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116 EW CORNEA March 2013 Free-floating transplantation by Enette Ngoei EyeWorld Contributing Writer New technique may leave keratoplasty behind for Fuchs' patients A new "no-keratoplasty" surgical technique, known as Descemet's membrane endothelial transfer, may be effective in the management of Fuchs' endothelial dystrophy (FED), according to a study by Gerrit Melles, M.D., the Netherlands Institute for Innovative Ocular Surgery, the Netherlands, and colleagues. In the past, Dr. Melles said that he and colleagues noticed that some host corneas showed "spontaneous clearance" following keratoplasty despite Descemet's graft detachment and that an attached graft therefore did not seem a prerequisite to obtain corneal clearance. Dr. Melles and colleagues recently conducted a non-randomized prospective study to assess the corneal clearance in eyes that undergo re-endothelialization of the recipient posterior stroma through Descemet's membrane endothelial transfer (DMET) (i.e., a "free-floating" donor Descemet's graft in the recipient anterior chamber after descemetorhexis) in the management of corneal endothelial disorders. The study included 12 eyes, seven suffering from Fuchs' endothelial dystrophy and five with bullous keratopathy. The clinical outcome was monitored by biomicroscopy, optical coherence tomography, confocal microscopy, endothelial cell density, and pachymetry measurements, the authors wrote. According to results of the study, published in the American Journal of Ophthalmology, all eyes operated on for Fuchs' endothelial dystrophy showed corneal clearance, with pachymetry values returning to normal (533 ±47 µm). The denuded recipient stroma re-endothelialized with an average endothelial cell density of 797 (±743) cells/mm2 at six months after surgery. By contrast, none of the bullous keratopathy eyes showed any improvement throughout the follow-up period. Dr. Melles said, "In the paper, we describe that if only a free-floating Descemet's graft is present in the host anterior chamber, corneal clear- At six months, the Descemet's graft is still "free-floating," while the recipient cornea has a virtually normal clarity and pachymetry. Source: Lisanne Ham, Ph.D. ance depends on the indication for surgery. In our opinion, this should be indicative that the host endothelial cells are involved in repopulating the host posterior stroma (after descemetorhexis). In other words, if there is an absolute depletion of endothelial cells (in bullous keratopathy eyes), there are no cells that can migrate or repopulate the stroma, while the peripheral endothelial cells in Fuchs' endothelial dystrophy may still have the capacity to migrate and become a functional endothelial cell layer across the host cornea." He continued: "At this moment we are trying to establish a proof of principle. If successful, host endothelial cell stimulation may be preferable over DMEK (or DSEK/ DSAEK) in Fuchs' endothelial dystrophy because a 'perfect' restoration of the corneal anatomy may be anticipated with (theoretically) no risk of allograft rejection (host cells)." In terms of complications, Dr. Melles said that so far, one would expect a lower risk, owing to shorter surgical time, and possibly the elimination of allograft rejection. However, the main drawback of the procedure will be that it takes months for the cornea to become repopulated by (host) endothelial cells, he said. Another drawback could be the lower final endothelial cell density as compared to DMEK, he added. Some skepticism In the U.S., Francis W. Price Jr., M.D., Price Vision Group, Indianapolis, acknowledged Dr. Melles' brilliant contributions to endothelial transplantation and that DMET was a natural progression of his work. However, he said that he's skeptical it can be applied on a wide scale. "[DMET is] not something we try to emulate," Dr. Price said. While it could be something that a surgeon might think about for a young patient who has Fuchs' dystrophy, it's not anything that he would recommend for most Fuchs' patients, he said. In addition, Dr. Price said, "Dr. Melles has also reported that he'll wait six months to see if the cornea will clear. Most of my patients don't want to go more than two to three weeks with a cloudy cornea so it's not something that I would recommend that people do." The future of corneal endothelial disease treatment What both corneal experts are in agreement about is that in the future, graft surgery may be replaced with stimulating agents that are instead used to reconstruct diseased tissues. "The future may very well hold some form of cell stimulation or cell regeneration, either by in-vivo genetic manipulation (Prof. Kinoshita's work) or re-enforcing of peripheral (stem) cells in the periphery. However, these cell manipulation techniques probably take longer recovery intervals after surgery, so it may just be that DSAEK and/or DMEK con- tinue to play a role. The best scientific result may not be the most practical approach," Dr. Melles said. Shigero Kinoshita, M.D., Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, is working on ROCK inhibitors that may help stimulate a patient's own cells to grow. "In a few human patients he's frozen the central cornea in eyes with non-guttae Fuchs' and stimulated peripheral endothelial cells to repopulate the central cornea with application of ROCK inhibitor eye drops. In animal studies he's injected laboratory expanded human endothelial cells along with ROCK inhibitor, and the cells have attached and repopulated the central cornea," Dr. Price said. "[At present] we don't know the switch to turn on the regenerative capacity of the endothelial cells in patients, and that's what we need to be able to do," he said. Other groups are also looking at growing endothelial cells and ways to inject them into the eye, which would make it easier too, he added. EW Editors' note: Drs. Melles and Price have no financial interests related to this article. Contact information Melles: +31 10 297 4444, Melles@niios.com Price: 317-814-282, fprice@pricevisiongroup.net