Study of the use of collagen crosslinking with riboflavin has been limited. Early experience with this technique, however, suggests it safely increases corneal rigidity and limits ectasia progression.
New Orleans-Experience using collagen crosslinking with riboflavin (C3R) for the treatment of post-refractive surgery ectasia is early, but the available evidence suggests it may be a useful modality and is probably better if performed earlier rather than later, said Sheraz M. Daya, MD, at the refractive surgery subspecialty day at the annual meeting of the American Academy of Ophthalmology.
"Reports to date show C3R is effective for improving corneal stability and reducing the progression of ectasia, and it appears safe based on measurement of endothelial cell counts and laboratory studies investigating the potential toxicities of exposure to ultraviolet-A (UVA) light," said Dr Daya, director and consultant, Corneoplastic Unit and Eye bank, Queen Victoria Hospital, East Grinstead, and medical director, Centre for Sight, London and East Grinstead, UK.
The goal of C3R is to improve the tensile strength of the cornea and arrest the process of ectasia, and that is achieved by promoting formation of covalent bonds between collagen fibers. Riboflavin is applied topically and serves as a photomediator. After absorbing UVA light, the riboflavin promotes formation of free radicals that leads to an increase in covalent bonds between the collagen fibers. Studies in human corneas document that the crosslinking results in an increase in tissue tensile strength, said Dr. Daya.
"As reported by Wollensak et al., the crosslinking resulted in a 328% increase in stress testing and a 4.5-fold increase in Young's modulus," he explained.
With currently used treatment parameters, maximal effects of the procedure are limited to the anterior 300 µm of the cornea. Although UVA light may cause keratocyte apoptosis and macular damage, the current dose of 3 mW/cm2 is considered safe.
Because riboflavin is a large molecule, it does not penetrate the epithelial tight junctions when applied to the ocular surface. To ensure that the riboflavin reaches its target site in the stroma, it is necessary to disrupt the tight junctions chemically, such as with the use of tetracaine drops, or to remove or disrupt the epithelium.
Describing his own technique, Dr. Daya said he uses a disrupting device he designed (Daya Epithelial Disruptor, Duckworth and Kent) that features a series of concentric spikes to pockmark the epithelial surface.
"The puncturing is performed on an anesthetized cornea, and with this protocol, there is no need to remove the epithelium to facilitate riboflavin penetration," he said.
Riboflavin drops (0.1% riboflavin in 20% dextran) are applied at 5-minute intervals over a period of 30 minutes, although Dr. Daya noted that adequate delivery can be achieved with less frequent instillation if the patient keeps the eyes closed and is lying supine. Confirmation that the absorption of riboflavin is sufficient is performed through slit-lamp evaluation to check that the cornea is stained yellow and riboflavin is present in the anterior chamber.
Exposure to the high UVA energy can damage the endothelium if the cornea is thinner than 400 µm. The C3R, however, still can be performed in such eyes with use of a dextran-free riboflavin solution, which is hypotonic and absorbed by the cornea, causing it to thicken. Corneal thickness is measured sequentially, and the treatment with the UVA light can be performed once the central thickness reaches 400 µm, Dr. Daya said.
Dr Daya uses an illumination system for corneal crosslinking (Peschke UV-X, Peschke Meditrade) to deliver UVA light at 370 nm with an irradiance of 3 mW/cm2.
"It is important that the device used for UVA irradiation can be calibrated to deliver the proper irradiance," he noted.
Post-treatment, the eye is covered with a bandage contact lens and treated with topical levofloxacin. The fluoroquinolone drops are coninued four times a day, and patients return after 24 to 48 hours for contact lens removal.
Dr. Daya's experience supports a role for C3R in the treatment of post-LASIK ectasia. He reported that he has performed this procedure in nine eyes of patients with a mean age of 35 years. Overall, mean keratometry declined over time as did mean astigmatism. Mean UCVA and BSCVA remained relatively unchanged, although the number of patients who benefited with an increase in BSCVA exceeded those with any loss in lines of BSCVA. Corneal pachymetry was decreased, but the change was not statistically significant, and no significant change in endothelial cell count was seen.
"The decrease in corneal thickness might be expected as a result of collagen fibril thickening and consequent shortening as well as a transient loss of keratocytes," he noted.