The association of peripheral refraction and relative peripheral refraction with astigmatism in Shanghai schoolchildren’s myopia: a cross-sectional study

doi:10.21203/rs.3.rs-4023576/v1

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The association of peripheral refraction and relative peripheral refraction with astigmatism in Shanghai schoolchildren’s myopia: a cross-sectional study

https://doi.org/10.21203/rs.3.rs-4023576/v1

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Purpose

Currently, no relevant studies have reported a relationship between astigmatism and peripheral refraction (PR). We aimed to describe the association between PR and relative peripheral refraction (RPR) with astigmatism in Chinese children with mild to moderate myopia, and to provide new insights into the influence of astigmatism.

Methods

Three-hundred-and-seven children (6–14 years old) from Shanghai were included in this study. The PR and RPR were measured using multispectral refraction topography (MRT). Cycloplegic refraction was measured using an autorefractor (KR-8900, Topcon), whereas axial length and ocular biological parameters were measured using Zeiss IOLMaster 700. Only data from the right eye were analyzed. Multivariate linear regression was used to explore the relationship between cylinder power and MRT parameters.

Results

Overall, the median spherical equivalent was − 1.50 D (interquartile range, IQR: -2.25, -0.88), showing an apparent trend of hyperopic defocus from the macula to the peripheral retina. Astigmatism was correlated with PR rather than RPR especially at eccentrically inferior and within a 45° radius of the retina (coefficients 0.12–0.18, P < 0.05). Multivariate linear regression analysis demonstrated that the effect of astigmatism on PR tended to increase with greater lens thickness.

Conclusions

Astigmatism may be a risk factor for myopia due to its impact on peripheral refraction as opposed to relative peripheral refraction. In this cohort, we also found evidence supporting the association between peripheral hyperopia and myopia development.

Astigmatism

peripheral refraction

relative peripheral refraction

myopia

Myopia is currently a worldwide public health problem, and it is estimated that by 2050, the global prevalence of myopia and high myopia will reach 50% and 10%, respectively. High myopia-induced fundus pathology and impaired vision are becoming the leading causes of global blindness and low vision, affecting quality of life and causing huge health care expenditures for society^{1, 2}. Therefore, a deeper understanding of the risk factors associated with the occurrence and development of myopia is important for public health.

Previous studies have found that astigmatism may be associated with the development of myopia and that astigmatism is a risk factor for the development of high myopia³, but the findings on the role of astigmatism in low-to-moderate myopia are equivocal^4–6. However, the mechanism by which astigmatism affects myopia progression remains ambiguous. A small number of studies have suggested that astigmatism-induced blurring of objects can lead to a lag in ocular accommodation, which in turn results in a physiological increase in the eye's axis^7–9. Recent reports indicate that toric orthokeratology may exhibit better myopia control than traditional spherical design orthokeratology^{10, 11}. This myopia control principle is based on the theory of retinal peripheral refraction¹⁰, suggesting that the effect of astigmatism on myopia progression may be related to retinal peripheral refraction.

Peripheral retinal refraction refers to a state of peripheral refraction (PR) at a distance of 10° or more from the central macular concavity¹². Animal trials have shown that the direction of macular refractive development is dominated by peripheral, rather than foveal visual stimuli^{13, 14}. Several cross-sectional studies have supported the hypothesis that relative peripheral hyperopia contributes to the development of myopia^15–17. However, longitudinal follow-up studies have shown that relative peripheral hyperopia exerts little consistent influence on the onset or development of myopia^{18, 19}. Therefore, the existence of other mechanisms of action in the theory of peripheral retinal defocusing requires further investigation. A potential explanation for this could be the use of the relative positions of both astigmatic focal surfaces, suggested by Charman²⁰. To the best of our knowledge, no relevant studies have reported a relationship between astigmatism and peripheral refraction.

Previous studies on the amount of peripheral refraction have typically used computerized optometry, repeated optometry by frequently changing the point of gaze, and manually plotting the results, making it difficult to pinpoint the measurements, and not uniformly accurate for visual field angles²¹. Recently, a novel approach called Multispectral Refraction Topography (MRT) has been developed, which uses monospectral light of different wavelengths to sequentially acquire fundus images. An in-depth computer algorithm can accurately detect refractive topography within 53° of the retina and quantify retinal refraction values with good repeatability^{22, 23}. Therefore, this study aimed to investigate the relationship between astigmatism and PR in children and adolescents with low-to-moderate astigmatism, and to further clarify the effect of astigmatism on the development of myopia and the mechanism of action via MRT.

2.1 Study design and participants

This cross-sectional study was conducted in accordance with the tenets of the Declaration of Helsinki and approved by the ethics committee of the Shanghai Eye Disease Prevention & Treatment Center in China. Children 6–14 years of age with emmetropia or low-to-moderate myopia were enrolled. A total of 307 right eyes from 307 healthy individuals were included in the study. The exclusion criteria were as follows: 1) intraocular pressure > 21 mmHg; 2) previous ocular diseases such as glaucoma, optic neuropathy, uveitis, and retinal diseases; 3) dioptric media opacity, which may affect imaging; 4) history of corneal, lens, and intraocular surgery; and 5) use of corneal contact lenses or myopia control medicines during the last three months.

2.2 Ophthalmic Measurements

The central spherical equivalent (SE) was used to classify the eyes as Emmetropia (E, − 0.5 to + 0.5D), Low Myopia (LM, −3D to − 0.5D), and Moderate Myopia (MM, −6D to − 3D). After mydriasis, all the participants underwent optical biometry to measure ocular biological parameters. Cycloplegic refraction was measured using an autorefractor (KR-8900; Topcon, Japan). The axial length (AL), corneal curvature (K1 and K2), and central anterior chamber depth (CACD) were measured using an IOL Master700 (Carl Zeiss Meditec, Inc., Dublin, OH, USA). Ocular refraction was measured using an automatic optometer. The retinal refraction difference value (RDV) was detected by multispectral refractive topography (MRT, MSI C2000, ShengDa TongZe, ShenZhen, China). MRT is a novel approach that can accurately measure the peripheral refraction of 128 × 128 points in the view of a field (VOF) of 53°. Fundus images were collected using a multispectrum technique and further processed using lens compensation and a computer algorithm for depth development. The RDV at each location on the retina (Fig. 1) was determined based on the actual refractive value of each pixel. Positive RDVs indicated hyperopic defocus and negative RDVs indicated myopic defocus. Relative peripheral refraction defocus (RPR) was defined as the difference between the absolute peripheral refraction and central macular refraction (Fig. 2). RPR measurements were performed twice at intervals of 30 min and then averaged.

2.3 Statistical analysis

Normally distributed continuous variables, such as age, axial length, and lens thickness, were summarized using means and standard deviations. For skewed continuous variables, descriptive statistics included the median and interquartile range. Categorical variables were presented as frequencies and percentages. Pearson’s correlation coefficient was used to explore the linear associations between continuous variables. Multivariate linear regression was employed to assess the relationship between the cylinder and MRT measurements while adjusting for covariates, including age, corneal radius (CR), central corneal thickness (CCT), anterior chamber depth (ACT), lens thickness (LT), and sphere degree. An interaction term was introduced into the model to examine the interactive effects of LT and the cylinder on the MRT measurements. For statistical analysis, 95% confidence intervals (95% CI) and two-sided P values were calculated. Data cleaning and analysis were conducted using two commercial software tools: SAS (version 9.4) and R.

3.1 The basic characteristics of the participants and MRT characteristics

Table 1 shows the characteristics of the study participants. A total of 307 children with a mean age 9.0 (SD = 1.0) were included in the analysis, 49.2% of whom were boys. The median of SE was − 1.50 (IQR: -2.25, -0.88)D and the mean axial length was 24.3 (SD, 0.9) mm. The PR and RPR values varied according to the location of the fundus. The median of absolute value in Center-D was − 1.06 (IQR: -1.65, -0.45)D, the most negative, and the other parts of RPR were relatively positive.

Table 1

General characteristics of study participants and refractive parameters
Characteristics	Total (N=307)
Age (years), mean (SD)	9.0 (1.0)
Gender
Male	151 (49.2)
Female	156 (50.8)
Sphere, median (IQR)	-1.25 (-2.00, -0.75)
Cylinder, median (IQR)	-0.50 (-0.75, -0.25)
Spherical equivalence, median (IQR)	-1.50 (-2.25, -0.88)
AL, mean (SD)	24.25 (0.86)
CCT, median (IQR)	549.00 (526.00, 569.75)
ACD, median (IQR)	3.77 (3.61, 3.91)
LT, mean (SD)	3.35 (0.15)
△K, median (IQR)	-1.12 (-1.47, -0.78)
△TK, median (IQR)	-1.08 (-1.39, -0.75)
Absolute Peripheral refraction, median (IQR)
Center-D	-1.06 (-1.65, -0.45)
TRDV	-0.66 (-1.37, -0.00)
RDV-15	-1.12 (-1.68, -0.52)
RDV-30	-1.12 (-1.47, -0.78)
RDV-45	-1.08 (-1.39, -0.75)
RDV-30-15	-1.06 (-1.65, -0.45)
RDV-45-30	-0.66 (-1.37, -0.00)
TRDV-30	-1.12 (-1.68, -0.52)
RDV-S	-1.06 (-1.69, -0.49)
RDV-I	-0.91 (-1.53, -0.24)
RDV-T	-1.06 (-1.67, -0.47)
RDV-N	-0.74 (-1.52, -0.10)
Relative Peripheral refraction, median (IQR)
Center-D	-1.06 (-1.65, -0.45)
TRDV	0.32 (0.06, 0.53)
RDV-15	-0.04 (-0.07, 0.00)
RDV-30	-0.01 (-0.11, 0.06)
RDV-45	0.13 (-0.07, 0.29)
RDV-30-15	0.00 (-0.13, 0.09)
RDV-45-30	0.24 (-0.07, 0.46)
TRDV-30	0.89 (0.29,0.93)
RDV-S	0.01 (-0.38, 0.30)
RDV-I	0.56 (0.25, 0.90)
RDV-T	0.73 (0.33, 0.92)
RDV-N	0.48 (0.10, 0.96)

Notes: Data from the right eye.

RDV: refraction difference value of the retina; RDVs at five retinal eccentricities, from the fovea to 53°, recorded as RDV-0-10, RDV-10-20, RDV-20-30, RDV-30-40, and RDV-40-53; TRDV: total RDV; RDV-S: RDV-superior; RDV-I: RDV-inferior; RDV-T: RDV-temporal; RDV-N: RDV-nasal; D: diopter.

AL: Axial length (mm); CCT: Central corneal thickness (μm); ACD: anterior chamber depth (mm); LT: lens thickness (mm); △K: K2-K1 (D); △TK: TK2-TK1 (D); SD: standard deviation; IQR: interquartile range.

3.2 Relationship between ocular biological parameters and peripheral refraction

The correlation between PR and other characteristics such as age, AL, SE, and other ocular biological parameters is shown in Fig. 3. The correlation coefficients of SE with PR were the highest compared to other ocular parameters, varying from 0.67 to 0.86. AL was also correlated with PR, with negative coefficients ranging from − 0.34 to -0.49. Apart from the sphere, the cylinder and LT were associated with PR, especially eccentrically inferior and within the 45°of the retina, with coefficients vibrating around 0.12 and 0.18.

Table 2 shows the adjusted results for astigmatism and PR from the linear multivariate regression model. In model 1, after adjusting age, CR, CCT, ACD, LT and sphere degree, cylinder was still positively associated with PR, with adjusted coefficients from 0.43 to 0.61 at each part. The forest plots indicate the 95% CI of the coefficients and are all statistically significant (P values less than 0.05). However, LT was not significantly associated with PR in any parameter after adjusting for covariates. In Model 3, an interaction association between LT and cylinder on PR showed that there was positive interactive associations between LT and cylinder on PR (P values less than 0.05). As LT increased, the cylinder was more positively associated with PR.

3.3 Relationship between ocular biological parameters and relative peripheral refraction

The correlation between RPR and other characteristics such as age, AL, SE, and other ocular biological parameters is shown in Fig. 4. SE, AL, and age were also correlated with most areas of RPR with similar correlation coefficients, but the directions of correlation were opposite to those of PR. Furthermore, cylinder and LT were not associated with RPR.

Astigmatism has been recognized in previous studies as a risk factor for the development of myopia³, but its exact mechanism remains unclear. In this cross-sectional study, we analyzed the relationship between refractive status and peripheral retinal refraction in 307 children with low-to-moderate myopia and prematurity and found that astigmatism had an important influence on peripheral retinal refraction and that greater astigmatism was associated with greater peripheral retinal hyperopic refraction. Interestingly, we further found by multivariate regression analysis that lens thickness, although not directly related to peripheral retinal refraction, might affect peripheral retinal refraction by altering intraocular astigmatism.

The impact of astigmatism on the development of myopia is an important question that has only been investigated in chick and monkey models. Animal studies indicate that astigmatism contributes to the growth of axial length, especially in cases of against-the-rule astigmatism, which might be explained by the fact that astigmatic blur results in deficient visual signaling pathways; however, how this works is still unknown^{6, 24, 25}. It has been suggested that astigmatism may also affect higher-order aberrations and visual developmental signaling^7–9. A clinical study by Huang et al. showed that the development of astigmatism was strongly associated with axial growth. However, whether astigmatism was a concomitant consequence or cause remains elusive²⁶. The results of the present study suggest that astigmatism has an important influence on retinal peripheral refraction and may interfere with the development of myopia by affecting retinal peripheral refraction. Tomiyama et al. found that toric orthokeratology can adequately correct astigmatism values and show good myopia management, which, in addition to their better orthokeratology positioning ability, may also suggest an important influence of astigmatism on peripheral retinal refraction¹⁰.

There was no significant correlation between LT and peripheral retinal refraction after controlling for covariates, similar to the findings of previous studies that concluded that there was no correlation between LT and crystalline refractive error in myopia development^{27, 28}. He et al. reported that LT substantially decreased over time before the age of 11 years to compensate for the growth of axial elongation during emmetropization and increased after the age of 11 years²⁹. In myopic children, the rate of thinning is faster, and the time to stop thinning is delayed at an older age²⁹. Interestingly, we found that the effect of astigmatism on peripheral retinal refraction tended to increase as the LT thickened, with the mean age of the children recruited in our study being 9 years. Thus, we speculate that in early childhood who develop myopia, delayed thinning of the LT might influence astigmatism and retinal peripheral refraction. However, whether a causal relationship exists between LT changes and astigmatism or radial peripheral refraction was not directly proven in this study. Further studies on the effects of LT on the development of myopia are required.

In our study, both PR and RPR were strongly correlated with the spherical equivalent, axial length, and age. As age and axial length increased, the spherical equivalent decreased, and peripheral relative hyperopia increased, suggesting that relative peripheral hyperopia remains an important risk factor for axial elongation and myopia development in children with low-to-moderate myopia. Saunders³⁰ and Lan³¹ conducted longitudinal studies and found that peripheral relative refraction was indicative of an increased risk for axial elongation and central myopia. However, as this was a cross-sectional study, it is not sufficient to indicate that peripheral relative hyperopia accelerates myopia development^{19, 32, 33}. Following Saunders³⁰ and Lan³¹, we need to investigate this further through a large-scale longitudinal study of PR and RPR.

This study had some limitations. First, this was a cross-sectional study. The long-term effects of astigmatism on retinal peripheral refraction need to be demonstrated with a larger sample size and a longer follow-up period. Second, this study mainly investigated the relationship between astigmatism and retinal peripheral refraction in low and moderate myopia, and this study needs to be further supplemented for high myopia. Third, the ocular biometric values in this study were measured after cycloplegia, which could not accurately reflect the effect of dynamic changes in crystalline lens thickness on retinal peripheral refraction. Further research could be conducted to investigate whether changes in crystalline lens thickness alter retinal peripheral refraction.

In summary, among children with low-to-moderate myopia, astigmatism may be a risk factor for the development of myopia by affecting the peripheral refraction of the retina. We also found evidence supporting the association between relative peripheral hyperopia and myopia development. Therefore, we suggest that adequate astigmatism correction should be considered in the management of myopia.

Acknowledgements

None.

Ethics approval and consent to participate

All subjects and their parents or guardians signed an informed assent and consent. The study protocol was approved by ethics committee of Shanghai Eye Disease Prevention & Treatment Center in China and was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Competing interests

The authors have no conflicts of financial interest.

Funding

This work was supported by Clinical Research Program of Shanghai Municipal Commission of Health and Family Planning of China (Program No.20214042); Shanghai Municipal Health Commission Youth Project (Grant 20214Y0424 and Grant 20234Y0107); Shanghai Municipal Health Commission Outstanding Youth Project in Public Health (GWVI-11.2-YQ20); National Natural Science Foundation Young Staff (Grant No.82301178, China)

Authors' contributions

YX and JC designed the study and gave guidance in writing. JC completed the statistical analysis. HYC was major contributor in writing the manuscript. All authors were responsible for data collection and reviewed the final version of the manuscript.

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Table 2 is available in the Supplementary Files section.

No competing interests reported.

Table2.docx

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The association of peripheral refraction and relative peripheral refraction with astigmatism in Shanghai schoolchildren’s myopia: a cross-sectional study

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusions

Figures

1. Intrduction

2. Methods

2.1 Study design and participants

2.2 Ophthalmic Measurements

2.3 Statistical analysis

3. Results

3.1 The basic characteristics of the participants and MRT characteristics

3.2 Relationship between ocular biological parameters and peripheral refraction

3.3 Relationship between ocular biological parameters and relative peripheral refraction

4. Discussion

5. Conclusion

Declarations

References

Table

Additional Declarations

Supplementary Files

Status:

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