Vitamin E TPGS-enhanced riboflavin accelerated transepithelial cross-linking versus accelerated epithelium-off protocol in progressive keratoconus: a prospective randomized trial.

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.