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EW CORNEA 96 September 2017 by Liz Hillman EyeWorld Staff Writer drug Y-27632 at 10 mM, while the two others received ripasudil hydro- chloride hydrate, the latter of which is currently on the market in Japan and has shown accelerated corneal endothelial healing in rabbit mod- els. 7 Dr. Moloney said he had per- sonal communication with Shigeru Kinoshita, MD, Kyoto Prefectural University of Medicine, Kyoto, Japan, whose group has pioneered Phase 1 trials with ROCK inhibitors for acceleration of corneal healing. The patient who received Y-27632 topical therapy showed no measurable improvement after 2 weeks and required endothelial ker- atoplasty. This patient's last best cor- rected visual acuity was 20/25. The other two cases received ripasudil and saw complete clearance within 2 weeks of therapy. "The ability of ripasudil to salvage failing cases was startling, and suggests that cases previously considered borderline may prove to be candidates for Descemetorhexis. Before this therapy, we firmly be- lieved that a graft would be required in the failing cases, and indeed, theater time and tissue were allocat- ed," Moloney et al. wrote, adding later, "We now believe that in the case proceeding to endothelial kera- toplasty, the use of ripasudil would have avoided this step." The study authors speculat- ed that the difference in success between the two ROCK inhibitors could be due to different inhibition factors. Complications in this study overall included three cases of partial Descemet detachment (two of which were in the non-responder group); rebubbling was not suc- cessful in these cases. There were also three patients with endothelial nodule formation, which faded over time but not completely, Moloney et al. wrote. Future research, Dr. Moloney said, needs to help physicians better identify who will be fast respond- ers to this technique. So far, the criteria has been elusive. He added that larger trials for the safety and efficacy of ROCK inhibitors to speed healing after Descemetorhexis are also needed. "We have further theo- ries we are working on to make the surgery more likely to succeed; these are unproven with work ongoing," Dr. Moloney said. resulted in slow visual recovery and poor postop visual acuity. 6 In November 2016, EyeWorld reported on Dr. Moloney's prior re- search on Descemetorhexis without a graft in Fuchs' patients. In this article, Dr. Moloney emphasized the importance of patient selection for the success of this technique. Moloney et al.'s more recent article reports clinical results in an attempt to better define the appropriate pa- tient population for this procedure and also presented a review of the ROCK inhibitor salvage therapy. All patients in this study had a central Descemetorhexis 4 mm in diameter or less. Measurements were taken monthly until patients experienced corneal clearance, after which point they were reviewed every 6 months. If patients did not show clearance by 2 months, they were observed more frequently and became candidates for EK. Three pa- tients were pulled to receive salvage therapy. Why some cases cleared sponta- neously while others didn't is "the great unanswered question that is clouding a full rollout of the proce- dure," Dr. Moloney said. "Some of my patients have now enjoyed excellent vision for years after Descemetorhexis, others have required salvage measures to resolve dense edema," he said. "We presume there is a cellular signal preventing migration in some patients. This may arise from overlying stroma, implicating surgical factors as im- portant in determining results, or it may arise from intrinsic patient fac- tors that we are yet to determine." Of those who did not clear spontaneously in the study, one patient received the compounded develop to a stage that it becomes a confident, first-line surgical op- tion," said Greg Moloney, MD, staff specialist, cornea and oculoplastics, Sydney Eye Hospital, and clinical senior lecturer, Sydney University, Sydney, Australia. "It is far quicker, less invasive and does not commit the patient to lifelong topical steroid therapy. It does not require donor tissue, so it expands the available pool of donor tissue for other patients. It also ensures availability of tissue is not a barrier to surgery in less developed countries. For the younger Fuchs' patient, it is far less likely to induce cataract, allowing retention of accommodation for longer." Previous research on Descem- etorhexis without a graft for Fuchs' dystrophy began several years ago after reports of spontaneous corneal clearance after graft detachment in a DMEK case. 2 Following there have been multiple reports detailing out- comes of Descemetorhexis without a graft, with varied success. 3,4 Com- plications that have been reported include corneal edema and damage to the posterior stroma, which has affected endothelial cell repopula- tion and led to inflammation. 5 Oth- ers have stated that Descemetorhexis without endothelial keratoplasty Rho kinase inhibitor rescues stalled healing in study evaluating technique that encourages a patient's own endothelial cell migration S urgical options for Fuchs' endothelial dystrophy typically include endo- thelial keratoplasty with a donor graft or a full corneal transplant to replace the pa- tient's dysfunctional corneal tissues producing clouded vision. However, there is a growing body of research that suggests removing Descemet's membrane and leaving the patient without a donor graft could be a viable alternative. Separately, there is also research showing increasing evidence that a drug, currently indicated for glauco- ma and ocular hypertension, could aid in corneal endothelium wound healing. Recent research by Moloney et al. combines these ideas, not only supporting the possibility of a spon- taneous corneal clearance post-De- scemetorhexis procedure in some patients, but also that a Rho-associ- ated kinase (ROCK) inhibitor might rescue cases where corneal clearance has stalled after Descemet's stripping alone. 1 This research published in the journal Cornea saw spontaneous clearance of the cornea in nine out of 12 patients who had a Descem- etorhexis due to visual symptoms resulting from central guttae. The three whose clearance stalled were put on a topical ROCK inhibitor; two of these achieved complete corneal clearance while one went on to endothelial keratoplasty. "There are many reasons that we as a corneal community are hoping that this technique can Glaucoma drug restarts endothelial healing in Fuchs' patients with Descemetorhexis but no graft " There are many reasons that we as a corneal community are hoping that this technique can develop to a stage that it becomes a confident, first-line surgical option. " —Greg Moloney, MD Research highlight Use the EyeWorldAR app to listen to the podcast "As Seen From Here," which featured a discussion between Dr. Moloney and Josh Young, MD, about this recent research.

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