CXL – what's next?

New enhancements to corneal crosslinking (CXL) techniques could help to overcome the disadvantages of the current standard protocols, according to a series of presenters at the 21st ESCRS Winter Meeting in Maastricht, The Netherlands. “CXL delivers excellent results in terms of halting the progression of keratoconus. However, we have begun to realise that many of our post-CXL patients do not achieve visual acuity improvement sufficient to provide functional vision, especially when they don’t tolerate contact lenses or spectacles,” said George Kymionis MD, Athens, Greece. Dr Kymionis described his approach, which he refers to as ‘CXL-plus’, which incorporates adjuvant refractive treatments in combination with CXL in an effort to provide both corneal stability and improved vision. “Tissue-saving approaches are an option, but we have been unable to achieve satisfactory outcomes. Intrastromal corneal ring segments followed by CXL delivers unpredictable results, while post-CXL toric phakic ICL implants are unable to treat the irregular astigmatism so frequently present in these patients,” he said. Dr Kymionis quickly moved to his preferred approach, simultaneous topography-guided photorefractive keratectomy (PRK) followed by CXL. He reminded the audience that the most accurate device in ophthalmology is the excimer laser. “The main advantage of this approach is that laser ablation does not interfere with the crosslinked cornea. This combination results in significant improvement in all parameters: keratometric values, spherical equivalent, defocus, uncorrected visual acuity and best corrected visual acuity,” said Dr Kymionis, adding that postoperative refractive stability has been demonstrated at five years post-surgery. A published report by Dr Kymionis’ team indicates that the mean steep and flat keratometry readings reduced by 2.35D and 1.18D, respectively. Complications include posterior linear stromal haze and mild grade 1 anterior stromal haze, which gradually becomes less dense over time. Considering the success of the PRK + CXL procedure in halting the progression of ectasia in keratoconus, Dr Kymionis addressed the use of CXL in refractive patients. “If we can successfully combine CXL with refractive surgery in keratoconic patients, why not combine the two in refractive patients in order to prevent iatrogenic ectasia?” he asked. The addition of CXL might compensate the biomechanical destabilisation caused by refractive surgery, particularly in light of our current inability to accurately detect high-risk corneas. “It sounds great, but we can’t forget that CXL has its own risks, such as corneal scarring, infiltrates, diffuse lamellar keratitis and endothelial cell damage. Further, how could we perform retreatments in these patients, as the ablation rate of a crosslinked cornea is different to that of a ‘virgin’ cornea,” he warned. When asked what the youngest treatable age is for combined PRK + CXL, Dr Kymionis reminded delegates that patient cooperation was essential, as the excimer laser procedure cannot be combined with general anaesthesia. That suggests 16 years is the minimum age. Beatrice Frueh MD, Bern, Switzerland, has extensive experience in treating children with CXL for keratoconus. “Standard, epi-off CXL is effective in arresting keratoconus progression in children. Progression after CXL in children is rare, although it can occur years after the procedure,” she said. Dr Frueh presented data of a prospective, five-year follow-up study of epi-off standard CXL in 23 eyes of 19 patients with a mean age of 14 years (4-17), which demonstrated flattened corneas and improved topographic indices. “There were no cases of scarring or haze. We had two cases of progression, both of which were retreated. Corrected distance visual acuity was unchanged in 16 patients and improved ≥ 2 lines in seven. However, there was a surprising, continual corneal thinning over these five years.” Mor Dickman MD, Maastricht, The Netherlands, presented an overview of the new CXL modalities and their potential applications. He shared the results using a novel photosensitising agent photoactivated by near-infrared (NIR) light. “Although the current standard of riboflavin and UVA light (RF/UVA) provides long-term stability in about 90% of patients with keratoconus, there are still great problems and limitations,” said Dr Dickman. Problems include the postoperative pain and infectious potential of epithelial debridement and toxicity to keratocytes and endothelium. CXL modalities can be divided into chromophore and pharmacological. Chromophore modalities include the standard RF/UVA technique; rose bengal stain + green light; and water-soluble taurine with dextran (WST-D) + NIR light. Pharmacological modalities comprise Genipin and Galacorin. Dr Dickman focused on WST-D/NIR, which was originally developed as an agent for photodynamic therapy for prostate cancer. Both corneal and scleral stiffening with this procedure has been demonstrated in rabbits, offering possibilities for the treatment of both infectious keratitis and progressive myopia. Further studies are needed to evaluate these novel CXL modalities before they can be incorporated into clinical practice, but their ability to overcome the current disadvantages of the standard RF/UVA protocol might make the effort worthwhile, he said. George Kymionis: kymionis@med.uoc.gr Beatrice Frueh: beatrice.frueh@insel.ch Mor Dickman: mor.dickman@mumc.nl

Tags: corneal crosslinking