ACCELERATED CROSS-LINKING

With the aim of reducing treatment time and increasing the throughput of patients, investigators are now considering the use of higher illumination intensities in the cross-linking procedure. In the standard cross-linking (SCXL) procedure 3 mWcm-2 is applied to the central 9mm of the cornea for 30 minutes, resulting in a total energy dose of 3.4 J or a radiant exposure of 5.4 Jcm-2. However, this same level of radiant exposure can be achieved by applying a higher intensity for a shorter time.  Laboratory studies on pig corneas showed that increasing the illuminance intensity to 9 mWcm-2 and reducing the exposure time to 10 minutes for an accelerated cross-linking (ACXL) procedure produced a similar increase in corneal stiffness and resistance to enzymatic digestion to that gained using the standard procedure [1-2] .  The safety of using higher intensities (up to 30 mWcm-2) in vivo has produced varying results. Konstantopoulos and Mehta [3] compared three protocols of CXL, and concluded that ACXL using 9 mW/cm2 for 10 minutes and 7 mW/cm2 for 15 minutes may be as efficacious as SCXL.  However, Shetty et al. [4] reported that at 6-months follow-up the flattening effect was better in patients treated with SCXL compared to those treated using ACXL protocols of 9 mW/cm2 for 10 minutes, 18 mW/cm2 for 5 minutes, and 30 mW/cm2 for 3 minutes. A meta-analysis of eleven clinical trials has revealed that overall, SCXL appears to have a greater effect than ACXL in terms of stabalising corneal topography but ACXL results in less reduction in corneal thickness [5].

[1] Schumacher, S. et al. Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Investigative Ophthalmology & Visual Science 2011; 52: 9048–9052.

[2] Aldahlawi NH, et al. Standard versus accelerated riboflavin-ultraviolet collagen crosslinking: resistance against enzymatic digestion. Investigative Ophthalmology & Visual Science 2015; 41:1989-96.

[3] Konstantopoulos A, Mehta JS. Conventional versus accelerated collagen cross-linking for keratoconus. Eye Contact Lens. 2015; 41: 65–71.

[4] Shetty R, Nagaraja H, Jayadev C, et al. Accelerated corneal collagen cross-linking in pediatric patients: two-year follow-up results. Biomed Res Int. 2014; 2014: 894095.

[5] Wen D., et al. Comparison of Standard Versus Accelerated Corneal Collagen Cross-Linking for Keratoconus: A Meta-Analysis. Investigative Ophthalmology & Visual Science 2018, 59: 3920-3931