Netarsudil and Corneal Edema: An Update and Review of the Literature

Netarsudil, a Rho-associated protein kinase (ROCK) inhibitor, was initially approved for the treatment of glaucoma and ocular hypertension due to its intraocular pressure-lowering effects. More recently, its pharmacologic activity in corneal tissues has generated interest in its therapeutic use for endothelial dysfunction. However, with widespread adoption, an unanticipated and visually significant adverse effect has emerged, reticular epithelial edema (REE). This condition is characterized by superficial microcystic epithelial changes arranged in a distinctive honeycomb pattern. REE most commonly arises in eyes with reduced endothelial reserve, such as those with Fuchs endothelial dystrophy, prior keratoplasty, or glaucoma drainage devices, and typically resolves following drug discontinuation. Experimental and clinical data suggest that while netarsudil enhances endothelial pump function and cellular adhesion, it may concurrently disrupt epithelial tight junctions, leading to paracellular fluid accumulation and REE. This review provides the first comprehensive synthesis of case reports, case series, clinical studies, and experimental data to characterize the dual effects of netarsudil on the cornea, with particular emphasis on the pathogenesis and risk factors for REE. By integrating mechanistic and clinical evidence, the review aims to support risk stratification and inform patient selection. Further research is needed to clarify the incidence, risk modifiers, and pathophysiology of REE, and to better identify patient populations most likely to benefit from netarsudil versus those at increased risk for epithelial adverse effects.