Eyeworld

EW CORNEA 36 August 2015 by Lauren Lipuma EyeWorld Staff Writer U sing donor cornea tissue, whether full- or partial- thickness, is the mainstay for treating corneal endo- thelial disease, 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 presentation at World Cornea Congress VII, "Future Directions in Corneal Endothelial Cell Biology." Using cultured 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 be- ing less invasive than an endothelial 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 out- comes. One patient with FECD he treated had a preop BCVA of 20/400 and a central corneal thickness of 778 µm, but after CEC injection, the patient had a BCVA of 20/20 and a central corneal thickness of 525 µm. Eye drop therapy 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 µm. The ROCK inhibitor eye drop method works well for treating cen- tral endothelial defects and edema, such as FECD, but not well for dif- fuse edema from BK, Dr. Kinoshita said. He has also worked on eluci- dating the molecular mechanisms behind ROCK activity, showing 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. Using CECs and eye drop thera- py allows physicians to treat disease at an earlier stage and offer a less in- vasive alternative to a corneal trans- plant. It is his hope, Dr. Kinoshita said, that this translational research will promote the development of even more novel therapies for the treatment 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 Pharmaceuticals Co. (Ashiya, Japan), Otsuka Pharmaceuti- cal Group (Tokyo), Pfizer (New York), Santen Pharmaceutical (Osaka, Japan), and Senju Pharmaceuticals (Osaka, Japan). Contact information Kinoshita: shigeruk@koto.kpu-m.ac.jp Translational research shows promise for treating corneal endothelial disease usiol.com | +1.859.259.4925 USIOL Inc | 2500 Sandersville Rd | Lexington KY 40511 USA Toll Free ( USA ) 800.354.7848 | Fax 859.259.4926 | usiol@aol.com © 2015 USIOL Inc. All rights reserved. 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