Netarsudil-associated reticular corneal epithelial edema

Abstract

Purpose To describe 8 cases of reversible reticular corneal epithelial edema of the cornea that developed after use of the topical Rho-kinase inhibitor netarsudil. Methods This is a retrospective chart review case series of 8 patients treated with netarsudil at an academic medical center. Observations Patients had predisposing corneal conditions including penetrating keratoplasty, corneal decompensation after trabeculectomy-associated endophthalmitis, congenital glaucoma with Haab striae, aphakic bullous keratopathy, history of Ahmed valve and silicone oil, and Fuchs endothelial corneal dystrophy undergoing Descemet stripping only. One patient did not have clear predisposing corneal disease other than low endothelial cell density and a history of trabeculectomy. All patients developed reticular corneal epithelial edema, which appeared as collections of moderate sized superficial epithelial bullae arranged in a reticular pattern resembling a honeycomb. Most developed these changes within weeks of initiating netarsudil, but unique to this series are 2 cases in which netarsudil was tolerated by the cornea for months before developing reticular corneal epithelial edema after diode laser cyclophotocoagulation. In cases which underwent anterior segment optical coherence tomography, the imaging demonstrated that the corneal stroma was not edematous, and the reticular corneal epithelial edema involved both host and donor corneal epithelium in cases of penetrating keratoplasty. This fully resolved in all cases upon cessation of netarsudil, and this series is the first to document resolution via a pattern in which the individual bullae become smaller and more widely spaced apart. Conclusion Netarsudil can cause a reversible reticular corneal epithelial edema.

Netarsudil-associated reticular epithelial corneal edema after phacoemulsification

“…[8][9][10][11] Previously identified risk factors for netarsudil-associated reticular corneal epitheliopathy include corneal transplant, diode cyclophotocoagulation, glaucoma drainage shunt implantation, and Fuchs corneal dystrophy. 12 Similar to other reported cases, our patient's VA was significantly affected by her corneal condition. Fortunately, this improved dramatically 2 weeks after netarsudil was discontinued.…”

“…8–11 Previously identified risk factors for netarsudil-associated reticular corneal epitheliopathy include corneal transplant, diode cyclophotocoagulation, glaucoma drainage shunt implantation, and Fuchs corneal dystrophy. 12…”

Topical Ripasudil for the Treatment of Primary Corneal Endothelial Degeneration in Dogs

“… 41 , 42 An additional adverse event was the development of reticular bullous epithelial edema, which has also been reported in a series of human patients receiving the topical ROCK inhibitor netarsudil. 43 , 44 However, unlike in human patients, the reticular bullous epithelial edema was transient in these dogs and resolved without discontinuation of ripasudil as this change was appreciated at some visits but not all. The cause of reticular bullous epithelial edema remains unknown but may involve ROCK-inhibitor induced disruption of actin cytoskeleton organization and tight junctions of corneal epithelial cells.…”

“…The cause of reticular bullous epithelial edema remains unknown but may involve ROCK-inhibitor induced disruption of actin cytoskeleton organization and tight junctions of corneal epithelial cells. 44 The disappearance of the bullae without cessation of ripasudil may indicate that the edema was present as a result of the underlying disease rather than an adverse drug event, that the adverse event was truly transient or occurred only shortly after administration, or that topical hypertonic saline ointment may have aided in resolution of the bullae. Corneal stromal hemorrhage is a rare occurrence reported in humans receiving ROCK inhibitors, including a case report of a 76-year-old man with pre-existing peripheral corneal neovascularization and concurrent primary open angle glaucoma treated with topical netarsudil.…”

Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis

“…A newer medical therapy used in glaucoma treatment and for corneal edema is the Rho-kinase inhibitor netarsudil. However, recent case reports demonstrate potential development of reversible reticular corneal epithelial edema with this therapy, which can cause transient blurry vision [35].…”