Eyeworld

DECEMBER 2021 | EYEWORLD | 79 C Contact Colby: Kathryn.Colby@nyulangone.org Moloney: gregorymoloney@yahoo.com.au Relevant disclosures Colby: Kowa has a research contract with New York University for Dr. Colby's services as U.S. chair for the K-321 clinical trial Moloney: Kowa Surgically, she said we know now that a smooth-edged tear is better than a jagged- edged tear. Dr. Colby said she uses blunt-tipped Gorovoy forceps (Moria). "They're good for making the break into De- scemet's membrane atraumatically, and it's easy to pull the Descemet's membrane and endotheli- um around and do a descemetorhexis," she said. She also said surgeons need to be careful to not dig the instrument into the posterior stroma because it will cause scarring. Though not often visually significant, Dr. Colby said surgeons don't like to see scarring. Overall, Dr. Moloney said there is a greater understanding, due to knowledge gained from the surgical journey of DSO, for the mecha- nisms and limitations for corneal clearance after endothelial trauma. This, he said, will serve the community well as we embark on the next surgical phase of cell replacement therapy. ROCK inhibitors Though reports have shown enhanced endo- thelial cell migration with the use of a ROCK inhibitor, there is not one approved for this indication in the U.S. Netarsudil (Rhopressa, Aerie Pharmaceuticals) is approved for reducing IOP but has been found in some cases to help in corneal clearance. Use of netarsudil after DSO for endothelial cell migration would be off label, Dr. Colby said. However, a Phase 2 trial evaluating a different ROCK inhibitor, ripasudil, for DSO is underway. The compound is already approved for use outside of the U.S. for glaucoma as Glanatec (Kowa). The study sponsored by the Kowa Research Institute has completed patient enrollment and is expected to have topline data in December 2021. Between 60–65 patients were enrolled in this double-masked, random- ized, placebo-controlled 12-week trial that eval- uated safety and efficacy of ripasudil (known as K-321 in the study) after DSO in patients with Fuchs, Dr. Colby said. The investigational drops were administered BID or QID with the cen- tral endothelial cell density being the primary outcome measure and number of participants with at least one adverse event the secondary outcome measure. Dr. Colby, the U.S. chair of the Kowa study, said if the results from the Phase 2 trial are positive, a Phase 3, FDA-approval trial could begin in 2022. Unable to speak to the Kowa trial data, Dr. Moloney, who consulted on the design of the trial, said anecdotal evidence and other small to medium trials have supported the role of ROCK inhibitors in promoting cell migration after DSO. "The observation of 'relapse edema' on cessation of the drop in some patients post-DSO is strong clinical evidence of the drug effect," he said. "In vitro and in vivo results also suggest that not all patients require ROCK inhibitors to achieve corneal clearance. Determining who best benefits from ROCK inhibitors and espe- cially at what dose requires a well-constructed, controlled, prospective clinical trial. The Kowa study is meeting this need." In general, Dr. Moloney said having an al- ternative procedure to treat a subset of patients with Fuchs without a transplant has been "ex- tremely gratifying." While he said the technique hasn't replaced DMEK for all Fuchs patients, in the way DMEK replaced DSEK, "for appropriate- ly selected patients, I think it provides a better surgical journey." An eye with Fuchs pre-DSO and post-DSO Source (all): Gregory Moloney, MD

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