From success with DSO to investigating ROCK inhibitors, NYU Langone specialists pioneer new approaches.
Since its introduction in the United States in the mid-2010s, Descemet stripping only (DSO) has revolutionized the surgical management of Fuchs dystrophy. Although similar procedures were originally explored in the 1950s and for some time after, these met with little success.
The current technique—pioneered in the United States by Kathryn A. Colby, MD, PhD, the Elisabeth J. Cohen, MD, Professor of Ophthalmology and chair of the Department of Ophthalmology at NYU Grossman School of Medicine—involves removal of the diseased endothelium and mound-shaped aggregates, known as guttae, without the need for a donor graft.
Further advancing the treatment, Dr. Colby currently serves as the U.S. chair for two ongoing phase 3 trials evaluating whether a topical Rho-associated protein kinase (ROCK) inhibitor administered in the weeks following DSO surgery or simultaneous cataract and DSO surgery may enhance the efficacy of the procedures for treating Fuchs dystrophy. Early studies report the topical agent aids corneal restoration following DSO.
NYU Langone enrolled the first patient in the world to one of the two phase 3 trials last summer. If successful, the trials may lead to FDA approval of topical ROCK inhibitor administration as an adjuvant therapy to DSO.
Adjuvant ROCK inhibitor eye drop use could become standard practice following DSO cases in the early postoperative period.”
“Adjuvant ROCK inhibitor eye drop use could become standard practice following DSO cases in the early postoperative period,” Dr. Colby says. “New evidence suggests these agents can enhance final endothelial cell count after a tissue corneal transplantation as well.”
Success with DSO
As an alternative to corneal transplantation, DSO boasts no risk of graft rejection and eliminates the need for long-term immunosuppression with topical steroids, making it a highly attractive option.
While the procedure has a high rate of success, it warrants careful patient selection, Dr. Colby explains.
“Candidates must have Fuchs that is severe enough to cause symptoms, but not so severe that they don’t have any remaining peripheral endothelium,” she says. “They should also be comfortable with experiencing blurred vision for several weeks after the procedure and must be willing to proceed with a corneal transplant if necessary.”
VIDEO: Dr. Colby performing the DSO procedure.
From a surgical perspective, Dr. Colby adds that it is crucial to ensure a smooth edge and prevent leftover tags when removing the diseased tissue. “It’s clear that a smooth edge tear makes it easier for cells to migrate and repopulate the corneal endothelium.”
Mounting Evidence for ROCK Inhibitors
Interest in ROCK inhibitors for DSO has been growing since a 2017 study found that ripasudil, a ROCK inhibitor approved as a therapy for glaucoma in Japan, rescued two patients who had Fuchs dystrophy that was slow to clear. Additional research has shown that administration of topical ripasudil after DSO for Fuchs dystrophy results in earlier corneal restoration.
As a result, Dr. Colby helped lead a recently completed phase 2 trial that evaluated ripasudil (K-321) in 65 patients undergoing DSO for Fuchs dystrophy.
“Preliminary data from the phase 2 trial indicates improvements in the speed of healing and the final endothelial cell count, and a reduction in the failure rate for DSO,” she says.
We’re optimistic that the trial results will make DSO available to an even larger patient population.
The ongoing phase 3 trials will each evaluate an additional 100 participants. The patients will follow a 12-week administration protocol, with a 2-week dose taper phase, and be followed for a total of 38 weeks.
“We’re optimistic that the trial results will make DSO available to an even larger patient population,” Dr. Colby says.
Disclosures
NYU Langone has a research contract with Kowa Inc. for Dr. Colby’s role as the U.S. chair for the K-321 development program.
