Descemet Endothelial Thickness Comparison Trial

Phase 4

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

Interventions: Procedure: DSAEK
Procedure: DMEK
Device: Endoserter
Drug: Prednisolone
Drug: Ofloxacin
Drug: Tropicamide
Device: Jones Tube
Drug: Phenylephrine

Registration Number: NCT02373137

Lead Sponsor: Oregon Health and Science University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: UNKNOWN

Sex: All

Target Recruitment: 38

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DSAEK	DSAEK	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.
DSAEK	Endoserter	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.
DSAEK	Ofloxacin	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.
DMEK	DMEK	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.
DMEK	Ofloxacin	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.
DMEK	Jones Tube	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.
DSAEK	Prednisolone	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.
DSAEK	Tropicamide	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.
DSAEK	Phenylephrine	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.
DMEK	Prednisolone	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.
DMEK	Tropicamide	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.
DMEK	Phenylephrine	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.

Primary Outcome Measures

Name	Time	Method
Best Spectacle-Corrected Visual Acuity	6 months	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).

Secondary Outcome Measures

Name	Time	Method
Best Spectacle-Corrected Visual Acuity	24 Months	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).
Endothelial Cell Count	24 months
Corneal Higher-Order Aberrations	24 months	As measured by Pentacam
Interface Haze	24 months	As measured by Pentacam densitometry
National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ)	Baseline, 12 months	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.
Graft Failure/Graft Rejection	Baseline to 24 months

Trial Locations

Locations (3): Byers Eye Institute, Stanford University
🇺🇸
Palo Alto, California, United States
F. I. Proctor Foundation, University of California, San Francisco
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San Francisco, California, United States
Casey Eye Institute, Oregon Health & Science University
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Portland, Oregon, United States