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Updated: Sep 4, 2026

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Outcomes of the Sub400 Protocol and Contact Lens-Assisted Corneal Cross-Linking in Advanced Thin-Cornea Keratoconus:
Emine Esra Karaca1, Yonca Asfuroğlu2, Döndü Melek Ulusoy2
1Department of Ophthalmology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey; and.
Purpose:
To compare the clinical outcomes of the sub400 protocol and contact lens-assisted corneal cross-linking (CACXL) in patients with keratoconus with corneal thickness below 400 μm.
Methods:
This retrospective study included 88 eyes of 88 patients with progressive keratoconus and thinnest pachymetry <400 μm. Group 1 (n = 50) underwent sub400 CXL using individualized fluence at 3 mW/cm2, whereas group 2 (n = 38) received CACXL with 10 mW/cm2 for 9 minutes after functional pachymetry was increased above 400 μm using a riboflavin-soaked contact lens. Outcomes at 12 months included corrected distance visual acuity, keratometric parameters, thinnest corneal thickness, demarcation line (DL) depth, endothelial cell density, and progression rate.
Results:
Twelve months after surgery, tomographic stability was maintained in 45 of 50 eyes (90%) in the sub400 CXL group and in 33 of 38 eyes (86.8%) in the CACXL group. No eyes in both groups showed signs of endothelial decompensation. DL depth was significantly greater in the CACXL group (296.32 ± 43.22 μm) than in the sub400 group (266.44 ± 48.63 μm; P = 0.002), with a negative correlation between baseline Kmax and DL depth (ρ = -0.226, P = 0.034). No significant changes were observed in Kmax, Kmean, or postoperative thinnest corneal thickness in both groups (P > 0.05).
Conclusions:
Sub400 and CACXL provide similar short-term efficacy and endothelial safety in thin corneas. CACXL achieves deeper stromal penetration, although without superior 12-month visual or topographic outcomes. Longer-term studies are needed to determine whether greater DL depth yields sustained biomechanical or refractive benefits.