DMEK or DMET?

As surgeons around the world contemplate shifting from DSAEK, or Descemet stripping automated endothelial keratoplasty, to the more effective but technically challenging DMEK (Descemet membrane endothelial keratoplasty), a third, simpler, option may be emerging for treating Fuchs' dystrophy, Gerrit R J Melles MD, PhD told Cornea 2013 at the annual meeting of the American Academy of Ophthalmology in New Orleans. Unlike earlier endothelial keratoplasty techniques, DMET, or Descemet membranemediated endothelial transfer, does not involve replacing damaged host endothelium with healthy donor cells. Instead, after a Descemetorhexis is performed on the host, donor Descemet tissue is injected and allowed to float freely in the anterior chamber. Over several weeks the cornea spontaneously clears and returns to normal thickness, with endothelial tissue covering the exposed posterior stroma despite a completely detached graft, Dr Melles reported. The early success of DMET calls into question not only the concept of keratoplasty to replace damaged host endothelium. It also suggests that the nature of Fuchs' should be reconsidered, said Dr Melles, director of the Netherlands Institute for Innovative Ocular Surgery in Rotterdam, which pioneered DMET, DMEK and other endothelial keratoplasty advances. “Maybe we should all take a step back and ask what are we actually treating. Does Fuchs' endothelial dystrophy actually exist or not? And is it really a dystrophy or something else? Because a dystrophy is something you really have to treat by doing surgery. But if it is not a dystrophy, but something you can reverse like a cellular dysfunction, it may open the door to completely different ways of treatment,” Dr Melles said. EVIDENCE OF FUCHS' REVERSAL As with many medical breakthroughs, DMET began with a clinical accident. DMEK surgery on an 80-year-old patient failed, leaving a roll of donor Descemet floating in the anterior chamber. The patient asked that the roll be left in place. One month later, the cornea began clearing, eventually thinning from 1,000 microns at centre to normal pachymetry. At six months, only slight oedema remained at the superior periphery, and endothelial cell density measured 830 cells/mm2 (Cornea. 2012 Feb;31(2):194-7). “We saw several DMEK eyes in which the graft detached but the corneas cleared. We received medical ethical approval to do this surgery on purpose,” Dr Melles said. In a prospective non-randomised series of 12 eyes, seven diagnosed with Fuchs' and five with bullous keratopathy, all the Fuchs' eyes cleared and returned to normal pachymetry with an average endothelial cell density of 797 cells/mm2 at six months. However, none of the eyes with bullous keratopathy cleared (Am J Ophthalmol. 2012 Aug;154(2):290-296). The research is ongoing. “At one month you have oedema, at three months the cornea starts to clear and at six months you have a fairly normal cornea,” Dr Melles said. These results suggest that, unlike bullous keratopathy, in Fuchs' the remaining peripheral host endothelium is capable of massive cell migration or regeneration to repopulate the exposed posterior stroma. “The series is so large that we now get the impression that the host cells are maybe somehow involved in the clearance or redistribution of endothelial cells after surgery,” Dr Melles said. This is also consistent with the observed pattern of re-endothelialisation, which moves from the peripheral toward the central cornea, and the cell densities observed. If the host cornea is capable of restoring corneal clarity, DMET may become a viable surgical approach for treating Fuchs' – and one that is much simpler than DSAEK or DMEK. It also raises the possibility of other management approaches, Dr Melles said. If Fuchs' is not truly a dystrophy, it might be that topical eye drops or other pharmaceuticals may be useful in managing it. Pre-clinical and early clinical results with rho-kinase inhibitors may bear this out. DMEK PEARLS For now, however, DMEK may be the best alternative for Fuchs', Dr Melles said. In his clinic, 80 per cent of DMEK patients achieve 20/25 or better corrected visual acuity six months after surgery with 44 per cent at 20/20 or better. DMEK rejection rates are also very low at less than one per cent, and most rejection events seem mild and can commonly be managed with intensified corticosteroid therapy, he added. Preparing the donor graft can be tricky, but beginning the dissection at the trabecular meshwork and moving in makes it easier, Dr Melles said. It may be desirable to let eye bank technicians do it as they generally are much more experienced. Before inserting the donor tissue, Dr Melles recommends irrigating with BSS to open it, and letting it roll up as a double roll, which is easier to unroll in the anterior chamber. Inside the eye, an air bubble on the Descemet side unrolls the graft, or tapping on the cornea may be enough. A bubble under the graft pushes it against the host tissue. The remaining bubble should be about 30 per cent of the graft diameter to avoid sliding under the pupil, which risks angle closure.