Descemet Endothelial Thickness Comparison Trial I

Study Overview
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Brief Summary
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Descemet Endothelial Thickness Comparison Trial (DETECT) I is a multi-center, outcome assessor-masked, placebo-controlled clinical trial randomizing 160 patients in a 2x2 factorial design. The purpose of this study is to determine differences in visual outcomes between two types of corneal transplant surgeries, ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK), and to determine the effect of rho-kinase inhibitors on endothelial cell loss.

Official Title
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Descemet Endothelial Thickness Comparison Trials (DETECT I & II)

Conditions
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Fuchs

Intervention / Treatment
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* Drug: Topical Ripasudil
* Drug: Topical Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dysfunctional endothelium from Fuchs Endothelial Corneal Dystrophy (FECD) with guttata extending beyond 4.5 mm of the central cornea or severe edema without visualization of guttata Dysfunctional endothelium from Pseudophakic Corneal Edema (PCE) or Iridocorneal Endothelial Syndrome (ICE) or other primary endothelial dysfuction such as Posterior Polymorphous Corneal Dystrophy (PPMD) Dysfunctional endothelium from prior graft failure after PKP or EK Controlled uveitis (defined as quiet for > 3 months off of topical steroids with or without systemic immunosuppression) or no uveitis Controlled glaucoma with topical medications and/or prior trabeculectomy or tube shunt without ongoing hypotony (IOP < 5 mmHg) or no glaucoma Good candidate for corneal transplantation for either DMEK or UT-DSAEK Willingness and ability to undergo corneal transplantation Willingness to consistently use study medications (i.e. ROCK-inhibitors) Willingness to participate in follow-up visits Age greater than 18 years Exclusion Criteria: Aphakia, or anterior chamber IOL or scleral fixated IOL in study eye prior to or anticipated during EK Pre-operative central sub-epithelial or stromal scarring that the investigator believes is visually significant and could impact post-operative stromal clarity assessment Peripheral anterior synechiae (iris to angle) in the angle greater than a total of three clock hours Visually significant optic nerve (ok to have small visual field defects) or macular severe pathology Inability to comply with post-operative instructions (i.e. unable to position) Pregnancy Cataract surgery within the last 3 months Fellow eye visual acuity <20/200

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UT-DSAEK plus topical ripasudil<br>This arm will receive UT-DSAEK plus topical ripasudil 0.4% | Drug: Topical Ripasudil<br>* To determine the effect of rho-kinase inhibitors on endothelial cell loss<br>* Other names: Ripasudil;|
| Placebo Comparator: UT-DSAEK plus topical placebo<br>This arm will receive UT-DSAEK plus topical placebo | Drug: Topical Placebo<br>* topical Placebo<br>* Other names: Placebo;|
| Experimental: DMEK plus topical ripasudil<br>This arm will receive DMEK plus topical ripasudil 0.4% | Drug: Topical Ripasudil<br>* To determine the effect of rho-kinase inhibitors on endothelial cell loss<br>* Other names: Ripasudil;|
| Placebo Comparator: DMEK plus topical placebo<br>This arm will receive DMEK plus topical placebo | Drug: Topical Placebo<br>* topical Placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best spectacle-corrected visual acuity (BSCVA) | Best spectacle-corrected visual acuity | 12 months | 
| Endothelial cell loss | Change between endothelial density at baseline versus density at 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best spectacle-corrected visual acuity (BSCVA) | Best spectacle-corrected visual acuity | 3, 6 and 24 months |