Ripasudil for Enhanced Corneal Clearing Following Descemet Membrane Endothelial Keratoplasty in Fuchs' Dystrophy

Study Overview
=================
Brief Summary
-----------------
Recently, published literature has reported that performing a descemetorhexis in combination with topical Rho kinase (ROCK) inhibitor therapy was successful in clearing edematous corneas in patients with Fuchs Endothelial Corneal Dystrophy. Ripasudil hydrochloride hydrate( Glanatec ophthalmic solution 0.4%), a potent ROCK inhibitor, has been approved in Japan since 2014 for ocular use in the treatment of glaucoma. Ripasudil acts as an IOP-lowering drug by affecting aqueous outflow through the trabecular meshwork and Schlemm's canal. The goal of this study is to test the potential benefits of Ripasudil therapy administered after Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. We believe that performing a standard DMEK surgery in combination with Ripasudil treatment in patients with Fuchs Endothelial Corneal Dystrophy could accelerate endothelial cell healing and clear edematous corneas faster, with less post-operative complications.

Official Title
-----------------
A Phase II, Interventional, Double-blind, Single-center Study of the Effects of Ripasudil on Cornea Clearing After Descemet Membrane Endothelial Keratoplasty in Subjects With Fuchs' Endothelial Corneal Dystrophy

Conditions
-----------------
Fuchs Endothelial Dystrophy

Intervention / Treatment
-----------------
* Drug: Glanatec
* Drug: Optive, Ophthalmic Solution
* Procedure: Descemet Membrane Endothelial Keratoplasty


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed clinically with Fuchs endothelial corneal dystrophy by the study investigator. Phakic or pseudophakic with posterior capsule supported, suture-fixated, or sulcus-supported posterior chamber intraocular lens. Fuchs dystrophy grades 2-5 on the Krachmer grading scale. Presence of central guttae and/or stromal edema being the primary cause of decreased vision. The peripheral cornea to the central 6mm is devoid of guttata changes. Best corrected visual acuity in the study eye is 20/40 or worse with glare testing at study enrollment. Exclusion Criteria: Uncontrolled glaucoma (IOP >25 mmHg). Presence of secondary corneal pathology such as infective or autoimmune keratitis. Advanced corneal stromal edema with bullae on slit-lamp biomicroscopy. History of herpes simplex virus or cytomegalovirus keratitis. Prior penetrating keratoplasty. Aphakic in study eye. Allergy to any component of the Ripasudil hydrochloride hydrate 0.4% that will be used in the course of the study. Tubes or trabeculectomy from prior glaucoma surgery.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glanatec<br>Glanatec eye drops will be administered 6x per day for 2-4 weeks | Drug: Glanatec<br>* Rho kinase Inhibitor<br>* Other names: Ripasudil;Procedure: Descemet Membrane Endothelial Keratoplasty<br>* Partial thickness corneal transplant that replaces only the diseased corneal endothelium and descemet membrane of the recipient.<br>* Other names: DMEK;|
| Placebo Comparator: Placebo Control<br>Optive artificial tears will be administered 6x per day for 2-4 weeks | Drug: Optive, Ophthalmic Solution<br>* artificial tears (placebo)<br>* Other names: Optive, artificial tears;Procedure: Descemet Membrane Endothelial Keratoplasty<br>* Partial thickness corneal transplant that replaces only the diseased corneal endothelium and descemet membrane of the recipient.<br>* Other names: DMEK;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to corneal clearance | Slit lamp examinations and corneal OCT measurements will be taken in a longitudinal fashion to compare corneal clearance and stabilization. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best corrected visual acuity | Longitudinal best corrected visual acuity tests will be performed to compare the time course of best vision attained and reported in Snellen units. | 6 months | 
| Endothelial cell density | Specular imaging will be conducted at 3 and 6 month postoperative to compare endothelial cells loss. | 6 months | 
| Post surgery complications | Number of graft detachments requiring a re-bubble procedure and number of graft failures will be recorded. | 6 months |