Longitudinal changes of refraction and visual acuity in children with early-onset high myopia

doi:10.21203/rs.3.rs-4505630/v1

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Longitudinal changes of refraction and visual acuity in children with early-onset high myopia

https://doi.org/10.21203/rs.3.rs-4505630/v1

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Objectives

To investigate the longitudinal changes of refraction and visual acuity in children with early-onset high myopia (eoHM).

Methods

We retrospectively included children with eoHM, defined as cycloplegic spherical equivalent (SE) ≤ − 6.00 D or axial length (AL) ≥ 26mm in both eyes in children under 7 years old, who had at least three visits with available cycloplegic autorefraction records based on the electronic medical records (EMR) at the Zhongshan Ophthalmic Center between 2003 to 2023. Data on children’s demographic and clinical characteristics, including age, sex, best corrected visual acuity (BCVA) and presence of strabismus were also extracted from the EMR.

Results

A total of 930 children were included (median baseline age: 4.33 years, interquartile range [IQR], 3.42 to 5.25 years, 64.84% boys). The median baseline spherical equivalent (SE) was − 8.25D (IQR, -10.00D to -7.00D), and the median duration of follow-up was 2.85 years (IQR, 2.03 to 3.57 years). The mean myopia progression rate was − 0.33 (SD, 0.37) D/year, with 298 children (32.04%) demonstrated myopia progression of ≥ 0.50D/year. Older age (ß= -0.041, P < 0.001), boys (ß= -0.067, P = 0.012), and less myopic at baseline (ß= -0.013, P = 0.021) were associated with faster myopia progression. The percentage of children with BCVA > 0.5 (20/40) ranged from 11.27% among the 4-year-olds to 73.58% among the 8-year-olds.

Conclusion

In this real-world hospital-based dataset, two-thirds of children with eoHM do not experience rapid myopia progression. Boys, children with older age and less myopic SE at baseline are more likely to experience faster myopia progression.

Health sciences/Diseases

Health sciences/Risk factors

The escalating prevalence of myopia, especially high myopia, has raised significant global concern. It is estimated that 938 million people will be diagnosed with high myopia worldwide by 2050 ¹. High myopia can lead to many irreversible ocular complications, such as myopic macular degeneration (MMD), retinal detachment (RD), cataract, open angle glaucoma (OAG), diffuse chorioretinal atrophy and so on, which are all associated with vision loss and reduced quality of life ^2–4. For each 1diptor (D) increase in myopia, the risk of MMD, RD, posterior subcapsular cataract, and OAG increases by 58%, 30%, 21%, 20% respectively ⁵. What’s more, it is reported that the prevalence of early-onset high myopia (eoHM), defined as high myopia that occurs before 7 years of age, has increased in different countries and regions. ^{6, 7} Theoretically, children with eoHM had longer period of myopia progression during childhood and may end up with more severe myopia in adulthood ^{8, 9}, thus conferring higher risk of visual impairment.

So it is necessary to monitor myopia progression in children with eoHM, but existing studies regarding children with eoHM mostly focused on genetic factors ^10–12, the myopia progression and visual acuity (VA) development pattern of these children have rarely been explored. Studies had reported that for preschool children with myopia, the myopia progression rate was associated with age, baseline myopia severity, family history of myopia, and astigmatism ^13–15, however, little is known regarding risk factors associated with myopia progression in children with eoHM. To our knowledge, only two studies existed regarding this issue, but were limited by small sample size and short follow-up time ^{16, 17}.

Thus in this study, we aimed to investigate the longitudinal changes of refraction and VA in Chinese children with eoHM based on a large hospital-based dataset, and explored the factors associated with longitudinal changes.

Study population

We retrospectively reviewed clinical records to identify children with eoHM, defined as cycloplegic SE ≤ − 6.00 D or AL ≥ 26mm in both eyes before 7 years of age, based on the electronic medical records (EMR) at Zhongshan Ophthalmic Center (ZOC) between 2003 and 2023. Those with available cycloplegic refraction data and BCVA at ≥ two follow-up visits were included in this study. Children fulfilling any of the following criteria were further excluded: (1) history of ocular surgery, (2) history of vision threatening ocular diseases, such as congenital cataract and retinal diseases, (3) history of ocular trauma. The study was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou and conducted in accordance with the Declaration of Helsinki.

For each study participant at each hospital visit, we retrospectively extracted data on their age, sex, cycloplegic refraction, best corrected visual acuity (BCVA) and presence of strabismus from EMR. At ZOC, cycloplegic refraction was measured using an autorefractor (Topcon, Tokyo, Japan) after complete cycloplegia (defined as the absence of light reflex and a dilated pupil at least 6 mm in diameter), BCVA was measured after subjective refraction by optometrist or ophthalmic nurse using an early treatment diabetic retinopathy study tumbling E chart at a standard testing distance of 5 meters, and recorded in Snellen decimal. Presence of strabismus was examined and determined by ophthalmologists.

The first visit of each child with eoHM at ZOC was defined as the baseline visit. The mean myopia progression rate was defined as the changes in SE between the last visit and the baseline visit divided by follow-up time in between. We categorized the population into three groups based on the rate of refractive progression. The myopia progression group was defined as those with an average myopic progression of 0.5D or more per year, that is, a SE change rate of ≤ -0.5D/year. The myopia regression group is defined as those with a SE change rate of ≥ + 0.5D/year, and those in between are classified as the myopia stable group. ¹⁷. Strabismus was deemed present if the child was diagnosed as strabismus based on the EMR during any hospital visit.

Statistical analysis:

SE was calculated as the sum of the spherical power and 1/2 cylindrical power. Because correlations between the right and left eyes in the same individual were high, so only the SE data and BCVA data from the right eyes were included. The Kolmogorov–Smirnov normality test and histogram were used to check the normality in the distribution of continuous variables. The baseline SE distribution was expressed as median (IQR) for children in different age groups, distribution of sex, SE and strabismus were expressed as absolute and relative frequencies.

Children were categorized into different age (< 3 years, 3 to 4 years, and 5 to 6 years), baseline SE (>-8D and ≤-6D, >-10D and ≤-8D, and ≤-10D), and strabismus (yes or no) groups. Independent t-tests were used to examine the differences of sex or strabismus at baseline in the mean myopia progression rate. Trend analyses were performed to detect any differences between different baseline SE subgroups and different age subgroups, as well as differences in BCVA between different age subgroups. Linear mixed-effect models were used to assess the association between sex, baseline SE, baseline age, and the presence of strabismus at baseline with SE change rates. SE change curves of each participant and linear mixed-effect regression lines for SE associated with age were plotted to visualize the longitudinal change in SE in study participants. Distribution of BCVA in children with different SE was represented as stacked bar graphs, and BCVA from all follow-up visits of each participant (except for underfitting) were included.

Statistical analyses were performed using SPSS software version 26.0 (SPSS, Inc., Chicago, IL, USA) and STATA version 18.0 (Stata Corporation, College Station, TX, USA). A two-sided P value < 0.05 was considered statistically significant.

From 2009 to 2023, a total of 4876 children with eoHM were identified based on the EMR, and a total of 930 children (19.07%) were found to be eligible for the current analysis. The median age of the included children at baseline was 4.33 years (IQR, 3.42 to 5.25 years), and 603 (64.84%) participants were boys, 170 (18.28%) children were diagnosed with strabismus. Study participants were followed for a median of 2.85 years (IQR, 2.03 to 3.57 years). Median baseline SE at baseline was -8.25D (IQR, -10.00D to -7.00D). Detailed characteristics of the study participants by baseline age are provided in Table 1.

Table 1. Baseline characteristics of children with eoHM included in this study according to the baseline age.

	Baseline Age (years)
	Total	1-2	3	4	5	6
Number	930	70	214	272	222	152
Sex, boy (%)	603 (64.84%)	42 (60.00%)	145 (67.76%)	180 (66.18%)	135 (60.81%)	101 (66.45%)
Baseline SE
Median (IQR), diopters		-9.375 (-10.781, -8.000)	-8.375 (-9.906, -7.250)	-8.250 (-10.000, -7.000)	-8.063 (-9.875, -6.875)	-8.313 (-9.969, -6.656)
>-8D and ≤-6D, n (%)	389 (41.83%)	16 (22.86%)	89 (41.59%)	112 (41.18%)	103 (46.40%)	69 (45.39%)
>-10D and ≤-8D, n (%)	297 (31.94%)	25 (35.71%)	72 (33.64%)	90 (33.08%)	65 (29.28%)	45 (29.61%)
≤-10D, n (%)	244 (26.24%)	29 (41.43%)	53 (24.77%)	70 (25.74%)	54 (24.32%)	38 (25.00%)
Strabismus, n (%)	170 (18.28%)	14 (20%)	42 (19.63%)	53 (19.49%)	37 (27.41%)	26 (17.11%)

For all 930 participants, the mean myopia progression rate was -0.33 D/year (SD, 0.37). A total of 10 participants (1.08%) demonstrated myopia regression over the follow-up period, 622 (66.88%) showed stable refraction, and 298 (32.04%) demonstrated myopia progression. Table 2 demonstrated the mean myopia progression rates for different children. Older children showed a greater mean myopia progression rate (P=0.029), and boys progressed faster than girls (-0.35 vs. -0.28 D/year, p=0.008). Those with less myopic baseline SE showed faster rate of myopia progression (P=0.002). Individual participant’s SE change curve and linear mixed-effect regression lines for SE associated with age are shown in Figure 1. Strabismus was not found to be related to the rate of myopia progression.

Table 2. Mean rate of myopia progression

Characteristics	Number	Mean rate of myopia progression (D/year), Mean (SD)
Sex
Boys	603	-0.35 (0.36)
Girls	327	-0.28 (0.39)
P		0.008
Baseline age (years)
≥2 and <3	70	-0.25 (0.38)
≥3 and <5	486	-0.32 (0.37)
≥5 and <7	374	-0.36 (0.38)
P for trend		0.029
Baseline SE (D)
>-8 and ≤-6	389	-0.38 (0.35)
>-10 and ≤-8	297	-0.29 (0.38)
≤-10	244	-0.29 (0.40)
P for trend		0.002
Strabismus at Baseline
Yes	170	-0.35 (0.40)
No	760	-0.32 (0.37)
P		0.310

Abbreviations: SD: standard; SE: spherical equivalent; eoHM: early-onset high myopia; D: diptor.

As shown in Table 3, older baseline age (ß= -0.041, P<0.001), boys (ß= -0.067, P=0.012), and less myopic SE at baseline (ß= -0.013, P=0.021) were associated with faster myopia progression.

Table 3. Linear mixed-effect models for associations between the rate of myopia progression with age, sex, SE at baseline and presence of strabismus.

	Mean rate of myopia progression (D/year)
	Model 1*		Model 2†
Characteristics	ß (95%CI)	P	ß (95%CI)	P
Baseline age (years)	-0.041 (-0.062, -0.019)	<0.001	-0.041 (-0.063, -0.019)	<0.001
Female, vs male	-0.065 (-0.118, -0.013)	0.015	-0.067(-0.120, -0.015)	0.012
Baseline SE (D)	-0.013 (-0.024, -0.002)	0.024	-0.013 (-0.024, -0.002)	0.021
Strabismus, yes vs no			0.051 (-0.014, 0.116)	0.122

Abbreviations: SE: spherical equivalent

Model 1* adjusted for baseline age, sex, and initial SE.

Model 2† adjusted for baseline age, sex, initial SE and strabismus at baseline.

Table 4 demonstrated the mean BCVA values and percentage of children with BCVA > 0.5 (20/40) for different ages. Overall, older children showed better BCVA (P<0.001). The distribution of SE in children with eoHM categorized by BCVA is shown in Figure 2, each BCVA group can encompass a variety of SE, likewise, each SE status can lead to different BCVA outcomes.

Table 4. Distribution of best corrected visual acuity stratified by baseline age.

Baseline Age	Number	Percentage of children with BCVA > 0.5 (%)	BCVA, Mean (SD)
4	426	11.27	0.36 (0.17)
5	661	30.56	0.46 (0.19)
6	748	50.27	0.54 (0.20)
7	629	63.28	0.61 (0.21)
8	405	73.58	0.68 (0.20)
P for trend			<0.001

Abbreviation: BCVA: best corrected visual acuity; SD: standard.

BCVA was recorded and analyzed in Snellen decimal. BCVA from each follow-up of each participant were placed into the corresponding age subgroups for calculation (except for underfitting).

In the current study, we reported longitudinal changes in SE and distributions of BCVA in Chinese children with eoHM based on a large hospital dataset. The mean myopia progression rate was -0.33D/year (SD, 0.37), with two-thirds of eoHM children exhibited myopic stability or regression. Children with older age, boys, and less myopic SE at baseline seems to experience faster myopia progression. Generally, BCVA improved with older age, but only half of these children achieved BCVA > 0.5 by the age of 6 years.

In a three-year longitudinal study of 60 children ≤ 6 years with eoHM in Korea, the myopia progression rate was -0.37D/year (SD, 0.39), with 40% of the children exhibiting myopic progression ¹⁷. Another study included 57 children with full-correction glasses under 5 years old from Taiwan with SE ≤-5.0D, the myopia progression rate for those with SE in the ≥-7.75D and ≤-5.0D, ≥-10.75D and ≤-8.0D, ≤-11.0D group was -0.47 (SD 1.33) D/year, -0.21 (SD,1.56) D/year and -0.07 (SD 1.38) D/year，respectively. Roughly 45% of the children showed binocular or monocular myopia progression, 23% showed binocular stability, the remaining 32% showed binocular or monocular regression ¹⁶. The myopia progression rate in our study was similar to these two studies, which collectively suggest that children with older age and less myopic SE at baseline tend to progress faster. Another study also reported associations between older age, less myopic SE and faster myopia progression among children with preschool myopia ¹³. This could be due to that children in this age group experience more schooling with older age and those with less severe myopia could imply more room for the eyeball to grow triggered by environmental risk factors. These findings are opposite to those found in school myopia, in which older age or less initial myopic SE were associated with slower myopia progression ^18-21.

Moreover, 55%-65% of the eoHM children could remain relatively stable or even regression in the above-mentioned studies, which could be partly attributed to the effectiveness of timely interventions. The research from Taiwan involved full-correction, whereas the studies from South Korea did not report on this aspect. Although our data does not directly reflect this, it is speculated that the majority of eoHM children who seek medical advice at ZOC are likely to follow the doctor's recommendations regarding wearing spectacles and receiving other treatments. This finding underscores the critical importance of early intervention for children with eoHM. Additionally, about one-third of the children still experienced relatively rapid myopia progression, these children warrant more attention in clinics and future studies.

The mean myopia progression rate of boys is higher than girls in our study, but the study in Korea reported that sex was not related to myopic progression rate. It has been reported that boys had quicker AL elongation than girls in the preschoolers ²², but more studies are needed to explore whether gender difference exists.

Previous longitudinal studies based on preschool children with low to moderate myopia had reported a myopia progression rate of -0.79 to -0.59 D/year ^{13, 23}, which is higher than the reported rates in children with eoHM above, the exact mechanisms underlying this are unclear. It might be due to that children with eoHM are more likely to be diagnosed and treated at early years, or that the already elongated AL in these children encountered biological growth constraints. The corresponding changes in biometric factors during the onset and progression of eoHM may help reveal the mechanisms, yet they remain unclear ^{24, 25}. Further studies about longitudinal changes in ocular biometric parameters, as well as refraction in children with eoHM, are warranted to better understand the mechanisms.

From our study, it was apparent that the BCVA of children with eoHM was lower than that of children without high myopia at the same age ^26-28, the risk of amblyopia is higher in children with eoHM ²⁹. Children with less myopic baseline SE may be associated with better VA than those with higher myopic baseline SE, the result was similar to the study from Taiwan ¹⁶, and it was consistent with physiological pattern of visual development ³⁰. It could be inferred that SE is not the only factor affecting BCVA (Figure 2). Up to now, our understanding of the visual prognosis and influencing factors for children with eoHM is still very limited, and further research is needed.

The strengths of the study included its large sample size of eoHM children, and the availability of cycloplegic SE and VA data on each study visit. But several limitations should be noted. First, this was a retrospective study from a single institution. Second, due to the retrospective study design, data on ocular biometrics, parental myopia, and length of time spent outdoors, were not available in this study, but this would not limit us from delineating the longitudinal changes in SE and BCVA. Third, different cycloplegia methods might be used at different visits. However, full pupil dilation was ensured before refraction examination regardless of the cycloplegia methods used, ensuring the accuracy of cycloplegic refraction. Fourth, whether the children have received myopia correction was unavailable in this dataset, but we assume that most of eoHM children, if not all, who come to ZOC have received optical correction. Still, the effect of different kinds of myopia interventions on the SE and VA changes among eoHM children warrants further investigation. Lastly, the mean follow-up period of the study was relatively short, prospective studies with longer follow-up period are encouraged in the future.

In conclusion, our study findings suggest that eoHM children generally exhibited slower myopia progression and poorer BCVA compared to those with low to moderate myopia, with two thirds of eoHM children maintaining stable in refraction or even regression. Boys, as well as those with older age and less myopic SE at baseline are associated with higher risk of myopia progression. Further studies are needed to elucidate the longitudinal changes in the SE, ocular biometrics, and VA in children with eoHM for better myopia control and visual prognosis.

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

Supported by the National Natural Science Foundation of China (No. 82101171, 82070941)

Acknowledgements

The authors thank the patients who participated in this study.

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You are reading this latest preprint version

Longitudinal changes of refraction and visual acuity in children with early-onset high myopia

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Abstract

Objectives

Methods

Results

Conclusion

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Introduction

Subjects and Methods

Study population

Statistical analysis:

Results

Discussion

Conclusions

Declarations

Conflict of Interest

Funding

Acknowledgements

References

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