Chemically-Boosted Corneal Cross-Linking for the Treatment of Keratoconus through a Riboflavin 0.25% Optimized Solution with High Superoxide Anion Release

Abstract

The purpose of this study was to evaluate the effectiveness and safety of a novel buffered riboflavin solution approved for corneal cross-linking (CXL) in progressive keratoconus and secondary corneal ectasia. Following the in vivo preclinical study performed on New Zealand rabbits comparing the novel 0.25% riboflavin solution (Safecross®) containing 1% hydroxypropyl methylcellulose (HPMC) with a 0.25% riboflavin solution containing 0.10% EDTA, accelerated epithelium-off CXL was performed on 10 patients (10 eyes treated, with the contralateral eye used as control) through UV-A at a power setting of 9 mW/cm2 with a total dose of 5.4 J/cm2. Re-epithelialization was evaluated in the postoperative 7 days by fluorescein dye test at biomicroscopy; endothelial cell count and morphology (ECD) were analyzed by specular microscopy at the 1st and 6th month of follow-up and demarcation line depth (DLD) measured by anterior segment optical coherence tomography (AS-OCT) one month after the treatment. We observed complete re-epithelization in all eyes between 72 and 96 h after surgery (88 h on average). ECD and morphology remained unchanged in all eyes. DLD was detected at a mean depth of 362 ± 50 µm, 20% over solutions with equivalent dosage. SafeCross® riboflavin solution chemically-boosted corneal cross-linking seems to optimize CXL oxidative reaction by higher superoxide anion release, improving DLD by a factor of 20%, without adverse events for corneal endothelium.

Enhanced Trans-Epithelial Accelerated Crosslinking Protocols: The Way Out of Future CXL

“…While corneal cross-linking can occur both under anaerobic (photodynamic Type II pathway) and aerobic (Type I pathway) conditions, the aerobic pathway seems to be more efficient in generating reactive oxygen species x molecule of riboflavin, by re-oxidizing reduced riboflavin to its original state [28]. Reaching and maintaining an adequate oxygen concentration throughout the whole corneal volume is desirable in order to carry-out a more efficient oxygen of CXL [27,[29][30][31]34]. That of oxygen concentration represents of course an important issue in case of epithelium-on procedures.…”

“…Besides riboflavin issues, there are other important determinants for an efficient by a photochemical point of view and a clinically efficacious corneal cross-linking requiring compensation in relation to the principles of photochemistry: the total energy dose (fluence) delivered to the stroma through the epithelium in situ; epithelium oxygen metabolic consumption; intra-stromal oxygen availability, diffusion and reactive oxygen species availability enabling crosslinking reaction. The compensation levels adopted to increase the overall efficiency and clinical outcome of modern trans-epithelial higher energies ACXL treatments [23,24,31] are displayed in Table 2.…”

“…Recently new techniques and strategies have been proposed [23,24,31] that are reducing the gap of efficacy with the Epi-off treatments as showed in Table 1. Moreover, we have tested a new protocol named Enhanced Fluence Pulsed Light M (Mazzotta) trans-epithelial CXL without iontophoresis mediated riboflavin soaking and without supplemental oxygen (EFPL-M-TECXL), adopting a higher Fluence of 7 J/cm 2 for a UV-A exposure time of 12 minutes and 58 seconds-Pulsed Light (1 sec on 1 sec off cycle)-UV-A Power 18mW/cm 2 , as in the same way as the new enhanced Fluence pulsed light iontophoresis (EFPL I-CXL) [23,24] without using the iontophoresis and without adding intraoperative oxygen supplement, with the advantage of additional simplification of the procedure, improving patient comfort and reducing costs, thus requiring no adjunctive kits and being less invasive and completely feasible in outpatient modality.…”

Comparative Results Between “Epi-Off” Accelerated and “Epi-Off” Standard Corneal Collagen Crosslinking-UVA in Progressive Keratoconus – 7 Years of Follow-Up

“…18 A recent preliminary study revealed the efficacy and safety of this solution in addition to the potential prevention of endothelium-toxic damage. 19 Up to now, the CXL procedure is the only method to stop KCN progression. In order to reduce the time of the procedure, to improve convenience and comfort of the patients, the accelerated "epi-off" CXL technique performed in a pulsed or a continuous manner was introduced.…”

“… 18 A recent preliminary study revealed the efficacy and safety of this solution in addition to the potential prevention of endothelium-toxic damage. 19 …”