Over the past decade, treatment of corneal ectatic diseases has fundamentally changed due to the introduction of corneal cross-linking. A number of former studies presented the beneficial effects of CXL [20, 24, 25]. Based on these results, treating of keratoconus with standard epithelium-off cross-linking seems to be safe and effective surgical technique. However, most of the available research provides results within two or three years after treatment. Existing literure of longer outcomes of conventional CXL is still limited. The goal of this study was to assess visual outcomes and corneal changes 6 years after conventional corneal cross-linking in patients with progressive keratoconus.
In the present study, enrolled patients were followed by a relatively long period of time (6 years), allowing for a potentially valuable analysis of the outcomes of conventional cross-linking using UV-A light at 3 mW/cm2 irradiace intensity with 370 ± 5 nm wavelength performed according to standard Dresden protocol.
In our study, SE, UCDVA and BCDVA improved significantly in the first postoperative year and remained stabile without any further significant changes between the subsequent visits up to 6 years. Outcomes of our analysis confirmed the results of several long-term studies, which assumed that CXL improves visual acuity [26–28]. Although in these studies, values were compared between different timepoints and baseline examination, thus, it was not revealed whether there was any further significant change between consecutive visits. Based on detailed statistical analyis between each visits, both Shaheen et al. and O’Brart et al. stated that significant visual and refractive improvement can occur even after the first postoperative year after CXL [29, 30]. Imrovement in SE and visual acuity is a consequence of more regularized corneal surface, which is indicated by reduced keratometry and improved topographic indices in our analysis. However, further continous significant improvement was found in some of these latter parameters in our data, results suggest that the extent of changes in keratometry and topographic indices did not generate further improvement in refraction and visual acuity after the first postoperative year in our cohort. Thus, according to our findigs, final visual and refractive ourcomes can be achieved until the end of the first postoperative year. In some recent studies, authors found deterioration in a few percent of involved eyes [29, 31]. Similarly, 2.9% of treated eyes had more than two-line-loss 6 years after CXL in our series. However, severe corneal scarring was not detected in any patients, cellular changes in the corneal stroma may induce increased scattering and changes in transparency, which might be related to visual loss. Although, the greater percent of treated eyes showed stabilization or improvement of visual acuity, the possibility of visual deterioration after treatment confirms that corneal cross-linking should only be performed on patients with documented progression of keratoconus as recommended in the literature for this treatment [32]. Further studies are warranted to determine the expectable changes in visual acuity and find those patients who have increased risk for visual loss in long-term after CXL.
In our series, both central and thinnest corneal pachymetry showed the greatest reduction in the first postoperative year. Measured at thinnest point of the cornea, pachymetry showed further thinning up to 3 years. Cellular changes after CXL, i.e. more compacted structure of collagen fibrils have an impact on pachymetry and may result in corneal thinning [33]. Meanwhile, findings about the evolution of corneal thickness after cross-linking are controversial. Greenstein et al. found that corneal thickness decreases after treatment, but later it recovers to preoperative values [33]. In contrast, Vinciguerra et al. found significant decrease in corneal thickness after CXL, but no recovering tendency [21]. According to our results, pachymetry did not change after 3 years, suggesting that the structure of the corneal stroma is stabilized thereafter.
In agreement with the results of previous studies [24, 30, 34], significant decrease in keratometry readings was observed after the treatment in our analysis. Flattening effect of CXL was most pronounced in the first postoperative year, although it was found to be continued even after the third postoperative year up to 6 year. Nicula et al. observed progressive decrease in maximum and average keratometry up to 10 years postoperatively [27]. In an other previous long-term study, similar tendency in improvement of keratometry readings was also obseved with significant decrease 1 year postoperatively, maintained up to 7 years [29]. The authors suggested that long-term topographic changes are not only due to CXL, but also increasing age-related corneal stiffness can modify corneal reshaping [29]. So far, the processes influencing changes of the corneal structure after conventional CXL in long term are unclear, but it has been confirmed by our results as well that corneal curvature changes can occur even several years after therapy. This change in curvature should be taking into consideration even long time after CXL in patients who require contact lens fitting. In the current series, none of the eyes had increasing keratometry values over follow-up period, confirming the long-term stabilization effect of CXL.
Findings of our study showed significant improvement of ISV, IVA, KI, CKI and Rmin in the first postoperative year. Greentstein et al. observed very similar results demonstrating improvement in ISV, IVA, KI and Rmin with a follow up of 12 months [35]. Koller et. al found significant improvement in KI, CKI, Rmin and IHA during the same follow-up period [13]. According to the study of Toprak et al., ISV, CKI and Rmin improved after conventional cross-linking [36]. In spite of the different findings, improvement of these indices mirrors that the corneal front surface become more optically reagular after CXL treatment. In addition, in this study, further improvement of ISV, CKI and Rmin was revealed up to 3 years. Moreover, the latter had additional improvement up to the end of the follow-up period, which is in consistent with our findings of continued decrease of keratometry in long-term. Meanwhile, no significant changes were observed in the remained two indices, i.e. IHD and IHA, suggesting postoperative stabilization of these values. Topographic indices are elevated in keratoconic eyes (except for Rmin, which showes decreased values in ectatic disorders) [35]. Improvement of ISV means decrease in deviation of corneal radii from the median value, which represents a more regularized corneal surface. Improvement of IVA indicates more symmetrical shape of anterior corneal surface with respect to horizontal meridian. Decrease of KI and CKI is in strong relationship with decrease of keratometry, thus, represents the regularization of keratoconic topography and improvement of the asymmetry between central and peripheral parts. Finally, increase of Rmin is related to flattening of the maximum steepness of the cone. Overall, comprehensive analysis of topographic indices suggests an optically more regular and symmetric corneal surface with flattening of the cone. To the best of our knowledge, our study is the first in the literature that presents data of topographic indices measured by Pentacam with the long follow-up period.
In the present study, we assessed refractive and visual outcomes, keratometry, pachymetry and topographic indices after conventional corneal cross-linking. However, our study has some main limitations. A prospective study with larger number of involved patients could provide more accurate results regarding data. Furthermore, detailed long-term evaluation also of the features of the posterior corneal surface and corneal densitometry would specify corneal changes after CXL more precisely. In addition, estimation of potential long-term visual outcomes and corneal flattening based on preoperative parameters would provide useful information for clinicians in predicting postoperative outcomes, therefore further studies are warranted.