EyeWorld Asia-Pacific September 2020 Issue

REFRACTIVE 38 EWAP SEPTEMBER 2020 performed epi-on crosslinking with other parameters adjusted (supplemental oxygen, modified riboflavin drug, intensified UV light) to enhance the treatment’s effect as part of a clinical trial. “We’re hoping that with these modifications we can achieve an equal degree of crosslinking,” he said of the currently ongoing study. The draw of epi-on, Dr. Ciolino said, is not so much pain relief, but safety. There is a higher risk of complications taking the epithelium off. “I talk to my patients about the pros and cons, and the thing is they’re both painful. The pain lasts longer with epithelium off, but they’re both painful,” he said. Measuring biomechanical effect As of right now, there’s not a ready-to-use device to measure the stiffening effect in real time. But Dr. Dupps said work is being done toward this goal, using Brillouin microscopy and OCT- based methods including a non- contact method in development called phase-decorrelation OCT. He said having this information would allow physicians to turn off the treatment system when the desired effect is reached, minimizing risks and shortening procedure time. Dr. Dupps said there is an immediate stiffening effect with crosslinking that can be measured in the lab, but additional flattening happens after that, which can vary patient by patient. At 1 month, Dr. Ciolino said most patients have a drop in vision, but by 2–3 months their Lim Li, MD Senior consultant, Singapore National Eye Centre lim.li@singhealth.com.sg ASIA-PACIFIC PERSPECTIVES C orneal crosslinking (CXL) for the treatment of progressive keratoconus has come a long way since Wollensak and Seiler reported the first clinical study in 2003. Their protocol (known as the Dresden protocol, –5.4 J UVA irradiation at 3 mW/cm 2 for 30 minutes with riboflavin 0.1% corneal pre- soak for 30 minutes, epithelium off) obtained U.S. FDA approval in 2016. Since then, there have been numerous modifications to the Dresden protocol: to shorten the duration of the procedure(accelerated CXL), to improve the recovery process and reduce complications (epithelium-on techniques), and to improve the visual outcome (customized CXL, combined CXL with topography-guided photorefractive keratectomy). Although epithelial-on corneal crosslinking has advantages over epithelium-off techniques in terms of safety and pain relief, studies show that it is less effective than the epithelium- off techniques. The challenge for CXL therefore is to develop an epithelium-on protocol that has similar efficacy to the epithelium-off protocol. Recent modifications to improve the efficacy of the epithelium-on technique include the use of supplemental oxygen, high UVA energy, and modified riboflavin formulations to enhance epithelial penetration (figure 1). A phase 3 randomized controlled trial is currently being conducted in the U.S. to evaluate the safety and efficacy of this technique. Customized crosslinking is performed epithelium-on and involves delivering a customized topography- guided UVA energy to the cornea with more energy focused on the cone and less in the periphery. Initial studies using the Mosaic delivery system (KXL II, Avedro Inc.) showed improvements in the visual outcomes. 1,2 Another technique aimed at improving visual outcome in addition to strengthening the cornea is CXL combined with topography-guided photorefractive keratectomy. 3 Advances in crosslinking are closely tied to advances in tomographic and biomechanical devices such as Pentacam (Oculus Optikgeräte GmbH) and Corvis ST devices (Oculus Optikgeräte GmbH). The Pentacam and the Corvis ST contain inbuilt software (Belin/Ambrosio Ectasia display with BAD-D index, Belin’s ABCD new classification system and CBI/TBI indices) that are able to detect keratoconus with a high degree of sensitivity and specificity and will enable keratoconus detection and progression to be more accurately determined, enabling timely management with the appropriate type of crosslinking. The future for CXL is likely to evolve towards epithelium-on CXL with additional applications to improve visual outcome. References 1. Roberts CJ, Dupps WJ., Jr. Biomechanics of corneal ectasia and biomechanical treatments.  J Cataract Refract Surg. 2014;40:991–8. 2. Seiler TG, et al. Customized corneal cross-linking: One-year results. Am J Ophthalmol . 2016;166:14–21. 3. Kanellopoulos AJ, Asimellis G. Keratoconus management: long-term stability of topography-guided normalization combined with high-fluence CXL stabilization (the Athens Protocol).  J Refract Surg .  2014;30(5):342-346. Figure 1. Epithelium-on CXL with supplemental oxygen.