Eyeworld Daily News

EW SHOW DAILY 48 Meeting Reporter Saturday, April 18, 2015 by Lauren Lipuma EyeWorld Staff Writer U sing donor cornea tis- sue, whether full- or partial-thickness, is the mainstay for treating corneal endothelial dis- ease, but new, innovative options in development are less invasive and could provide better outcomes. Shigeru Kinoshita, MD, PhD, Kyoto, Japan, described 2 "out of the box" approaches he has taken to treat corneal disease in his presen- tation, "Future Directions in Cor- neal Endothelial Cell Biology," the keynote lecture at Friday's "Corneal Tissue Engineering, Physiology, and Wound Healing" session. Injecting cultured endothelial cells One of the options Dr. Kinoshita has begun to explore is injecting cultivated corneal endothelial cells (CECs) from a donor cornea for advanced-stage diseases such as Fuchs' endothelial corneal dystro- phy (FECD) or pseudophakic bullous keratopathy (BK). In addition to being less invasive than an endo- thelial keratoplasty, this technique helps conserve precious donor tissue—1 donor cornea can provide enough cells to treat more than 200 patients. The surgical procedure involves removing the pathologic endotheli- um, aspirating the aqueous humor, pumping in rho-kinase (ROCK) in- hibitors, and injecting a suspension of 1 million CECs. After the proce- dure, the patient must remain face down for 3 hours to allow the cells to adhere to Descemet's membrane. After initial success in animal models, Dr. Kinoshita began cul- turing cells for use in the clinic. So far, he has injected CECs into 11 patients with either FECD or BK and has achieved excellent visual outcomes. One patient with FECD he treated had a preop BCVA of 20/400 and a central corneal thick- ness of 778 microns, but after CEC injection, had a BCVA of 20/20 and a central corneal thickness of 525 microns. The eye drop method For early phase endothelial disease, Dr. Kinoshita has been developing a method of using ROCK inhibitor eye drops to stimulate recovery of a patient's endothelial function. ROCK inhibitors promote cell adhe- sion and proliferation and inhibit apoptosis, making them excellent candidates for this procedure. In the eye drop procedure, Dr. Kinoshita uses transcorneal freezing to induce a partial endothelial defect in the patient's central cornea and then applies the ROCK inhibitor drops 6 times daily for 7 days. The patient's peripheral endothelial cells then migrate to the center of the cornea and repopulate the lost cells. Using a rabbit model, Dr. Kinoshita showed that ROCK inhib- itors promoted wound healing and closed the endothelial defect in 48 hours. Dr. Kinoshita then success- fully performed the procedure on a 52-year-old patient with FECD. Three years after the treatment, the patient had a BCVA of 20/20 and central corneal thickness of 568 microns. The ROCK inhibitor eye drop method works well for treating central endothelial defects and edema, such as FECD, but not well for diffuse edema from BK, Dr. Kinoshita said. He has also worked on elucidating the molecular mech- anisms behind ROCK activity, show- ing that ROCK inhibition increases cell proliferation by controlling the G1/S transition, the "point of no return" in the cell cycle that forces it to divide. The future of endothelial treatment Using CECs and eye drop therapy al- lows physicians to treat disease at an earlier stage and offer a less invasive alternative to a corneal transplant. It is his hope, Dr. Kinoshita said, that this translational research will promote the development of even more novel therapies for the treat- ment of corneal endothelial diseases. As these methods embody the shift from highly invasive to minimally invasive procedures, Dr. Kinoshita believes they represent the future of corneal endothelial dysfunction treatment. EW Editors' note: Dr. Kinoshita has fi- nancial interests with Abbott Medical Optics (Abbott Park, Ill.), Alcon (Fort Worth, Texas), Hoya Surgical Optics (Tokyo), JCR Pharmaceutical Co. (Ash- iya, Japan), Otsuka Pharmaceutical Group (Tokyo), Pfizer (New York), Sant- en Pharmaceutical (Napa, Calif.), and Senju Pharmaceuticals (Osaka, Japan). Translational research shows promise for treating corneal endothelial disease 'Corneal Tissue Engineering, Physiology, and Wound Healing' I n addition to Dr. Kinoshita's keynote lecture, "Future directions in corneal endothelial cell biology," these physicians spoke on the following topics: • Jodhbir S. Mehta, MBBS, FRCS(Ed), Singapore, spoke on "Corneal Endothelial Cell Transfer for Endothelial Dysfunction." • Thomas Fuchsluger, MD, PhD, Erlangen, Germany, spoke on "Genetic Engineering in Endothelial Transplantation." • Zuguo Liu, MD, PhD, Xiamen, China, spoke on "Xeno-Lamellar Corneal Tissue Engineering." • Mark I. Rosenblatt, MD, PhD, Chicago, spoke on "Update on Wound Healing." • Gerard Sutton, MD, Sydney, spoke on "New Insights Into the Cellular Pathogenesis of Keratoconus." • May Griffith, PhD, Linköping, Sweden, spoke on "New Developments Into Corneal Bioengineering." • Reza Dana, MD, Boston, spoke on "Pathophysiology and Management of Corneal Neovascularization." EW Dr. Kinoshita describes 2 new minimally invasive techniques for treating corneal endothelial disease.

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