Medical Treatment of Fuchs' Dystrophy in our Lifetime?

Introduction

Ernst Fuchs described the corneal dystrophy that bears his name over 100 years ago. Ongoing research has implicated damage from oxidative stress, ¹ and unfolded protein response activation and apoptosis. ² However, in 2013 the basic mechanisms that underlie Fuchs' endothelial dystrophy (FED) remain unknown. Despite our relative ignorance of the biology of FED, tremendous advances have been made in the surgical management of this condition in the last two decades. ³ Selective replacement of the diseased corneal endothelium while leaving the anterior cornea intact is now the standard of care. Results are good, but complications still exist, including graft dislocation, glaucoma, and rejection. How much better would it be if we could treat FED without surgery? Okumura et al. ⁴ present some tantalizing data suggesting that this may be more than just a corneal specialist's fantasy. Using Y-27632, a topical Rho kinase inhibitor, and transcorneal cryotherapy to release contact inhibition of the corneal endothelium, they demonstrate recovery of the corneal endothelial mosaic in cynomolgus monkeys. More importantly, in a pilot series of four FED patients, transcorneal freezing and just 42 drops of Y-27632 given over 1 week produced corneal deturgescence and recovery of corneal endothelial cell count in patients able to be imaged. In contrast, patients with nondystrophic corneal decompensation did not recover, for reasons that are not yet understood. These results suggest that it may be possible to stimulate peripheral corneal endothelial cell proliferation in FED, thus potentially delaying (or avoiding) surgery. This truly is a revolutionary finding and we await further studies of this promising therapeutic agent.