Comparison of cyclopentolate versus tropicamide cycloplegia: A systematic review and meta-analysis

Methodological quality of the review: Medium confidence

Author: Negareh Yazdania, Ramin Sadeghic, Hamed Momeni-Moghaddama, Leili Zarifmahmoudic, Asieh Ehsaeia

Region: China, India, USA

Sector: Refractive error

Subsector: RE diagnostic

Equity focus: No

Study population: Children and adults

Type of programme: Hospital based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Refractive assessment, especially in patients younger than 40 years, is usually impressed by the accommodative spasm and possibly a myopic shift in the results. Spasm of accommodation becomes evident as pseudomyopia or latent hyperopia. Therefore, cycloplegic refraction using cycloplegic drugs is an effective way to reduce fluctuation in accommodation or spasm of ciliary muscle. Cyclopentolate is a synthetic antimuscarinic cycloplegic agent and is available in 0.5% and 1% solutions. It is widely accepted to be the drug of first choice for patients of all ages which provides excellent short-term cycloplegia. Tropicamide, as an alternative, is a synthetic analog of tropic acid, and is known as a safe agent for cycloplegic refraction. Several studies have been conducted to compare the cycloplegic effect of these two agents, and different results have been reported, but there are still inconsistencies in the available results.

Objectives: To summarise the results regarding the comparison of the cycloplegic effect, in terms of refractive outcome, between cyclopentolate and tropicamide and provide a final conclusion.

Main findings: Overall, six studies were included in the present meta-analysis. Three studies had randomised controlled trial (RCT) design and three studies were case control. The pooled difference in mean of refractive change was 0.175 D (95% CI: -0.089, 0.438) higher in the cyclopentolate group as compared to the tropicamide group (P=0.194); Cochrane Q value=171.72 (P< 0.05); I²=95.34%) cycloplegic refraction results with cyclopentolate was more plus than tropicamide. Overall, cyclopentolate had a stronger but not statistically significant cycloplegic effect. Egger’s regression intercept was -5.33, P=0.170. The forest plots of the main analysis shows that difference between two drugs was more evident with retinoscopy (P<0.001, 95% CI: 0.199, 0.417) compared to the auto-refractor (P=0.519, 95% CI: -0.079, 0.157).

Authors suggest that tropicamide may be considered as a viable substitute for cyclopentolate due to its rapid onset of action. Although these results should be used cautiously in infants and in patients with high hyperopia or strabismus when using tropicamide as the sole cycloplegic agent, especially in situations where the findings are variable or there is no consistency between the examination results and clinical manifestations of the visual problems.

Methodology: Inclusion criteria consisted of studies including participants who had no history of cardiovascular or neurological diseases, no history of ocular pathology, no history of allergy to drops, taking no ocular or systemic medicines, and no history of amblyopia or strabismus.

A comprehensive literature search of PubMed, Scopus, ScienceDirect and Ovid databases was carried out to find the relevant peer-reviewed publications that investigated the effects of cyclopentolate and tropicamide cycloplegic agents with regard to the changes in the mean spherical equivalent for each drop. To find the relevant studies, a search algorithm based on the combination of the terms: tropicamide, cyclopentolate, cycloplegia and cycloplegic was used. The search was performed from inception to September 2016. In addition, references lists of relevant studies were reviewed for possible missing citations. The search was performed by two authors independently. Quality scoring of included studies were carried out using the Newcastle-Ottawa Quality Assessment Scale for case control studies and Oxford Centre for Evidence-Based Medicine for randomised controlled trials studies. For each study, difference in mean of the changes in the spherical equivalent for the cyclopentolate and tropicamide groups was used as the main effect size. To pool the effect sizes across studies, a random effects model was used. Heterogeneity was evaluated by the Cochrane Q test (the significance level was considered to be 0.05.), and I² index. Publication bias was evaluated graphically by funnel plots and statistically by Egger’s regression intercept method.

Applicability/external validity: Not discussed.

Geographic focus: Not discussed.

Summary of quality assessment:

Overall, this review was attributed medium confidence. Although authors conducted rigorous methods to analyse data of included studies, the literature search was not thorough enough that we can be confident that relevant studies were not omitted in the review. In addition, it is not clear if two authors independently extracted data of included studies.