Prospective two year study of changes in corneal density following transepithelial pulsed, epithelium-off continuous and epithelium-off pulsed, corneal crosslinking for keratoconus

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.