Effects of Cycloplegic Agents on Ocular Parameters in Children with Myopia and Hyperopia

doi:10.21203/rs.3.rs-1423614/v1

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Effects of Cycloplegic Agents on Ocular Parameters in Children with Myopia and Hyperopia

https://doi.org/10.21203/rs.3.rs-1423614/v1

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Background

To study the effect of cycloplegia on ocular parameters in children with myopia and hyperopia.

Methods

Forty two myopia and forty four hyperopia eyes in children between 5 and 10 years of age were included. Measurements were taken before and after cycloplegia using 1% atropine sulfate ointment. The ocular parameters included central corneal thickness (CCT), corneal curvature (CC), anterior chamber depth (ACD), pupil diameter (PD), axial length (AL) and central retinal thickness (CRT).

Results

There was no significant difference in CCT, CC and CRT between the two groups without cycloplegia, but the ACD of myopia (3.64 ± 0.28mm) group was significantly higher than that of hyperopia (3.40 ± 0.24mm, t=-4.522, P < .0001). The average PD of myopia (4.85 ± 0.87mm) group was significantly smaller than that of hyperopia group (5.47 ± 1.15mm, t = 2.903, P < .0046). The average AL of myopia (24.25 ± 0.77mm) was significantly higher than that of hyperopia (21.73 ± 1.24mm, t = 12.084, P < .0001). However, it was found that the average PD of myopia (7.68 ± 0.51mm) was significantly larger than that of hyperopia (7.41 ± 0.57mm, t = 2.364, P = .0202) under cycloplegia. As for the changes of refractive factors before and after cycloplegia, Deepened ACD and enlarged PD was noted in both group after cycloplegia.

Conclusions

Cycloplegia not only affects ACD and PD, but also leads to the reversal of PD difference between the two groups. The cycloplegia effects enabled us to study changes in all known ocular parameters in a short period of time.

cycloplegia

biometrics

myopia

hyperopia

refractive components

Myopia has not only become a public health problem of increasing concern in the world, but also a "national disease" in China. The rapidly rising myopia prevalence, which has reached epidemic levels among middle and high schoolers in recent decades, has triggered renewed concerns about protecting Chinese students' vision. On 30 August 2018, eight departments of the Chinese government, including the Ministry of Education and National Health Commission, jointly resolved to implement the Comprehensive Plan to Prevent Nearsightedness Among Children and Teenagers.¹

Myopia has plagued human beings for more than three centuries, but its specific pathogenesis has not been elucidated. Excessive near-work is one of the most commonly known environmental factors relating to myopia in terms of perception. However, the precise mechanism of structural changes of the myopia eye is not well-understood. Indeed, a significant transient elongation of axial length during short periods of accommodation has been observed in young adults.^2-5 Similar findings were found in our previous study about 20 years ago.⁶ The development of ocular biometric technology, especially the non-contact biometric technology in the past 20 years has prompted us to carry out the research again to make up for the possible defects of previous research.

Subjects

This study was approved by the institutional review board at Weifang Eye Hospital and was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from their parents. Considering that the children enrolled were too young and have a state of hyperopia, the cycloplegia agent used in this study was 1% atropine sulfate ointment (Shenyang Xingqi Eye Medicine Co, Ltd.) twice a day for 5 days at home. All the ocular parameters measurement was taken at least 12 hours after the last administration of atropine ointment, in order to reduce the possible effect of the ointment on corneal curvature and thickness.

Children with myopia or hypermetropia after cycloplegia were included in the study, regardless of whether they had strabismus or astigmatism. All children in the study underwent a comprehensive ophthalmologic examination including slit-lamp biomicroscopy, fundoscopy. Exclusion criterion were active eye pathology, previous ophthalmic surgery, corneal opacities, glaucoma, retinal disease, poor ocular fixation. No subject had worn contact lenses ever. For children with binocular ametropia, the measurement data of the right eye are required to be included in the final analysis, and if the ametropia is monocular, it is automatically included in the study.

Measurements

Childrens aged between five to ten years with myopia or hyperopia were recruited from the Optometry Clinic of Weifang Eye Hospital. The refractive state and corneal curvature were measured with the KR-1 auto kerato-refractometer (Topcon Corporation, Japan) after cycloplegia. Hypermetropia was defined as spherical equivalent refraction greater than 0.75D. Myopia was defined as spherical equivalent refraction less than − 0.50D. Central corneal thickness before and after cycloplegia was obtained by Topcon Sp-3000p corneal endothelial cytometry (Topcon Corporation, Japan). Anterior chamber depth, pupil diameter and axial length were measured by IOL master 500 (Carl Zeiss, Meditec, Germany). Central retinal thickness was automatically obtained with Heidelberg Spectralis OCT (Heidelberg Engineering, Germany). Three measurements were taken with each instrument under normal indoor lighting and all the instruments are operated by experienced technicians and calibrated regularly to ensure their accuracy and repeatability.

Statistical Methods

All data were processed by SPSS 20 software, and chi-square test was used to compare the classified data. The measurement data were expressed as mean ± standard deviation. Under the condition of normal distribution and homogeneity of variance, independent and paired T test were used. If the variance is not equal, the Mann-Whitney U test are used. A P-value of < .05 was considered statistically significant.

A total of 86 eyes from 86 patients between the ages of 5 and 10 years were enrolled in this study, which included 42 myopia(19M, 23F)and 44 hyperopia patients (20M, 24F). The mean age of myopia group was 8.4 ± 2.3 years and the mean age of the hypermetropic group was 7.7 ± 2.1 years. There was no significant difference in the sex ratio (χ2 = 0.608, P = .7378) and mean age (t = -1.540, P = .1273) between the two groups. The mean diopter of myopia group was − 2.25 ± 1.36D (95% CI -2.76 to -2.02D), and that of hyperopia group was 3.32 ± 2.94D (95% CI 3.55 to 5.02D).The results of a normality test showed that the distribution of all variables both before and after cycloplegia was normal (1 < Skewness < 1).

Differences in refractive components between myopia group and hyperopia group before cycloplegia

There were no significant differences in mean central corneal thickness, corneal curvature and central retinal thickness between the two groups. The mean anterior chamber depth of myopia was 3.64 ± 0.28mm, which was significantly greater than that of hyperopia (3.40 ± 0.24mm); The mean pupillary diameter of myopia (4.85 ± 0.87mm) was significantly smaller than that of hyperopia (5.47 ± 1.15mm); The mean axial length of myopic eyes (24.25 ± 0.77mm) was significantly longer than that of hyperopic eyes (21.73 ± 1.24mm, Table 1).

Table 1

Comparison of mean values of refractive components before cycloplegia
Refractive components	Myopia x ± S, CI	Hyperopia x ± S, CI	T	P
CCT(um)	521.74 ± 32.25 511.69-531.79	528.70 ± 34.85 517.97-539.42	0.955,	.3423
CC(D)	43.51 ± 1.40 43.11–43.90	43.54 ± 1.56 43.07-44.00	0.973,	.9227
ACD(mm)	3.64 ± 0.28 3.56–3.72	3.40 ± 0.24 3.32–3.47	-4.522,	༜.0001
PD(mm)	4.85 ± 0.87 4.60–5.11	5.47 ± 1.15 5.12–5.81	2.903	.0046
AL(mm)	24.25 ± 0.77 24.03–24.46	21.73 ± 1.24 21.36–22.10	-12.084	༜.0001
CRT(um)	217.23 ± 36.05 206.14-228.33	211.60 ± 18.95 205.54-217.66	-0.881	.3809
CCT = central corneal thickness; CC = corneal curvature; ACD = anterior chamber depth; PD = pupillary diameter; AL = axial length; CRT = central retinal thickness; x ± S = mean ± standard deviation; CI = Confidence Interval

Differences in refractive components between myopia group and hyperopia group after cycloplegia

The refractive components of the two groups were regained with the same measuring equipment after cycloplegia. The results showed that the differences of ocular parameters in the two groups except pupillary diameter were the same as those under non cycloplegia, but the pupillary diameter of myopia after cycloplegia (7.68 ± 0.51mm) was significantly larger than that of hyperopia (7.41 ± 0.57mm) after cycloplegia (Table 2).

Table 2

Comparison of mean values of refractive components after cycloplegia
Refractive components	Myopia x ± S,CI	Hyperopia x ± S,CI	T	P
CCT(um)	520.26 ± 32.56 510.12-530.41	527.82 ± 34.75 517.38-538.26	1.045	.2988
CC(D)	43.01 ± 1.36 42.63–43.40	43.53 ± 1.56 43.07-44.00	1.726,	.0877
ACD(mm)	3.75 ± 0.24 3.68–3.82	3.63 ± 0.17 3.59–3.69	-2.356,	.0206
PD(mm)	7.68 ± 0.51 7.53–7.83	7.41 ± 0.57 7.25–7.59	-2.364	.0202
AL(mm)	24.22 ± 0.76 24.01–24.43	21.73 ± 1.22 21.37–22.10	-12.137	< .0001
CRT(um)	215.86 ± 28.84 206.99-227.74	213.51 ± 26.80 204.83–222.20	-0.381	.7044
CCT = central corneal thickness; CC = corneal curvature; ACD = anterior chamber depth; PD = pupillary diameter; AL = axial length;CRT = central retinal thickness;
x ± S = mean ± standard deviation; CI = Confidence Interval

Effects of atropine on refractive components in myopia and hyperopia groups

Atropine significantly increased the anterior chamber depth and pupillary diameter in both groups, while other refractive components had no significant changes (Table 3).

Table 3

Effects of atropine on refractive components in myopia and hyperopia groups
Refractive components	Before cycloplegia x ± S	After cycloplegia x ± S	T	P
M-CCT(um)	522.49 ± 32.28	520.68 ± 32.84	-1.332	.1903
H-CCT(um)	528.70 ± 34.85	529.67 ± 34.44	0.924	.3606
M-CC(D)	43.51 ± 1.40	43.01 ± 1.36	-1.809	.0734
H-CC(D)	43.54 ± 1.56	43.53 ± 1.56	-0.364	.7175
M-ACD(mm)	3.64 ± 0.28	3.75 ± 0.24	4.137	.0001
H-ACD(mm)	3.40 ± 0.24	3.65 ± 0.16	13.057	< .0001
M-PD(mm)	4.86 ± 0.88	7.68 ± 0.52	22.563	< .0001
H-PD(mm)	5.47 ± 1.15	7.42 ± 0.57	11.535	< .0001
M-AL(mm)	24.25 ± 0.77	24.22 ± 0.76	-1.976	.0537
H-AL(mm)	21.73 ± 1.24	21.73 ± 1.22	0.339	.7364
M-CRT(um)	217.23 ± 36.05	215.86 ± 28.84	-0.516	.6086
H-CRT(um)	211.95 ± 19.07	213.51 ± 26.80	0.379	.7066
M = myopic group; H = hyperopic group; CCT = central corneal thickness; CC = corneal curvature; ACD = anterior chamber depth; PD = pupillary diameter; AL = axial length; CRT = central retinal thickness; x ± S = mean ± standard deviation; CI = Confidence Interval

Although the optical mechanism of myopia has long been understood, the research on the pathogenesis, natural course and effective prevention of myopia has made slow progress. On the contrary, with the development of information society and the change of human eye habits, the increase of myopia is obvious and supported by epidemiology in terms of absolute and relative number.^6–9 The occurrence and development of myopia are closely related to intensity of reading and near work, which is almost the consensus of all ordinary people and clinical ophthalmologists. but how reading and near work behavior induces the occurrence and development of myopia and the mechanism of pathological changes of myopia have not yet been clarified so far.

It is well known that before presbyopia occurs in the eyes, our eyes can quickly switch between distant and near vision, and the main known physiological mechanism is to initiate accommodation, and the amplitude of this accommodation decreases with age. The amplitude of accommodation decreased from about 15D in early infancy to 1.00D at the age of 60.¹⁰ Therefore, if we can obtain the difference of ocular parameters of the eye in far and near vision, it will help to explore the impact of accommodation priming on ocular parameters of the eye. However, due to the limitations of today's measurement technology, it is not possible to obtain the instantaneous changes of all known ocular parameters in the two physiological states of far and near vision. To this end, we used the cycloplegic atropine ointment in this study, using it to simulate or even amplify the accommodation activity to study the impact of this “enlarged accommodation” on the known ocular parameters of the eye.⁶ The data we obtained before cycloplegia represented the state of one eye in near viewing condition, whereas the data under cycloplegia represented that of one eye in far viewing condition. So it would be reasonable for us to learn the effect of “enlarged accommodation”—the amplitude of accommodation was enlarged by the application of atropine—on ocular parameters before and after cycloplegia. However, this “enlarged accommodation” would have an influence on ocular parameters similar to that of physiological or real accommodation from the viewpoint of lens changes, because the accommodation of human eyes mainly relies on the change of the lens in shape. This was fully proven in our experiment by the significant decrease in lens thickness after cycloplegia for each group.⁶ As two diametrically opposed refractive states, we found that there was no significant difference in central corneal thickness, corneal curvature and central retinal thickness between myopia and hyperopia, except for the well-known difference in average AL. However, there were significant differences in anterior chamber depth and pupil diameter.

Anterior chamber depth

Anterior chamber depth is undoubtedly an important ocular biometric parameter because the anterior chamber depth is located in the relative position of the lens. In this study, we found that the mean anterior chamber depth in myopia was significantly greater than that in hyperopia both before and after cycloplegia, and the anterior chamber depth was significantly deepened after cycloplegia in both group, which was consistent with our previous research conclusion of anterior chamber depth measured by A-ultrasound.⁶ Zhang J et al used IOL master to compare myopia and emmetropia in children of the same age. It was found that the anterior chamber depth in myopia was greater than that in emmetropia.¹¹ Considering that there is no significant difference in corneal curvature and central corneal thickness between the two groups in this study, we have reason to believe that the deeper anterior chamber depth in the myopia group may be closely related to the thinning of lens thickness.⁶ Malyugin et al studied the accommodative changes in the anterior chamber depth in patients with high myopia using anterior segment optical coherence tomography (AS-OCT). the results showed that accommodative changes in the ACD were significantly less pronounced in eyes with high myopia than in emmetropic eyes, indicating that the change of lens configuration or thickness in myopia was less than that in emmetropia,¹²which is also consistent with our previous study.

Pupil diameter

The difference of PD between myopic and hyperopic eyes was significant (t = 2.903, P = .0046). Whether refractive error affects pupillary diameter was controversial.^13–15 Although Orr JB et al suggested that refractive error had no effect on pupil diameter,¹⁶ studies with larger samples have confirmed that adult myopes have larger pupillary diameter than hyperopes.^13,14 However, our study seems to be contrary to the above conclusions. In addition to age group differences, our study did not receive the support based on children group.¹⁶ Gu Xinzu et al dynamically observed the pupil size of normal and myopia people with infrared pupil tester, and found that the pupil size of myopia was larger than that of emmetropia, and the pupil size increased with the deepening of myopia, especially in high myopia.¹⁷ How to explain this seemingly contradictory phenomenon in the conclusion between our study and the above research? We note that the above three related studies all conducted under dark adaptation conditions, which is also supported by their average pupillary diameter obtained without cycloplegia. For example, the average pupillary diameter of children's myopia was 6.78 ± 0.81mm ¹⁶ and that of adult myopia was 6.33 ± 0.82mm ¹³ and 6.51 ± 0.8mm.¹⁴ The average pupil diameter of the three studies is closer to that of our myopia after cycloplegia. But not 4.85 ± 0.87mm before cycloplegia. It is well known that the size of the pupil mainly determines by the intensity of light. It is regulated by the pupil sphincter and pupil dilator and through the sympathetic and parasympathetic nerves and the higher central E-W nucleus. Rosenfield et al considered that myopic eyes have weak sympathetic or strong parasympathetic innervation, which may not only explain the smaller pupil size of myopic eyes than that of hyperopic eyes in natural conditions, but also help to understand the different effects of atropine.¹⁸

Axial length

Our previous studies on children's axial length were based on traditional A-ultrasound measurement, although the potential impact of corneal curvature had been considered at that time, but the potential impact of corneal curvature and central retinal thickness changes on axial length had not been considered. Therefore, in this study, we included all factors that potentially affect the measurement of axial length, although no statistical validation was obtained to support our previous conclusions. However, the change of average 30 um axial length of myopic eyes before and after cycloplegia and the corresponding statistical analysis (t=-1.976, P = .0537) may reveal a similar change rule. Moreover, the effect of cycloplegia on axial length has also been confirmed by some researchers. Raina UK et al used Lenstar LS900 to study the axial length of 56 normal children aged 5 to 15 years, and found that after 2% homatropine cycloplegia, the axial length of these children was significantly shortened compared with that before medication.¹⁹ Unfortunately, the study did not focus on the refractive status of children. Tang XP et al ²⁰ used optical coherence biometry to measure the eye axis of children aged 4 to 11 years, and found that the eye axis of the hyperopia group was significantly shortened after atropine cycloplegic treatment, while the myopia group did not change significantly, and similar research conclusions were also supported by Wang LH et al.²¹ If the above studies were conducted using different cycloplegic agents, Woodman EC et al used IOL Master to measure the effect of continuous 5D accommodation near work for 30 minutes on the axial length of adult myopes and emmetropes, and found that near accommodation could significantly increase their axial length.²² Some people used LenStar to perform 3.00 and 4.50 D near stress tests on 35 adult emmetropic eyes and 37 myopic eyes, and found that the axial lengths of the eyes in both groups increased significantly.¹⁰

In a word, from the point of view of the anatomical and physiological characteristics of human eyes, the only known refractive factor that can actively change instantaneously in visual activities is the change of lens, which is caused by a series of mechanical changes involving intraocular muscles and has been confirmed by many studies. From the perspective of biological evolution, accommodation is the most primitive and basic visual control mechanism in the process of near reflex.²³ As long as we live in this three-dimensional world, retinal image defocus phenomenon is inevitable, and only eye accommodation can correct this defocus. Therefore, it may be a feasible way to study the changes of ocular parameters in a short time by studying the differences of refractive components in children and using the accommodative amplification effect of atropine.

Acknowledgements

Not applicable.

Authors’contributions

Guagnzhi Qu and Lei Gao contributed to analysis and manuscript preparation; Xiaocui Liu and Saiai Ding performed the data analyses; Xuli Wang helped perform the analysis with constructive discussions. The author(s) read and approved the final manuscript.

Ethics approval and consent to participate

The study was carried out in accordance with the Helsinki Declaration.

Informed consent was obtained from all patients parents.

This study protocol was reviewed and approved by the Ethics Committee of

the Weifang Eye Hospital, approval number No. 2019-05.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

None

Availability of data and materials

The data sets used and/or analyzed during the current study are not publicly

available due to their containing information that could compromise the privacy of research participants, but are available from the corresponding author

Lei Gao([email protected]) on reasonable request.

http://www.moe.gov.cn/jyb_xwfb/gzdt_gzdt/s5987/201808/t20180830_346673.html
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No competing interests reported.

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Effects of Cycloplegic Agents on Ocular Parameters in Children with Myopia and Hyperopia

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Introduction

Methods

Subjects

Measurements

Statistical Methods

Results

Differences in refractive components between myopia group and hyperopia group before cycloplegia

Differences in refractive components between myopia group and hyperopia group after cycloplegia

Effects of atropine on refractive components in myopia and hyperopia groups

Discussion

Declarations

References

Additional Declarations

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