Clinical trial NCT03575130: Ripasudil 0.4% Eye Drops in Fuchs Endothelial Corneal Dystrophy
Official title: Prospective Single-centre Randomized Observer-blind Placebo-controlled Parallel-group Phase IIa Clinical Trial to Investigate the Safety and Efficacy of Ripasudil 0.4% Eye Drops After Descemetorhexis in Patients With Moderate to Advanced Fuchs Endothelial Corneal Dystrophy (FECD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Fuchs' Endothelial Dystrophy
Fuchs Dystrophy
Corneal Endothelial Dystrophy
Corneal Endothelial Cell Loss
Cornea Guttata
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2018-07-02
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The cornea forms our "window to the world". Hence, its transparency is of utmost importance for vision. Corneal endothelium plays a central role in the maintenance of a transparent corneal stroma. It limits stromal fluid uptake from the anterior chamber of the eye through the formation of tight junctions. Simultaneously, fluid is actively transported from corneal stroma into the anterior chamber. This maintains the corneal stroma in a state of relative dehydration, thereby ensuring a constant distance of stromal collagen lamellae to each other, which in turn forms the basis for transparency of this tissue. If however corneal endothelial function is impaired, stromal swelling leads to corneal clouding and loss of vision.

Fuchs endothelial corneal dystrophy represents the most common form of corneal dystrophy. It occurs sporadically, however in some cases autosomal dominant inheritance has been described. This condition leads to progressive loss of corneal endothelium (typically around the age of 50-60 years), causing visual impairment due to swelling and opacification of corneal stroma.

Cell culture experiments have been able to show that chemical inhibitors of Rho-Kinase promote corneal endothelial cell proliferation and reduce apoptosis, while topical application in an animal model promoted corneal endothelial wound healing. This has prompted the notion of using topical Rho-kinase-inhibitor treatment to support endothelial cell regeneration in Fuchs endothelial corneal dystrophy.

Since September 2014, Rho-kinase-inhibitor eye drops (ripasudil) are clinically available in Japan for reduction of intraocular pressure in Glaucoma patients. Ripasudil eye drops therefore represent a strong candidate for safe and effective adjunctive treatment in patients with Fuchs corneal endothelial cell dystrophy.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained from the subject
2. Understanding of study procedures and willingness to abide by all procedures during the course of the study.
3. Age range: 18-70 years
4. Diagnosis of moderate to advanced FECD with central guttae and clinical relevant corneal endothelial cell loss of \<1,000 cells/mm2 and clinical indication of surgical intervention (descemetorhexis) with or without accompanying cataract operation
5. Reduced visual acuity, defined as BCVA \<20/30
6. Woman of childbearing potential must be using a highly effective method of birth control.

Primary outcomes:
measure: The occurrence of serious adverse reaction within the observation period of 3 months after descemetorhexis.
timeFrame: 3 Months
Secondary outcomes:
measure: rate of adverse event, adverse reaction, serious adverse event, serious adverse reaction and suspected unexpected serious adverse reaction
timeFrame: within the observation period of 6 months
measure: effect of ripasudil on corneal endothelial cell density (ECD)
timeFrame: within the observation period of 6 months
measure: effect of ripasudil on corneal thickness
timeFrame: within the observation period of 6 months
measure: effect of on visual acuity (BCVA)
timeFrame: within the observation period of 6 months
measure: effect of ripasudil on contrast sensitivity
timeFrame: within the observation period of 6 months
measure: assess the need of rescue therapy (DMEK)
timeFrame: within the observation period of 6 months
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Ophthalmology, University of Erlangen-Nürnberg
Study officials:
References: