Posterior Eye Curvature as a Biomarker for Differentiating Pathologic Myopia From High Myopia





Highlights





  • Our study developed 3 curvature parameters derived from spectral-domain optical coherence tomography images to comprehensively characterize the posterior eye shape.



  • The posterior eye curvature increased with myopia severity and demonstrated a sharp increase between simple high myopia and pathologic myopia groups.



  • The posterior eye curvature was a superior biomarker to differentiate pathologic myopia from simple high myopia compared to traditional axial length and refractive errors.



PURPOSE


To characterize posterior eye curvature and to assess its diagnostic performance in differentiating pathologic myopia (PM) from simple high myopia (SHM).


DESIGN


Population-based, cross-sectional study.


PARTICIPANTS


A total of 790 eyes from 790 participants (mean age: 60.6 ± 8.3 years; 59% female) were randomly selected from the Beijing Eye Study, including 406 nonmyopic eyes, 175 eyes with mild myopia, 102 eyes with moderate myopia, 76 eyes with simple SHM, and 31 eyes with PM.


METHODS


Posterior eye curvature was calculated using the outer boundary of the retinal pigment epithelium layer, derived from automatically segmented spectral-domain optical coherence tomography images. Three curvature parameters were computed: curvature mean , curvature max and curvature macula .


MAIN OUTCOME MEASURES


The values and spatial distribution of curvature parameters across different myopia groups, and their diagnostic performance in distinguishing PM from SHM.


RESULTS


Higher curvature parameters were significantly associated with older age, longer axial length (AL), more myopic refractive error (RE), lower best-corrected visual activity, and smaller subfoveal choroidal thickness (all P < .001). These parameters increased progressively with myopia severity (all P < .001). Unlike traditional metrics such as AL, which demonstrated a steady increase across the entire spectrum of myopia, curvature parameters showed a significantly sharper increase between SHM and PM, compared to other pairwise comparisons (nonmyopia vs mild myopia, mild vs moderate myopia, and moderate myopia vs SHM) (all P < .001). After adjusting for age, AL, and RE, the curvature parameters remained significantly associated with the occurrence of PM (all P ≤ .003). In distinguishing PM from SHM, curvature max achieved the highest diagnostic performance, with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% CI, 0.87-0.98), followed by 0.86 (95% CI, 0.78-0.94) for curvature mean , 0.84 (95% CI, 0.76-0.93) for curvature macula , 0.75 (95% CI, 0.62-0.89) for AL, and 0.76 (95% CI, 0.66-0.86) for RE. The performance of curvature max was significantly higher than AL ( P = .020) and RE ( P = .006).


CONCLUSIONS


Posterior eye curvature increased with myopia severity and outperformed traditional AL and RE, suggesting its potential as a desirable biomarker in differentiating PM from SHM. Further research, particularly longitudinal studies, is warranted to evaluate whether the curvature can predict myopia prognosis and the development of pathologic changes.


M yopia has emerged as a significant global health problem, with prevalence escalating in young people, particularly in East and Southeast Asia. The global population affected by myopia has been estimated to grow from 1.406 billion in 2000 to 4.758 billion by 2050, potentially encompassing nearly 50% of the world’s population. The increase in myopia prevalence also precipitated a rise in the prevalence of pathologic myopia (PM) and other myopia-related ocular complications and is estimated to account for 10% to 30% of global vision loss and an estimated annual productivity loss of $202 billion.


PM is characterized by degenerative changes, accompanied by axial elongation, and especially by a posterior deformation of the eye, leading to usually irreversible vision loss. , There is no clear boundary between “simple high myopia” (SHM) and PM, yet their impact on clinical visual outcomes and the broader public health implication significantly. , , Therefore, it is crucial to establish a precise and reliable biomarker for early differentiation between SHM and PM, which would enable targeted prevention, monitoring, and, where available, treatment of patients at risk of PM. Refractive error (RE) and axial length (AL) are 2 simple and well-acknowledged parameters indicating the severity of myopia. More myopic RE and longer AL are generally related to an increased risk of PM. However, exceptions to this correlation exist. For example, patients with an AL shorter than 26.0 mm or an RE less severe than −6.0 D may also exhibit posterior staphylomas and other myopic pathological changes. In contrast, many people with longer AL greater and more severe myopic RE do not have PM.


Given the crucial role of posterior changes in PM, it will be useful to investigate whether the posterior eye shape could serve as a viable biomarker to differentiate SHM and PM. Two approaches have been previously employed to analyze the posterior eye shape. The first involves direct observation via MRI scans followed by 3D reconstruction. However, this method is limited by lack of MRI access, low resolution of MRI and the lack of correlation with the delicate structures of the eye. Recent studies have quantified specific parameters (eg, curvature, depth, width) using optical coherence tomography (OCT) imaging to depict the posterior eye shape. However, current studies are limited by their 2-dimensional nature and have only used oversimplified parameters, which could not adequately characterize the full posterior characteristics of an individual eye. Additionally, very few studies have applied these techniques to large populations, and the effectiveness of these biomarkers for assessing myopia severity and differentiating SHM and PM remained underexplored.


In the current study, we comprehensively depicted the posterior eye shape from OCT images and applied it to a large, population-based sample. We developed 3 curvature parameters to represent the posterior eye shape: curvature mean , curvature max and curvature macula . Our aim is to thoroughly understand the posterior eye shape in the general population, particularly in individuals with myopia and high myopia, and to evaluate its potential to differentiate SHM and PM.


METHOD


STUDY DESIGN AND PARTICIPANTS


A subset of normal eyes with varied refractive statuses was randomly selected from the population-based Beijing Eye Study 2011. , For eyes with RE, defined as spherical equivalent values between +1.00 and −4.00 diopters (D), a best-corrected visual acuity (BCVA) of 20/25 or better was required. For eyes with RE ranging from −4.00 D to −6.00 D, a BCVA of 20/33 or better was required. Highly myopic eyes, identified as having an RE of ≤ −6.00 D or an AL of ≥ 26.00 mm, were included irrespective of their visual acuity. One eye per participant was selected. Eyes presenting with retinal diseases or optic neuropathies, including diabetic retinopathy, ocular trauma, retinal detachment, retinal vein occlusions, age-related macular degeneration, glaucoma, or nonglaucomatous optic neuropathy, were excluded. Additionally, eyes with poor OCT image quality, insufficient for segmentation, or inadequate fundus imaging for analysis were also excluded.


The included eyes were categorized into 5 groups: nonmyopia (RE +1.00 D to −0.50 D), mild myopia (RE −0.50 D to −3.00 D), moderate myopia (RE < −3.00 D but not high myopia), simple high myopia (SHM), and PM. High myopic eyes, with RE of ≤ −6.00 D or an AL of ≥ 26.00 mm, were further classified as SHM or PM, with PM defined by the META-PM Study Group criteria as the presence of myopic retinal degenerative lesions, including diffuse chorioretinal atrophy, patchy chorioretinal atrophy, or macular atrophy (categories 2, 3, and 4). All fundus photographs were independently assessed by 2 experienced ophthalmologists (YM and YXW), who were blinded to the participants’ refractive statuses.


QUANTIFICATION OF POSTERIOR CURVATURE


All eyes were scanned using spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) in a cube scan mode. The scans consisted of 31 continuous horizontal B-scans, covering an area of 30° × 30°, centered on the fovea. The image penetration resolution was 3.87 µm/pixel along the z-axis, 13.71 µm/pixel along the x-axis, and 292.07 µm/pixel along the y-axis, with each scan line averaged over 100 scans for enhanced quality.


OCT images were segmented using a multiple-surface OCT segmentation algorithm developed with a deep-learning approach and an interior point method. This algorithm has demonstrated a test error of less than one pixel. , Automatic segmentations were reviewed meticulously, and any errors were manually corrected by a trained examiner (ZP) using OCT Explorer software. For curvature analysis, the outer boundary of the retinal pigment epithelium (RPE) was extracted. A screening area of 30° × 25° was selected to exclude the optic nerve head. Before analysis, all scans were smoothed using locally weighted scatterplot smoothing (LOWESS). ,


The posterior eye curvature was represented using 3 parameters. The first parameter, Curvature mean , represented the mean global curvature across all 31 B-scans. To calculate this, each B-scan within the target region was sampled at 50-pixel intervals and fitted to a circle using a least-square fitting method. The global curvature of each B-scan was then calculated as the inverse of the radius of the fitted circle. The second parameter, Curvature max , represented the highest 5% of pointwise curvature values. This was determined using a pointwise curvature calculation, where the curvature at each pixel was computed using a calculus-based formula, allowing for a detailed analysis of local curvature variations. The third parameter, Curvature macula represented the curvature of the macula and was calculated as the average of the pointwise curvature of the central scan passing through the macula ( Figure 1 ). Notably, we did not standardize the OCT images to a reference eye for a more accurate curvature calculation, , as the highly deformed eyes, especially those with high myopia in our study, may not align with a reference eye.




FIGURE 1


The method to calculate posterior eye curvatures. A. A representative fundus image with a red rectangle illustrating the curvature analysis area. B. The strategy to calculate global curvature with least squares fitting. Curvature mean was derived from the global curvature calculation approach. C. The strategy to calculate pointwise curvature with calculus. Curvature max and curvature macula were derived from the pointwise curvature calculation approach. D. A representative heatmap of pointwise curvature, with red regions indicating higher curvature and black regions indicating lower curvature. The 3 dotted white lines correspond to the OCT B-scan images shown on the right, which depict retinal cross-sections at the marked positions in the heatmap.


In addition to numerical curvature values, the spatial distribution of curvature was analyzed. The position of peak curvature was determined by averaging the locations of points with the top 10% highest pointwise curvature values.


STATISTICAL ANALYSIS


Curvature indexes were calculated using Python V.3.11 (Python Software Foundation, Wilmington, Delaware, USA; https://www.python.org/ ). Statistical analyses were performed using SPSS v.29.0 and Prism 10. All data were presented as means ± standard deviations. A P value <.05 was taken to be statistically significant. The linear regression was conducted to demonstrate the correlation of curvature parameters with age, AL, RE, BCVA, subfoveal choroidal thickness (SFCT), intraocular pressure (IOP), central corneal thickness (CCT), and anterior chamber depth (ACD). An Independent t-test was performed to evaluate the curvature difference between genders. A one-way ANOVA analysis was performed to assess whether differences exist in curvature parameters, SFCT, AL, and BCVA across various stages of myopia, followed by a trend test. Post hoc analyses were conducted to compare curvature parameters, SFCT, AL, and BCVA among pairwise myopia groups. Two sample Z-tests were performed to assess whether the differences in the curvature and ophthalmic parameters between SHM and PM were significantly greater than other pairs. To investigate the association of curvature parameters with PM occurrence in the high myopia population, logistic regression analysis was conducted, both unadjusted and adjusted for age, AL and RE. The areas under the receiver operating characteristic curve (AUROC) of the 3 curvature parameters, axial length, and refractive error were calculated and compared using MedCalc (Version 23.0.9). The cut-off value was determined by the maximal value of the Youden index (sensitivity + specificity −1). To assess the relationship between the spatial distribution of peak curvature points and different myopia groups, Pearson Chi-square tests were performed. A Cochran-Armitage test was further performed to evaluate whether the percentage of peak curvature points located in the fovea exhibited a trend across myopia severity groups.


RESULTS


A total of 790 eyes from 790 participants (41.4% male, 58.6% female) with a mean age of 60.6 ± 8.3 years (range: 50-90 years) were included in the study. This cohort comprised 406 nonmyopic eyes, 175 eyes with mild myopia, 102 eyes with moderate myopia, 76 eyes with SHM, and 31 eyes with PM. Detailed demographic and ocular parameters are presented in Table 1 . In all participants, the mean values of Curvature mean , Curvature max , and Curvature macula were 0.062 ± 0.045, 0.146 ± 0.089, and 0.052 ± 0.037, respectively ( Table 1 , Figure S1). All 3 curvature parameters demonstrated positive correlations with age, axial length, and ACD while being negatively correlated with RE, BCVA, and SFCT (all P < .001) ( Table 2 , Figure S2). However, no significant associations were found with gender ( P ≥ .41). Consistent results were observed after further adjustment for age and gender ( Table 2 ).



TABLE 1

Characteristics and Posterior Eye Curvatures Across Different Myopia Groups.




































































































All Nonmyopia Mild Myopia Moderate Myopia Simple High Myopia Pathologic Myopia
( n = 706) ( n = 406) ( n = 175) ( n = 102) ( n = 76) ( n = 31)
Age 60.56 ± 8.28 58.41 ± 6.74 59.34 ± 8.10 66.16 ± 8.84 63.79 ± 9.06 69.32 ± 7.64
Gender (male/female) 327/463 155/251 80/95 39/63 44/32 9/22
(41.4%/58.6%) (38.2%/61.8%) (45.7%/54.3%) (38.2%/61.8%) (57.9%/42.1%) (29.0%/71.0%)
Refractive error (D) −1.83 ± 3.33 0.34 ± 0.37 −1.28 ± 0.70 −4.68 ± 2.03 −7.41 ± 1.96 −10.30 ± 4.13
BCVA (logMAR units) 0.97 ± 0.21 1.06 ± 0.14 0.99 ± 0.12 0.81 ± 0.26 0.86 ± 0.21 0.60 ± 0.26
Axial length (mm) 23.77 ± 1.56 22.97 ± 0.72 23.47 ± 0.88 24.68 ± 1.29 26.43 ± 0.68 27.87 ± 1.63
SFCT(µm) 244.20 ± 102.56 283.26 ± 81.43 266.19 ± 93.80 167.30 ± 77.96 152.58 ± 78.03 49.46 ± 34.34
Curvature mean 0.062 ± 0.450 0.047 ± 0.020 0.057 ± 0.029 0.076 ± 0.042 0.084 ± 0.060 0.188 ± 0.078
Curvature max 0.145 ± 0.088 0.111 ± 0.027 0.127 ± 0.037 0.178 ± 0.077 0.203 ± 0.072 0.447 ± 0.170
Curvature macula 0.052 ± 0.036 0.038 ± 0.015 0.047 ± 0.021 0.065 ± 0.031 0.083 ± 0.040 0.159 ± 0.062

BCVA = best-corrected visual acuity; SFTC = subfoveal choroidal thickness. Data are presented with mean ± standard deviation. Gender is presented with percent.


TABLE 2

Association of Demographic and Ophthalmic Factors With Posterior Eye Curvatures.


























































































































































































































Curvature mean Curvature max Curvature macula
Mean Difference SD P Mean Difference SD P Mean Difference SD P
Gender 0.002 0.003 .465 0.005 0.006 .405 0.002 0.003 .453
Coefficient (✕10 3 ) R 2 P Coefficient (✕10 3 ) R 2 P Coefficient (✕10 3 ) R 2 P
Age 1.494 0.075 <.001 4.409 0.170 <.001 1.614 0.134 <.001
Axial length (mm) 14.930 0.293 <.001 34.930 0.471 <.001 13.949 0.411 <.001
Refractive error (D) −8.120 0.358 <.001 −19.221 0.526 <.001 −7.450 0.465 <.001
BCVA (logMAR units) −90.767 0.172 <.001 −227.476 0.283 <.001 −84.490 0.230 <.001
SFCT (µm) −0.180 0.191 <.001 −0.467 0.401 <.001 −0.197 0.351 <.001
IOP (mmHg) −0.194 0.000 .754 −1.099 0.001 .362 −0.231 0.000 .642
CCT (µm) 0.068 0.003 .168 0.077 0.001 .400 0.041 0.002 .290
ACD (µm) 22.517 0.045 <.001 47.472 0.060 <.001 21.074 0.064 <.001
Coefficient* (✕10 3 ) R 2 * P * Coefficient* (✕10 3 ) R 2 * P * Coefficient* (✕10 3 ) R 2 * P *
Axial length (mm) 14.851 0.318 <.001 33.453 0.542 <.001 13.444 0.463 <.001
Refractive error (D) −7.721 0.366 <.001 −17.509 0.563 <.001 −6.870 0.490 <.001
BCVA (logMAR units) −83.140 0.183 <.001 −190.297 0.319 <.001 −71.315 0.257 <.001
SFCT (µm) −0.165 0.195 <.001 −0.405 0.425 <.001 −0.180 0.360 <.001
IOP (mmHg) 0.447 0.075 .456 0.798 0.171 .473 0.467 0.136 .318
CCT (µm) 0.072 0.064 .137 0.085 0.161 .311 0.044 0.127 .232
ACD (µm) 23.322 0.102 <.001 48.648 0.215 <.001 21.513 0.183 <.001

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Jul 26, 2025 | Posted by in OPHTHALMOLOGY | Comments Off on Posterior Eye Curvature as a Biomarker for Differentiating Pathologic Myopia From High Myopia

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