Eyeworld

53 EW FEATURE January 2019 • Crosslinking playbook crosslinking can induce predictable refractive change in normal corneas, and we are eagerly anticipating larger scale trials to evaluate this noninvasive refractive technology." The stroma is loaded with riboflavin and a zonal UV pattern is applied, creating regional dif- ferences in corneal biomechanics. Combined with advanced epi-on treatment strategies, the cornea can thus be reshaped without adding or removing tissue. "The noninvasive nature of this procedure could make it particu- larly appealing to early presbyopes, and we can also envision potential applications for patients who have undergone prior refractive surgery and have 'aged out,' now requiring add power for near and not want- ing to return to spectacle wear," Dr. Thompson said. At this time, riboflavin is the gold standard for clinical use due to its excellent clinical track record and well-known safety and efficacy properties. Source (all): Vance Thompson, MD Dr. Alió sees the indications of CXL expanding to include a supple- mental role in corneal infections. "We have important and good experience in using CXL for corneal infection but always associated with the topical treatment, which is very much enhanced in its effectivity thanks to CXL," he said. "I do not think that CXL alone will be the way to treat corneal infections." Dr. Alió cited scleral CXL as another potential application, while Dr. Parker went even further, won- dering if the technology might not expand to tissues outside the eye. "What other stressed connective tissues in the body could use some non-invasive strengthening?" he asked. Stem cells "At first blush, it's not obvious how stem cells would help. In patients with keratoconus, the cornea is mechanically stretched into some distorted conformation, and there's scarring, and it's not entirely clear what stem cells would do about either of those problems," Dr. Parker said. "On the other hand, the cornea may possess a surprising ability to rebound back to normal shape and strength, given the right stimulus. For example, rarely, preg- nancy may trigger the development of keratoconus. Nevertheless, after delivery, the cornea almost always returns to its previous configuration. To my knowledge, no one current- ly understands how that happens, but it suggests that there is some chemical pathway for flattening and stabilizing ectasia." Dr. Alió is actively researching stem cells and CXL, with published results for Phase 2 and 3 clinical trials. 2,3 Preliminary results suggest that adipose-derived stem cells implanted into a stromal pocket dif- ferentiate into keratocytes and may produce new extracellular matrix. Their 1-year data is currently under peer review. Dr. Alió thinks that the corneal stromal regeneration that stem cells may facilitate will change the para- digm of CXL. "I am sure that in the future corneal transplantation will be avoided in most cases thanks to the use of stem cells," he said. Bowman's layer transplantation Physicians are divided on Bowman's layer transplantation. While Dr. Thompson considers the technique experimental, citing the advantages as an acellular graft and a sutureless procedure, Dr. Alió is skeptical. "I do not think the use of Bowman's layer will solve the problem of keratoconus but rather the therapy of the diseased cells, the keratocytes, which are those responsible for ker- atoconus," he said. "Bowman's layer transplantation is too complicated and not clear in its outcomes, which are complicated and only partially consistent." On the other hand, the proce- dure is Dr. Parker's preferred option for patients with advanced, progres- sive keratoconus. "By supplement- ing the keratoconic cornea with the strongest layer from a healthy donor cornea (the Bowman's layer), the progression of the patient's ectasia is almost always arrested," he said. "In addition, a significant flattening of the patient's cornea is usually achieved, on average, ~9 D. This amount of flattening frequently en- ables patients to comfortably wear their contact lenses and achieve satisfactory vision. At the same time, it spares them the more invasive alternatives of full or nearly full thickness keratoplasty." Whichever way research ultimately takes CXL, Dr. Thomp- son highlighted the importance of catching patients who would benefit from the procedure as early as possible. "Our goal is to slow the progression of ectasia before we lose the ability to bring patients to their full visual potential, and therefore, we think it is of great benefit to catch these patients early, watch them closely for progression, and to treat with CXL as soon as it is indicated," he said. "Hopefully, we are getting better at catching more of our keratoconus patients earlier and stabilizing progression with CXL before more extreme measures are needed." EW References 1. Vega-Estrada A, et al. Biocompatibility and biomechanical effect of single wall carbon nanotubes implanted in the corneal stroma: a proof of concept investigation. J Ophthalmol. 2016;2016:4041767. 2. Alió Del Barrio JL, et al. Cellular therapy with human autologous adipose-derived adult stem cells for advanced keratoconus. Cornea. 2017;36:952–960. 3. Alió Del Barrio JL, et al. Corneal stroma enhancement with decellularized stromal lam- inas with or without stem cell recellularization for advanced keratoconus. Am J Ophthalmol. 2018;186:47–58. Editors' note: Dr. Thompson has finan- cial interests with Avedro. Dr. Alió and Dr. Parker have no financial interests related to their comments. Contact information Alió: jlalio@vissum.com Parker: jack.parker@gmail.com Thompson: vance.thompson@vancethompsonvision.com

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