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Updated: Dec 12, 2025

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Epi-off-lenticule-on corneal collagen cross-linking in thin keratoconic corneas
Carlo Cagini1, F Riccitelli2, M Messina2
1Department of Biomedical and Surgical Sciences, Ophthalmology Section, University of Perugia, Perugia, Italy. carlo.cagini@unipg.it.
Purpose:
To evaluate the safety and efficacy of corneal collagen cross-linking (CXL) performed on overlaying a corneal lenticule to thin recipient corneas of progressive keratoconus (KC) patients.
Methods:
In this study were enrolled eyes of patients affected by progressive KC with a minimum corneal thickness less than 400 µm, after overlaying a lenticule of human corneal stroma prepared with the femtosecond laser. The lenticules used were 100 µm thick and of 8.5 mm diameter in all the cases. Both the host cornea and the lenticules were subjected to epithelial debridement. CXL was carried out according to the standard protocol. Visual acuity, refraction, slit-lamp examination, endothelial cell density, pachymetry and keratometry, anterior segment tomography (AS-OCT) and confocal microscopy were evaluated preoperatively and at 1, 3, 6 and 12 months postoperatively.
Results:
CXL was performed in 10 eyes of 8 patients (main age 23), corneal thickness range 379-414 µm, mean 387.6 µm. One patient was lost at follow-up. In all other cases, visual acuity and the endothelial cell density remained stable over a 12-month follow-up. Preoperative mean K1 and mean K2 were 46.91 ± 1.9 and 50.75 ± 2.93, respectively, and at 12 months mean K1 was 47.36 ± 2.66 and mean K2 50.53 ± 3.35. The AS-OCT clearly showed a demarcation line in all patients at 1, 3 (mean depth 283 µm and 267 µm, respectively) and in some cases at 6 months. Reduced keratocyte density and stromal oedema were observed immediately up to 1 month after treatment, while a slight subepithelial haze was present at 1-month and completely disappeared by 6 months.
Conclusion:
This new technique seems to offer a therapeutic opportunity for young patients suffering from progressive KC with very thin corneas, in which the standard treatment is not indicate, and delay or avoid the need for a corneal transplant.
Insights
This study shows that overlaying a corneal lenticule before corneal collagen cross-linking (CXL) is a safe and effective treatment for progressive keratoconus (KC) in thin corneas. This innovative CXL technique offers a new therapeutic option, potentially delaying or preventing the need for a corneal transplant in young patients.
Area of Science:
- Ophthalmology
- Corneal Surgery
- Biomaterials Science
Background:
- Progressive keratoconus (KC) in patients with thin corneas (<400 µm) presents a challenge for standard treatments.
- Corneal collagen cross-linking (CXL) is a standard procedure to halt KC progression, but its application is limited in very thin corneas.
Purpose of the Study:
- To evaluate the safety and efficacy of a novel CXL technique.
- This technique involves overlaying a corneal lenticule onto thin recipient corneas of progressive KC patients.
Main Methods:
- Eyes of progressive KC patients with thin corneas (<400 µm) underwent CXL after overlaying a 100 µm thick femtosecond laser-prepared corneal lenticule.
- Standard CXL protocol was applied to both host cornea and lenticule after epithelial debridement.
- Preoperative and 12-month postoperative evaluations included visual acuity, refraction, pachymetry, keratometry, endothelial cell density, AS-OCT, and confocal microscopy.
Main Results:
- CXL was successfully performed in 9 out of 10 eyes (mean corneal thickness 387.6 µm).
- Visual acuity and endothelial cell density remained stable over 12 months.
- Anterior segment OCT confirmed a demarcation line, and while transient stromal edema and reduced keratocyte density were noted, a subepithelial haze resolved by 6 months.
Conclusions:
- Overlaying a corneal lenticule before CXL is a viable therapeutic option for progressive KC in thin corneas.
- This technique may help delay or avoid corneal transplantation in young patients.
- It expands treatment possibilities for KC patients unsuitable for standard CXL.

