Transient Reticular Cystic Corneal Epithelial Edema With Topical Netarsudil: A Case Series and Review

To describe cases in which netarsudil ophthalmic solution 0.02% precipitated reversible, reticular cystic epithelial edema.

A retrospective case review at the Brooklyn Veteran's Association Hospital of patients with corneal stromal edema that were treated with netarsudil and subsequently developed cystic epithelial edema.

Four male patients with a mean age of 72 ± 8.0 years developed a reticular, honeycomb-like pattern of epithelial edema located in the interpalpebral and inferior cornea. In 3 of 4 patients, epithelial edema arose within 1 month compared with 2 months in 1 patient. New epithelial cysts did not correlate with worsening central corneal thickness and best spectacle-corrected visual acuity in every patient, which was likely due to the location of the cysts. Two of 4 patients developed increased central corneal thickness with worsening best spectacle-corrected visual acuity. In comparison, 1 patient had improvement in both parameters, whereas 1 patient had no significant change. In all cases, there was resolution of the epithelial cysts after discontinuation of netarsudil.

Although rho-kinase inhibitors have been suggested to improve endothelial function, we have documented worsening epithelial cysts in a subset of patients with pre-existing corneal edema. These effects of netarsudil were transient and resolved after discontinuing treatment within 2 weeks in most patients. We hypothesize that the incidence of this adverse finding is more common than previously believed. Nevertheless, large-scale studies are needed to accurately report on the incidence and clinical significance of this novel finding.