Aldo Vagge, MD, PhD, Eye Clinic of Genoa, DiNOGMI, University of Genoa, IRCCS Ospedale Policlinico San Martino, Viale Benedetto XV, 5, 16132 Genova, Italy. Email: aldo.vagge@unige.it

Received: March 04, 2020
Accepted: May 27, 2020

10.3928/01913913-20200803-01

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