Reticular epithelial corneal edema as a novel side-effect of Rho Kinase Inhibitors: An Indian scenario

Abstract

Purpose: To describe clinical course, characteristics, and outcome of reticular epithelial corneal edema (RECE) occurring as a not-so-infrequent adverse effect of a novel drug, Rho-kinase inhibitors (ROCK-I)- netarsudil (0.02%) and ripasudil (0.4%).

Methods: This was a retrospective observational non-randomized study. In this study, 12 eyes of 11 patients presenting at a tertiary eye care center between April 2021 and September 2021 were included. All 12 eyes developed a distinctive honeycomb pattern of RECE after starting topical ROCK-I. All patients were subjected to detailed ophthalmic examinations.

Results: Eight patients were started on netarsudil (0.02%) and three on ripasudil (0.4%). Five eyes had a prior history of corneal edema. The remaining seven had the presence of ocular comorbidities predisposing to corneal edema. The average time for RECE occurrence was 25 days for netarsudil and 82 days for ripasudil. Visual acuity decreased in two eyes, remained unaffected in four eyes, and could not be quantified in four eyes due to preexisting profound visual impairment. Five eyes had symptoms of ocular surface discomfort associated with bullae. Symptoms and bullae resolved in all eyes in whom ROCK-I was stopped. The average time to resolution of RECE was 10 days for netarsudil and 25 days for ripasudil.

Conclusion: RECE after ROCK-I occurs with the use of both netarsudil and ripasudil, although the characteristics differ. The presence of corneal edema and endothelial decompensation seem to be a risk factor, and cautious use is warranted in these patients. Four clinical stages of RECE are described. ROCK-I act as a double-edged sword in patients with endothelial decompensation. Large-scale studies are required to know the exact incidence, pathophysiology, and long-term consequences of the aforementioned side-effect.

Keywords: Anterior segment optical coherence tomography; honeycomb edema; reticular epithelial corneal edema; rho-kinase inhibitors.

Figure 1

Manifestation and resolution of RECE (a), (b) honeycomb RECE after netarsudil use; (c) inferiorly localized bullae in FECD after ripasudil use; (d), (e), (f)-resolution of bullae after stopping ROCK-I

Figure 2

RECE in corneal grafts (a) 360° of RECE in a circinate pattern near GHJ sparing visual axis after netarsudil use; (b) inferiorly localized bullae near GHJ after ripasudil instillation; (c) diffuse micro and macro-bullae in failed graft after ripasudil use; (d) better visualization of RECE in the same patient as (c) after fluorescein stain with cobalt blue filter

Figure 3

ASOCT features of RECE (a), (c) epithelial macro-bullae due to ROCK-I use. Note the contiguous nature of epithelial bullae and non-involvement of stroma; (b), (d) resolution of bullae post cessation of ROCK-I

Figure 4

Stages of RECE (a) epithelial roughening; (b) microcystic bullae; (c) micro and macro-bullae; (d) full-blown RECE