The Association of Myopia Progression with Changes in Retinal Thickness among Primary School Students with Myopia

Purpose To observe the relationship between myopia progression and changes in retinal thickness during one year of follow-up among primary school children. Methods The study included 1161 eyes of 708 myopic children, with 616 (53.06%) right eyes and 545 (46.94%) left eyes. The participants underwent a comprehensive ophthalmic examination, including visual acuity, axial length (AL), autorefraction, and optical coherence tomography (OCT) examination in 2016 and in 2017. An analysis was conducted on the differences in retinal thickness between different genders and between high myopia and nonhigh myopia. Furthermore, the study delved into the correlation between the progression of myopia and the changes of retinal thickness. Results The average diopter was −1.83 ± 1.29D, average AL was 23.78 ± 0.94 mm, and average foveal thickness was 228.02 ± 23.00 μm. For the inner retina, the median value [the lower quartile value, the upper quartile value] of the foveal thickness was thicker in the high myopia group than the nonhigh myopia group (67 [64; 74] μm vs. 63 [56; 70] μm), while the parafoveal region and perifoveal region were thinner in the high myopia group than the nonhigh myopia group (106 [100; 123] μm vs. 124 [117; 130] μm; 95.0 [93; 102] μm vs. 104 [100; 108] μm). Among all the children with myopia, 67.53% (784/1161) of them have a diopter progression within one year. The AL progression was 95.43% (1108/1161). The retinal thickness of all children has slightly increased in various regions. As the AL of the eye increased and the diopter decreased, the progression degree of inner retinal thickness and full retinal thickness (exclusive of full fovea) decreased. Conclusion For the school-age myopic children, the inner foveal retinal thickness were thicker in highly myopic students than in the nonhighly myopic students, while the parafoveal and perifoveal retina were thinner in highly myopic students. The inner and full retinal thicknesses of male students were thicker than that of females. The progression of myopia mainly affected the changes of the inner retinal thickness in the one-year follow-up.


Introduction
Myopia is becoming increasingly common around the world.Myopia afects 30% of the world's population today, and it is anticipated to afect nearly half of the population by 2050 [1].Te excessive increase of the myopic diopter and AL may lead to the thinning of the retina [2,3].Studies on the thinning of the central regions of the retina in patients with high or pathological myopia have been carried out [4,5].Meanwhile, the study on the changes of thickness in diferent retinal regions (fovea, parafovea, and perifovea) and layers (full, inner, and outer retinas) in nonmyopic and myopic participants was also conducted [6].However, the change of thickness in diferent regions of retina between high myopia and nonhigh myopia has not been clearly studied.
With the accelerated increase in the incidence and progression of myopia in school-age children, researchers are putting more focus on retinal thickness in children with myopia.A study on 11-year-old myopic children revealed thickened macular fovea and thinned parafovea, indicating changes in retinal thickness as an early indicator of myopia development.Moreover, the consistent thinning of the parafoveal retina in the inferior region suggests the potential of monitoring regional retinal changes to track myopia progression at an early stage [7].To gain a deeper understanding of the anatomical and morphological alterations in the retinal layer among children with diferent refractive conditions, a cross-sectional study was conducted to examine retinal thickness [8].Read et al. further explored macular thickness and the thickness of each retinal layer, discovering that in myopic children aged 10-15 years, the outer and inner layers surrounding the fovea tend to become thinner [9].However, the changes in retinal thickness in children with myopia during follow-up may require further observation and analysis.
Terefore, this study compared and analyzed the distribution of retinal thickness in diferent regions among school-age children with high myopia and nonhigh myopia.At the same time, it conducted a one-year follow-up on these students with myopia, observing and analyzing the association between the progression of myopia and changes in retinal thickness in diferent regions.

Methods
2.1.Participants.Te current school-based, prospective investigation invited children from six primary schools in Sanhe city of Hebei province in Northern China to participate in the Sanhe Cohort Study of the Risk Factors for Myopia (SCSRFM) [10].At the baseline, children with eye diseases or undergoing myopia control interventions, such as low concentration atropine and orthokeratology, were excluded.Te study was approved by the Institutional Review Board of Beijing Tongren Hospital (QN20150228), Capital Medical University, and the protocol adhered to the Declaration of Helsinki.

Ocular Examination.
Te participants underwent a comprehensive ophthalmic examination, including visual acuity measurement, autorefraction, and posterior segment examination.Te Lenstar LS 900 (Haag-Streit, Koeniz, Switzerland) was used to measure AL.Ametropia was confrmed with subjective refraction, and the automatic refractometer RK-3000 (Topcon, Tokyo, Japan) without cycloplegia was used for the objective refraction to generate the reference value.Te retinal thickness of each region was collected using the RTVue spectral domain OCT (Optovue Inc., remont, CA, USA).All examinations were performed by trained ophthalmologists and optometrists.

OCT Measurements.
Both eyes of all students underwent OCT examination without cycloplegia.Only the OCT images with signal strength greater than 50% of maximal strength and without imaging artifacts or distortion were included.All scans examined the entire thickness of the retina.Using RTVue OCT instrument software, the whole retinal thickness was automatically measured in three concentric annular areas as follows: 1 mm centered on the fovea, the parafoveal region was 1∼3 mm diameter circle near the fovea, and the perifoveal region of 3∼5 mm diameter circle around the parafoveal region.Te nine areas of OCT detection of retinal maps were shown by the standard early treatment of diabetic retinopathy (ETDRS) form, and the parafoveal region and perifoveal region were divided into tempo, nasal, superior, and inferior subregions (Figure 1) [6].Te analysis was conducted based on the boundary retinal thickness segmented by OCT software, namely, the full retinal thickness (from inner limiting membrane to outer retinal pigment epithelium), the thickness of the inner retina (from the inner limiting membrane to the outer boundary of the inner plexiform layer), and the thickness of the outer retina (from the outer boundary of the inner plexiform layer to the outer retinal pigment epithelium) (Figure 2).

Statistical Analysis.
Normally distributed data were expressed as the mean value ± standard deviation, and the diferences between males and female was analyzed using the T-test.As for the data of the high myopia group and the nonhigh myopia group were not normally distributed, the median value and interquartile range (the median value [the lower quartile value, the upper quartile value]) were used for statistical description, and the diferences between the two groups were analyzed using the Wilcoxon rank-sum test.Te correlation between the parameters was explored using

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Journal of Ophthalmology Spearman's rank correlation coefcients.Te value of progression mainly refers to the mean ± standard deviation of the diference between 2017 and 2016 for various parameters.P < 0.05 was considered to be statistically significant.All analyses were performed using SPSS software version 20.0 (SPSS, Inc., IBM, NY, USA).  5 for details).

Association of the Progression in AL and Diopter with the
Progression in Retinal Tickness.Further analysis was carried out on the association of the progression in AL and diopter with the changes in the thickness of diferent retinal regions.As the AL of the eye increased and the diopter decreased, the progression degree of inner retinal thickness and full retinal thickness\(exclusive of full fovea) decreased, and the correlation with the parafoveal and perifoveal regions were statistically signifcant (all P < 0.05).For most outer retinal thickness, as the axial length of the eye increased and the diopter decreased, the progression degree of its thickness increased, but the correlation was not statistically signifcant (see Table 6 for details).

Discussion
Tis study revealed that among myopic children, the foveal thickness of the inner retina was signifcantly thicker in the high myopia group compared to that in the nonhigh myopia group, whereas the parafoveal retina and perifoveal retina displayed a thinner pattern in the high myopia group.However, when considering the full-thickness retina, the fovea was thicker in the high myopia group.When comparing male and female participants, for the inner retina, outer retina, and full retina, the thickness of the foveal and parafoveal region were thicker in males.Tis pioneering study delved into the relationship between the progression of myopia and variations in retinal thickness among myopic children over a one-year follow-up period.It revealed a signifcant yet moderate augmentation in retinal thickness across all myopic children, particularly notable in the foveal region compared to the perifoveal region.Intriguingly, the study established a correlation between AL progression and diopter progression with alterations in both the inner retina and the full retina.Furthermore, the thinning of the inner and full retina accelerated with myopia progression.Te previous study on healthy eyes showed that the retinal thickness was not associated with the spherical equivalent refraction (SER), age, or AL [12].Jin et al. measured the retinal thickness of 7-13 -year-old children and found that the mean central foveal retinal thickness was 234 ± 22 μm in myopic participants and the retinal thickness was thinner in the superior parafoveal and perifoveal regions and in the inferior perifoveal region.In addition, in the study by Jin et al., SER and AL were not correlated with subfoveal/parafoveal retinal thickness, while subfoveal retinal thickness was negatively related to age and positively related to intraocular pressure [8].Chen et al. reported that central macular thickness was 240.93 ± 17.35 μm and 244.13 ± 22.26 μm in the 6-17 -years-old Chinese low myopia (3.00 D < SER 0.50D) and moderateto-high myopia (SER: 3.00 D) children.Te foveal thickness was signifcantly greater in highly myopic eyes compared with the nonmyopic eyes, while the diference was not statistically signifcant for low, moderate, and low-to-moderate myopic eyes [13].In the current study, the foveal thickness of myopic children was 228.02 ± 23.00 μm, which was thinner than the fndings of other studies and may be related to the younger age and lower diopter (−1.83 ± 1.29D) in the current study.In children with high myopia, the retina was signifcantly thicker than that in children with nonhigh myopia.However, during the one-year follow-up, the progression of foveal thickness was not signifcantly associated with the progression of diopter and AL.
Te changes in diferent regions of the retina difer when the degree of myopia is diferent.Te study by Sam et al. on the thickness of the peripheral retina showed signifcantly thinned retina in myopic eyes, while the foveal retina and other retinal regions were thicker in myopic eyes.Meanwhile, the peripheral retina was 7% thinner from the nasal region to the temporal region in myopic eyes [14].
Another study found that average parafoveal thickness was thinner in highly myopic eyes without signifcant diference across all regions [13].Compared with nonmyopic eyes, the thickness of the superior perifoveal region, inferior perifoveal region, and the temporal perifoveal region were signifcantly thinner in low, moderate, and highly myopic eyes.In addition, the nasal perifovea was signifcantly thinned in highly myopic eyes, while the fnding for the perifoveal thickness in low-to-moderate myopic eyes was not available due to the lack of adequate data [15,16].Te current study compared high myopia groups and nonhigh myopia groups found that the full parafoveal and perifoveal retina were relatively thin in children with high myopia in diferent quadrants, without statistical diference between the two groups.Vurgese et al. reported that AL increase was associated with thinning of the parafoveal retina and was not related to foveal retinal thickness, which was consistent with the hypothesis that axial increase of the globe walls in the midperiphery could be the main driver of myopic globe enlargement [17].During the 1-year follow-up in the current study, the thickness of the parafoveal and peripheral retina also decreased with the progression of myopia.Te changes in the inner and outer layers of the retina difer in eyes with diferent degrees of myopia.A study on highly myopic adults revealed thinned outer retina with a noticeably thinned myoid and ellipsoid zone [18].Te inner and outer macula was signifcantly thinned in the high myopia group.Te thinning of the inner and outer retina may be attributable to the myopic globe expansion, with which the inner retina would be tangentially stretched and the anteroposterior tractional force would be imposed on the outer retina [19].In highly myopic eyes, the outer segment of the receptors layer thickened in the central region, and the increase was associated with the AL growth.Apart from the ganglion cell and inner plexiform layer, the thickness of all layers in the pericentral and peripheral regions changed in highly myopic eyes.Since the inner nuclear layer, combined Henle fber and outer nuclear layer, and outer segment of receptors layer were all thinner in myopic eyes, the total thickness of the peripheral region was also smaller.However, increased thickness was found in the combined myoid and ellipsoid zone, the combined interdigitation zone, and the retinal pigment epithelium/Bruch complex in myopic eyes [15].Te current study found thickened inner and outer foveal retina in children with high myopia, while the parafoveal and perifoveal inner retina was thinned and the outer retina was thickened, with statistical signifcance for most of the parameters.During follow-up, with the progression of myopia, the thinning of inner and full parafoveal and perifoveal retina thickness accelerated with a statistical diference.No statistically signifcant changing trend was found for the outer retina.
Tere were also reports on the infuence of gender on retinal thickness.Te central fovea and nasal fovea were found to be thicker in males, urban residents, and those with thinner lens, thinner subfoveal choroid, and longer AL [20].In terms of the macular thickness across ETDTS regions in males and females, the macular thickness in the foveal, superior inner, nasal inner, inferior inner, temporal inner, and temporal outer quadrants were signifcantly thicker in males, without signifcant diferences in average macular thickness and average macular volume [21].Zhang et al. reported that the values of minimum foveal thickness, foveal volume, and average inner ring and temporal outer quadrant macular thickness were signifcantly greater in males, and no signifcant diference was found in total macular volume [22].Macular measurements by gender showed thicker central fovea, average inner macula, and temporal and nasal quadrant outer macula in males [23].Nevertheless, there was another study revealing a lack of signifcant association between the central foveal retinal thickness and gender [8].However, in the current study, the foveal and parafoveal thickness were thinker in male participants with statistical signifcance, and the perifoveal retina was thinner in male participants with statistical signifcance.
Te relatively short follow-up period, one year, is one of the limitations of the current study.While one-year followup revealed the trend of the changes in the thickness of diferent retinal regions, the trend would be clearer and more defnitive with a longer follow-up period.Due to the fact that the participants in this study were mainly 10-year-old schoolchildren with myopia, among whom the number of participants with high myopia was indeed relatively small, the data between the two groups were not well matched.However, we described the data for the high myopia group and the nonhigh myopia group using medians values and performed Wilcoxon rank-sum test to analyze the diferences between the two groups, aiming to reduce the impact of data bias.In addition, with the further progression of myopia, in addition to the changes in retinal thickness, the thickness of the choroid would also change signifcantly, which should be further studied in future research.
Analyses of the diopter, AL, and retinal thickness in school-age myopic children showed that the inner foveal retinal thickness were thicker in highly myopic students than in the nonhighly myopic students, while the parafoveal and perifoveal retina were thinner in highly myopic students.Te inner and full retinal thicknesses of male students were thicker than that of females.Te progression of myopia mainly afected the changes of the inner retinal thickness in the one-year follow-up.

Figure 1 :
Figure 1: Te map of the diferent retinal region.

Table 2 :
Comparison of baseline retinal thickness in two myopia subgroups.

Table 3 :
Comparison of baseline retinal thickness in two AL subgroups.

Table 4 :
Comparison of baseline retinal thickness in male and female participants.

Table 5 :
Progression in AL, diopter, and retinal thickness.

Table 6 :
Correlation of the progression in AL and diopter with the progression in retinal thickness.