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PURPOSE: To evaluate the effect of conventional and accelerated corneal crosslinking (CXL) on visual acuity, corneal topography, corneal epithelial thickness, and subbasal nerve morphology in progressive keratoconus patients. METHODS: In this prospective and randomized study, twenty eyes of 20 patients were treated with conventional CXL (3 mW/cm2, 30 min, C-CXL) and 19 eyes of 19 patients were treated with accelerated CXL (9 mW/cm2, 10 min, A-CXL). The spherical equivalent, uncorrected visual acuity, best-corrected visual acuity, keratometric measurements, demarcation line measurement and epithelial thickness mapping analyses, and subbasal nerve morphology with in vivo confocal microscopy (IVCCM) were evaluated at baseline and at postoperative months 1, 3 and 6. RESULTS: At postoperative 6 months, a significant improvement was observed in all keratometric values in both treatment groups (p < 0.05). All epithelial thickness indices, except central, temporal, and inferotemporal thickness, were reduced at 1 month postoperatively in both treatment groups. The epithelial map uniformity indices (standard deviation and difference between min-max thickness) were significantly lower than the baseline values at all time points after CXL in both treatment groups (p < 0.001). Compared with the preoperative values, there was a significant decrease in all IVCCM parameters at 1 month postoperatively (p < 0.05). At 6 months postoperatively, corneal nerve fiber density and corneal nerve branch density recovered to preoperative values in the A-CXL group, whereas corneal nerve regeneration was not complete in the C-CXL group. CONCLUSION: Both conventional and accelerated CXL treatments appear to be effective in halting the progression of KC. Corneal epithelial irregularity slightly improves after CXL. The regeneration of subbasal nerves is faster after A-CXL treatment.

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BACKGROUND: Our aim was to determine associations of pachymetry, keratometry, and their changes with haze formation and corneal flattening after collagen cross-linking, and to analyse the relationship between postoperative haze and visual outcome. METHODS: Retrospective analysis was performed on 47 eyes of 47 patients with keratoconus using the Pentacam HR Scheimpflug camera before and 1, 3, 6 and 12 months after cross-linking. Corneal backscattered light values in grey scale unit were recorded in the anterior, center and posterior corneal layers and in four concentric rings. Surface area- and thickness-corrected grey scale unit values were assessed with an additional calculation. Friedman test with post hoc Wilcoxon signed-rank test was used to analyse changes in visual acuity, pachymetry, keratometry and densitometry. Spearman's rank correlation test was used to detect correlations of haze formation and corneal flattening with pachymetry, keratometry and their postoperative change. Generalized estimating equations analysis was used to investigate the influence of densitometry values on postoperative visual acuity after controlling for the effect of preoperative keratometry. RESULTS: One year after treatment, significant flattening was observed in maximum and mean keratometry readings (p < 0.001). Significantly increased densitometry values were observed in three central rings compared to baseline (post hoc p < 0.0125). According to receiver operating characteristic curve, densitometry value of the anterior layer of 0-2 mm ring was the most characteristic parameter of densitometry changes after cross-linking (area under the curve = 0.936). Changes in haze significantly correlated with preoperative maximum keratometry (R = 0.303, p = 0.038) and with the changes in maximum keratometry (R = -0.412, p = 0.004). Changes in maximum keratometry correlated with preoperative maximum keratometry (R = -0.302, p = 0.038). Postoperative haze had a significant impact on uncorrected and best corrected distance visual acuity (ß coefficient = 0.006, p = 0.041 and ß coefficient = 0.003, p = 0.039, respectively). CONCLUSIONS: Our findings indicate that in more advanced keratoconus more significant corneal flattening effect parallel with haze formation can be observed after cross-linking. Despite significant reduction of keratometry, postoperative corneal haze may limit final visual acuity.

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PURPOSE: The aim of our study was to evaluate the efficacy and safety of epi-off conventional and accelerated corneal collagen cross-linking in the treatment of progressive keratoconus in pediatric patients up to 4 years after treatment. PATIENTS AND METHODS: Conventional (standard) CXL epi-off technique was performed in 37 eyes (S-CXL group) and accelerated CXL in 27 eyes (A-CXL group). Refraction, keratometry, cylindrical equivalent, spherical equivalent, slit lamp examination, pachymetry, corneal tomography, anterior segment ocular coherence tomography and visual acuity were performed up to 4 years. RESULTS: In the S-CXL group: the flat K values decreased from 47.41±3.39 D to 45.36±3.62 D at 4 years (p=0.004); steep K decreased from 51.98±4.11 to 50.21±4.81 D at 4 years (p=0.0078); mean K decreased with 1.99 D at 4 years (p=0.009). In the A-CXL group: the flat K values decreased from 46.97±4.17 D to 44.97±4.24 D at 4 years (p=0.048); steep K decreased from 50.55±4.10 D to 48.75±4.17 D at 4 years (p=0.0287); mean K decreased from 48.79±3.86 D to 46.86±4.11 D at 4 years (p=0.0356). The preoperative mean UCVA in the S-CXL group was 0.8 ±0.23 logMar and improved during the follow-up reaching 0.65 ±0.24 logMar at 4 years (p=0.072). The baseline mean UCVA in A-CXL group was 0.77±0.25 logMar and increased during the follow-up to 0.63 ±0.25 logMar at 4 years (p=0.0039). A similar improvement of BCVA was observed during the follow-up. CONCLUSION: Epi-off conventional and accelerated CXL are efficient procedures for progressive keratoconus in pediatric patients. Accelerated and conventional CXL were comparable at all time points and both represent viable options for the therapy of KC in these patients.

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Corneal collagen crosslinking has revolutionized the treatment of keratoconus and post-refractive corneal ectasia in the past decade. Corneal crosslinking with riboflavin and ultraviolet A is proposed to halt the progression of keratectasia. In the original "Conventional Dresden Protocol" (C-CXL), the epithelium is removed prior to the crosslinking process to facilitate better absorption of riboflavin into the corneal stroma. Studies analyzing its short- and long-term outcomes revealed that although there are inconsistencies as to the effectiveness of this technique, the advantages prevail over the disadvantages. Therefore, corneal crosslinking (CXL) is widely used in current practice to treat keratoconus. In an attempt to improve the visual and topographical outcomes of C-CXL and to minimize time-related discomfort and endothelial-related side effects, various modifications such as accelerated crosslinking and transepithelial crosslinking methods have been introduced. The comparison of outcomes of these modified techniques with C-CXL has also returned contradictory results. Hence, it is difficult to clearly identify an optimal procedure that can overcome issues associated with the CXL. This review provides an up-to-date analysis on clinical and laboratory findings of these popular crosslinking protocols used in the treatment of keratoconus. It is evident from this review that in general, these modified techniques have succeeded in minimizing the immediate complications of the C-CXL technique. However, there were contradictory viewpoints regarding their effectiveness when compared with the conventional technique. Therefore, these modified techniques need to be further investigated to arrive at an optimal treatment option for keratoconus.

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