Relationship between the morphology of the posterior pole of the eyeball and changes in choroidal structure and blood flow in myopia
Introduction
The prevalence of myopia is increasing dramatically worldwide (1). It is estimated that the number of myopia patients will increase to about 5 billion in 2050, representing 50% of the global population, of which high myopia patients may increase to about 1 billion, representing about 10% of the global population (1). High myopia complications such as choroidal neovascularization, retinal detachment, and myopic traction maculopathy (MTM), can cause irreversible damage to a patient’s visual function (2). Therefore, it is necessary to explore effective monitoring indicators and implement intervention measures, otherwise the global economic burden caused by myopia will increase significantly as its prevalence increases (3).
Myopia is related to the optical power of the crystalline lens, the cornea, and the axial length (AL) of the eyeball (4). Reports have shown that intraocular pressure (IOP) and the morphology of the intraocular and extraocular muscles are also correlated with myopia (5-7). AL elongation is considered the main cause of refractive error progression (8), and is related to various non-pathological and pathological changes in the posterior of the eyeball (9).
In addition to changes in the AL, changes in the shape of the posterior pole of the eye in myopia have also been observed. Research has shown that myopic axial elongation changes the eye shape from an emmetropia oblate or globose to a prolate ellipsoid (10,11). It may be that sclera remodeling occurs during AL elongation, and its thickness becomes thinner most notably at the posterior pole (12). Under the effect of IOP, the shape of the posterior pole of the eyeball further alters and axial elongation occurs (13). Conversely, it may be that in an emmetropia with a steep retinal shape, the peripheral retina produces hyperopic defocus, stimulating the compensatory growth of the eyeball and producing axial elongation, such that the posterior-pole retina becomes steeper (14,15). Further research is required to determine the causal relationship between changes in the retinal shape and AL in the development of myopia. A recent study reported that the steeper the retina, the more likely MTM is to occur (16). This suggests that abnormal ocular morphological changes cause not only myopic refractive error but a variety of other ocular complications. Therefore, further research into the role of eyeball shape in the development of myopia needs to be conducted.
At present, there is sufficient literature to study the relationship between the AL and choroid. Studies have shown that choroidal thickness (ChT) and choroidal vascular volume (CVV) decreased with the aggravation of myopia and axial elongation (17,18). The choroidal vascularity index (CVI) is a novel reliable parameter proposed in 2016 by Agrawal et al., and defined as the ratio of the vascular luminal area to the total choroidal area (19). A decreased CVI has been shown to be related to myopia, age-related macular degeneration, and diabetic retinopathy, and it can also be used to detect ocular inflammatory and infectious diseases (20). However, few studies have examined the relationship between the eye shape and the above indicators, especially the choroidal vessels in the periphery of the macular area.
Eyeball shape may be of importance in understanding the development of myopia. Thus, this study modeled ellipse curves to establish a quantifiable index to evaluate the shape of the posterior pole of the eyeball, and analyzed the correlation between the shape of the posterior pole and ChT, CVV, and three-dimensional choroidal vascularity index (3DCVI). We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-829/rc).
Methods
This study was conducted in accordance with the principles of the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of the First Hospital of China Medical University (No. [2017]2017-74-2). All participants were informed of the purpose of the study and provided written informed consent. A total of 170 volunteers were recruited in May 2021, of whom, 147 met the inclusion criteria (Figure 1).
To be eligible for inclusion in this study, the participants had to meet the following inclusion criteria: be aged between 20 and 30 years; have myopia or emmetropia; have healthy eyes (as determined by ophthalmologic examination); and have no systemic disease. Patients were excluded from the study if they met any of the following exclusion criteria: had best corrected visual acuity (BCVA) <0.8; had non-physiological astigmatism >0.75 D; had IOP >21 mmHg; had a history of wearing orthokeratology lenses; had a history of eye surgery; had severe pathological myopia, such as obvious posterior staphyloma (PS); and/or had choroidal neovascularization. Due to the symmetry of both eyes in the same individual, only the right eye was included in the analysis, unless poor optical coherence tomography (OCT)/optical coherence tomography angiography (OCTA) images were obtained due to fixed problems or the OCT signal strength was <8, in which case the left eye was included in the analysis (n=17). The participants were divided into the following three group based on the AL: the short AL group (22.0 mm < AL ≤24.0 mm); the medium AL group (24.0 mm < AL ≤26.0 mm); and the long AL group (AL >26.0 mm) (21). PS was defined as the curvature of the retinal pigment epithelium (RPE) (22), and was diagnosed using both the OCT and fundus images by retinal specialists.
Examination procedures
Medical histories were collected, and the height and weight of the participants were measured, and the average of three measurements was taken as the final result to calculate the mean body mass index (BMI), which was expressed as follows BMI = weight/height2 (kg/m2). All participants underwent a comprehensive eye examination, including a BCVA and slit-lamp examination. Computer optometry (KR-800, TOPCON, Tokyo, Japan) was used to measure the diopter of spherical power (DS) and the diopter of cylindrical power (DC), which were finally converted to the spherical equivalent (SE) using the following formula: SE = DS + DC/2. After obtaining three IOP measurements using non-contact tonometry (TOPCON, Japan), the average was calculated. The AL and corneal power (CP) were measured using an IOL Master 500 (Carl Zeiss Meditec, Germany), and the average of five consecutive measurements was used as the final result for each participant. Choroidal imaging was performed with swept-source optical coherence tomography (SS-OCT) (VG 200 S; SVision Imaging, Henan, China) and OCTA as detailed below. All of the above inspections were performed by technicians with at least five years of experience. In addition, to minimize the effects of circadian variations, all measurements were obtained during the same period, and the participants were asked to avoid caffeine and alcohol consumption for 24 hours before choroidal imaging (23).
SS-OCT and OCTA imaging and analysis
Images of the posterior pole of the eyeball and choroidal parameters were acquired using SS-OCT/OCTA, and the proportions of all images were automatically corrected according to the AL (24). This SS-OCT device has a number of advantages, including an ultra-wide angle and ultra-high resolution, uses a swept-source laser with a center wavelength of approximately 1050 nm and a scanning speed of 200,000 A-scans per second, and is equipped with an eye-tracking program to eliminate eye-movement artifacts (25). The scan line length used was 16 mm, the scanning depth was 3 mm, the axial resolution was 5 µm, and the lateral resolution was 13 µm. The scan line passing through both the fovea centralis and the center of the optic disc was selected for analysis, which was obtained after 2,048 A-scans and 64 B-scans.
OCTA was performed using 512 horizontal B-scans, with each B-scan containing 512 A-scans, repeated four times and averaged. After three-dimensional (3D) modeling processed by the system’s algorithms to identify the signals flowing in the structure (25), Niblack localization threshold technology was used to semi-automatically segment the images and binarize them to distinguish the vascular region and the stroma region of the choroid (19). The scanning area was a 12×12 mm—square centered on the macular center concave reflective spot. The position of the reflective point was determined by automatic recognition by the machine after patient fixation, and the center was adjusted manually if the position was not accurate.
Fitted curve and fitting the posterior-pole vertex curvature
The scan line passing through both the fovea centralis and the center of the optic disc was selected for analysis. The collected original images (2,048×1,383 pixels each) were imported into the ImageJ (version 1.47, National Institutes of Health, USA) software and Bruch’s membrane (BM) was selected as the representative layer of the shape of the posterior pole (Figure 2A). Next, 33 points were manually plotted with equal horizontal spacing (64 pixels), eliminating the localization points in the optic disk area, and the pixel coordinates (x, y) of the remaining points were automatically obtained. The dataset of the obtained coordinates was imported into the Anaconda 3 (Continuum Analytics, USA) scientific computing environment, where an algorithm for fitting an elliptical curve using the least squares method was implemented in the Python 3.0 programming language and executed in Jupyter Notebook (version 7.2.1 Jupyter Team, U.S.). The fitting process employed a multidimensional unconstrained non-linear minimization algorithm, coupled with the iterative Nelder-Mead procedure. At each iteration, an ellipse was constructed based on a given set of coordinates, and the root mean square error (RMSE) between the fitted ellipse and the actual BM curve was computed. The RMSE provided a goodness-of-fit evaluation criterion for each ellipse-fitting process, and the program was iteratively terminated until the minimum value of the RMSE was reached, at which point the optimal fitting curve and its associated parameters were obtained (Figure 2B). The standard equation for an ellipse is expressed as: x2/a2 + y2/b2 = 1, where a represents the half-axis length of the fitted elliptic curve parallel to the X-axis, and b represents the half-axis length of the fitted elliptic curve parallel to the Y-axis. The scan line length of the SS-OCT used in this experiment was 16 mm, which was larger than the scanning range of the previous OCT, allowing the fitting ellipse to conform to the shape of the posterior pole to a greater extent. The vertex curvature of the fitting ellipse was chosen as the index to quantify the shape of the posterior pole of the eyeball, which was called the fitting posterior-pole vertex curvature (fPVC), and was expressed as: fPVC = b/a2. A larger fPVC represents steeper posterior-pole morphology.
Measurement of choroidal parameters
SS-OCT uses deep-layer artificial intelligence for accurate stratification, and previous studies have shown that choroid measurement using this device has good repeatability and reproducibility (26). The choroid is defined as the volume from the RPE-BM complex to the choroidal-scleral interface. The choroid is composed of stroma and blood vessels, which contain the following three vascular sublayers: the choriocapillaris, medium-sized vessels (Sattler’s layer), and large vessels (Haller’s layer) (27). The CVV was defined as the medium- and large-sized vessels detected by the threshold binarization algorithm built-in software of SS-OCT/OCTA from the choroid-sclera to 25 µm below the BM (28). The 3DCVI was defined as the ratio of the CVV to the total choroidal volume. The zoning scheme for this experiment comprised three concentric circles, 3, 6, and 9 mm in diameter, centered on the foveola. The results of the Early Treatment Diabetic Retinopathy Study (ETDRS) were applied to the choroidal zonation, which was divided into the superior, temporal, inferior, and nasal areas. The nasal choroid in the 6–9 mm region was greatly affected by the optic disc; therefore, this portion was not examined in this analysis. The valid regions included in the study were: A1: 0–3 mm; A2: 3–6 mm; A3: 6–9 mm (except the nasal side); and total area (TA) = A1 + A2 + A3 (Figure 3). Finally, the ChT, CVV, and 3DCVI were calculated separately for the above effective regions.
Statistics
SPSS Statistics 27.0 (IBM, Armonk, NY, USA) was used for the statistical analysis. The normal distribution was evaluated using the Kolmogorov-Smirnov normality test combined with observation via histogram and scatter plot. The continuous variables are expressed as the mean ± standard deviation, and the categorical variables are expressed as the number and proportion. A one-way analysis of variance, least significance difference test, and the Kruskal-Wallis H test were used to analyze the differences between groups. A univariate correlation analysis was used to analyze the relationship between the AL, fPVC, and systemic and ocular parameters. A multiple stepwise regression analysis was used to investigate the independent factors affecting the choroid parameters. In all the analyses, we reported and interpreted both the effect size and statistical significance (p value) to ensure the objectivity of the results (29). The ChT and CVV were excluded from the 3DCVI regression model because of the intrinsic physiological relationships between these choroidal indicators, which are mediating rather than confounding factors (30,31). Stata MP software (version 15.0; StataCorp LP, College Station, Texas, USA) was used to perform local weighted regression scatter smoothing (LOWESS) on the 3DCVI to observe any changing trends among the 3DCVI and the AL and fPVC. In all the analyses, a P value <0.05 for the two-tailed test was considered statistically significant.
Results
A total of 147 participants (94 female, 63.95%) were included in this study. The age of the participants ranged from 20–30 years. The mean AL was 25.15±1.35 mm (22.30–27.92 mm). The mean SE was −3.59±2.62 D (+0.5 to −11.75 D), and the mean fPVC was 0.158±0.036 mm−1 (0.071–0.261 mm−1). As Table 1 shows, there were 30 eyes in the short AL group (22.0 mm < AL ≤24.0 mm), 76 eyes in the medium AL group (24.0 mm < AL ≤26.0 mm), and 41 eyes in the long AL group (AL >26.0 mm). The mean CP, SE, and fPVC were statistically different among the three groups (all P<0.001). The mean height of the long AL group was higher than that of the medium AL group (P<0.05, η2=0.063). There were no significant differences among the three groups in terms of sex (P=0.629), age (P=0.057), weight (P=0.092), and BMI (P=0.519).
Table 1
Parameters | Total (n=147) | Short AL (n=30) | Medium AL (n=76) | Long AL (n=41) | F/χ2 | η2 | P value |
---|---|---|---|---|---|---|---|
Sex, male (%) | 36.05 | 30 | 39.47 | 34.15 | – | – | 0.629 |
Age (years) | 23 (1) | 24 (1.25) | 23 (2) | 23 (1) | 5.73 | – | 0.057 |
Height (cm) | 168.71±7.54 | 165.80±7.81 | 168.47±6.80 | 171.27±7.96b | 4.879 | 0.063 | 0.009 |
Weight (kg) | 62.09±10.55 | 60.13±8.35 | 61.25±10.65 | 65.06±11.40 | 2.43 | – | 0.092 |
BMI (kg/m2) | 21.73±2.82 | 21.80±2.03 | 21.49±2.89 | 22.11±3.17 | 0.66 | – | 0.519 |
CP (diopter) | 43.25±1.39 | 44.27±1.26 | 43.15±1.20a | 42.67±1.45ab | 13.78 | 0.161 | <0.001 |
SE (diopter) | −3.59±2.62 | −0.79±1.15 | −3.33±1.84a | −6.11±2.28ab | 75.67 | 0.501 | <0.001 |
AL (mm) | 25.15±1.35 | 23.28±0.52 | 24.98±0.56a | 26.83±0.53ab | 372.84 | 0.838 | <0.001 |
fPVC (mm−1) | 0.158±0.036 | 0.123±0.030 | 0.157±0.029a | 0.186±0.028ab | 41.92 | 0.368 | <0.001 |
Continuous variables are expressed as the mean ± standard deviation, and categorical variables are expressed as the number and proportion. The LSD test was used for multiple between-group comparisons and a, P<0.05 vs. short AL; b, P<0.05 vs. medium AL. AL, axial length; η2, the effect size for the analysis of differences among the three groups; P value, comparison of differences among the three groups; BMI, body mass index; CP, corneal power; SE, spherical equivalent; fPVC, fitting posterior-pole vertex curvature.
Because SE is affected by the optical power of the crystalline lens and the cornea, this study focused on the correlation between the fPVC and choroidal features by comparing it with the AL. Table 2 shows the correlations between the AL, fPVC, CP, SE, age, sex, height, weight, and BMI, respectively, for all participants. The results revealed a positive correlation between the AL and fPVC (r=0.639, P<0.001). Notably, the AL was negatively correlated with CP (r=−0.438, P<0.001) and SE (r=−0.775, P<0.001), and positively correlated with height (r=0.231, P=0.005) and weight (r=0.163, P=0.048). Notably, the r2 for height (r2=0.053) and weight (r2=0.027) were extremely small. Therefore, they were statistically relevant in this trial, but may lack practical significance. In addition to the AL, the fPVC was only negatively correlated with the SE (r=−0.666, P<0.001).
Table 2
Parameters | AL | fPVC | |||||
---|---|---|---|---|---|---|---|
r | r2 | P value | r | r2 | P value | ||
AL (mm) | 1 | – | 0.639 | 0.408 | <0.001 | ||
fPVC (mm−1) | 0.639 | 0.408 | <0.001 | 1 | – | ||
CP (diopter) | −0.438 | 0.192 | <0.001 | −0.052 | 0.003 | 0.532 | |
SE (diopter) | −0.775 | 0.601 | <0.001 | −0.666 | 0.443 | <0.001 | |
Age (years) | −0.063 | 0.004 | 0.446 | −0.121 | 0.015 | 0.144 | |
Sex (male) | −0.019 | 0.000 | 0.824 | 0.126 | 0.016 | 0.127 | |
Height (cm) | 0.231 | 0.053 | 0.005 | 0.013 | 0.000 | 0.875 | |
Weight (kg) | 0.163 | 0.027 | 0.048 | −0.095 | 0.009 | 0.254 | |
BMI (kg/m2) | 0.053 | 0.003 | 0.520 | −0.139 | 0.019 | 0.092 |
AL, axial length; fPVC, fitting posterior-pole vertex curvature; r, coefficient of correlation; r2, coefficient of determination; CP, corneal power; SE, spherical equivalent; BMI, body mass index.
Table 3 sets out the choroidal parameters of each region. There were statistical differences in the ChT (all P<0.001), CVV (all P<0.001), and 3DCVI (all P<0.05) among the three groups, and the multiple between-group comparisons were further tested, respectively. In the four areas, the ChT gradually decreased from short AL group to long AL group. The CVV of each area decreased from short AL group to long AL group, except for the CVV between the short and medium AL groups in A3, for which no significant difference was found. In the 3DCVI, the effect size of the difference analysis among the three groups was very small in each area (all η2<0.2), and there was no significant difference between the medium and long AL groups in terms of the A2, A3 and TA. Therefore, the inter-group differences for the 3DCVI require further analysis.
Table 3
Parameters | Total (n=147) | Short AL (n=30) | Medium AL (n=76) | Long AL (n=41) | F/χ2 | η2 | P value |
---|---|---|---|---|---|---|---|
ChT (μm) | |||||||
A1 | 299.98±82.75 | 370.82±62.49 | 304.06±70.97a | 240.58±72.83ab | 30.355 | 0.297 | <0.001 |
A2 | 294.23±70.68 | 346.61±60.36 | 299.43±60.94a | 246.27±64.51ab | 23.360 | 0.245 | <0.001 |
A3 | 308.51±63.01 | 344.68±66.95 | 310.94±54.59a | 277.55±60.65ab | 19.24 | 0.136 | <0.001 |
TA | 301.88±67.20 | 348.81±62.16 | 305.59±58.01a | 260.67±62.88ab | 31.74 | 0.207 | <0.001 |
CVV (mm3) | |||||||
A1 | 0.69±0.19 | 0.82±0.13 | 0.71±0.15a | 0.55±0.20ab | 24.734 | 0.256 | <0.001 |
A2 | 2.01±0.48 | 2.31±0.39 | 2.09±0.40a | 1.63±0.47ab | 26.517 | 0.269 | <0.001 |
A3 | 2.67±0.67 | 2.91±0.66 | 2.77±0.69 | 2.32±0.50ab | 20.98 | 0.112 | <0.001 |
TA | 5.32±1.24 | 6.04±1.14 | 5.50±0.98a | 4.46±1.27ab | 29.92 | 0.215 | <0.001 |
3DCVI (%) | |||||||
A1 | 40.51±5.92 | 36.81±5.70 | 40.55±5.39a | 43.13±5.72ab | 11.243 | 0.069 | <0.001 |
A2 | 40.19±4.48 | 37.61±4.56 | 40.75±4.27a | 41.02±4.20a | 6.768 | 0.025 | 0.002 |
A3 | 39.40±3.90 | 37.74±4.23 | 39.79±3.57a | 39.90±4.00a | 3.573 | 0.010 | 0.031 |
TA | 39.84±4.17 | 37.57±4.41 | 40.25±3.88a | 40.75±4.00a | 6.224 | 0.020 | 0.003 |
Continuous variables are expressed as the mean ± standard deviation. The LSD test was used for multiple between-group comparisons and a, P<0.05 vs. short AL; b, P<0.05 vs. medium AL. AL, axial length; η2, the effect size for the analysis of differences among the three groups; P value, comparison of differences among the three groups; ChT, choroidal thickness; A1, 0–3 mm; A2, 3–6 mm; A3, 6–9 mm (except nasal); TA = A1 + A2 + A3; CVV, choroidal vascular volume; 3DCVI, three-dimensional choroidal vascularity index.
Next, we explored the relationship between the ocular factors (i.e., the AL, fPVC, SE, and CP) and ChT (Table 4). In the univariate analysis, the AL, fPVC, and SE were significantly correlated with the ChT in all areas (all P<0.001), while the CP was only correlated with the ChT in the A1. To exclude the interference of confounding factors, statistically significant variables (P<0.5) from the univariate analysis were included in the multiple stepwise regression analysis. The results showed that the SE and CP were not significant in all areas. From the A1 (near the fovea) to A2 (slightly away from the fovea), the correlation between the fPVC (A1: β=−0.363, P<0.001; A2: β=−0.375, P<0.001) and ChT was stronger than that of the AL (A1: β=−0.376, P<0.001; A2: β=−0.317, P<0.001). In the peripheral area A3, the fPVC (β=−0.529, P<0.001, radjusted2=0.275) was the factor most highly correlated with the ChT among the four variables. Moreover, the correlation between the fPVC (β=−0.410, P<0.001) and ChT was also stronger than that between the AL and the ChT (β=−0.252, P=0.004) in TA.
Table 4
Region | Univariate | Multivariate | |||||
---|---|---|---|---|---|---|---|
r | P | β | P | VIF | radjusted2 | ||
A1 | 0.440 | ||||||
AL (mm) | −0.608 | <0.001 | −0.376 | <0.001 | 1.690 | ||
fPVC (mm−1) | −0.603 | <0.001 | −0.363 | <0.001 | 1.690 | ||
SE (diopter) | 0.561 | <0.001 | 0.092 | 0.383 | 2.859 | ||
CP (diopter) | 0.165 | 0.046 | −0.026 | 0.725 | 1.389 | ||
A2 | 0.385 | ||||||
AL (mm) | −0.557 | <0.001 | −0.317 | <0.001 | 1.690 | ||
fPVC (mm−1) | −0.578 | <0.001 | −0.375 | <0.001 | 1.690 | ||
SE (diopter) | 0.504 | <0.001 | 0.075 | 0.499 | 2.859 | ||
CP (diopter) | 0.127 | 0.125 | – | – | – | ||
A3 | 0.275 | ||||||
AL (mm) | −0.402 | <0.001 | −0.140 | 0.127 | 1.690 | ||
fPVC (mm−1) | −0.527 | <0.001 | −0.529 | <0.001 | 1.000 | ||
SE (diopter) | 0.407 | <0.001 | 0.153 | 0.106 | 1.797 | ||
CP (diopter) | 0.026 | 0.755 | – | – | – | ||
TA | 0.355 | ||||||
AL (mm) | −0.514 | <0.001 | −0.252 | 0.004 | 1.690 | ||
fPVC (mm−1) | −0.571 | <0.001 | −0.410 | <0.001 | 1.690 | ||
SE (diopter) | 0.479 | <0.001 | 0.092 | 0.416 | 2.859 | ||
CP (diopter) | 0.094 | 0.257 | – | – | – |
ChT, choroidal thickness; r, correlation coefficient of univariate linear regression; variables with P<0.05 in the univariate linear regression were entered into the multiple linear regression; β, standardized regression coefficient; VIF, variance inflation factors; radjusted2, adjusted goodness of fit; A1, 0–3 mm; A2, 3–6 mm; A3, 6–9 mm (except nasal); TA = A1 + A2 + A3; AL, axial length; fPVC, fitting posterior-pole vertex curvatures; SE, spherical equivalent; CP, corneal power.
The factors related to the CVV were analyzed using the above-mentioned method (Table 5). In all areas, the CP was not associated with the CVV, and the SE was excluded from the multiple stepwise linear regression model even though it was positively associated with the CVV. In the A1, A2, and the TA, both the AL and fPVC were significantly negatively correlated with the CVV. However, in the peripheral choroid A3, which is far from the macula, the fPVC was the only variable independently correlated with the CVV (β=−0.441, P<0.001).
Table 5
Region | Univariate | Multivariate | |||||
---|---|---|---|---|---|---|---|
r | P | β | P | VIF | radjusted2 | ||
A1 | 0.361 | ||||||
AL (mm) | −0.556 | <0.001 | −0.351 | <0.001 | 1.690 | ||
fPVC (mm−1) | −0.544 | <0.001 | −0.320 | <0.001 | 1.690 | ||
SE (diopter) | 0.504 | <0.001 | 0.148 | 0.186 | 2.859 | ||
CP (diopter) | 0.106 | 0.202 | – | – | – | ||
A2 | 0.343 | ||||||
AL (mm) | −0.543 | <0.001 | −0.344 | <0.001 | 1.690 | ||
fPVC (mm−1) | −0.531 | <0.001 | −0.311 | <0.001 | 1.690 | ||
SE (diopter) | 0.475 | <0.001 | 0.103 | 0.364 | 2.859 | ||
CP (diopter) | 0.099 | 0.233 | – | – | – | ||
A3 | 0.189 | ||||||
AL (mm) | −0.357 | <0.001 | −0.127 | 0.190 | 1.690 | ||
fPVC (mm−1) | −0.441 | <0.001 | −0.441 | <0.001 | 1.000 | ||
SE (diopter) | 0.398 | <0.001 | 0.115 | 0.250 | 1.797 | ||
CP (diopter) | 0.035 | 0.674 | – | – | – | ||
TA | 0.282 | ||||||
AL (mm) | −0.485 | <0.001 | −0.286 | 0.002 | 1.690 | ||
fPVC (mm−1) | −0.494 | <0.001 | −0.311 | <0.001 | 1.690 | ||
SE (diopter) | 0.465 | <0.001 | 0.098 | 0.410 | 2.859 | ||
CP (diopter) | 0.072 | 0.385 | – | – | – |
CVV, choroidal vascular volume; r, correlation coefficient of univariate linear regression; variables with P<0.05 in the univariate linear regression were entered into the multiple linear regression; β, standardized regression coefficient; VIF, variance inflation factors; radjusted2, adjusted goodness of fit; A1, 0–3 mm; A2, 3–6 mm; A3, 6–9 mm (except nasal); TA = A1 + A2 + A3; AL, axial length; fPVC, fitting posterior-pole vertex curvatures; SE, spherical equivalent; CP, corneal power.
In the univariate analysis, the AL and fPVC were positively correlated with the 3DCVI, while the CP and SE were negatively correlated with the 3DCVI (Table 6). The multiple stepwise regression analysis showed that the AL was an independent factor associated with the 3DCVI in the macular area (the A1 and A2) and TA, and the fPVC and CP were both correlated with the 3DCVI in the peripheral choroid (the A3). However, notably, the 3DCVI linear model had poor goodness of fit (A1 radjusted2=0.155, A2 radjusted2=0.069, A3 radjusted2=0.058, TA radjusted2=0.072), indicating that while there is a correlation between the 3DCVI and the variables, it may not be linear.
Table 6
Region | Univariate | Multivariate | |||||
---|---|---|---|---|---|---|---|
r | P | β | P | VIF | radjusted2 | ||
A1 | 0.155 | ||||||
AL (mm) | 0.401 | <0.001 | 0.401 | <0.001 | 1.000 | ||
fPVC (mm−1) | 0.355 | <0.001 | 0.167 | 0.092 | 1.690 | ||
SE (diopter) | −0.278 | 0.001 | 0.120 | 0.320 | 2.507 | ||
CP (diopter) | −0.260 | 0.001 | −0.104 | 0.220 | 1.238 | ||
A2 | 0.069 | ||||||
AL (mm) | 0.274 | 0.001 | 0.274 | <0.001 | 1.000 | ||
fPVC (mm−1) | 0.264 | 0.001 | 0.150 | 0.150 | 1.690 | ||
SE (diopter) | −0.167 | 0.043 | 0.172 | 0.174 | 2.507 | ||
CP (diopter) | −0.253 | 0.002 | −0.165 | 0.063 | 1.238 | ||
A3 | 0.058 | ||||||
AL (mm) | 0.203 | 0.014 | 0.006 | 0.963 | 2.342 | ||
fPVC (mm−1) | 0.209 | 0.011 | 0.200 | 0.014 | 1.003 | ||
SE (diopter) | −0.130 | 0.117 | – | – | – | ||
CP (diopter) | −0.176 | 0.033 | −0.165 | 0.042 | 1.003 | ||
TA | 0.072 | ||||||
AL (mm) | 0.279 | 0.001 | 0.279 | <0.001 | 1.000 | ||
fPVC (mm−1) | 0.269 | 0.001 | 0.153 | 0.141 | 1.690 | ||
SE (diopter) | −0.175 | 0.034 | 0.132 | 0.299 | 2.507 | ||
CP (diopter) | −0.233 | 0.005 | −0.137 | 0.124 | 1.238 |
3DCVI, three-dimensional choroidal vascularity index; r, correlation coefficient of univariate linear regression; variables with P<0.05 in the univariate linear regression were entered into the multiple linear regression; β, standardized regression coefficient; VIF, variance inflation factors; radjusted2, adjusted goodness of fit; A1, 0–3 mm; A2, 3–6 mm; A3, 6–9 mm (except nasal); TA = A1 + A2 + A3; AL, axial length; fPVC, fitting posterior-pole vertex curvatures; SE, spherical equivalent; CP, corneal power.
Therefore, we performed LOWESS on the 3DCVI (Figure 4). The trends of the 3DCVI LOWESS curves of the AL and fPVC in the four areas were generally consistent. The overall trend of the LOWESS curve of the 3DCVI and AL showed that the relationship between the two was positive, but the curve tended to be flat or show a downward trend when the AL was 25–27 mm. Compared with the AL, the fPVC had a clearer inflection point. The 3DCVI increased with the fPVC when the fPVC was <0.21 mm−1, and showed an obvious decreasing trend when the fPVC was >0.21 mm−1.
Discussion
Previous studies have observed changes in eyeball morphology in myopic patients by X-ray (32), ultrasound (33), and magnetic resonance imaging (34,35). Such changes may be important biological indicators of myopia. However, these methods are expensive, complex, and have poor resolution. OCT and OCTA provide high-resolution images and detailed data. The SS-OCT scan line length used in this study was 16 mm, which is twice the length of that used in most previous studies (22,36), and which greatly improved the goodness of fit and better characterized the overall contour of the posterior pole of the eye. Previously, retinal morphology was usually evaluated by circle fitting (37), but the circle fitting curve cannot be used when the eyeball is prolate or oblate, especially in myopic eyes; thus, elliptic curve fitting was adopted in this study. The choroidal data obtained in this study were all 3D data, which is more valuable than the previous two-dimensional data (22).
The ChT, a popular topic in myopia research, has been extensively studied. The AL has always been considered the key factor for the development of myopia; an increase in the AL is closely related to choroid thinning, which is accompanied by a decrease in choroidal blood perfusion (25,26,38). A positive correlation between the ChT and SE has also been reported (39,40). This study not only confirmed the above findings but also reached a similar conclusion in relation to the fPVC. We divided the choroid into areas, and observed a negative correlation between the fPVC and ChT in all areas. This finding is similar to that of previous studies, which suggests that ChT thinning is more obvious in eyes with more structural changes, such as a longer AL and steeper macular curvature (41,42).
In addition, a positive correlation was found between the fPVC and AL (P<0.001), and a negative correlation was found between the fPVC and SE (P<0.001). To obtain a relatively accurate relationship between the fPVC and ChT, we adjusted for other confounding factors and the possible effects of the AL and SE on the fPVC. Multiple stepwise regression analyses were performed on the AL, fPVC, SE, and CP simultaneously. The final results showed that the AL and fPVC were relatively independent factors associated with the ChT (VIF =1.690), while the SE and CP were excluded from the model, which showed that the relationship between the fPVC and ChT was independent and not mediated by the AL. As a previous study showed, the posterior scleral curvature in mild and moderate myopia does not usually change significantly with AL elongation (41).
Further research revealed that in the area close to the fovea (A1: 0–3 mm), the AL was slightly more closely associated with the ChT than the fPVC. Conversely, in the area far away from the fovea (A2: 3–6 mm), the correlation between the fPVC and ChT was slightly better than that between the AL and the ChT, and it even became the most closely related factor to the ChT in the perimacular (A3: 6–9 mm) in this study. As previous studies have found, the choroid thinned as the AL increased, and the most significant thinning occurred in the macular subfoveal region (43), while steep retinal morphology had an impact on peripheral choroid development (44). In addition, the fPVC was also more closely associated with the ChT in the posterior choroid (0–9 mm) than the AL. Therefore, attention should be paid not only to the role of the AL in myopia, but also to the correlation between the steepness of the posterior pole and ChT, and its important significance in the development of myopia.
The shape of the posterior pole is not only related to the change in the ChT but also to the choroidal vessels. AL lengthening and ChT thinning are often accompanied by reduced choroidal vascular perfusion in individuals with emmetropia and myopia (25,26,38). This study confirmed a negative correlation between the AL and CVV, and a negative correlation between the fPVC and CVV. Previous studies have shown that in individuals with high myopia, a longer AL is associated with higher choroidal blood flow defects in the area around the fovea (45). Similarly, we found that both the AL and fPVC were negatively correlated with the CVV in the macular area (0–6 mm), but only the fPVC was correlated with the CVV in the perimacular area (6–9 mm). In summary, not only is a larger AL a risk factor for weakened choroid circulation (46), but a larger fPVC may be also a risk factor for reduced choroidal perfusion. And peripheral choroidal perfusion decreased seems to be more associated with fPVC.
The choroid is a highly vascularized tissue, and its blood flow can change rapidly. It has been pointed out that the change in choroid blood flow appears to be the main reason for the change in the ChT (47). To evaluate the status of the choroidal vessels and structures, Agrawal et al. (19) proposed a quantitative index, the CVI, which was defined as the ratio of the luminal area to the total choroidal area, and is calculated based on the binarization method, to differentiate between the choroidal luminal and stromal areas. A larger 3DCVI indicates that the choroid contains more vascular components per unit volume.
First, our study found that the 3DCVI closer to the fovea region (0–6 mm) was associated more with the AL than the fPVC, and the 3DCVI farther away from the fovea was associated more with the fPVC than the AL. However, little is known about the specific relationship between the AL and CVI. Yazdani et al. found that patients with myopia had a greater CVI than those with emmetropia, and attributed this phenomenon to the thinning of the choroidal stroma rather than decreased blood flow (48). Agrawal et al. and Aşıkgarip et al. argued that the AL is unrelated to the CVI (19,49). Other studies have shown that the CVI is negatively correlated with the AL (46,50). The linear regression analysis results of the present study appear to support the first view, but as the models had a small statistical effect size, the linear regression relationship may not accurately describe the relationship between the AL, fPVC, and 3DCVI. Therefore, LOWESS regression was performed for further analysis.
The LOWESS curve revealed a positive correlation with the 3DCVI when the AL was <25 mm, a flattening or decreasing trend when the AL was 25–27 mm, and a positive correlation again when the AL was >27 mm. A previous study also suggested that the relationship between the CVI and axial elongation was more complex than a simple linear correlation, and suggested that there was no significant relationship between the CVI and AL when the AL was <27.26 mm, the AL exceeded this critical point, or the CVI of pathological myopia was negatively correlated with the AL (51). Another study suggested that the 3DCVI decreased as the severity of myopia increased, but acknowledged that there was no difference in the 3DCVI between low and moderate myopia groups (52). This discrepancy may be related to the non-uniform grouping criteria and different sample sizes of each group; for example, only non-pathological myopia patients with an AL <28 mm were included in this study. In summary, the specific relationship between the 3DCVI and AL is currently undetermined; thus, further research needs to be conducted.
The LOWESS curve trend for the 3DCVI and fPVC had a significant inflection point compared with the AL, indicating that the relationship between the fPVC and 3DCVI may be clearer than that of the AL. The results revealed a positive correlation between the 3DCVI and fPVC before the inflection point and a negative correlation after the inflection point. It seems that the steep posterior-polar shape of the eyeball is closely related to the atrophy of the choroidal stroma; such that when the steep shape is outside a normal range, choroidal perfusion will be significantly reduced, which will lead to a series of complications related to high myopia. The inflection point of 0.21 mm−1 in this study could serve as the fPVC threshold for maintaining ocular mechanical stability. This finding also shows the significance of studying the morphology of the posterior pole.
The question arises: Would the same results be found in emmetropia eyes? The results of the preliminary analysis showed that the ChT and CVV in all regions were only related to the fPVC (and not to the AL) (Supplementary Material). Therefore, the fPVC may be a sensitive indicator of choroidal changes, especially in the early stage of myopia or when there is no significant abnormality in the AL. However, the number of participants with emmetropia in this study was very small, and these results need to be further verified.
The present study had several limitations. First, since age is a critical factor associated with choroidal changes (53,54), only participants aged 20 to 30 years with relatively stable myopia development were included in this study (55). Therefore, the results of this study cannot be generalized to children and the elderly. Second, this study only included patients with emmetropia and myopia without pathological myopia. Patients with hyperopia or high myopia patients with PS were not included in the study. However, the relationships among the variables in this study reflect an intrinsic link or an underlying mechanism between myopic eyeball morphology and structural changes. Finally, given the cross-sectional nature of this study, the implications of these results for causality and potential mechanisms must be interpreted with caution. Further longitudinal studies need to be conducted to fully characterize these associations.
Conclusions
The structure and microcirculation of the choroid are not only closely related to the AL but also to the morphology of the posterior pole of the eyeball. In addition, the posterior-pole shape has a particularly significant association with the peripheral choroid. Our findings on posterior-polar eye shape could provide new perspectives for the in-depth study of the pathogenesis of myopia and myopia-related complications, especially in individuals with low myopia or a small AL but a steep posterior-polar shape.
Acknowledgments
Funding: The study was funded by
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-829/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-829/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 conformed to the principles of the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of the First Hospital of China Medical University (No. [2017]2017-74-2). All participants were informed of the purpose of the study and provided written informed consent.
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