Keratoconus progression, especially at younger ages, is aggressive and may not stop on its own. Improving the biomechanical strength of the cornea could be a greater benefit than waiting for patients to undergo corneal transplantation. CXL provides the effect of stopping the progression of keratoconus by increasing the degree of interfibrillar linkages through photopolymerization of riboflavin. The long-term results of patients undergoing standard CXL have proven the positive effect of this treatment on stabilizing the keratometric parameters [13,14,15,16,17,18]. However, this protocol is time-consuming and with their time- and cost-saving benefits, accelerated CXL protocols have been replaced in recent years in ophthalmology practice [3,4,5,6,7, 19].
The first article comparing the standard and accelerated techniques was published by Tomita et al. . They reported no significant differences in postoperative changes in UCVA and BCVA, in the manifest refraction spherical equivalent or in the postoperative changes in the keratometric readings and the corneal biomechanical responses between the two procedures. According to their findings, a similar demarcation line was formed by three minutes 30 mW/cm2 accelerated CXL and conventional CXL. This first result encouraged ophthalmologists in the use of accelerated technique as a valid alternative for the standard protocol.
Since 2014, many published clinical trials, with at least one year of follow-up, were conducted to investigate the therapeutic effect of different types of accelerated CXL techniques (9 mW/cm2, 18 mW/cm2, 30 mW/cm2 and 45 mW/cm2), comparing them with the Dresden protocol [6,7,8, 20,21,22,23]. Even though most of these studies demonstrated successful clinical results, they could not achieve a different perspective. One of the reports that compared the two different types of protocols for accelerated CXL (30 mW/cm2 for four minutes and 18 mW/cm2 for five minutes) with a one-year follow-up in a larger cohort was recently published and showed no significant changes in spherical equivalent, visual and topographic results . According to their findings, the authors concluded that both modalities of accelerated CXL (total doses of 7.2 J/cm2 and 5.4 J/cm2) exhibited comparable efficacy and applying higher energy for longer periods of time could reach satisfactory results in the stabilization of keratoconus progression following a mean of 12 months. In contrast to these findings, Choi et al.  reported that increasing the UV intensity (30 mW/cm2) and decreasing the irradiation time (to three minutes and 40 s) exhibited less topographical flattening than that of the conventional Dresden protocol. Another study published by Peyman et al.  supported Choi’s conclusion by investigating the stromal demarcation line depth in pulsed and continuous four minutes of accelerated CXL protocols. Peyman and associates reported that total fluence of 7.2 J/cm2 could not induce a deeper demarcation line in contrast to previous studies.
Although the results of all these studies are chaotic diversity, most of them indicate that the lower threshold of human corneas for irradiance is the main reason for Bunsen-Roscoe reciprocity law becoming invalid. Our observation corroborates with previous literature reports. Our study showed a strong positive relationship between CXL duration and topographic flattening. Although improvement in visual acuity was similar in both groups, the change in keratometric values K1, K2, AvgK, and AKf were significantly higher in 9 mW/cm2 for the 10 min group (P < 0.05 for all). Also, the change in SIf was significantly higher in the 9 mW/cm2 protocol.
Shetty et al.  compared the three accelerated CXL protocols (9 mW/cm2 for 10 min, 18 mW/cm2 for five minutes, and 30 mW/cm2 for three minutes) with the conventional CXL. In their prospective randomized interventional study, they reported that conventional CXL and 10 min accelerated CXL provided similar topographic improvement, while the effect of three minutes accelerated CXL was lower compared with the other groups at the end of 12 months. Furthermore, they highlighted the relationship between the flattening effect and energy of radiation, concluding that the efficiency decreases as the amount of energy increases. Although the authors provided a valuable contribution to the treatment capacity of accelerated CXL types, a few points in the study have overshadowed the results. Following CXL, improvements in topographical and aberrometry parameters indicate CXL’s functional success, even if its long term biomechanical impact in stabilizing progressive corneal ectasia is limited. Epstein et al.  reported that the Kmax value was the most important criterion in the follow-up of the progression of keratoconus. Many long-term studies that support this conclusion have stated that Kmax is the most commonly used parameter to determine keratoconus progression [16, 26]. The use of Kmax as an indicator of CXL success is the most important difference that distinguishes our work from Shetty and colleagues. We also verified Shetty’s preliminary results by changing methods and using Sirius topography. Since Sirius combines Placido disk topography with Sheimpflug tomography of the anterior segment, we could measure the large number of topographic parameters more precisely in a short period of time. Previous studies have found that these two devices differed significantly; Sirius showed good to excellent repeatability for all measured parameters, especially in healthy corneas [27,28,29]. In another study, Shetty and colleagues analyzed the effect of post collagen CXL haze on the measurement and repeatability of pachymetry and mean keratometry of four corneal topographers . They reported that postoperative mean keratometry values measured with the Pentacam were affected by post-CXL haze. As a result of all these studies, we believe that the Sirius device gives more reliable results than the Pentacam for the tests performed after crosslinking.
In another retrospective case series supporting our findings, Toker and colleagues examined a series of 134 crosslinked eyes. They reported that although the standard and accelerated CXL (10 min, 9 mW/cm2; 4 min, 30 mW/cm2) results were similar in terms of keratometric stabilization, the four-minute method showed less topographic improvement. In this study, the demarcation line depth was similar between the standard and 10-min groups (266 mμ, and 273 mμ, respectively), and it was found 173 mμ in the four-minute group . In our study, despite no correlation emerging between demarcation line depth and AKf, the change in corneal coma value was significantly higher in Group 2 (P < 0.05) where the demarcation line was deeper and closer to conventional epithelium-off CXL. Another consideration was that the concept of “efficacy” after CXL should be based mainly on its biomechanical impact because it is not a refractive procedure. The shallower demarcation line in the 18 mW/cm2 group may be due to the limited CXL activity because of insufficient oxygen in the environment due to increased oxygen consumption with high UVA intensity. Therefore, Mazzotta et al.  showed that the demarcation line reached an average of 280 mμ when they used 15 mW/cm2 UV-A power with pulsed light applied for 6 min.
In keratoconus, increased corneal HOAs further worsen optical quality and visual acuity . By interpreting the changes in HOAs after CXL, it is possible to establish the benefit of CXL on optical and refractive functions. Studies have shown that in progressive keratoconus, there is an apparent reduction in HOAs after CXL . However, to the best of our knowledge, there is no study in the literature comparing the corneal HOAs changes after accelerated CXL.
Alió and Shabayek  suggested using anterior corneal aberrations to evaluate keratoconus and reported that in eyes with keratoconus, coma-like aberrations were found to be significantly higher compared with normal eyes. In our study, we evaluated anterior corneal HOAs and compared their changes in the 6 mm zone. All anterior corneal aberrations demonstrated a significant reduction in both groups, in accordance with previous studies presenting improvement in HOAs [33, 35]. In their study with 96 eyes and a 12-month follow-up time, Greenstein et al.  reported a significant reduction in total anterior corneal HOAs, total coma, three order coma, and vertical coma. Caporossi et al.  also found a significant reduction in the total cornea HOAs and coma aberration from immediately after treatment up to 24 months in 44 eyes. In our study, further improvement was observed in coma values in the 9 mW/cm2 group (Group 2) at 12 months.
Another point to consider is the real association between the success rate of accelerated CXL types and preoperative keratoconus severity. Comparisons between the two subgroups revealed that there was no significant difference in terms of the mean change in UCVA and BCVA between the mild to moderate and advanced keratoconus at any examination. However, both subgroups showed a significant decrease in the mean changes in K2 and AvgK for the 9 mW/cm2 protocol, with K1 in advanced cases. Even though the differences did not reach a significant level, the 9 mW/cm2 for 10 min application had a greater flattening effect in the maximum keratometry in both subgroups.
Some limitations of this study are that there was no comparison with conventional CXL, this study had a short follow-up period, and the sample size was relatively small.