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Updated: Feb 28, 2026
Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis
Published on: November 12, 2015
Vitamin E TPGS-enhanced riboflavin accelerated transepithelial cross-linking versus accelerated epithelium-off
Parul Jain1, Pushkar Rangari2, Paromita Dutta2
1Department of Cornea, Refractive and Ocular Surface Services, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi, 110002, India. pjain811@gmail.com.
Purpose:
To compare the efficacy and safety of accelerated transepithelial (epi-on) corneal collagen cross-linking (CXL) using a Vitamin E D-α-tocopheryl polyethylene glycol succinate (TPGS)-enhanced riboflavin formulation with an accelerated epithelium-off (epi-off) CXL protocol in progressive keratoconus.
Design:
Prospective randomized comparative clinical trial.
Methods:
Fifty eyes of fifty patients aged 12-35 years with documented progressive keratoconus were randomized (1:1). In the epi-on group, 0.1% riboflavin enhanced with Vitamin E TPGS was used followed by UVA irradiation at 9 mW/cm2 for 10 min (total fluence 5.4 J/cm2). In the epi-off group, the epithelium was removed, the cornea was saturated with iso-osmolar 0.1% riboflavin, and identical UVA irradiation was applied. The primary outcome was change in maximum keratometry (Kmax) at 12 months. Secondary outcomes included UDVA, CDVA, refractive error, keratometric indices, corneal pachymetry, higher-order aberrations, stromal demarcation line depth, endothelial cell density, and safety parameters (infectious keratitis, persistent epithelial defect, clinically significant haze, endothelial decompensation, and sustained IOP rise requiring therapy).
Results:
Both groups showed significant improvement in UDVA/CDVA and significant flattening of keratometric parameters at 12 months (all intragroup p < 0.001). Mean corneal thickness behavior differed between groups, with relative pachymetric preservation in the epi-on arm compared with thinning in the epi-off arm (intergroup p < 0.05). Demarcation line depth was deeper in the epi-off arm (p < 0.001). No sight-threatening complications, endothelial decompensation, or sustained IOP elevation were observed in either group.
Conclusions:
At 12 months, accelerated transepithelial CXL using a Vitamin E TPGS-enhanced riboflavin formulation demonstrated visual and tomographic stabilization comparable to accelerated epi-off CXL.
Clinical Trial Registration:
CTRI /2024/06/069279.
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