Descemet Endothelial Thickness Comparison Trial

Study Overview
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Brief Summary
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The purpose of this study is to compare visual acuity outcomes of two types of endothelial keratoplasty: 1) Ultrathin Descemet's Stripping Endothelial Keratoplasty (DSAEK) or 2) Descemet's Membrane Endothelial Keratoplasty (DMEK). Half of the participants will be randomized to have DSAEK and the other half will have DMEK.

Detailed Description
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Corneal transplantation has evolved rapidly in recent years. Lamellar keratoplasty to replace diseased endothelium has led to faster recovery times, fewer complications, and better visual acuity outcomes. Currently, Descemet's Stripping Endothelial Keratoplasty (DSAEK) is the most common procedure because of its relative ease and good outcomes. Newer techniques such as Descemet's Membrane Endothelial Keratoplasty (DMEK), where Descemet's membrane alone is transplanted, has the potential to further improve visual acuity outcomes, produce fewer higher-order corneal aberrations and decrease rejection rates. However, donor preparation, increased intra-operative times, and problems with donor attachment in DMEK are all important limitations. There are three potential mechanisms by which DMEK may provide better visual acuity outcomes than DSAEK; graft thickness, interface haze and corneal higher-order aberrations. Graft thickness has been correlated with best spectacle corrected visual acuity (BSCVA) outcomes among thinner grafts. One retrospective case series found that 71% of thin endothelial grafts (defined as <131μm) had BSCVA of 20/25 or better while only 50% of thick grafts (defined as ≥131) achieved this. In addition, higher-order aberrations, in particular of the posterior cornea, are increased after DSAEK. Theoretically, given the decreased tissue transplanted after DMEK this would be lessened, however, one retrospective series looking at higher order aberrations in DMEK compared with DSAEK found no difference in posterior aberrations of the central 4.0 mm zone between the two groups. Finally, interface haze may be increased in DSAEK and has been correlated with BSCVA. Ultrathin DSAEK involves donor preparation with a deep microkeratome pass to produce donor grafts less than 100 um thick. This procedure may have similar results to DMEK but without the technical difficulties. Several large prospective series show similar visual outcome results and rates of immunologic rejection between ultrathin DSAEK and DMEK, however comparisons are difficult. This comparative effectiveness clinical trial could directly address these important issues. The investigators also anticipate that secondary analyses of the trial data will allow us to address several more.

Official Title
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Descemet Endothelial Thickness Comparison Trial

Conditions
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Keratoplasty, Grafting, Corneal, Transplantation, Corneal, Transplantation, Cornea, Keratoplasty, Lamellar

Intervention / Treatment
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* Procedure: DSAEK
* Procedure: DMEK
* Device: Endoserter
* Drug: Prednisolone
* Drug: Ofloxacin
* Drug: Tropicamide
* Drug: Phenylephrine
* Device: Jones Tube


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Damaged or diseased endothelium from Fuchs or Pseudophakic Bullous Keratopathy Good candidates for corneal transplantation for either DMEK or DSAEK Willingness and ability to undergo a cornea transplantation Willingness to participate in follow-up visits Exclusion Criteria: Participants who are decisionally and/or cognitively impaired Participants who are not suitable for the DMEK or DSAEK surgeries Prior Endothelial Keratoplasty (EK) or any other ophthalmic surgery except uncomplicated cataract surgery Indication for surgery that is not suitable for EK (e.g. keratoconus, stromal dystrophies and scars) Presence of a condition that increases the probability for failure (e.g., heavily vascularized cornea, uncontrolled uveitis) Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy Aphakia, or anterior chamber intraocular lens (IOL) in study eye prior to or anticipated during EK Planned intraocular lens exchange of an anterior chamber IOL with a posterior chamber IOL in study at time of study 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 Hypotony (Intraocular pressure <10mmHg) Uncontrolled (defined as intraocular pressure >25mmHg) glaucoma Visually significant optic nerve or macular pathology Visually significant optic nerve or macular pathology

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: DSAEK<br>Type of corneal transplant; Tissue grafts will be cut to the right thickness using a microkeratome prepared at the eye bank per standard eye bank protocol (about 60-90 microns thick). A 4 mm corneal incision will be used, with Endoserter as the means of inserting the graft, an FDA approved device for this purpose. | Procedure: DSAEK<br> <br> Device: Endoserter<br>* The Endoserter, a corneal endothelium device, is an approved FDA device. This will be used to insert and position the graft into the anterior chamber during endothelial replacement surgery. It is a sterile, single-use instrument.<br>Drug: Prednisolone<br>* Prednisolone is a corticosteroid used to alleviate swelling post-surgery.<br>* Other names: Flo-Pred;Drug: Ofloxacin<br>* Ofloxacin is an antibiotic used to treat bacterial infections of the eye.<br>* Other names: Floxin;Drug: Tropicamide<br>* Tropicamide is a prescription drug used to dilate pupils during an eye exam.<br>* Other names: Mydriacyl;Drug: Phenylephrine<br>* Phenylephrine is a prescription drug used to dilate pupils during an eye exam.<br>|
| Other: DMEK<br>Type of corneal transplant; Endothelial grafts will be pre-peeled at the eyebank (70%). In the operating room the remaining 30% will be peeled, and the endothelium will be stained with trypan blue. A 3.5 mm corneal incision will be used and the graft will be inserted with a modified jones tube injector. The tap technique will be used to position the graft. | Procedure: DMEK<br> <br> Drug: Prednisolone<br>* Prednisolone is a corticosteroid used to alleviate swelling post-surgery.<br>* Other names: Flo-Pred;Drug: Ofloxacin<br>* Ofloxacin is an antibiotic used to treat bacterial infections of the eye.<br>* Other names: Floxin;Drug: Tropicamide<br>* Tropicamide is a prescription drug used to dilate pupils during an eye exam.<br>* Other names: Mydriacyl;Drug: Phenylephrine<br>* Phenylephrine is a prescription drug used to dilate pupils during an eye exam.<br>Device: Jones Tube<br>* The Jones Tube will be used to insert the graft into a 3.5 mm corneal incision during endothelial replacement surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Spectacle-Corrected Visual Acuity | The BSCVA was recorded at 4 meters by a masked refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Spectacle-Corrected Visual Acuity | The BSCVA was recorded at 4 meters by a masked refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 3 and 12 months | 
| Best Spectacle-Corrected Visual Acuity | The BSCVA was recorded at 4 meters by a masked refractionist certified for the study using a protocol adapted from the Age-Related Eye Disease Study using Early Treatment Diabetic Retinopathy Study charts: chart R(2110), chart 1(2111), and chart 2(2112) (Precision Vision, Woodstock, IL). | 24 Months | 
| Endothelial Cell Count |  | 3, 6, 12 months | 
| Endothelial Cell Count |  | 24 months | 
| Corneal Higher-Order Aberrations | Corneal anterior and posterior surface higher-order aberrations (HOA) were measured with Scheimpflug imaging (Pentacam) before surgery and at 3, 6, and 12 months post-operatively. Zernike orders 3-8 were calculated at 4.0- and 6.0-mm-diameter optical zones. The results reported here represent total HOA (Sum of Zernike orders 3-8). Note a single observation was not available for one eye in the DMEK group at 6 months, this was analyzed with last observation carried forward. | 3, 6, 12 months | 
| Corneal Higher-Order Aberrations | As measured by Pentacam | 24 months | 
| Interface Haze | As measured by Pentacam densitometry | 3, 6, 12 months | 
| Interface Haze | As measured by Pentacam densitometry | 24 months | 
| National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ) | The National Eye Institute has developed the validated Visual Functioning Questionnaire (NEI-VFQ) to assess the effect of ocular conditions and vision on patient quality of life. The answers to the questionnaire are transformed into sub-scales, including: general health, general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision. Participants are assigned a numerical value for each sub-scale based on their answers between 0-100, where higher numbers indicate better visual function. These sub-scales are then combined according to National Eye Institute guidelines into an overall composite score for each participant. This overall composite score is also on a scale of 0-100, where higher numbers indicate better visual function. Composite score based on National Eye Institute guidelines. | Baseline, 12 months | 
| Graft Failure/Graft Rejection |  | Baseline 12 months | 
| Graft Failure/Graft Rejection |  | Baseline to 24 months |