Analysis of The Study on Adverse Reactions to 1% Cyclopentolate Eye Drop in Children

Cyclopentolate hydrochloride is a drug used before routine eye examinations such as refraction exams. It is often characterized by a faster onset and shorter duration of action compared to its alternative cycloplegic eye drop atropine sulfate hydrate.

Refractive errors are known to cause decreased visual acuity and problems in binocularity (e.g. strabismus). Because of their strong accommodative reflexes and inability to respond to subjective refraction, objective refraction in children is required to assess their refractive state.

Objective refraction can be done with cycloplegia through an anticholinergic eye drop such as cyclopentolate and tropicamide. Based on the patient’s ocular alignment, the refractive error, and iris color, cyclopentolate should be applied 1-3 times.

Cycloplegic autorefraction is considered the standard in epidemiological studies on refractive development and randomized controlled trials in testing myopia control treatment. However, cyclopentolate causes adverse reactions with multiple severities.

Some mild cases include itching, heat sensation, facial flush, drowsiness, and restlessness. Severe cases include psychosis, hallucination, seizure, impaired consciousness, and memory loss. Past studies have indicated that young age, lower body mass index, repeated instillation, and central nervous system complications are significant risk factors.

What is Cyclopentolate?

Cyclopentolate is a type of muscarinic receptor antagonist (MRA) that is used during eye examinations to dilate the eye (mydriasis). It prevents the eye from focusing (cycloplegic).

Cyclopentolate is a type of medication called mydriatics which works by blocking receptors in the eye to provide short-term paralysis or relaxation to the eye muscles. Cyclopentolate or atropine can also be applied to reverse muscarinic and central nervous system effects of indirect cholinomimetic administration.

Both the adverse and side effects of cyclopentolate are similar to other anticholinergic medications which is why extreme precaution is needed when prescribing cyclopentolate to patients that are taking anticholinergic medications. Other uses of cyclopentolate include the treatment of uveitis (inflammation of the eye).

Some of the common side effects of cyclopentolate include:

• Eyelid swelling
• Eye redness
• Eye burning or heat sensation
• Blurred vision
• Eye sensitivity to light
• Increased eye pressure

Purpose of study

The purpose of the study is to determine the symptoms, risk factors, and frequency for the adverse reactions of two-times installation of 1% cyclopentolate in children.

The Study Population

The study consists of 690 consecutive patients who visited the Department of Ophthalmology at Kawasaki Medical School’’s General Medical Center. This was conducted between April 2016 to March 2017. 44 patients who had eye diseases were excluded except for those who had refractive errors, strabismus, amblyopia, or were older than 15 years old. From there the data was analyzed from the remaining 646 patients.

The age range was from 3 months to 14.8 years of age (with a mean of 7). There were 314 boys and 332 girls. The study was approved by the ethics committee of Kawasaki Medical School. It was also conducted under the principles of the Declaration of Helsinki. Informed consent was also obtained from the children’s guardians before the examination.

The Study Design

The study is prospective and observational with a goal to determine three things:

1. Frequency
2. Symptoms
3. Risk Factors

This is in relation to the adverse reaction of 1% cyclopentolate in children. The sample has a total of 646 patients who had cycloplegic refraction with cyclopentolate. The age range of the study is from 0 to 15 years and the mean range of the children in the study is 7.

Methods

646 patients underwent cycloplegic refraction with cyclopentolate. They were instilled with 0.4% oxybuprocaine hydrochloride. After five minutes, they were given two certified 1% cyclopentolate eye drops with an interval time of 10 minutes.

After 50 minutes, two orthoptics evaluated the reactions using a questionnaire and interviewed the patients’ guardians. Data about the patient’s adverse reaction rate, gender, age, season, and complications of the central nervous system was gathered. The results were analyzed using binomial and polytomous logistic regression models.

The Results

Based on the data, the overall frequency of adverse reaction was at 18.3% or 118 of the 646 patients. This frequency is higher than expected but is not serious. The main symptoms found are the following:

• Facial flush (mostly in children younger than 4 years)
• Drowsiness
• Conjunctival injection

The adverse reactions to 1% cyclopentolate eye drops were more common than previously believed but all reactions were mild. Furthermore, the symptom was correlated with age. The odds ratio of conjunctival injections increased with age in boys and during winter. The odds ratio of drowsiness decreased with age.

Facial flush was observed mostly in children younger than 4 years. Because of this, we recommend using 0.5% cyclopentolate rather than % for this age range. The study also found that CNS complications did not pose a significant risk factor for any of the symptoms. Based on the data, it’s clear that the adverse reactions have an age-specific trend.

Limitations of the Study

There are several limitations to the study. First, the doctors compressed the lacrimal sac after the instillation. Insufficient compression often leads to a higher frequency of adverse reactions.

Second, 0.4% oxybuprocaine eye drops were applied before the instillation of cyclopentolate. Topical anesthesia is often used in clinics to measure intraocular pressure or when placing diagnostic contact lenses. Adverse reactions are rare but there has been mild damage to the corneal and conjunctival epithelial cells caused by the oxybuprocaine.

Patients who had asthmas and were using oral anticholinergics may have produced a synergistic effect during the time of cycloplegic refraction.

The study design did not allow the determination of the exact time of onset or duration of the symptoms. Some of the symptoms were also still present when some patients left the clinic

which means it lasted at least 60-90 minutes after onset.

There have been no cases of severe reaction such that patients had to postpone their departure due. Furthermore, none of the guardians contacted any adverse reaction.