Corneal collagen cross-linking (CXL) was first introduced by Wollensak and colleagues
27 with an ultraviolet-A (UVA) protocol of 3 mW/cm
2 intensity at 370 nm over an exposure time of 30 minutes (now termed the “Dresden protocol”). It uses the photochemical interaction of UVA and riboflavin (vitamin B2), to induce cross-links between corneal stromal macromolecules. Studies have reported that UVA absorption coefficient has a linear correlation with the concentrations of riboflavin up to 0% to 0.5%, suggesting that different riboflavin concentrations may impact clinical outcomes.
28–30 CXL has been proved in its effectiveness and safety in halting the progression of keratoconus and improving topographic and visual parameters in numerous prospective, published studies, including randomized controlled trials.
31–36 However, given the prolonged irradiation time of this standard CXL (SCXL) protocol, with total treatment times in excess of 1 hour, researchers have proposed accelerated CXL (ACXL) protocols, to improve convenience and comfort for patients. These ACXL protocols have the aim of decreasing UVA exposure time by increasing UVA fluency to achieve the same overall total UVA dosage. According to the rule of Bunsen and Roscoe, a photochemical reaction is directly proportional to the total energy dose, irrespective of the time over which this dose is delivered.
37 At present the ACXL protocols are carried out in a shorter period such as 3, 5, or 10 minutes by using 30, 18, or 9 mW/cm
2 irradiance, respectively, with a cumulative irradiation dose of 5.4 J/cm
2. The shorter corneal exposure time of ACXL, it has been proposed, might have the potential advantages of reducing the rate of complications such as corneal thinning, haze, infection, and melting. However, it may affect efficacy.
38 Schumacher et al.
39 have found equivalent biomechanical responses between standard (3 mW/cm
2, 30 minutes) protocols and accelerated (10 mW/cm
2, 9 minutes) treatment protocols. Touboul and colleagues
40 have compared corneal alterations after standard and accelerated procedures (30 mW/cm
2 for 3 minutes) and found similar alterations in the subbasal nerve plexus and anterior stromal keratocytes. Numerous clinical studies have now been published to demonstrate the efficacy and safety of ACXL.
41–49 Shajari et al.
50 have compared conventional and accelerated CXL and found a significant difference in the D value (a value that involves anterior and posterior corneal elevation, corneal pachymetry, and progression of corneal thinning) with more favorable results for the conventional procedure. However, other studies have demonstrated that both procedures have a comparable effect in stabilizing keratometry.
51,52 It is of note that typically both SCXL and ACXL are generally preceded with epithelial removal (epithelium-off CXL), although investigations have been conducted to explore the potential influence on clinical outcomes between epithelium-off and transepithelial (epithelium-on) procedures using both SXCL and ACXL protocols.
53,54 In an attempt to try to clarify the potential benefits of CXL, we undertook this current meta-analysis to compare the effectiveness and safety of ACXL in comparison to SCXL.