VKC is a chronic allergic disease of the eyes and occurs mainly in boys, which is consistent with the demography of participants in our study. Children with VKC confront risks from ocular surface remodeling that may lead to eye-sight loss. A clinical study showed that mixed type VKC patients had lower corneal resistance factor and Goldmann correlated IOP, while researches about three subtypes of VKC patients and changes in their CBPs are still deficient [10]. Therefore, we further explored the CBPs changes between VKC patients and non-VKC patients, and first carried out a preliminary study to distinguish the CBPs discrepancies among three subtypes in VKC patients.
In 2013, Emre et al. [10] used ocular response analyzer (ORA) to detect corneal biomechanical changes between mixed form VKC patients and healthy control subjects with minor reflective errors. The authors found that the measurements of corneal resistance factor and Goldmann correlated IOP were lower in VKC patients (9.5 ± 1.7 versus 10.8 ± 1.7, p = 0.016; 13.3 ± 3.4 versus 16.6 ± 3.6, p = 0.013). The corneal resistance factor is the overall indicator of corneal resistance and is dominated by corneal elastic properties. They thought the decrease of corneal resistance factor was related to the impairment of linkages between keratocytes or collagen bundles, which might be caused by the abnormal immunological environment of cornea, conjunctiva, and tear film in VKC patients. Although Emre et al. [10] discovered mixed type VKC patients had significantly lower Goldmann correlated IOP, we did not find any difference in either IOP or bIOP between VKC patients and non-VKC patients. In addition to it, Wang et al. [11] also found no significant difference in IOP or bIOP between allergic conjunctivitis patients and non-allergic conjunctivitis patients.
In our study, VKC patients had lower A1 length, ARTh, SP-A1, and higher A1 velocity compared to non-VKC patients. A1 length is the length of the flattened cornea at first applanation and A1 velocity is the velocity of the corneal apex during the first applanation [12]. The lower A1 length and higher A1 velocity indicated the shape of the cornea was more protruding, which was in accord with the results of ARTh. ARTh is the Ambrosio relational thickness in the horizontal 8mm cornea, and the lower values of it mean that the measured cornea is steeper in shape [13]. In this study, ARTh in the VKC group was 452 ± 121.2 while ARTh in the non-VKC group was 518 ± 101.2 (p = 0.007), showing an obvious decline. Moreover, SP-A1, a stiffness parameter at first applanation, presented a significant decrease in our study as well (99.8 ± 17.7 in the VKC group versus 110.2 ± 17.2 in the non-VKC group, p = 0.04), indicating corneas of VKC patients were softer. ARTh, SPA1, A1 velocity, DA ratio, and integrated radius are proved to be stable individual parameters in CBI, which provides proof of keratoconus (KC) propensity [14]. In combination with the above findings, we postulated that the steeper shape and softer texture of corneas might cause VKC patients to tend to become KC patients.
Furthermore, we discovered that the course of the disease was related to values of A1 velocity. With the progression of the disease, A1 velocity became higher, which indicated that the corneas of VKC patients would become steeper in shape gradually. The pathogenesis of VKC is still unclear, immunity and inflammation were supposed to drive disease progress [15]. Kumagai et al. [16] found that corneal stromal fibroblasts could be activated by some bioactive substances in tear fluid such as proinflammatory and T helper 2 cell-derived cytokines, due to the incomplete corneal epithelium in VKC patients. Then, the activated fibroblasts of the corneal stroma enhanced the allergic reaction of the ocular surface by the means of promoting the expression of some chemokines and adhesion molecules and the infiltration of eosinophils and Th2 lymphocytes. As the result of chronic inflammation and immune reaction, further consequences of corneas in VKC patients were corneal stem cell deficiency, tissue remodeling reactions, superficial corneal opacification and so on [17].
We first conducted comparisons about the CBPs of three subtypes in VKC patients. The CCT of limbal form in VKC patients was significantly lower than the other two forms (514 ± 11 µm in limbal form; 548 ± 20 µm in palpebral form; 565 ± 23 µm in mixed form; p < 0.001), whereas no significant difference was found between palpebral form and mixed form. Similar to CCT, SP-A1 was also lower in limbal form compared to the other two forms (79.9 ± 9.4 in limbal form; 100.3 ± 15.4 in palpebral form; 110.5 ± 13.0 in mixed form; p < 0.001), illustrating the patients with limbal form VKC had a softer cornea. In keeping with the outcomes of SP-A1, the measurement of the integrated radius was significantly higher in limbal form, which means the lower corneal stiffness of patients with limbal form VKC. Moreover, DA ratio as an index for delineating the corneal deformability was significantly higher in limbal form than in the other two forms as well (5.39 ± 1.7 in limbal form; 4.36 ± 0.3 in palpebral form; 4.24 ± 0.3 in mixed form; p < 0.001). The above outcomes showed the CBPs of limbal form were thinner, softer, and easier to deform, whereas the mechanism for that was unclear. In addition, the A1 length of limbal form was lower than that of palpebral form while A1velocity and integrated radius were higher than mixed form, demonstrating the corneal shape of limbal form was more protruding and its cornea was softer as well. Last but not least, CBI is a reliable diagnostic index for KC with a cut-off value of 0.5 [18]. In this study, we also found that values of CBI were significantly higher in limbal form (0.49 ± 0.35 in limbal form; 0.12 ± 0.19 in palpebral form; 0.13 ± 0.18 in mixed form; p = 0.02), demonstrating VKC patients of limbal form might be more possible to get KC. Totan et al. [19] studied the incidence of KC in VKC patients, they found that 26.3% of the mixed form subjects (10 of 38 subjects), 22.2% of palpebral form subjects (8 of 36 subjects), and 50.0% of the limbal form subjects (4 of 8 subjects) were KC patients, which also confirmed that VKC patients in limbal form were more likely to evolve into KC patients. Although VKC patients frequently rubbed their eyes due to severe itching of eyes, Totan et al. [19] did not find the chronic problem in most subjects of their research so they supposed hereditary or environmental factors were the main causes to propel VKC patients into getting KC. Combined with our study, corneas of patients with limbal form VKC showed differences in CBPs compared to the other two subtypes though subjects from all three subjects had a history of eye rubbing, which also indicated factors such as ocular immunity, heredity, etc. were the potential pathogeny rather than mechanical rubs.
The limitation of this primary study was the small sample size. Only 20 VKC patients participated in this study. Despite the subtype analysis, the numbers of the three subtypes were uneven. A prospective clinical trial with a larger sample scale should be designed to further verify the difference between VKC patients and non-VKC patients and the disparity among three subtypes in the VKC group.