Comparison of cycloplegic effects of atropine and tropicamide in children with refractive error

Introduction

The primary cause of vision loss in children and adolescents is refractive error, especially in China where myopia is becoming increasingly common (1,2). For accurate diagnosis of refractive error in children, cycloplegic refraction is required. This is because the accommodative power of the eye can change as the ciliary body contracts to change the curvature of the lens (3). Cycloplegia reduces the eye’s ability to accommodate, by preventing the ciliary muscle from contracting, making it possible to assess the eye’s true refractive error. Myopia usually occurs due to excessive elongation of the eyeball, causing light to focus in front of the retina rather than on it. Over the past 50 years, myopia has become increasingly common in East Asia (4). High myopia, in particular, poses a major risk to physical and mental health and can even result in blindness. Approximately 2 billion individuals worldwide have myopia, accounting for 28.3% of all cases of refractive error (5). Around 277 million people globally, or 4.0% of the population, experience high myopia with refractive error greater than 5 D (6). Every year, the prevalence of myopia and high myopia is rising globally (7).

There are different eye medications that can be used to induce cycloplegia in children for refraction (8). The three most commonly used pharmacological diagnostic agents, cyclopentolate, tropicamide, and atropine, suppress ciliary muscle contraction by competing with the physiological muscarinic substance acetylcholine. The cycloplegic effect of homatropine was weaker than that of atropine and cyclopentolate (9). A study has confirmed the efficacy of these cycloplegic medications, but findings related to efficacy of these agents for cycloplegic refraction remain inconsistent (10). In the appropriate management of refractive errors, strabismus, amblyopia, and other eye problems in children, accurate measurement of refraction error is critical. As children’s ciliary muscles are strong for accommodation, it is crucial to completely paralyze these muscles with an effective cycloplegic agent before refraction. On the other hand, the use of atropine, a long acting cycloplegic agent, for refraction in school-aged children results in long-lasting pupil dilation and potential blurring of near vision which may affect classroom activities.

In this study, we compared the cycloplegic refraction obtained using 8 g/L of atropine eye ointment and 4 g/L of tropicamide eye drops in children with suspected refractive error. The aim is to find the ciliary muscle paralysis drug which is more suitable for the refraction of children with different refractive errors. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-404/rc).

Methods

Participants

This is a prospective study. In Chengdu Women’s and Children’s Central Hospital, 110 children (202 eyes) with refractive problems were enrolled between January 2023 and December 2023.

Inclusion criteria: (I) patients complained of decreased visual acuity, such as blurred vision, double vision, eye fatigue, etc.; (II) initial refraction showed abnormal diopter: myopia ≥−0.50 D, hyperopia ≥+3.50 D in children aged 2–5 years, ≥2.00 D in children aged 5-6 years, ≥1.50 D in children over 6 years, astigmatism ≥−1.50 D; (III) uncorrected or best corrected visual acuity ≤0.4 in 3-year-olds, best corrected visual acuity ≤0.5 in 4-year-old, best corrected visual acuity ≤0.8 in children ≥5 years, which was directly related to abnormal refractive status; (IV) compared with the previous visual acuity, the current visual acuity decreased by more than 2 lines on the Snellen visual acuity chart, or improved by more than 2 lines after correction.

Exclusion criteria: (I) other ocular organic diseases (such as keratitis, cataract, glaucoma, fundus diseases, etc.); (II) systemic diseases. All refractions have been done by the same optometrist.

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the appropriate Institutional Review Board (IRB) of Chengdu Women’s and Children’s Central Hospital [IRB approval No. 2023 (98)]. Informed consent was obtained from the parents or guardians of all children involved in the study. The children ranged in age from 2 to 12 years (mean 6.9 years), with 74 males and 36 females. The children were divided into three age groups: 2 to 6 years, 7 to 9 years, and 10 to 12 years.

Study procedure

Visual acuity was assessed using Snellen visual acuity chart. Eye position was measured using the cover test to rule out strabismus. For individuals who were suspected of having refractive error, 4 g/L of tropicamide eye drops were applied four times, 5 minutes apart. After 30 to 40 minutes, an optometrist with expertise in pediatric retinoscopy completed the refraction.

Three days later, parents were instructed to apply 8 g/L of atropine eye ointment to the eyes of the children, three times a day for a duration based on the eye position (7 days for esotropia and 3 days for exotropia or eutropia). Following this, cycloplegic refraction was repeated using retinoscopy by the same optometrist, who also documented the findings. Children with esotropia were prescribed fully corrective eyeglasses.

Statistical analysis

After tropicamide eye drops were used to dilate the pupil, the cases were separated into three categories: mixed astigmatism, hyperopia (including hyperopic astigmatism), and myopia (including myopic astigmatism). Retinoscopy was used to compare the effects of two pupil dilation techniques in the same patient. GraphPad Prism version 7.8 (Dotmatics, Boston, MA, USA) was used to conduct the chi-squared tests. Statistics were deemed significant at P<0.05.

Results

Paired comparison of the spherical and cylindrical correction obtained using two pupil dilation methods in hyperopia

None of the children had adverse reactions to these eye drops. The outcomes of the two pupil dilation techniques in the hyperopic spherical and cylindrical correction were examined (Table 1). For spherical lenses, only 8.45% (12/142) of the 142 eyes exhibited identical findings, 90 (63.38%) showed a difference of ≤0.50 D, and the mean difference was 0.66 D. The cycloplegic effect of using 8 g/L atropine eye ointment in pediatric patients was significantly better than that of 4 g/L tropicamide eye drops. In terms of age, in the 2 to 6-year-old group, the efficacy of the two methods was the same in 9.5% (4/42) of the spherical lenses, 90.47% (38/42) had a difference of ≥0.25 D, 47.6% (20/42) had a difference of ≥0.50 D, 4.76% had a difference of ≥1.00 D (2/42), and the maximum difference was 2.00 D. In the 7 to 9-year-old group, among the 46 eyes, 13.04% (6/46) had the same results, 86.9% (40/46) had a difference of ≥0.25 D, 60.87% (28/46) had a difference of ≥0.50 D, 4.34% (2/46) had a difference of ≥1.00 D, and the maximum difference was 1.25 D. In the 10 to 12-year-old group, 3.70% (2/54) had the same results, 96.3% had differences of varying degrees, 66.67% (36/54) had a difference of ≥0.50 D, and the maximum difference was 0.75 D. When the hyperopic spherical lens was compared across age groups, a significance was observed (P<0.001).

For cylindrical lenses, out of 126 eyes, 14.28% (18/126) had the same findings, 85.71% (108/126) had a difference of ≥0.25 D, and 82.54% (104/126) had a difference of ≤0.50 D. Treatment with 8 g/L of atropine eye ointment produced greater cycloplegic effects than did the treatment with 4 g/L of tropicamide eye drops. The largest difference, at 0.75 D, occurred in only 17.46% (22/126). Compared with 4 g/L of tropicamide eye drops, 8 g/L of atropine eye ointment had a significantly higher mydriatic effect on cylindrical lenses in all age groups, and the difference was statistically significant (P<0.001).

Paired comparison of the spherical and cylindrical results of the two pupil dilation methods in myopia

The results of the two pupil dilation methods for myopia (spherical and cylindrical) were compared.

For spherical lenses, of the 46 eyes, 13.04% (6/46) had the same findings, 86.9% (40/46) had a difference of ≥0.25 D, 69.57% (32/46) had a difference of ≤0.50 D, and the largest difference was 1.25 D, which was observed in cases of high myopia. For patients with astigmatism, 4 g/L of tropicamide eye drops were more effective than 8 g/L of atropine eye ointment (Table 2).

We compared the therapeutic effects of the two pupillary dilation methods at different age stages, and found that there was no significant difference between the therapeutic effects of the two pupillary dilation methods in the 2 to 6-year-old group versus the 7 to 9-year-old group and in the 2 to 6-year-old group versus the 10 to 12-year-old group (P=0.39). However, there was a significant difference between the 7 to 9-year-old group and the 10 to 12-year-old group (P=0.04).

For cylindrical lenses, out of 30 astigmatic eyes, 20% (6/30) showed no change, 80% (24/30) showed a difference of ≥0.25 D, and 73.33% (22/30) showed a difference of ≤0.50 D. There was no significant difference between the two pupillary dilation methods in any age categories (P<0.001).

Paired comparison of the spherical and cylindrical results of the two pupil dilation methods in mixed astigmatism

The results of the two pupil dilation methods for mixed astigmatism (spherical and cylindrical) were compared.

For cylindrical lenses, of the 14 eyes, 35.7% (5/14) had the same findings, and 64.3% (9/14) had a difference of 0.25–0.5 D. For spherical lenses, of the 14 eyes, 100.0% had a difference of ≥0.25 D, and the largest difference was 1.25 D. This indicated that treatment with 4 g/L of tropicamide eye drops exerted a substantial impact on spherical lenses with mixed astigmatism (Table 3).

Mixed astigmatism was detected after 14 eyes were dilated with 4 g/L of tropicamide eye drops. However, when the same eyes were dilated with 8 g/L of atropine eye ointment, pure hyperopic astigmatism was found. There were significant differences between the 2 to 6- and 7 to 9-year-old groups. We compared the therapeutic effects of the two pupillary dilation methods at different age stages and found that there were significant differences between the 2 to 6- and 7 to 9-year-old groups (P=0.03) and between the 10 to 12- and 7 to 9-year-old groups (P=0.03).

Discussion

The most prevalent cause of vision issues in children is refractive error, which can lead to amblyopia and strabismus if left untreated. The diagnosis and treatment of strabismus and amblyopia rely heavily on optometry, which is also essential for accurate guidance in vision correction and amblyopia therapy. Objective assessment through cycloplegic refraction forms the foundation for the prescription of eyeglasses. Atropine eye ointment is a common medication for pupil dilation in children in clinical settings. Its most potent effect is to paralyze the ciliary muscle. By inhibiting the M cholinergic receptors, tropine relaxes the ciliary muscle and dilates the pupil. As it allows for precise measurement of the eye’s refractive power and has a profound cycloplegic effect, it is the mainstay of cycloplegic refraction in children. But it also has some adverse reactions. Systemic adverse reactions include blushing, fever, dry mouth, tachycardia, nausea, dizziness, delirium, skin erythema, ataxia, difficulty in positioning, etc. Local allergic reactions include conjunctivitis, eyelid edema, and dermatitis.

Due to the long half-life of atropine eye ointment, which results in blurred near vision and accommodative paralysis, it cannot be administered to school-age children during the school day. This creates a conflict between the diagnosis and treatment of children’s refractive errors and their education, thus prompting clinical professionals to search for viable alternative medications for cycloplegic refraction in this population.

The pupillary dilator muscle is regulated by the parasympathetic nervous system, and its release of acetylcholine can contract and relax the pupillary sphincter, while atropine, an anticholinergic receptor blocker, can relax the pupillary sphincter. The dilator muscle contracts to dilate the pupil, acting quickly and easily to restore pupil function. To investigate the viability of using atropine eye ointment for mydriatic refraction in children, we examined the mydriatic refraction outcomes produced from 8 g/L of atropine eye ointment and from 4 g/L of tropicamide eye drops in children aged 2 to 12 years.

Atropine preferred in hyperopia

Pupil dilation induced with 4 g/L of tropicamide eye drops significantly affected the hyperopia’s spherical and cylindrical lenses. The spherical lens showed a difference rate of 91.54%, with 91.54% of eyes exhibiting a difference of ≤0.50 D. The mydriatic refraction induced by 4 g/L of tropicamide eye drops was less pronounced than that by 8 g/L of atropine eye ointment, which is consistent with the study by Zhou et al. (11). The efficacy of the two methods was the same in 8.45% of the spherical lenses. For cylindrical lenses, in accordance with the findings of Chen et al. (12), 14.28% (18/126) were the same, 85.71% (108/126) had a difference of 0.25 D, and 82.53% (104/126) had a difference of ≤0.50 D. The largest difference was 0.75 D, and the disparity was greater in the younger age groups. Compared to treatment with 8 g/L atropine of eye ointment, that with 4 g/L of tropicamide eye drops produced a reduced mydriatic effect. Furthermore, in relaxing the pupillary dilator muscle, 8 g/L of atropine eye ointment paralyzed the ciliary muscle more effectively than did 4 g/L of tropicamide eye drops. When 4 g/L of tropicamide eye drops are applied for cycloplegic refraction in children who are hyperopic, the correction of hyperopia may not be sufficient, thus reducing the efficacy of treatment. Therefore, 8 g/L of atropine eye ointment should be used to dilate the pupil and induce refraction for hyperopic eyes in children under the age of 12 years. This can offer a more dependable foundation for prescribing eyeglasses.

Pharmacological effects comparison in myopia

The effects of tropicamide eye drops (4 g/L) and atropine eye ointment (8 g/L) on spherical and cylindrical lenses in myopic eyes were observed. For spherical lenses, 13.04% (6/46) of the findings were the same, 86.9% (40/46) had a difference of ≥0.25 D, 69.6% (32/46) had a difference of ≤0.50 D, and the average difference (absolute value) was >0.43 D. We compared the therapeutic effects of the two pupillary dilation methods (8 g/L of atropine eye ointment and 4 g/L of tropicamide eye drops) at different age stages and found that there was significant difference between the 7 to 9-year-old group and the 10 to 12-year-old group (P=0.04). As it pertains to cylindrical lenses, 20% (6/30) of the 30 eyes had the same results, 80% (24/30) had a difference of ≤0.50 D, the maximum difference was 1.5 D, and the average difference was >0.45 D (absolute value). This discrepancy might have resulted from the differences in mydriatic drug selection. In our study, 8 g/L of atropine eye ointment had a greater mydriatic effect than did 4 g/L of tropicamide eye drops, with no statistically significant difference between the age groups in this regard (P>0.99). The results were in contrast to Li et al.’s study (13). Li et al. found that 4 g/L of tropicamide eye drops had a greater mydriatic effect than did 8 g/L of atropine eye ointment; this may be related to the different people and the different shades of the iris. Children with poor cooperation during visual acuity assessment and those with amblyopia may exhibit apparent spherical overcorrection due to incomplete cycloplegia with tropicamide.

Agent selection for mixed astigmatism

Regardless of myopia, hyperopia, or astigmatism, the pupil dilation refraction outcomes from treatment with 4 g/L of tropicamide eye drops were substantially different from those with 8 g/L og atropine eye ointment. Of the 14 eyes with mixed astigmatism, 35.7% (5/14) exhibited cylindrical differences of 0.25–0.5 D, while 100% of the eyes had varying degrees of spherical discrepancies. When eyes were administered 4 g/L tropicamide of eye drops, 14 eyes were diagnosed with mixed astigmatism. However, when the same eyes were dilated with 8 g/L of atropine eye ointment, they were diagnosed with pure hyperopic astigmatism. The findings demonstrate that pupil dilation with 4 g/L of tropicamide eye drops significantly affected the assessment of mixed astigmatism, which directly influenced lens prescription. In clinical practice, due to individual differences in children, the adjustment of the ciliary muscle was robust after the pupil recovered from being dilated with 8 g/L of atropine eye ointment, and the eye test showed pure hyperopic astigmatism. The corrected vision was not as good as it was when the pupil was dilated and when the lenses were originally prescribed. Conversely, the corrected vision resulting from pure myopic astigmatism was optimal. When optometrists administered 4 g/L of tropicamide eye drops to dilate the pupil, there was a risk of misdiagnosing myopic or mixed astigmatism as pure hyperopic astigmatism.

Practical considerations in pediatric cycloplegia

Examining children’s eyes is more challenging than examining those of adults, as there are numerous interfering factors. The examination is highly dependent on the children’s mood, surroundings, level of cooperation, accommodation, and other variables, and there exist varying degrees of amblyopia. As children age, their vision gradually improves; therefore, age should be taken into account in the diagnosis of amblyopia. Tokoro (14) reported that distribution of the refractive status of children between the ages of 4 and 7 years is as follows: 77.3% have hyperopia, 11.4% have myopia, 11.3% have mixed astigmatism, 74.6% have hyperopia plus amblyopia, 45.3% have myopia plus amblyopia, and 63.5% have mixed astigmatism plus amblyopia. Therefore, we do not recommend using 4 g/L of tropicamide eye drops for pupil dilation in these age groups, as the difference in results compared to those from atropine would require reexamination. To prescribe appropriate eyeglasses, the objective examination findings from cycloplegic refraction should be combined with subjective refraction and eye position assessment. Thus, in line with Farassat et al. (15), we believe that cycloplegic refraction via atropine should be used for young children with hyperopia (including hyperopic astigmatism), mixed astigmatism, strabismus, and amblyopia, among similar conditions. According to Wolffsohn et al. (16), children younger than 12 years old with hyperopia and those with esotropia associated with hyperopia should undergo pupil dilation and retinoscopy via atropine eye ointment. For school-age children with myopia, especially those over 9 years old—among whom the maximum difference for children between 10 and 12 years old was found to be 0.75 D in our study—4 g/L of tropicamide eye drops can be used for pupil dilation and optometry. Reexamination should strictly adhere to myopia-correction guidelines to account for any differences, allowing children to receive appropriate correction during school hours.

Limitations

This study not only compared the cycloplegic effects of tropicamide and atropine in children under 12 years of age with simple myopia or hyperopia, but also confirmed that the effect of atropine was better than that of tropicamide in children under 12 years of age with mixed astigmatism. The limitation of this paper is that the initial pupil size of the subjects was not analyzed, which may lead to biased results.

Conclusions

Children under 12 years old with mixed astigmatism and hyperopia should be administered 8 g/L of atropine eye ointment for pupil dilation in order to ensure the accuracy of refraction results. Children should be administered atropine in order to relax the ciliary muscle and dilate the pupil while they are on vacation from school, which would allow them time to recover normal eye function. Meanwhile, under total paralysis of the ciliary muscle, the refractive power may be more thoroughly and promptly measured, enabling an accurate prescription of eyeglasses.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-404/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-404/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-404/prf

Funding: This study was supported by the Chengdu Health Commission Project (No. 202307023051). The funding source had no role in the study design, data collection, analysis, interpretation of data, or in the writing of this manuscript.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-404/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethical approval was obtained from the appropriate Institutional Review Board (IRB) of Chengdu Women’s and Children’s Central Hospital [IRB approval No. 2023 (98)]. Informed consent was obtained from the parents or guardians of all children involved in the study. They were fully informed about the purpose, procedures, potential risks, and benefits of the research before providing written consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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