Ripasudil
Pipeline
Ripasudil is a rho-kinase inhibitor. Rho-associated protein kinase (ROCK) is a protein which regulates the shape and movement of cells in a number of tissues, including the eye. It is known that Ripasudil is absorbed into the eye when it is applied as eye-drops, because one of the effects of rho-kinase inhibitors is to reduce intraocular pressure, and Ripasudil is approved under the trade name GLANATEC® as a treatment for glaucoma and ocular hypertension in some countries, including Japan and South Korea. One of the other effects of Ripasudil is that it can increase the mobility of corneal endothelial cells and their number when maintained in culture.
This formulation of Ripasudil is different from Glanatec and if it has the same effects on corneal endothelial cells in the eye as it does on cells in culture, may prove to be a novel potential treatment for Fuch’s endothelial corneal dystrophy (FECD). It is currently under investigation to be used as an adjunct to healing following Descemet Stripping Only (DSO) surgery as a treatment for FECD. (Phase 2 trial in FECD patients)
FAQs
What is Fuch’s Endothelial Corneal Dystrophy (FECD)?
FECD is an abnormality of the cornea which generally occurs in later life. The primary defect in FECD seems to lie with the endothelial cells which form a thin cellular layer on a basement membrane (Descemet’s membrane) on the inside of the cornea. An important function of these cells is to remove water from the cornea, which keeps this part of the eye thin and clear. When the corneal dystrophy manifests itself, drop-like depositions of extracellular matrix appear on Descemet’s membrane. These are known as guttae and cause unevenness of the membrane, which reduces the acuity of vision. Endothelial cells are lost at an increased rate, starting in the centre of the cornea and spreading towards the limbus, the outside edge of the cornea. Eventually the corneal endothelium ceases to function effectively, and the cornea begins to thicken and cloud, leading eventually to blindness.
What treatments are there for endothelial dystrophy?
There are no effective medical treatments for FECD. The most effective treatment has been corneal transplantation, aimed at replacing the damaged cornea with an undamaged donor cornea, and FECD is the most common indication for corneal transplantation. Over a period of some years the transplantation technique has been improved so that only the posterior part of the cornea, to the inside, has to be replaced, rather than the entire thickness of cornea. The most refined operation involves transplanting only Descemet’s membrane and the associated endothelial cells, having first removed an area of the patient’s own uneven membrane. This is a procedure called Descemet Membrane Endothelial Keratoplasty (DMEK) and requires a surgeon with considerable skill and training. DMEK may sometimes be delayed in patients with FECD and mild visual impairment because of the cost and shortage of availability of donor corneas, and concerns about the risks of transplantation, which may include graft inversion, detachment or failure, as well as the rarer risk of rejection.
How does Ripasudil help patients with Fuch’s?
Recently, a simpler procedure has been proposed for some patients, in which the affected area at the back of the cornea is removed, a procedure known as descemetorhexis, but no transplant is performed. Instead, the operated area is allowed to heal by the migration of remaining endothelial cells from surrounding areas. The main advantage of the procedure is that there are no risks related to the graft, and because no donor cornea is required, it may be possible for the operation to be performed earlier in the course of the disease. The main disadvantage is the time that it takes for the endothelial cells to migrate and heal the cornea, and for vision to be restored. If Ripasudil can be shown to speed the rate of healing of the cornea by increasing the rate of cell migration, and lead to an increase in the number of cells, then it may improve the utility of descemetorhexis as a treatment for FECD, and help slow the rate of the underlying corneal dystrophy.