Table. Randomized controlled trials on cross-linking (CXL, Dresdner protocol) in keratoconus.
| Study | Patient number | Follow-up (months) | Age (mean)(years) | Intervention | Outcome | Primary endpoint | Limitations | Complications | Evidence level |
| O’Brart et al., 2011 (27) |
24 | 18 | 29.6 | Same patients with one eye as control, one eye CXL | Statistically significant effect of cross-linking on the change in maximum topographic K-reading | Mean change in Ksim at 18 months CXL: –0.66 D Control: +0.14 D |
Interdependence of eyes if both patient eyes included, no sham treatment | One Patient with temporary recurrent erosion | Ib |
| Hersh et al., 2011 (28) |
59 | 12 | n.s. | 28 patients sham-treated, 31 patients CXL, crossover pos‧sible after 3 months | Best-corrected visual acuity and Kmax were significantly better than baseline findings and control group findings | Mean change in Kmax after 12 months CXL: –2.0 ± 4.4 D Control: Not specified due to crossover |
Crossover design, only small number of patients in the control group for the analysis | Not specified | Ib |
| Wittig-Silva et al., 2014 (23) |
100 Eyes | 36 | 25.7 | 50 control eyes, 50 CLX eyes, in some cases both patient eyes randomized | Statistically significant difference in maximum corneal refractive power and uncorrected visual acuity | Mean change in Kmax after 36 months CXL: –1.03 ± 0.19 D Control: +1.75 ± 0.38 D |
Interdependence of eyes if both patient eyes included, no sham treatment | Two sterile temporary infiltrates with no permanent damage | Ib |
| Lang et al., 2015 (29) |
29 | 36 | 29.5 | 14 sham-treatedpatients, 15 CXL patients | Statistically significant effect of cross-linking on the change in maximum topographic K-reading | Mean change in Kmax after 36 months CXL: –0.35 ± 0.58 D Control: +0.11 ± 0.61 D |
Low patient number (weak power) | Temporary corneal opacities (haze) and complete remission | Ib |
| Seyedian et al., 2015 (30) |
26 | 12 | 25.6 | Same patients with one eye as control, one eye CXL | Statistically significant effect of cross-linking on the change in maximum topographic K-reading | Mean change in Kmax after 12 months CXL: –0.22 ± 0.6 D Control: +0.41 ± 0.74 D |
Interdependence of eyes if both patient eyes included, no sham treatment | Temporary corneal opacities (haze) and complete remission | Ib |
| Hersh et al., 2017 (31) |
205 | 12 | 33.0 | 102 CXL; 103 sham-treated patients | Statistically significant effect of cross-linking on the change in maximum topographic K-reading and corrected visual acuity | Kmax after 12 months CXL: –1.6 ± 4.2 D Control: +1.0 ± 5.1 D |
High drop-out rate, summary of two independent studies (published in part in Hersh et al. 2011 [28], see above), crossover ‧design, only a small number of patients in the control group (n = 2) for the analysis | Short term: one patient with ulcerative keratitis; long term: persistent corneal opacities (haze) in two eyes, ‧endothelial folds in one eye; corneal scarring in one eye, irregular epithelium in one eye | Ib |
CXL = cross-linking; n. s.= not specified; Kmax = maximum keratometry reading; Control = control group; Ksim = simulated ketatometry