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Updated: Dec 25, 2025

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Prospective two year study of changes in corneal density following transepithelial pulsed, epithelium-off continuous
Mohammed Ziaei1, Akilesh Gokul1, Hans Vellara1
1Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Purpose:
To compare the corneal densitometry changes after transepithelial pulsed (t-ACXL), epithelium-off continuous (c-ACXL) and epithelium-off pulsed (p-ACXL), accelerated corneal crosslinking for patients with progressive keratoconus.
Methods:
Prospective, interventional case series at a university hospital tertiary referral center. Forty eyes received t-ACXL, 40 eyes received c-ACXL, and 40 eyes received p-ACXL. Corneal tomography, densitometry and visual acuity were evaluated preoperatively and at 1, 3, 6, 12 and 24 months postoperatively.
Results:
Total densitometry values of the total layer over the annular diameters 0-12 mm expressed in grayscale units (GSU) showed no significant change after t-ACXL and p-ACXL but increased significantly after c-ACXL at 1 month (16.76 ± 2.38, P value < 0.01) and 3 months (16.12 ± 2.22, P value 0.04), returning to baseline levels at month 6 (14.97 ± 2.13, P value 0.99) and remained stable until final follow-up. At 1 month, the mean change in total densitometry value of the t-ACXL group (-0.53 ± 2.08) was significantly lower than the p-ACXL (0.70 ± 1.96 P value 0.04) and c-ACXL (1.97 ± 2.65 P value < 0.01). There was no statistical difference in the mean change in total densitometry between the three groups from 6 to 24 months. In the c-ACXL group, a higher degree of CXL-induced corneal haze at 1 month was observed in patients with steeper preoperative keratometry readings and in individuals where a greater flattening effect was achieved at 24 months.
Conclusions:
Continuous epithelium-off accelerated cornea crosslinking appears to induce more corneal haze than pulsed epithelium-off and transepithelial pulsed cornea crosslinking in the early postoperative period. Differences resolve by six-months.

