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Updated: May 19, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Transepithelial cross-linking in keratoconus patients: confocal analysis
Massimo Filippello1, Edoardo Stagni, Donato Buccoliero
1Clinica Di Stefano-Velona, Catania, Italy. m.filippello@gmail.com
Purpose:
To analyze the modifications of the corneal layers after transepithelial (TE) corneal cross-linking (CXL).
Methods:
Twenty eyes of 20 patients with progressive keratoconus were treated with TE-CXL (without epithelium debridement), and their corneas analyzed at different times, up to 18 months, by confocal microscopy using a Nidek Confoscan 4.
Results:
The epithelial layer, after an initial disorganization due to the TE technique, returned to a normal state after 2 weeks. Keratocytes and nerve fibers in the stroma decreased in number (approximately 25%), to return to a normal density at about 6 months after the procedure. A demarcation dense line indicative of effective cross-linking could be observed after 6 months at a depth of around 60 μm below the Bowman membrane. The endothelium remained unaffected at all examination times.
Conclusions:
The TE-CXL procedure appears to be safe and effective at least up to 18 months. The absence of epithelium debridement (necessary in the classical technique) makes the procedure more comfortable for the patient, and allows the treatment of thinner corneas (between 360 and 400 μm) and problematic patients.
Insights
Transepithelial corneal cross-linking (TE-CXL) is safe and effective for keratoconus up to 18 months. This procedure offers improved patient comfort and treats thinner corneas without epithelium removal.
Area of Science:
- Ophthalmology
- Corneal Surgery
- Biomaterials Science
Background:
- Keratoconus is a progressive thinning disorder of the cornea.
- Conventional corneal cross-linking (CXL) requires epithelium removal, which can be uncomfortable and limit treatment options.
- Transepithelial corneal cross-linking (TE-CXL) aims to improve patient comfort and expand treatment indications.
Purpose of the Study:
- To evaluate the corneal layer modifications following transepithelial corneal cross-linking (TE-CXL).
- To assess the safety and efficacy of TE-CXL in patients with progressive keratoconus.
Main Methods:
- Twenty eyes of 20 patients with progressive keratoconus underwent TE-CXL without epithelial debridement.
- Corneal changes were analyzed using confocal microscopy (Nidek Confoscan 4) up to 18 months post-procedure.
Main Results:
- The corneal epithelium initially disorganized but normalized within 2 weeks.
- Stromal keratocytes and nerve fibers decreased by ~25% but recovered density by 6 months.
- A distinct demarcation line at ~60 μm confirmed effective cross-linking; endothelium remained unaffected.
Conclusions:
- TE-CXL demonstrates safety and efficacy for keratoconus treatment up to 18 months.
- The epithelium-sparing approach enhances patient comfort and enables treatment of thinner corneas (360-400 μm).
- TE-CXL is a viable alternative for patients unsuitable for conventional CXL.
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