Clinical trial NCT02373137: Descemet Endothelial Thickness Comparison Trial
Official title: Descemet Endothelial Thickness Comparison Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Keratoplasty
Grafting, Corneal
Transplantation, Corneal
Transplantation, Cornea
Keratoplasty, Lamellar
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
name: Stanford University
First posted: 2015-02-26
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Best Spectacle-Corrected Visual Acuity
timeFrame: 6 months
Secondary outcomes:
measure: Best Spectacle-Corrected Visual Acuity
timeFrame: 3 and 12 months
measure: Best Spectacle-Corrected Visual Acuity
timeFrame: 24 Months
measure: Endothelial Cell Count
timeFrame: 3, 6, 12 months
measure: Endothelial Cell Count
timeFrame: 24 months
measure: Corneal Higher-Order Aberrations
timeFrame: 3, 6, 12 months
measure: Corneal Higher-Order Aberrations
timeFrame: 24 months
measure: Interface Haze
timeFrame: 3, 6, 12 months
measure: Interface Haze
timeFrame: 24 months
measure: National Eye Institute - Visual Functioning Questionnaire (NEI-VFQ)
timeFrame: Baseline, 12 months
measure: Graft Failure/Graft Rejection
timeFrame: Baseline 12 months
measure: Graft Failure/Graft Rejection
timeFrame: Baseline to 24 months
Other outcomes:
measure: Refraction
timeFrame: 3, 6, 12, 24 months
measure: Graft Thickness
timeFrame: 3, 6, 12, 24 months
measure: Operative Times
timeFrame: Baseline
measure: Adverse Events/Complication Rates
timeFrame: 3, 6, 12, 24 months
Locations:
city: Palo Alto
country: United States
facility: Byers Eye Institute, Stanford University
state: California
city: San Francisco
country: United States
facility: F. I. Proctor Foundation, University of California, San Francisco
state: California
city: Portland
country: United States
facility: Casey Eye Institute, Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Winston Chamberlain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Jennifer Rose-Nussbaumer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Charles Lin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Price FW Jr, Price MO. Evolution of endothelial keratoplasty. Cornea. 2013 Nov;32 Suppl 1:S28-32. doi: 10.1097/ICO.0b013e3182a0a307.
citation: Chen ES, Terry MA, Shamie N, Hoar KL, Friend DJ. Descemet-stripping automated endothelial keratoplasty: six-month results in a prospective study of 100 eyes. Cornea. 2008 Jun;27(5):514-20. doi: 10.1097/ICO.0b013e3181611c50.
citation: Ham L, Dapena I, van Luijk C, van der Wees J, Melles GR. Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy: review of the first 50 consecutive cases. Eye (Lond). 2009 Oct;23(10):1990-8. doi: 10.1038/eye.2008.393. Epub 2009 Jan 30.
citation: Dirisamer M, van Dijk K, Dapena I, Ham L, Oganes O, Frank LE, Melles GR. Prevention and management of graft detachment in descemet membrane endothelial keratoplasty. Arch Ophthalmol. 2012 Mar;130(3):280-91. doi: 10.1001/archophthalmol.2011.343. Epub 2011 Nov 14.
citation: Kruse FE, Laaser K, Cursiefen C, Heindl LM, Schlotzer-Schrehardt U, Riss S, Bachmann BO. A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty. Cornea. 2011 May;30(5):580-7. doi: 10.1097/ico.0b013e3182000e2e.
citation: Rudolph M, Laaser K, Bachmann BO, Cursiefen C, Epstein D, Kruse FE. Corneal higher-order aberrations after Descemet's membrane endothelial keratoplasty. Ophthalmology. 2012 Mar;119(3):528-35. doi: 10.1016/j.ophtha.2011.08.034. Epub 2011 Dec 22.
citation: Busin M, Madi S, Santorum P, Scorcia V, Beltz J. Ultrathin descemet's stripping automated endothelial keratoplasty with the microkeratome double-pass technique: two-year outcomes. Ophthalmology. 2013 Jun;120(6):1186-94. doi: 10.1016/j.ophtha.2012.11.030. Epub 2013 Mar 1.
citation: Guerra FP, Anshu A, Price MO, Giebel AW, Price FW. Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss. Ophthalmology. 2011 Dec;118(12):2368-73. doi: 10.1016/j.ophtha.2011.06.002. Epub 2011 Aug 27.
citation: Ang MJ, Chamberlain W, Lin CC, Pickel J, Austin A, Rose-Nussbaumer J. Effect of Unilateral Endothelial Keratoplasty on Vision-Related Quality-of-Life Outcomes in the Descemet Endothelial Thickness Comparison Trial (DETECT): A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2019 Jul 1;137(7):747-754. doi: 10.1001/jamaophthalmol.2019.0877.
citation: Chamberlain W, Lin CC, Austin A, Schubach N, Clover J, McLeod SD, Porco TC, Lietman TM, Rose-Nussbaumer J. Descemet Endothelial Thickness Comparison Trial: A Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty. Ophthalmology. 2019 Jan;126(1):19-26. doi: 10.1016/j.ophtha.2018.05.019. Epub 2018 Jun 23.