EyeWorld Asia-Pacific December 2017 Issue

December 2017 EWAP SECONDARY FEATURE 43 included a 2-minute and 40-sec- ond treatment, a 4-minute treat- ment, and an 8-minute treatment. The patients we followed seemed to do well in all treatment groups. I do not have a sense that any one protocol worked better than the other,” Dr. Rapuano said. “The faster/higher intensity treatments were easier for the patients than the current 30-minute treatments. On the other hand, if the patient was a little skittish and kept look- ing around during a short treat- ment, with the light not centered on the cornea for 10–20 seconds, we could have lost 10% of our treatment, whereas almost noth- ing gets lost in a 30-minute treat- ment. I think that I am getting a more consistent treatment with a 30-minute protocol and less vari- ability. But there is no doubt that a shorter treatment would be ben- eficial. I think a 10-minute proto- col might be a happy medium.” Accelerated CXL uses 30 mW/ cm 2 for a 3-minute duration and is based the Bunsen-Roscoe law of reciprocity that assumes a constant radiant exposure of 5.4 J/cm 2 . Although a number of current studies are using acceler- ated protocols with encouraging results, it is too early to evaluate the short-term outcomes. “We need to see results for at least 1 year. Anything else is too early,” Dr. Rapuano said. “You can see complications in a lot less than a year but not the efficacy of the procedure. It is best to follow out- comes for 5 years to understand if the keratometry readings look stable, like the Kmax, but also astigmatism and corneal thick- ness. You want Kmax and cylinder to be similar to their preoperative value, if not a little bit less, and thickness should be similar and not thinning over time.” Faster/higher intensity treat- ments may not be the answer to improving CXL protocols. A re- port that evaluated studies using different higher intensity proto- cols on corneal stiffening found a failure of the Bunsen-Roscoe law of reciprocity for short illumina- tion time and high intensities, probably due to the complex photochemistry involved in CXL. 6 The same report discussed the role of oxygen consumption in higher intensity treatments, which was consumed too quickly with new oxygen not able to diffuse into the stroma. The report main- tained that the clinical benefits of increasing the intensity and reducing the treatment time were still not known, claiming that one might even expect reduced effi- cacy based on the in vitro results. The report concluded that higher intensity treatments of more than 10 mW/cm 2 had a reduced bio- mechanical effect compared to the standard protocol of 3 mW/ cm 2 for 30 minutes. Based on the evidence, a reduction in the treat- ment time by simply increasing the intensity might not lead to the same level of efficacy of stop- ping the progression of corneal ectasia. In contrast to this study, Dr. Kanellopoulos has found that fast- er/ higher intensity protocols can be beneficial. “One of our studies looked at in vitro human corneas, not porcine corneas, showing that fluences of 3–30 mW/cm 2 gave a similar crosslinking effect when saline-based riboflavin was used, and fluences more than 30 mW/ cm 2 appeared to have no differ- ence in effect and in sham. Spe- cifically, the 45 mW/cm 2 fluence showed no difference in sham,” he said. More studies with long- term results are needed to further validate these data. Post-refractive use Relevant to many medical prac- tices is the use of corneal CXL in post-refractive patients. According to Dr. Kanellopoulos, “The ap- plication of corneal crosslinking and corneal laser surgery has been considered experimental. Howev- er, there have been several in vivo and in vitro studies establishing the crosslinking effect of higher fluence crosslinking applied in combination with LASIK. Also, evaluating this model in vitro and using bidirectional tensiometry showed that higher fluence CXL on the stromal bed in human corneas that were subjected to femto LASIK of –8 D increased the cornea rigidity over 100% and had no effect on the flap versus controls. The control cases showed a significant decrease in cornea stability due to the tissue removal.” Dr. Kanellopoulos said both prospective clinical studies and laboratory simulations provide significant evidence that higher fluence and routine LASIK can increase the adhesion between the LASIK flap and the underlying stromal bed and may significantly reinforce the underlying stromal bed rigidity. “This may be consid- ered the single most adverse effect as far as cornea biomechanics and LASIK procedures are concerned, which to date is the most com- mon laser refractive surgery pro- cedure performed in the cornea,” he said. EWAP References 1. Kanellopoulos AJ, et al. Management of corneal ectasia after LASIK with combined, same-day, topography-guided partial tran- sepithelial PRK and collagen crosslink- ing: the Athens protocol. J Refract Surg. 2011;27:323–31. 2. Kanellopoulos AJ, et al. Revisiting kera- toconus diagnosis and progression classifi- cation based on evaluation of corneal asym- metry indices, derived from Scheimpflug imaging in keratoconic and suspect cases. Clin Ophthalmol. 2013;7:1539–48. 3. Kanellopoulos AJ, et al. Keratoconus management: long-term stability of topog- raphy-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol). J Refract Surg. 2014;30:88–93. 4. Gomes JA, et al. Global consensus on keratoconus and ectatic diseases. Cornea . 2015;34:359–69. 5. Kanellopoulos AJ, et al. Collagen cross- linking (CCL) with sequential topography- guided PRK: a temporizing alternative for keratoconus to penetrating keratoplasty. Cornea. 2007;26:891–5. 6. Mrochen M. Current status of acceler- ated corneal cross-linking. Indian J Oph- thalmol . 2013;61:428–9. Editors’ note: Dr. Rapuano has financial interests with Avedro. Dr. Kanellopoulos has no financial inter- ests related to his comments. Contact information Kanellopoulos: thanos@laservision.gr Rapuano: cjrapuano@willseye.org