Corneal Endothelial Decompensation, Fuchs' Endothelial Dystrophy
Conditions
Brief summary
This double-masked multi-center trial will evaluate the association of diabetes in the cornea donor with transplant success and loss of endothelial cells through 1 year following Descemet membrane endothelial keratoplasty (DMEK). Study eyes are assigned to receive either a cornea from a donor without diabetes or a cornea from a donor with diabetes.
Detailed description
This study will address concerns about the suitability of corneas from donors with diabetes for use with DMEK through a prospective, masked, multi-center clinical trial in which the donor corneas are assigned by diabetes status in the same distribution proportion (2:1 distribution of tissue from donors without diabetes to tissue from donors with diabetes) currently used in the USA. The DEKS will assess graft success and endothelial cell density through 1 year following DMEK to determine whether the surgical success rate with corneas from donors with well characterized diabetes (including post-mortem hemoglobin A1c (HbA1c) and advanced glycation end products (AGE) testing) is inferior to the rate with donors without diabetes. The investigators hypothesize that the majority of donor corneas from individuals with diabetes will be suitable, but that a portion of donors with a higher diabetes severity scale, and/or poorer control based on HbA1c will have a greater risk for graft failure and endothelial cell loss. This study will also examine collected skin biopsies to determine whether high levels of AGE biomarkers in donor skin tissue - which quantifies disease severity over many years (and possibly coupled with elevated HbA1c levels) - is associated with greater risk for graft failure and cell loss. This novel approach to characterization of donor tissue can provide a paradigm shift in the risk assessment of transplanted corneas from diabetic donors. The effect of recipient diabetes on keratoplasty success and cell loss will also be studied in a rigorous manner to determine the potential combined effect of donor and recipient diabetes status. In summary, this study is designed to determine if non-diabetic donor corneas are superior to diabetic donor corneas in terms of both graft success and endothelial cell density outcomes, with an additional specific aim to determine whether donors with a higher diabetes severity scale, and/or poorer control based on HbA1c are driving the effect. This study will also determine whether a high AGE/A1c metric is also associated with the potential superiority finding and establish a novel composite score (severity score, HbA1c and AGE/A1c) based on these metrics that can be used to identify high versus low risk diabetic donors. This distinction may enable eye banks to potentially utilize the majority of donors with diabetes for EK surgery, while excluding the severely affected donors with diabetes.
Interventions
cornea transplant procedure to replace dysfunctional endothelial cell layer
Sponsors
Case Western Reserve University
Jaeb Center for Health Research
National Eye Institute (NEI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The participants and the clinical site staff, including the investigators and outcomes assessor will be masked to all donor tissue parameters except storage solution.
Intervention model description
Prospective, randomized, double-masked (participant and clinical site) clinical trial
Eligibility
Sex/Gender
ALL
Age
30 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria: 1. Age range 30- \< 91 years with minimum life expectancy of at least 1 year 2. Willingness to return to study site for follow up at 1 month and 1 year 3. Fluent in English or Spanish 4. Willingness to have fingerstick blood sample collected to determine HbA1c level at entry and at 1 year. The participant must agree to have their primary care provider contacted (or an appropriate referral provided) if they were not known to have diabetes and the HbA1c suggests they may have diabetes. Similarly, if already known to have diabetes and the HbA1c is high, the participant must agree to have their primary care provider contacted or an appropriate referral provided. 5. Has at least one eye clinically recommended for Descemet membrane endothelial keratoplasty (DMEK) that is able to be scheduled for DMEK between 5 to 90 days after enrollment. If second eye is enrolled, it must be scheduled for DMEK between 7 days and 6 months after DMEK on the first eye. 6. Has a condition related to endothelial dysfunction which will be treated by DMEK. Eligible indications for DMEK include: 1. Presence of Fuchs endothelial corneal dystrophy (FECD) meeting at least one of the following: phakic FECD with or without cataract (triple procedure including DMEK for FECD, cataract extraction and posterior chamber intraocular lens implantation (IOL) is allowed) 2. pseudophakic FECD with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL 3. pseudophakic corneal edema with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL without FECD 4. failed Descemet stripping automated endothelial keratoplasty (DSAEK) or DMEK originally performed for the same indications above without current exclusionary criteria, as described below
Exclusion criteria
1. Pregnant or planning to become pregnant prior to the DMEK study surgery, based on verbal report. 2. Lack cognitive capacity such that consent could not be provided. 3. Presence of a condition that has a high probability for failure (e.g., failed penetrating keratoplasty, uncontrolled uveitis) 4. Stromal vascularization that will impede assessment of recipient stroma clarity 5. Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy. 6. Indication for surgery that is not suitable for DMEK (e.g, keratoconus, stromal dystrophies and scars) 7. Aphakic corneal edema with or without FECD 8. Anterior chamber IOL in study eye prior to DMEK or planned placement of anterior chamber IOL during DMEK 9. Presence of vitreous in the anterior chamber 10. Planned IOL exchange of an anterior chamber IOL with a posterior chamber IOL in study eye at time of study DMEK 11. Pre-operative central sub-epithelial or stromal scarring that could impact post-operative recipient stromal clarity assessment 12. Presence of anterior synechiae 13. Peripheral anterior synechiae in the angle greater than a total of three clock hours 14. Uncontrolled glaucoma with or without prior filtering surgery, tube shunt placement, or MIGS. Uncontrolled glaucoma is defined as intraocular pressure \> 25mm Hg. 15. Controlled glaucoma with prior tube shunt placement for glaucoma (controlled glaucoma with minimally invasive glaucoma surgery (MIGS) or trabeculectomy is allowed) 16. Fellow eye visual acuity \< 20/200 due to an ocular condition other than a cornea disease that would be a candidate for DMEK 17. Intraocular pressure \<8 mmHg 18. Topical Rho kinase inhibitor, including netarsudil, used within 1 month prior to study entry and anticipated during the course of the study 19. Fellow eye enrolled in the DEKS that has met study-criteria for graft failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft Failure | 1 year | Graft failure is defined as the occurrence of one of the following: a graft which requires replacement for any reason or the recipient cornea remains cloudy after surgery without clearing for 8 weeks or longer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Cell Density | 1 year | Central corneal endothelial cell density assessed with specular microscopy |
Countries
United States
Contacts
STUDY_CHAIRJonathan Lass, MD
Case Western Reserve University
Participant flow
Recruitment details
Eligible recipients were aged 30 to 90 years old and scheduled to have Descemet membrane endothelial keratoplasty to treat a low to moderate risk condition including Fuchs endothelial corneal dystrophy (FECD), pseudophakic corneal edema, or failed DSAEK or DMEK.
Pre-assignment details
If a study participant received a study cornea from a donor with diabetes in one eye and a study cornea from a donor without diabetes in the fellow eye, the baseline characteristics collected at the time of enrollment of the first eye were counted in BOTH study arms (n=177). Thus 1097 participants were enrolled and 1274 participant characteristics are reported.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71 years |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Eyes |
| Race (NIH/OMB) Asian | 0 Eyes |
| Race (NIH/OMB) Black or African American | 23 Eyes |
| Race (NIH/OMB) More than one race | 5 Eyes |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Eyes |
| Race (NIH/OMB) Unknown or Not Reported | 0 Eyes |
| Race (NIH/OMB) White | 1369 Eyes |
| Region of Enrollment United States | 509 Eyes |
| Sex: Female, Male Female | 502 Eyes |
| Sex: Female, Male Male | 208 Eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 912 | 4 / 509 |
| other Total, other adverse events | 402 / 912 | 224 / 509 |
| serious Total, serious adverse events | 4 / 912 | 2 / 509 |
Outcome results
None listed