Keratoconus has different characteristics in the pediatric and adult age group in terms of the progression and severity of the disease. Keratoconus has a more progressive and severe course in pediatric patients [22]. Stabilization of the disorder as soon as possible is of great importance in this age group in terms of providing better visual function and decreasing the need for keratoplasty. The standard corneal crosslinking procedure (S-CXL, Dresden protocol) has been used for years to stop the progression of keratoconus, after being defined by Wollensak et al [10]. There are many studies reporting that the procedure (30-minute exposure to 3 mW/cm2 UVA rays) is an effective and reliable treatment for the stabilization of pediatric and adult progressive keratoconus [23–27]. The accelerated cross linking (A-CXL) procedure is based on the Bunsen-Roscoe reciprocity law using the principle that shorter exposure to higher intensity UVA rays has similar photochemical effects on the cornea. A short procedure time has advantages such as higher compliance with treatment in the pediatric age group, less corneal dehydration, and less intraoperative corneal thinning. S-CXL and A-CXL procedures have been reported in many studies to have similar efficiency and reliability in the stabilization of progressive keratoconus in the pediatric and adult age groups [28–33]. The 1-year results of accelerated CXL (9 mV/cm2 UVA, 10 min) treatment for progressive keratoconus in the pediatric and adult age groups were compared in the current study.
Flattening after the CXL procedure was first defined as a decrease of ˃1D in the Kmax value by Koller et al. in their 2011 study [34]. The ratio of the eyes with a Kmax decrease of more than 1D was reported as 37.7% while the ratio of a Kmax decrease of more than 2D was 13% at the 12th month following the CXL surgery performed on 103 eyes with keratoconus and 32 with pellucid marginal degeneration. Uçakhan et al. have found a flattening rate of 32.5% (˃1D) and 17.5% (˃2D) 4 years after CXL treatment in the pediatric age group [23]. Sloot et al. have noted the flattening rate at the 12th month after CXL surgery performed in the keratoconus patient group with the mean age of 21.5 years as 59% [35]. Soeters et al. have divided their patients who had undergone standard CXL into 3 groups as a pediatric group [mean age 15 (range 12–17) years], an adolescent group [mean age 22 (range 18–26) years], and an adult group [mean age 33 (range 26–49) years] and found the postoperative 12th month flattening rates to be 52%, 43%, and 50%, respectively [25]. They have attributed the high flattening rate in the pediatric patients to their high corneal collagen plasticity. Unlike the study of Soeters et al., the flattening rates in the current study were 48.2% (˃1D) and 20.6% (˃2D) in the pediatric age group, and 51.5% (˃1D) and 24.2% (˃2D) in the adult age group, with the flattening rates found to be higher in the adult group.
The progression rate after corneal CXL has been the subject of a multitude of studies. Keratoconus has been found to be more progressive and more aggressive in the pediatric age group in many of these [22, 36–39]. Barbisan et al. have divided their progressive keratoconus patients treated with CXL using the standard Dresden protocol into 2 groups as a pediatric group aged 16 years or under and an adult group aged 17 years or over. The postoperative 12th month progression rates of the groups were reported as 19.2% and 20.7%, respectively [26]. Toker et al. have reported the postoperative 12th month progression rate of their patients treated with accelerated CXL using a value of 9 mW/cm2 and with a mean age of 22.4 years as 7% in their study where they compared the efficacy of various CXL procedures in patients with progressive keratoconus [40]. Mazzotta et al. have found a progression rate of 24% in their study where they investigated the 10-year results on 62 pediatric age group eyes with a mean age of 14.1 years who had received standard CXL treatment [41]. Uçakhan et al. have found no progression at the postoperative 24th month in the standard CXL group with a mean age of 23.13 years while the progression rate in the group receiving accelerated CXL with a value of 9 mW/cm2 and with a mean age of 24.69 years was 11.1% in their study where they compared the standard CXL and 9 mW/cm2 accelerated CXL procedures [42]. The postoperative 12th month progression rate was 24.1% in the pediatric patient group and 12.1% in the adult group in the current study where the accelerated CXL procedure was performed with a value of 9 mW/cm2 for progressive keratoconus, and the difference between the two groups was not statistically significant (p:0.367).
Best-corrected visual acuity (BCVA) is the most important indicator of functional recovery in keratoconus. Henriquez et al. have reported a statistically significant improvement in the postoperative 3rd year BCVA of the pediatric group patients treated with standard CXL (p:0.01) [43]. Padmanabhan et al. have reported a 38.7% improvement rate in the postoperative 1st year BCVAs of the pediatric group patients treated with standard CXL [44]. Sadoughi et al. have found an improvement compared to the preoperative period in the postoperative 12th month BCVA of their patients with mean age of 19.4 (range 13–30) years treated with 9 mW/cm2 accelerated CXL but this was not statistically significant (p:0.058) [45]. Soeters et al. have observed a significant BCVA improvement in all groups at the postoperative 1st year, but this improvement was more pronounced in the pediatric group in their study where they divided the 119 eyes of 95 patients treated with standard CXL into pediatric (aged ˂18 years), adolescent (aged 18–26 years) and adult (aged ˃26 years) age groups [25]. We also found a significant BCVA improvement in the postoperative 12th month compared to the preoperative period in both the pediatric and adult patient groups, but the improvement was more significant in the adult group, unlike the Soeters et al. study (p:0.033, p:0.001). This can be explained by the fact that keratoconus is more progressive and aggressive in the pediatric patients. The difference between the BCVAs of the groups after 12 months was not statistically significant in our study (p: 0.091). Similarly, the BCVA difference between the two groups at the postoperative 12th month was reported not to be significant in the Barbisan et al. study where the 1-year results of standard CXL for the treatment of progressive keratoconus was compared in the pediatric group aged 16 years or less and the adult group aged 17 years or more (p:0.941) [26]. Uçakhan et al. have also reported no statistically significant BCVA difference between their two groups at the end of the 3rd year in their recent study where the 192 eyes of 122 patients treated with standard CXL were divided into two groups as pediatric (aged ≤ 18 years) and adult (aged ˃18 years) [27].
Comparison of the preoperative and postoperative keratometry values revealed that the postoperative 12th month Kmax, K1 and K2 values showed a decrease compared to the preoperative values in the pediatric group patients but the difference was not statistically significant (p: 0.306, p: 0.609, p: 0.282). Similarly, Barbisan et al. have reported no significant difference between the preoperative and postoperative 1st year Kmax, K1 and K2 values in the pediatric group with a mean age of 13.8 (range 10–16) years treated with standard CXL treatment for progressive keratoconus [26]. Tian et al. have found lower postoperative 1st year Kmax, K1 and K2 values compared to the preoperative period in their pediatric patients treated with A-CXL but the difference was not statistically significant [46]. Uçakhan et al. have also reported lower postoperative 1st year Kmax, K1 and K2 values than the preoperative period but the difference was again not statistically significant in the study where they investigated the 4-year results of S-CXL in pediatric age group [23]. However, the 4th year results were lower than in the preoperative period. Soeters et al. have reported significantly lower postoperative 1st year Kmax values in the pediatric age group compared to the adolescent and adult groups while the lower K1 and K2 values were not significant in the study they conducted with S-CXL [25].
In the current study, the 12th month Kmax, K1 and K2 values in the adult group were statistically significantly lower (p: 0.005, p: 0.025, p: 0.011). Similarly, Belviranlı et al. have found the 2nd year Kmax, K1 and K2 values after A-CXL treatment in their patient group with a mean age of 22.7 (14–38) years to be statistically significantly lower compared to our results [47]. Uysal et al. have also reported that the Kmax, K1 and K2 values were statistically significantly lower at the postoperative 12th month compared to preoperative period in their keratoconus patients treated with S-CXL with a mean age of 22.9 years [48]. Barbisan has reported that the postoperative 12th month Kmax, K1 and K2 values of the patients over the age of 17 who underwent S-CXL treatment were lower than in the preoperative period, but the difference was not significant [26]. Soeters et al. have found significantly lower Kmax and K2 values at the 12th month after S-CXL in their adolescent (aged 18–26 years) patients but the concurrent decrease in the K1 was not significant; they also found a significant decrease in the Kmax value in the adult (aged ˃26 years) group patients while the decrease in K1 and K2 was not significant in this group [25]. Tomita et al. have reported decreased Kmax, K1 and K2 values at the 1st year compared to the preoperative period, but these were again not significant, in the study where they compared the 1-year results of A-CXL and S-CXL treatments in the adult patient group [33].
In the current study, no significant difference was present between the preoperative Kmax, K1 and K2 values of the adult and pediatric groups. Postoperative 12th month K1 values were statistically significantly lower in the adult patients (p: 0.022), while the Kmax and K2 values were also lower in the adult patients but without statistical significance (p: 0.073, p: 0.096). Similarly, other studies where pediatric and adult age groups who underwent S-CXL were compared have reported no significant difference between the two groups in terms of postoperative 1st year keratometry values [25–27].
The mean thCT values were statistically significantly lower at the postoperative 12th month than in preoperative period (p < 0.001, p < 0.001) in both groups in the current study. Similarly, Soeters et al. have reported a statistically significant decrease in the thCT values at the 12th month after S-CXL treatment in the pediatric, adolescent and adult groups [25]. Barbisan et al. have measured statistically significantly lower postoperative 12th month CCT values in pediatric and adult patients treated with S-CXL when compared to our study [26]. In contrast, Tian et al. and Henriques et al. have found the postoperative 1st year CCT of the pediatric group patients treated with A-CXL to be lower when compared to our study, but this difference was not statistically significant [30, 46].
When the two groups were compared, there was no significant difference between the postoperative 12th month mean thCT values (p: 0.809). Similarly, no significant difference was found between 1st year thCT results after CXL treatment of the pediatric and adult patients in other studies [25, 26].
Although a decrease was present in the mean CA values of the pediatric group patients at the 12th month compared to the preoperative period, the difference was not statistically significant (p: 0.345). Similarly, the difference between the postoperative 1st year CA values and the preoperative ones was not found to be significant for either procedure in the study by Nicula et al. comparing S-CXL and A-CXL treatments [49]. However, postoperative 2nd year CA values were found to be significantly lower in the study of Padmanabhan et al. where the S-CXL results in pediatric patients were investigated [44]. Although there was an increase in the mean CA values of adult patients at the postoperative 12th month compared to the preoperative period, the difference was not statistically significant (p: 0.856). In contrast, two recent studies have found a significant decrease in CA values in adult patients 1 year after S-CXL treatment [45, 48].
Comparison of the pediatric and adult groups revealed no significant difference between the postoperative 12th month mean CA values (p: 0.125). We did not find any study investigating the pre and post CXL CA values in the pediatric and adult age groups.
Only a limited number of studies have compared the results of CXL treatment in pediatric and adult patients with progressive keratoconus [25–27]. The S-CXL protocol has been used in all these studies. In contrast, we have compared the 1st year results of A-CXL (9 mV/cm2 for 10 minutes) treatment between two groups in our study. As far as we know, our study is a first in this field.
The limitations of our study can be listed as its retrospective nature, the small number of patients, not including optic aberrations, and not providing spherical equivalent information.
In conclusion, the A-CXL (9 mV/cm2 for 10 minutes) procedure is an effective and reliable method for the treatment of pediatric and adult progressive keratoconus patients. Better visual acuity improvement, a higher flattening rate, and less progression occur with A-CXL treatment after 12 months in adult progressive keratoconus patients compared to the pediatric age group. Besides, there was a greater decrease in Kmax, simK1 and simK2 values in the adult group. Further studies with larger participation and longer follow-up are required for results with greater impact.
Declarations