In our study, we investigated the general prognostic features that potentially contribute to failed standard CXL treatment. In the literature, CXL treatment results have been reported from several long-term studies [5, 6, 12–14]. Based on the findings from these earlier studies, we now know that the standard CXL protocol is not worse than other protocols in stopping progression. However, in patients in whom the condition progresses despite standard CXL treatment, the factors affecting this condition have yet to be fully clarified. In this context, the results of our study provide additional insight into this progression.
In a meta-analysis [15] of the natural progression of patients with untreated keratoconus, the results showed that patients under 17 years of age and with a Kmax steeper than 55.0 D face a high risk of progression. Middle Eastern populations show a significantly greater increase in Kmax than Europeans and East Asians. Our study was conducted with data from two centers. The mean Kmax values were greater than 55.0 D for both centers. In addition, Center 1 consisted of patients who were slightly younger and who had slightly greater preoperative Kmax values than the other center. There was also a sharper increase in the Kmax values of patients from Center 1 after CXL treatment.
Due to the nature of keratoconus disease, some groups of patients may progress despite CXL treatment. This is important, as emphasized by Koller et al [16], in that changing the inclusion criteria in CXL therapy could significantly reduce the complications and failures of CXL treatment. Cone location is known to be mostly central in all stages of keratoconus [17]. In our study, the data overwhelmingly indicated a central cone location in patients from both centers. Because having a central cone is a common condition in keratoconic eyes, it may not be an effective factor with respect to the development of progression. Of the patients included in our study, 65% were female. Studies show that gender is not a clear factor in patient selection for CXL [18]. Especially in Center 1, the female gender percentage was 75%, and in Center 2 it was 50%. Allergic conjunctivitis was present in 75% of the cases. In Center 1, this rate reached 92%, and in Center 2 it reached 88%. Bilateral progression was observed in one patient with excessive tear scratching. The relationship between eye scratching and keratoconus progression is a well-known association. The presence of allergic conjunctivitis may be a good indicator for progression.
Preoperative corneal thickness in Center 1 was evaluated as being ~ 40 µm thinner, and the SE and Kmax values were 3 D and 2 D higher, respectively (Table 2). We were unable to obtain any data showing that the preoperative ECC affects the progression of keratoconus. In our study, the ECC was higher in Center 1. The fact that patients with advanced and endothelial damage were not included in the study when selecting patients for CXL treatment may have been effective.
The surgical technique used in both centers was the same standard protocol; however, the UVA devices used were different. Here, the calibration error of the devices and care in administering the UVA radiation should be examined carefully, even if the standard protocol was applied in both centers.
With respect to the cause of keratoconus progression, patients with a high preoperative Kmax (> 57.0 D), thin corneal thickness (< 430 µm), presence of allergic conjunctivitis, female gender, and those under 17 years of age may show a more aggressive condition and early progression. The longer follow-up periods of the centers provide more stable results with regard to our analysis. However, it seems that progression may develop after a long follow-up, especially in those who are younger. Providing an effective strategy for preventing the development of aggressive progression is the main contribution of this study.