In this study, we developed a method to construct normal corneal and early keratoconus phantom models. The NCP model was fabricated using a self-designed mold. Based on this mold, two types of early keratoconus phantoms with locally softened areas were fabricated using a two-step molding process. The results showed that the overall morphology and thickness distribution of the corneal phantoms fabricated by our mold were basically consistent with the designed size and could be used for the Corvis ST test. The DCR parameters HCDA, PD, HR, A1V, A2V, A1T, A2T, IR, and SPA1 of the corneal phantoms were significantly correlated with SIOP. HCDA, PD, HR, A1V, A2V, A1T, A2T, and IR of early keratoconus phantoms were significantly different from those of the NCPs. These results suggest that our method for generating the corneal phantoms is both feasible and effective, and the corneal phantoms generated using this method are well suited for investigating the mechanical behavior of the cornea under an air puff; the pertinent findings will facilitate a more profound comprehension of the biomechanical characteristics of keratoconus, thus offering valuable insights for the early diagnosis of keratoconus.
Elastic modulus is an extremely important parameter that characterizes the mechanical properties of the cornea. Based on data from the Corvis ST test, the range of human corneal elastic modulus is 0.05 to 1.24 MPa.
22,24,25 In this study, the elastic modulus of silicone materials prepared by adjusting the silicone oil content ranged from 0.13 MPa to 0.45 MPa, which is consistent with human corneal elastic modulus ranges reported in relevant literature. By comparing the HCDA of normal human corneas with those of normal corneal phantoms with four different elastic moduli, we determined that the normal corneal phantom with 44.44% silicone oil content (elastic modulus, 0.18 MPa) was suitable for simulating the normal human cornea and performing the Corvis ST test. The results showed that HCDA, PD, HCT, A1V, A2T, and IR were negatively correlated with SIOP, whereas HR, A2V, A1T, and SPA1 were positively correlated with SIOP. This result was consistent with relevant research results based on ex vivo animal eyes
22,26 and the clinical test results of Wu et al.
27 based on the Corvis ST. The above results indicate that the corneal phantoms can simulate the mechanical behavior of the cornea under an air puff.
The main innovation of this study is the preparation of two types of early keratoconus phantoms using the two-step molding method. The geometry of the model matched that of the normal cornea, and the locally softened area was used to simulate the keratoconus cone area. The size of the softened area directly affects the overall mechanical response of the cornea. Therefore, it is crucial to carefully design and control the softened area. In this study, 12 early keratoconus phantoms were prepared using the two-step molding method, and the size of the softened area exhibited minimal variation (
Table 1), indicating that this method could ensure consistent sizing of the softened area across different samples. The diameter of the softened area was approximately 4.5 mm, which was determined based on the size of the keratoconus cone area.
28,29 The elastic modulus of the softened area was 0.134 MPa, which was 26.3% lower than that of the normal area. Zhao et al.
30 determined that the difference in the elastic modulus between the keratoconus cone and its surrounding area can be up to 29%. Giraudet et al.
31 established a multiscale mechanical finite element model and found that, when the local fiber stiffness of the corneal model was reduced by 30% to 40%, it was able to reproduce the keratoconus changes in SimK (a clinical indicator of corneal curvature). Therefore, the size and degree of softened area of the early keratoconus phantom designed in this study are reasonable. In addition, the early keratoconus phantoms were tested under water injection. No noticeable local protrusion was found when the pressure reached 50 mmHg, and no cracks or leaks were observed (
Fig. 5), indicating that the mechanical strength of the corneal phantom prepared by the two-step molding method was acceptable.
32
The cone location is an important feature of keratoconus, and keratoconus can be classified into central keratoconus and paracentral keratoconus according to the cone location.
28,33 In this paper, two types of early keratoconus phantoms (CKP and PKP) were fabricated to simulate central keratoconus and paracentral keratoconus, respectively. The Corvis ST test results showed that several DCR parameters (HCDA, HR, A1V, A1T, and IR) exhibited greater differences between CKPs and NCPs compared to the differences between PKPs and NCPs (
Table 2,
Fig. 9). This suggests that the closer the softened area is to the geometric center of the cornea, the greater the effect on the overall mechanical properties of the cornea, resulting in softer behavior under mechanical stress. Several studies have investigated differences in the locations of various keratoconus cones, including optical differences,
34 corneal topographic differences,
35 differences in surgical outcomes such as corneal collagen cross-linking,
36,37 and differences in the symmetry of corneal deformation.
38 A recent study found that the location of the keratoconus cone affects corneal biomechanical parameters measured by the Ocular Response Analyzer (Reichert Technologies, Depew, NY).
39 The paracentral keratoconus shows greater stiffness than the central keratoconus, which is consistent with our results. Such findings indicate that the paracentral keratoconus is less likely to be detected than the central keratoconus, which may explain why some patients who undergo refractive surgery are at risk of developing corneal ectasia after the surgery.
40
DCR parameters can be used to distinguish clinical keratoconus from normal corneas,
41-45 but there is no consensus on the ability of DCR parameters to distinguish early keratoconus. One reason is that the response of DCR parameters to changes in the local mechanical properties of the cornea is not fully understood. Our results show that the HCDA, PD, HR, A1V, A1T, A2T, and IR of normal and early keratoconus phantoms are significantly different in the normal range of IOP, so these parameters and their changes should receive more attention in the diagnosis of keratoconus. Recently, artificial intelligence methods have shown significant application potential in diagnosing keratoconus; however, further algorithmic optimization is required for the early diagnosis of keratoconus.
8,46 Introducing the influence of changes in corneal mechanical properties on DCR parameters as a prior knowledge into these algorithms may improve their diagnostic performance.
47,48
The distribution of collagen fiber bundles in normal corneas exhibits directionality and density variations, which lead to anisotropic mechanical properties in the cornea.
49,50 This study ignored the anisotropic mechanical properties of the cornea and used isotropic silicone to construct corneal phantoms for investigating the corneal mechanical response under an air puff. The results show that the DCR parameters of the normal corneal model exhibit a response trend to SIOP changes similar to that observed in ex vivo animal eyes. The mechanical properties of keratoconus exhibit regional inhomogeneity. Compared to the anisotropic mechanical properties of the cornea, the regional inhomogeneity of the mechanical properties of keratoconus has a more significant impact on DCR parameters. Based on these considerations, this study ignored the anisotropic mechanical properties of the cornea when constructing normal corneal phantoms and early keratoconus corneal phantoms. This approach allowed us to eliminate additional variables, ensuring that the experimental results would directly reflect the macroscopic effects of the mechanical property changes.
In conclusion, we proposed a method for fabricating early keratoconus phantom models by using two silicone materials with different elastic moduli to modify the local mechanical properties of the corneal models. These corneal models can be used to study the biomechanical behavior of keratoconus under an air puff. In the future, we can utilize this method to create keratoconus models with different cone characteristics (such as cone size, cone position, and cone stiffness), to study the effects of these characteristics on DCR parameters, and to combine them with clinical data to enhance the performance of the Corvis ST in diagnosing early keratoconus.