Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis

Abstract

The aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus. Methods A retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively. Results Sixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and K max significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, K max was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) μm after C-CXL, and at (251.2 ± 28.1) μm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups. Conclusion EI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol. Keywords Progressive keratoconus. Iontophoresis. Transepithelial corneal crosslinking. Tomography. In vivo confocal scanning microscopy Key message Most previous data revealed inferior efficacy of transepithelial corneal crosslinking assisted by iontophoresis when compared to conventional corneal crosslinking. The limited riboflavin penetration into the corneal stroma is considered as one of the critical inadequacies of standard transepithelial iontophoresis. In this retrospective five-year analysis, no significant differences of the long-term refractive and visual outcome were found between conventional corneal crosslinking and transepithelial corneal crosslinking assisted by two continuous cycles of iontophoresis. Improved stromal penetration depth was achieved by two continuous cycles of iontophoresis.

Transepithelial Iontophoresis-Assisted Cross Linking for Progressive Keratoconus: Up to 7 Years of Follow Up

“…To the authors' knowledge, this is the first study to report very long-term follow-up of I-CXL since most of the reports showed a maximum of 3 years of follow-up with little or no evidence of progression [15,17,18]. Wu et al partially concurs with our manuscript and shows a 11% progression rate at 5 years, nevertheless with no clear definition of progression [20].…”

“…Furthermore, the latter used a different protocol compared to the one that we presented and that is suggested by the manufacturer. As a matter of fact, instead of the standard iontophoretic current of 5 mA/5 min, they used two continuous cycles of 5 mA/5 min (total 10 mA/10) minutes [20].…”

“…Many mid-term reports showed the efficacy and safety of I-CXL even when compared to S-CXL [15][16][17][18][19]. A recent long-term study presented 5 years results; however, the published technique differs from the one suggested by the manufacturer (the authors used two continuous cycles of 5 mA/5 min) [20].…”

Advances in the diagnosis and treatment of keratoconus

“…Iontophoresis procedure was split into two cycles by another group allowing time for riboflavin to penetrate the deeper stromal layers. 49 Iontophoresis has also been found useful in an ex vivo rabbit eye model in increasing stromal penetration depth of rose bengal, another cross-linking agent that can only diffuse through the 100 to 125 µm of the corneal stroma with conventional approaches.…”

Analysis of Tear Function Outcomes following Collagen Cross-Linking Treatment in Ectatic Corneas

“…Various CXL protocols have been extensively investigated and applied [ 5 ], including epithelium-on (epi-on) and epithelium-off (epi-off) protocols with transepithelial riboflavin application. Both of these surgical methods are popular and well researched [ 6 , 7 ]. Although keratoconus is associated with dry eye [ 8 ], alterations in tear indices after any corneal procedure are of concern to the surgeon.…”