HIGHLIGHTS
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Axial length correlates with corneal biomechanical parameters in myopic eyes.
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Maximal deflection amplitude is independently linked to myopic maculopathy.
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Subfoveal choroidal thickness is associated with corneal biomechanics in high myopia.
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Corneal biomechanics may predict development and progression of myopic maculopathy.
PURPOSE
Corneal biomechanical properties are associated with axial elongation. We aimed to characterize corneal biomechanical properties in highly myopic eyes with myopic maculopathy (MM).
DESIGN
Retrospective cross-sectional study.
METHODS
We included patients examined between June 2022 and August 2023 who underwent corneal visualization Scheimpflug technology (Corvis ST) measurements. MM in highly myopic eyes (axial length >26.0 mm) was evaluated using META-PM (meta-analyses of pathologic myopia) study classification based on fundus photographs with subfoveal choroidal thickness measured via spectral domain optical coherence tomography. A linear mixed model was used to analyze the association of MM features with axial length (AL) and corneal biomechanical parameters, followed by model selection using the second-order–corrected Akaike information criterion.
RESULTS
We included 189 eyes from 109 participants. A significant correlation was observed between AL and biomechanical parameters that characterize maximal corneal deformation (maximal deflection amplitude and peak distance) and stiffness parameter (stress–strain index) ( P < .05). Model selection revealed that both AL and maximal deflection amplitude were independently associated with MM with category ≥2 severe, as well as with subfoveal choroidal thickness in highly myopic eyes (AL >26.0 mm).
CONCLUSIONS
In highly myopic eyes, a greater maximal deflection amplitude was identified as a risk factor for MM. Corneal biomechanical properties may serve as biomarkers for predicting the development and progression of MM.
P athologic myopia is emerging as a leading cause of blindness, with the global incidence of myopia projected to increase from approximately 23% in 2000 to 50% by 2050. Myopic maculopathy (MM) is a major cause of vision impairment due to pathologic myopia, not only in Asian countries, , where myopia is prevalent, but also in Western countries. , Despite the increasing prevalence, preventive treatments are currently unavailable, as the pathogenesis of MM is not yet fully understood. The key risk factors for MM development and progression include ocular axial elongation and posterior staphyloma, an outpouching of the posterior sclera. The sclera has a role in maintaining the structural integrity of the eyeball, and its biomechanical properties determine its physical strength and tissue remodeling in response to intraocular pressure. Therefore, scleral biomechanics should be assessed in the context of MM. Although direct biomechanics assessment of the posterior sclera is challenging in clinical practice, corneal biomechanical properties could serve as a surrogate markers for those of the sclera in various ocular pathologies, since the corneal and scleral stroma share common extracellular matrix components and scleral properties can directly affect corneal deformation. ,
Corneal biomechanics can be noninvasively assessed using corneal visualization Scheimpflug technology (Corvis ST) is a noncontact tonometer equipped with an ultrahigh speed camera, which visualizes dynamic corneal behavior in response to air jet application. Recent clinical studies in adults and children with myopia have documented changes in corneal biomechanical properties measured using Corvis ST, indicating an association with myopia progression. , However, the relationship between corneal biomechanical properties and MM has yet to be explored. We hypothesize that corneal biomechanical properties are associated with MM development through changes in scleral biomechanics. We examined corneal biomechanical properties in individuals with and without MM to test this hypothesis.
METHODS
This retrospective, observational, cross-sectional study was conducted according to the tenets of the Declaration of Helsinki and approved by the institutional review board of the University of Tokyo (reference number: 2217). In alignment with the Japanese Guidelines for Epidemiologic Study issued by the Japanese Government, the ethics committee waived the requirement for patients’ informed consent for the use of their medical record data. As a form of transparency, the study protocol was displayed at the outpatient clinic to keep patients informed about the ongoing research. Patients who declined the use of their medical records for research purposes were subsequently excluded. The study included patients who underwent intraocular pressure measurement using Corvis ST at our department between June 2022 and September 2023. The exclusion criteria were eyes with any history of corneal disease, corneal refractive surgery, intraocular surgery including cataract surgery, and retinal diseases other than MM. Glaucomatous eyes, including those with a history of receiving anti-glaucoma medications, were excluded, because topical anti-glaucoma medications may influence corneal biomechanical properties , and glaucomatous eyes themselves may have different corneal biomechanical characteristics, , potentially confounding the study results.
We collected baseline demographic data, such as age and axial length (AL) from the medical records. Moreover, the spherical equivalent was calculated by adding half of the cylinder power to the principal spherical power. ALs were measured using an OA-2000 (TOMEY). Spectral domain optical coherence tomography (OCT) (Heidelberg Engineering GmbH) was used to acquire horizontal line scan images of the macula, and subfoveal choroidal thickness was manually measured. Two physicians assessed the choroidal thickness, measuring the vertical distance between the choroid–scleral junction and the retinal pigment epithelium–Bruch membrane complex. The actual choroid was carefully distinguished from macular intrachoroidal cavitation, often seen on and around patchy chorioretinal atrophy. To evaluate the interobserver repeatability, the 2 graders independently measured the subfoveal choroidal thickness of 30 randomly selected highly myopic eyes, and the intraclass correlation coefficient (ICC) was calculated to assess agreement between the 2 graders. Corneal biomechanical parameters were measured using Corvis ST.
CORVIS ST MEASUREMENT
The principles of the Corvis ST measurements have been described previously. The instrument has a high-speed Scheimpflug camera that records 140 images, showing the corneal changes induced by an air jet, in more than 30 milliseconds. Analysis of the recorded images focuses on 2 moments of flattening: the initial inward flattening (A1) and subsequent outward movement (A2), as well as its deepest point of deformation, the highest concavity (HC). The Corvis ST device calculates numerous indicators, such as the cornea’s degree of flattening, the speed of the apex’s motion, and the occurrence times of A1, A2, and HC. These parameters are computed using the latest version of the Corvis ST software (version 1.6r2223). Because of the large number and intercorrelation of these parameters, we focused only on parameters related to AL and corneal stiffness from previous literature. The “peak distance” and “maximal deflection amplitude” measure the horizontal length and depth of the most indented cornea at HC, respectively ( Figure 1 ). The “integrated inverse radius” measures the curvature across the concave phase of the cornea. An elevated value suggests a more pronounced corneal indentation, indicating a softer cornea. Corvis ST also provides the stress–strain index (SSI), which is related to corneal stiffness. SSI assesses the nonlinear stress–strain relationship of the cornea by using numerical simulation, reflecting corneal stiffness independent of intraocular pressure (IOP) and corneal geometry. The SSI value is standardized, with 1 corresponding to the average corneal stiffness of a 50-year-old individual, with higher values indicating more rigid, less deformable cornea.
MYOPIC MACULOPATHY CHARACTERIZATION AND STATISTICAL ANALYSIS
A linear mixed model was used to analyze the relationship between corneal biomechanical parameters and AL in all 197 eyes. Furthermore, this analysis was specified for 86 eyes with high myopia, defined as having an AL of ≥26.0 mm.
The eyes were classified into categories of MM (0 = no macular degenerative lesions; 1 = tessellated fundus only; 2 = diffuse choroidal atrophy; 3 = patchy chorioretinal atrophy; and 4 = macular atrophy) based on the META-PM (meta-analyses of pathologic myopia) study classification by using fundus photographs evaluated by 2 physicians. If the 2 physicians disagreed, the category was determined by their discussion.
Highly myopic eyes were subjected to subsequent analysis on MM; non–highly myopic eyes were excluded, as they all had MM category ≤1, which would cause a significant numerical imbalance between categories and potential bias in analysis. To assess the relationship between MM and ocular parameters, MM categories were divided into 2 groups: mild (categories 0 and 1) and severe (categories 2-4), resulting in a binarized MM category. This binarization is based on previous findings that category 1 does not imply macular functional impairment, and that a significant proportion of highly myopic eyes remain at this stage without progressing to category 2 and beyond. The key stage in the progression of MM is category 2, characterized by significant choroidal thinning with functional decline of the macula, from which natural progression to categories 3 and 4 is observed. A logistic mixed-effects model was used to examine associations between the binarized MM, treated as a dependent variable, and AL and 4 corneal biomechanical parameters (peak distance, maximal deflection amplitude, integrated inverse radius, and SSI), treated as independent variables in highly myopic eyes. The mixed models treated patients as a random effect considering the inclusion of 1 or 2 eyes from the same patient. Subsequently, the optimal model to explain the binarized MM category was selected from all combinations of these 5 independent variables by using a second-order bias-corrected Akaike information criterion (AICc). The AICc is used to compare the relative quality of statistical models for a given dataset, adjusting for the balance between model complexity and goodness of fit. A decreased AICc value indicates improvement in the model’s performance. The likelihood that a specific model is the best at minimizing information loss can be determined using the formula exp([AICc min − AICc x ]/2), where AICc x represents the AICc value of a given model X, and AICc min is the lowest AICc value among all considered models.
Additionally, a linear mixed model was used to investigate the relationship between subfoveal choroidal thickness, AL, and biomechanical parameters. However, patchy chorioretinal atrophy or macular atrophy occurring because of myopic neovascularization results in complete localized loss of the choroid. Therefore, we excluded cases with patchy chorioretinal atrophy or macular atrophy at the fovea. Additionally, AICc was used for model comparisons to determine the optimal model for explaining subfoveal choroidal thickness.
Statistical significance was determined at <.05. All data processing and analyses were conducted using R software (R Foundation for Statistical Computing).
RESULTS
We included 189 eyes from 105 participants, including 86 highly myopic eyes from 50 patients and 103 non–highly myopic eyes from 59 patients. Table 1 shows the basic demographics and biomechanical characteristics. Table 2 shows the relationships between AL and biomechanical parameters. Significant associations were observed between AL and the values of peak distance, maximal deflection amplitude, and SSI, whereas AL and integrated inverse radius showed no significant association. Figure 2 shows a scatter plot of AL against SSI, illustrating a negative correlation.
| Parameter | Overall (n = 189 Eyes) | High Myopia (n = 86 Eyes) |
|---|---|---|
| Age (y) | 56.0 ± 12.9 [29-81] | 54.4 ± 12.6 [33-77] |
| Axial length (mm) | 26.04 ± 2.48 [21.52-31.84] | 28.30 ± 1.70 [26.01-31.84] |
| Central corneal thickness (µm) | 562.1 ± 33.5 [466-667] | 568.9 ± 28.3 [512-639] |
| bIOP (mm Hg) | 14.10 ± 2.56 [8.5-23.4] | 14.66 ± 2.45 [8.8-23.4] |
| Maximal deflection amplitude (mm) | 0.97 ± 0.12 [0.57-1.23] | 0.99 ± 0.12 [0.66-1.23] |
| Peak distance (mm) | 5.06 ± 0.30 [4.01-5.73] | 5.10 ± 0.26 [4.37-5.73] |
| Integrated inverse radius (mm) | 8.21 ± 1.21 [5.17-11.12] | 8.17 ± 1.26 [5.17-11.04] |
| SSI | 1.04 ± 0.23 [0.62-1.88] | 0.94 ± 0.17 [0.62-1.35] |
| Parameter | Regression Coefficient | P Value a |
|---|---|---|
| Central corneal thickness (µm) | 0.63 | .67 |
| bIOP (mm Hg) | 0.19 | .053 |
| Peak distance (mm) | 0.033 | .0013 b |
| Maximal deflection amplitude (mm) | 0.015 | <.001 b |
| Integrated inverse radius (mm) | −0.057 | .168 |
| SSI | −0.043 | <.001 b |
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