Abstract
Purpose :
Canine corneal endothelial dystrophy (CED) represents a spontaneous model for Fuchs endothelial corneal dystrophy (FECD). Current therapies for CED are palliative, warranting investigation of new therapeutics addressing the underlying endothelial degeneration. This study evaluates the tolerability and efficacy of the topical rho-kinase inhibitor, ripasudil, in the treatment of a canine model of FECD through a prospective, single-arm clinical trial.
Methods :
Twenty-four eyes of 14 client-owned CED-affected dogs received topical ripasudil 4 times daily. Ophthalmic examination, intraocular pressure (IOP) measurement, ultrasonic pachymetry, in-vivo confocal microscopy, and Fourier-domain optical coherence tomography were performed at baseline and at 1, 3, and 6 months after enrollment. Central corneal thickness, percentage of cornea affected by edema, and corneal endothelial cell density at each time point were determined by a masked analyst. One-way repeated measures analysis of variance or Friedman’s test were used to evaluate the effect of treatment on disease progression. Due to high variability in disease severity and response to therapy, individual eyes were also classified as improved, progressed, or stable at the 6-month time point based on defined clinical response criteria (Table 1).
Results :
During the treatment period, all 14 dogs developed some degree of conjunctival hyperemia, 4 dogs demonstrated reticulated intraepithelial bullae, and 2 dogs developed corneal stromal hemorrhage. These adverse events did not necessitate permanent cessation of ripasudil treatment in any dog. No significant differences were found in corneal endothelial cell density, corneal thickness, extent of corneal edema, or IOP between baseline, 3-month, and 6-month measurements. When considered individually, 5 eyes improved, 14 eyes remained stable, and 5 eyes progressed during the treatment period.
Conclusions :
Topical ripasudil was well-tolerated in the eyes of dogs with CED. As previously reported, conjunctival hyperemia and reticulated intraepithelial bullae were the most common adverse events encountered. Variable response to therapy was observed, with some eyes, particularly those with early disease, showing a favorable response while others progressed during the treatment period. Further studies are needed to investigate factors that influence the response to ripasudil therapy in a canine model of FECD.
This is a 2021 ARVO Annual Meeting abstract.