Choroidal vascular changes in early-stage myopic maculopathy from deep learning choroidal analysis: a hospital-based SS-OCT study

General characteristics of participants

In the initial assessment of 811 individuals, 723 participants (1446 eyes) aged 18–60 years were eligible for study inclusion. We further checked for image quality, fundus pathological changes affecting the analysis of choroidal parameters, and categorization of myopic maculopathy. The analysis ultimately incorporated data from 706 right eyes and 712 left eyes of 720 participants. The exclusion of 17 right eyes was due to choroiditis (n = 2), polypoidal choroidal vasculopathy (n = 1), myopic maculopathy severer than C3 or the presence of “plus lesions” (n = 8), and focal choroidal excavation or peripapillary intrachoroidal cavitation (FCE or PICC, n = 8). Similarly, 11 left eyes were excluded due to choroiditis (n = 1), long-standing retinal detachment (n = 1), myopic maculopathy severer than C3 or the presence of “plus lesions” (n = 5), and FCE or PICC (n = 5).

The general characteristics among eyes with no macular lesions (C0), tessellated fundus (C1) and DCA (C2) were compared (Table 1). C0 was observed in 94 eyes (6.6%), C1 in 1077 eyes (76.0%), and C2 in 247 eyes (17.4%). The mean AL was 26.33 ± 1.02 mm in the C0 group, 26.79 ± 1.02 mm in the C1 group, and 27.90 ± 1.20 mm in the C2 group. The mean SER was − 7.37 ± 1.23 D in the C0 group, − 8.06 ± 1.69 D in the C1 group, and − 10.11 ± 2.69 D in the C2 group. There were significant differences among the three groups and between any one of the groups compared to the other two groups in AL and SER (all P < 0.001). There were no significant differences among three groups with respect to gender, weight, blood pressure, ACD and IOP. Compared with the C1 group, the individuals in the C2 group were older, had lower height, thicker lenses, and worse BCVA and visual function [P < 0.001 for age, BCVA, visual field index (VFI), mean deviation (MD), pattern standard deviation (PSD); P = 0.023 for height and LT]. However, there were no significant differences between the C1 and C0 groups in age, height, LT, BCVA, MD and PSD.

Table 1 Comparisons of general characteristics among highly myopic eyes with C0, C1 and C2Global and regional characteristics of choroidal vasculature among different types of myopic maculopathy

Compared with the C1 group, the C2 group showed significant decreases in ChT, LA and SA, and increases in CVI at both vertical and horizontal meridians after adjusting for age and AL (all P < 0.001; Fig. 2). Compared with the C0 group, the C1 group also showed significant decreases in ChT, LA and SA, and increases in CVI at the vertical and horizontal meridians (all P < 0.001). Additional file 1: Table S2 presents the quantified reductions in choroidal parameters for the C1 and C2 groups in comparison to the C0 group after adjusting for age and AL. Regional analysis of choroidal parameters showed that the C2 group had lower ChT, LA, and SA across all regions than the C1 group (all P < 0.001; Fig. 3). Additionally, the C2 group had higher CVI across all regions except N2, I2 and S2 than the C1 group (all P < 0.05). Compared with the C0 group, the C1 group had lower ChT, LA, and SA across all regions (all P < 0.001). The C1 group had higher CVI across all regions except C region at the horizontal meridian, N2 and I2 regions than the C0 group (all P < 0.05).

Fig. 2figure 2

Violin plots comparing the global choroidal vascular parameters among the C0, C1 and C2 groups. a1 ChT at the vertical meridian; b1 LA at the vertical meridian; c1 SA at the vertical meridian; d1 CVI at the vertical meridian; a2 ChT at the horizontal meridian; b2 LA at the horizontal meridian; c2 SA at the horizontal meridian; d2 CVI at the horizontal meridian. The median was represented by the middle line within each violin, and the lower and upper quartiles were represented by the lower and upper lines within each violin, respectively. C0, no macular lesions; C1, tessellated fundus; C2, diffuse chorioretinal atrophy; ChT, choroidal thickness; LA, luminal area; SA, stromal area; CVI, choroidal vascular index. n = 94, 1077 and 247 eyes in the C0, C1 and C2 groups, respectively. The level of significance was detected with GEE adjusted for age, AL and the correlation between both eyes of an individual, ***P < 0.001

Fig. 3figure 3

Regional analysis of choroidal vascular parameters among the C0, C1 and C2 groups. a1 ChT at the vertical meridian; b1 LA at the vertical meridian; c1 SA at the vertical meridian; d1 CVI at the vertical meridian; a2 ChT at the horizontal meridian; b2 LA at the horizontal meridian; c2 SA at the horizontal meridian; d2 CVI at the horizontal meridian. The values of LA and SA in the perifoveal regions were divided by 1.5 to eliminate the effects of inconsistent widths in each region. C0, no macular lesions; C1, tessellated fundus; C2, diffuse chorioretinal atrophy; C, fovea; I1, inferior parafovea; I2, inferior perifovea; S1, superior parafovea; S2, superior perifovea; T1, temporal parafovea; T2, temporal perifovea; N1, nasal parafovea; N2, nasal perifovea; ChT, choroidal thickness; LA, luminal area; SA, stromal area; CVI, choroidal vascular index. n = 94, 1077 and 247 eyes in C0, C1 and C2 groups, respectively. The level of significance was detected with GEE adjusted for age, AL and the correlation between both eyes of an individual; ns, not significant; **P < 0.01, ***P < 0.001

Associations between the presence of DCA and choroidal vascular parameters

After adjusting for age, gender, AL, and the correlation between both eyes of an individual, multivariable logistic regression models revealed significant associations between the presence of DCA and choroidal vascular parameters (dependent variable: without or with DCA; Fig. 4a). Specifically, negative correlations were observed between DCA presence and both ChT [odds ratio (OR): 0.083, 95% CI: 0.056–0.121, P < 0.001] and LA (OR: 0.099, 95% CI: 0.069–0.143, P < 0.001), as well as SA (OR: 0.079, 95% CI: 0.054–0.116, P < 0.001). Conversely, a positive correlation was identified between DCA presence and CVI (OR: 1.458, 95% CI: 1.259–1.689, P < 0.001). Regional analysis showed that the most pronounced negative association with the presence of DCA was observed with LA in the N2 region (OR: 0.038, 95% CI: 0.023–0.064, P < 0.001; Fig. 4b–c), when compared to LA and SA in other regions. These findings imply that an increase of one standard deviation in LA within the N2 region (0.044 mm2) corresponds to a 96.2% decrease in the probability of DCA presence.

Fig. 4figure 4

Forest plot showing risks of the presence of diffuse chorioretinal atrophy (DCA). a Association of the presence of DCA and choroidal parameters; b Association of the presence of DCA and choroidal LA at separated submacular regions; c Association of the presence of DCA and choroidal SA at separated submacular regions. Data were all standardized. There were 1171 eyes without DCA and 247 eyes with DCA. ChT, choroidal thickness; LA, luminal area; SA, stromal area; CVI, choroidal vascular index; CI, confidence interval. The level of significance was detected with logistic regression analysis adjusted for age, gender, AL and the correlation between both eyes of an individual

Correlations between visual function and choroidal vascular parameters

Univariate linear regression analysis showed that the mean deviation (MD) was significantly and positively correlated with height (B = 0.027; P = 0.001), SER (B = 0.286; P < 0.001), ChT at the vertical meridian (B = 0.008; P < 0.001), LA at the vertical meridian (B = 2.286; P < 0.001), and SA at the vertical meridian (B = 3.176; P < 0.001), and inversely correlated with age (B =  − 0.009; P = 0.006), AL (B =  − 0.301; P < 0.001), and corneal curvature (B =  − 0.130; P = 0.005). Multivariable linear regression analysis showed that MD was positively associated with the mean LA at the vertical meridian (B = 1.512; P < 0.001; Table 2) after adjusting for the age, height, AL and corneal curvature. The results of the regression analysis in eyes with non-pathological myopia and pathological myopia are shown in Table 2. The results indicate that the impact of LA on visual function in eyes with pathological myopia is approximately six times greater than in eyes without pathological myopia.

Table 2 Correlations between MD and the mean LA at the vertical meridian

Multivariable linear regression analysis showed that MD was positively associated with the mean SA at the vertical meridian (B = 1.956; P < 0.001; Additional file 1: Table S3) after adjusting for the age, height, AL and corneal curvature. The results of the regression analysis in eyes with non-pathological myopia and pathological myopia are shown in Additional file 1: Table S3. The results indicate that MD is not significantly affected by SA at the vertical meridian in eyes with non-pathological myopia. The impact of SA on visual function in eyes with pathological myopia is approximately three times greater than in all highly myopic eyes.

Cut-off values of choroidal parameters to classify pathological myopia

ROC curve analysis was performed to determine the optimal ChT, LA and SA value that will aid in diagnosing pathological myopia at different locations (Fig. 5) in the overall population (Table 3). The optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region [area under the curve (AUC), 0.916; sensitivity, 89.5%; specificity, 78.5%], and 145.5 µm at the vertical meridian (AUC, 0.899; sensitivity, 84.2%; specificity, 80.4%). The optimal LA to diagnose pathological myopia was 0.076 mm2 in the N2 region (AUC, 0.908; sensitivity, 89.1%; specificity, 78.6%), and 0.528 mm2 at the vertical meridian (AUC, 0.890; sensitivity, 85.0%; specificity, 80.2%). The optimal SA to diagnose pathological myopia was 0.049 mm2 in the N2 region (AUC, 0.895; sensitivity, 89.1%; specificity, 75.5%), and 0.325 mm2 at the vertical meridian (AUC, 0.901; sensitivity, 80.6%; specificity, 83.6%).

Fig. 5figure 5

ROC curve analysis of optimal ChT, LA, and SA to diagnose pathological myopia. a ChT in different regions to diagnose pathological myopia; b LA in different regions to diagnose pathological myopia; c SA in different regions to diagnose pathological myopia. ROC, receiver operating characteristic; ChT, choroidal thickness; LA, luminal area; SA, stromal area; V, vertical; H, horizontal

Table 3 Optimal cut-off values of ChT, LA, and SA to classify pathological myopia using ROC curve analysis

The values of choroidal parameters at the vertical meridian and the N2 region had better performance in diagnosing pathological myopia for the overall participants. There were also significant differences in choroidal parameters at the vertical meridian and N2 region among different age groups after adjusting for AL (Additional file 1: Table S4). Therefore, we calculated the cut-off values for these two regions in each age group (Table 3). In patients aged ≤ 40 years, the cut-off values for ChT, LA, and SA in the N2 region exhibited higher Youden indexes. Conversely, in patients aged between 40 and 60 years, the cut-off values for ChT, LA, and SA at the vertical meridian showed higher Youden indexes.

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