Descemet Endothelial Thickness Comparison Trial
Phase: PHASE4
Conditions: Keratoplasty, Grafting, Corneal, Transplantation, Corneal, Transplantation, Cornea, Keratoplasty, Lamellar
Sponsor: Oregon Health and Science University

DETECT Manual of Operations and Procedures 
Descemets Endothelial Thickness Comparison Trial 
 
Manual of Operations and Procedures 
 
 
Casey Eye Institute, Oregon Health & Science University 
Francis I. Proctor Foundation, University of California San Francisco                            
Byers Eye Institute, Stanford University 
 
 
Investigators: 
Winston Chamberlain*1 
Charles C. Lin*2 
Ariana Austin3 
Nicholas Shubach1 
Jameson Clover4 
Stephen D McLeod5 
Travis C. Porco3,6 
Thomas M. Lietman3,5,6 
Jennifer Rose-Nussbaumer*3,5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Principal Investigator 
 
1Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon 
2Byers Eye Institute, Stanford University, Palo Alto, California 
3Francis I. Proctor Foundation, University of California, San Francisco 
4Lions VisionGift, Portland, Oregon  
5Department of Ophthalmology, University of California, San Francisco  
6Epidemiology and Biostatistics, University of California San Francisco  
 
 

DETECT Manual of Operations and Procedures 
CONTENTS 
1. 
INTRODUCTION AND BACKGROUND ................................................................................................................... 1 
1.1 
Specific Aims .......................................................................................................................................................... 1 
1.2 
Study Outcomes ..................................................................................................................................................... 2 
1.3 
Study Design .......................................................................................................................................................... 2 
2. 
ORGANIZATION .................................................................................................................................................. 2 
2.1 
Collaborating Institutions ..................................................................................................................................... 2 
3. 
PATIENT FLOW .................................................................................................................................................... 4 
3.1 
Study Timeline ....................................................................................................................................................... 4 
3.2 
Eligibility Requirements ........................................................................................................................................ 4 
3.3 
Randomization ...................................................................................................................................................... 5 
3.4 
Study Visits ............................................................................................................................................................ 5 
3.5 
Adverse Events (AEs) ............................................................................................................................................. 6 
4. 
PROCEDURES ...................................................................................................................................................... 7 
4.1 
Masking ................................................................................................................................................................. 7 
4.2 
Treatment .............................................................................................................................................................. 7 
4.3 
Examinations During Follow-up Visits .................................................................................................................... 7 
4.4 
Study Schedule ...................................................................................................................................................... 8 
5. 
STUDY MEDICATIONS ......................................................................................................................................... 8 
5.1 
Prednisolone, Ofloxacin, and Tropicamide/Phenylephrine .................................................................................... 8 
5.2 
Possible Side Effects of Study Medications ............................................................................................................ 9 
6. 
PROTECTION OF HUMAN SUBJECTS .................................................................................................................... 9 
6.1 
Institutional Review Board Approval ...................................................................................................................... 9 
6.2 
Informed Consent ................................................................................................................................................... 9 
6.3 
Risks to Study Participants ................................................................................................................................... 9 
6.4 
Privacy, Confidentiality, and Data Security ........................................................................................................ 10 
6.5 
Exclusion of Vulnerable Populations .................................................................................................................. 10 
6.6 
Compensation to Participants .............................................................................................................................. 11 
7. 
DATA COLLECTION AND MANAGEMENT ........................................................................................................... 11 
7.1 
Data Collection and Entry .................................................................................................................................... 11 
7.2 
Data Consistency, Validity, and Monitoring ......................................................................................................... 11 
7.3 
Data Storage and Security ................................................................................................................................... 11 
8. 
STATISTICAL ANALYSIS ...................................................................................................................................... 11 
9. 
REFERENCES ...................................................................................................................................................... 12 
10. 
APPENDICES ...................................................................................................................................................... 13 
10.1 
Study Forms .................................................................................................................................................... 13 
10.2 
Protocols .......................................................................................................................................................... 13 
 
 
 
 
 

 
 
 
 
 
 
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1. INTRODUCTION AND BACKGROUND 
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.1 Currently, Descemet’s Stripping Endothelial Keratoplasty (DSAEK) is the most common 
procedure because of its relative ease and good outcomes.2 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.3-7 However, donor preparation, increased intra-operative 
times, and problems with donor attachment in DMEK are all important limitations.8-10    
 
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.11 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.10 Finally, 
interface haze may be increased in DSAEK and has been correlated with BSCVA.12 
 
Ultrathin DSAEK involves donor preparation with a double 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.11,13-15 This randomized controlled trial could directly address these important issues. We 
also anticipate that secondary analyses of the trial data will allow us to address several more.  
 
Research Question: Are BSCVA outcomes, endothelial cell counts, and post-operative corneal light 
scatter and higher-order aberrations different between patients undergoing ultrathin DSAEK 
versus DMEK? 
1.1 Specific Aims 
1) To determine whether there is a difference in best spectacle-corrected visual 
acuity (BSCVA) at 6 months between patients receiving ultrathin DSAEK and 
DMEK. We hypothesize that the DMEK group will have improved visual acuity 
compared with DSAEK at 3 months, but not at 6 months.  By randomizing 25 patients 
per arm, we anticipate 80% power to detect a one standard deviation, or approximately 
1.2 Snellen lines, difference in BSCVA between the DMEK and DSAEK groups.   
 
2) To evaluate endothelial cell loss at 6 months between patients receiving ultrathin 
DSAEK and DMEK. We hypothesize that there will be a difference in endothelial cell 
loss at 6 months between patients receiving ultrathin DSAEK and DMEK, accounting for 
pre-operative endothelial cell count.  
 
3) To assess the relative role of light scatter, higher-order aberrations and graft 
thickness on visual acuity. We predict that there will be increased light scatter at the 

 
 
 
 
 
 
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graft-host interface and but no difference in posterior corneal higher-order aberrations 
of the central 4mm in DSAEK versus DMEK.10   
 
While long-term outcomes such as graft rejection and survival are beyond the scope of the initial 
phase of this study, we anticipate we will be able to evaluate these as we follow patients at 12 and 
24 months.    
1.2 Study Outcomes 
Primary Outcome: 
• 
BSCVA at 6 months  
 
Secondary Outcomes: 
• 
Endothelial cell counts 
• 
Corneal higher-order aberrations as measured by Pentacam 
• 
Interface haze as measured by Pentacam densitometry 
• 
Change in NEI-VFQ from baseline to 3 months and 12 months 
• 
Primary graft failure, defined as a lack of graft clearing or need for re-graft within the first 2 
months  
• 
Graft rejection, defined as loss of graft clarity due to edema with evidence of inflammation 
such as anterior chamber cell or keratic precipitates. 
 
Other Outcomes measured: 
• 
Refraction 
• 
Graft thickness as measured by OCT and pachymetry 
• 
Operative times 
• 
Adverse events/Complication rates 
 
1.3 Study Design 
Descemets Endothelial Thickness Comparison Trial (DETECT) is a randomized double-masked, 
two-arm clinical trial. The purpose of this study is to determine differences in visual outcomes 
between two types of corneal transplant surgeries. There will be 1:1 randomization to one of two 
treatment groups – 1.) Ultrathin Descemet’s Stripping Endothelial Keratoplasty (DSAEK) OR 2.) 
Descemet’s Membrane Endothelial Keratoplasty (DMEK). The enrollment period is 24 months.  
 
 
2. ORGANIZATION 
Oregon Health & Science University (OHSU) along with the University of California San Francisco 
(UCSF) will jointly execute this clinical trial. OHSU will mainly be responsible for recruitment and 
enrollment, intervention implementation, and follow-up visits. UCSF will take the lead on all data 
analysis, writing of study-related materials, and journal publications. 
2.1 Collaborating Institutions 
Oregon Health & Science University  
As a teaching institution and part of OHSU, Casey Eye Institute has state-of-the-art facilities and 
access to specialists in all areas of eye care. The Casey Eye Institute will serve as one of the sites for 
recruitment, treatment/intervention, and follow-up visits. All study personnel assisting with the 
research will be adequately informed about the protocol, the research procedures, and their duties 
and functions through ongoing communication between Casey Eye Institute and UCSF.  
 

 
 
 
 
 
 
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Winston Chamberlain, MD, PhD is the PI for this study and works as a lead surgeon at Casey Eye 
Institute. Dr. Chamberlain received his BS in biology from California Institute of Technology. He 
holds a PhD in immunology and an MD from the University of Colorado Health Sciences Center. He 
is board certified in ophthalmology, and a member of the American Academy of Ophthalmology. His 
research interests include the outcomes of corneal transplant surgery with the femtosecond laser 
and DSAEK techniques, and inflammatory responses in the cornea. 
 
Brenda Purvis is the OHSU study coordinator. She works as the Cornea Division Manager at Casey 
Eye Institute. 
 
Stanford University 
The Byers Eye Institute at Stanford University is dedicated to combating blindness and preserving 
sight by delivering an effective, integrated collection of comprehensive vision care specialties. The 
Byers Eye Institute will be a second site for recruitment, treatment/intervention, and follow-up 
visits. All study personnel assisting with the research will be adequately informed about the 
protocol, the research procedures, and their duties and functions through ongoing communication 
between Byers Eye Institute and UCSF. 
 
Charles C. Lin, MD is a board-certified ophthalmologist and cornea specialist. He is the co-PI at the 
Byers Eye Institute at Stanford University School of Medicine. Dr. Lin received his AB in 
Environmental Science and Public Policy from Harvard University, graduating summa cum laude. 
He attended medical school at the University of California, San Francisco, where he received his 
M.D. with honors. Following an internship in Internal Medicine at Cedars-Sinai Hospital, he 
completed his ophthalmology residency at the University of California, San Francisco. He received 
subspecialty Cornea, External Disease, and Refractive Surgery training at the F.I. Proctor 
Foundation and University of California, San Francisco, one of the premier fellowships in the 
country. He spearheads the cornea transplant program at Stanford University and has launched 
cutting edge surgical procedures including ultra-thin DSAEK, DMEK and DALK at Stanford. 
 
Pauline Lacoste has strong expertise working on ophthalmology studies and is successfully trained 
to CITI, HIPAA and GCP.  
 
Francis I. Proctor Foundation 
The Proctor Foundation is an organized research unit at the University of California, San Francisco. 
The Foundation has a 56-year history of research in ocular infectious and inflammatory disease and 
runs one of the leading corneal fellowship training programs in the United States.  Proctor 
Foundation faculty have been involved in prevention of blindness research in developing countries 
since the Foundation’s inception. The impetus for establishing the Foundation in 1947 was to 
eradicate trachoma in the American Southwest and other parts of the world. 
 
UCSF will perform the data analysis. UCSF will not consent any participants, perform surgeries, or 
collect study data. UCSF will have the most current protocol, consent documents and HIPAA 
authorization for reference. UCSF has received IRB approval for this study (IRB number: 14-13728). 
All modifications to either IRB of record will be communicated between sites. UCSF will ensure 
protection of all study-related data by using de-identified information over a secure server. All non-
compliance with the study protocol or applicable requirements will be reported in accordance with 
local policy. There will be ongoing communication of problems, interim results, and study closure 
between both sites. 
 

 
 
 
 
 
 
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Jennifer Rose-Nussbaumer, MD is the co-PI at UCSF for this study. Dr. Rose-Nussbaumer is a Cornea 
fellowship trained Ophthalmologist at F. I. Proctor Foundation. In addition to her clinical work in 
cataract and corneal transplant surgery, she is an NIH funded clinical researcher. She is studying 
corneal ulcer treatment in India and Nepal and corneal transplant outcomes in Ethiopia. She is the 
principle investigator on the Corneal Preservation Time study at UCSF. Her previous vision 
research in Ophthalmology includes work with the World Health Organization on Trachoma, as well 
as investigating the ocular manifestations of HIV disease. Dr. Rose-Nussbaumer’s role in this study 
will be to perform data analysis, to collaborate with surgery site and eye bank, and to collaborate 
with OHSU and Stanford PIs regarding study design and protocols. 
 
Ariana Austin, MS is the UCSF study coordinator for this study. She has experience working on 
international and ophthalmology studies and currently serves as a study coordinator for several 
surgical studies at F. I. Proctor Foundation. 
 
 
3. PATIENT FLOW 
3.1 Study Timeline  
The enrollment period will be 24 months. Study participants will be required to have follow-up 
visits at months 3 (visit window: 2-4 months), 6 (visit window: 5-7 months), 12 (visit window: 10-
14 months), and 24 (visit window: 20-28) from the time of surgery. Additional visits may be needed 
and will be determined by the surgeon/investigator. 
3.2 Eligibility Requirements 
3.2.1 
Study Area 
Recruitment of eligible participants will be done at the Casey Eye Institute and Byers Eye Institute. 
Eligible participants will be screened by the primary surgeon and research staff at OHSU and 
Stanford. Potential participants will be approached during a standard of care clinical visit in the 
outpatient practice of the primary investigator at Casey Eye Institute, OHSU. These are patients that 
need to have corneal surgery whether or not they participate in this study. 
3.2.2 
Eligibility criteria for study participants 
Only those who meet all of the inclusion criteria and none of the exclusion criteria will be enrolled 
in this study.  
 
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 

 
 
 
 
 
 
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• 
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 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 
 
3.3 Randomization 
Each study eye will be randomly assigned to the 1) DSAEK or 2) DMEK treatment group. Block 
randomization will be performed using a computer program (Statistical package R; Version 2.12; R 
Foundation for Statistical Computing, Vienna, Austria) by the coordinating site.  
 
Once an eye is enrolled in the study, the study coordinator will assign the study participant’s eye an 
ID (alpha-numeric code) and inform the eye bank (Note: The eye bank will assign tissue to the 
study participant prior to knowing which arm the study participant is assigned to). The eye bank 
will then sign into the Dropbox account associated with this study, open the “New Patient” folder, 
and then open the file named with the particular study participant ID.  
 
Once the eye bank has opened the file, the study eye has been assigned a study participant ID and 
randomized to treatment group; therefore, they will be included in the intention to treat analysis. 
(Note: See eye bank protocol for full donor tissue procurement and assignment information). 
 
The treatment assignment will not contain identifiable patient information and will be shared using 
a password that is only known by the eye bank. The eye bank may only open the document for a 
given study participant and not for past or future study participants. The treatment assignment 
document should be moved from the “New Patients” folder to the “Old Patients” folder once 
opened.  
3.4 Study Visits  
3.4.1 
Baseline Visit 
During this visit, eligible patients who are enrolling for the first time will be enrolled in the study 
and will give consent. The baseline patient form will be completed and the NEI-VFQ will also be 
administered. If a patient includes a second eye in the study, they will complete an abbreviated 
baseline patient form for that study eye prior to surgery. They will not complete a second NEI-VFQ 
at the baseline visit for their second eye. Patients will also complete BSCVA, IOP, Pachymetry, and 
Pentacam tests at baseline.  

 
 
 
 
 
 
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3.4.2 
Surgery Visit  
The enrolled study participant’s eye(s) will undergo either DSAEK or DMEK surgery. If both of a 
participant’s eyes are included in the study, randomization to DSAEK or DMEK will be performed 
independently for each eye. 
3.4.3 
Follow-Up Visits 
The follow-up patient form will be completed at each visit, for each enrolled eye. Data collected for 
each follow-up visit will include: 
 
3 month follow-up: BSCVA, IOP, pentacam topography and densitometry pachymetry, optical 
coherence tomography, and endothelial imaging will be performed. The NEI-VFQ form will also be 
completed 
 
6 month follow-up data: BSCVA, IOP, pentacam topography and densitometry pachymetry, optical 
coherence tomography, endothelial imaging, and slit-lamp photography will be performed.  
 
12 month follow-up: BSCVA, IOP, pentacam topography and densitometry pachymetry, optical 
coherence tomography, and endothelial imaging will be performed. The NEI-VFQ form will also be 
completed 
3.4.4 
Final Visit 
During the Month 24 final visit, the final status and follow-up patient forms will be completed. 
BSCVA, IOP, pentacam topography and densitometry pachymetry, optical coherence tomography, 
and endothelial imaging will also be performed.  
3.5 Adverse Events (AEs) 
During each study visit, the subject will be questioned about AEs in a non-leading manner. All AEs, 
whether observed by the Investigator, elicited by the Investigator, or spontaneously reported by 
the subject, will be documented in the subject's chart and the adverse event form. Slit lamp 
photography will also be completed after any adverse event takes place.  
 
All AEs should be followed until they are resolved or until a stable clinical endpoint is reached. Each 
AE is to be classified by the Investigator as SERIOUS (SAE) or NONSERIOUS (NSAE). 
 
If a SAE occurs, the investigator at OHSU or Stanford must verbally and/or in writing notify 
OHSU/Stanford or its designee within 24 hours of the occurrence of the SAE.  
 
The initial SAE report must be followed by a written report, signed by the investigator, and received 
by OHSU/Stanford or its designee via fax within two working days. The investigator must provide 
written follow-up reports until the SAE or clinically significant AE has resolved or until a stable 
clinical endpoint is reached. Notification of an SAE or clinically significant AE must also be 
submitted to the Institutional Review Board (IRB)/Ethics Committee (EC) in accordance with its 
requirements. All AEs must be reported from the time that the subject provides informed consent 
through the last study visit.  
 
 

 
 
 
 
 
 
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4. PROCEDURES 
4.1 Masking 
All study participants will be masked to their intervention. The refractionist performing the BSCVA 
will also be masked. Due to the nature of the intervention, the surgeon and technician performing 
study visit endothelial cell counts and other imaging will not be masked; however, graders will be 
masked when possible. Eye bank and UCSF study personnel will not be given any identifying 
information. 
4.2 Treatment 
For each procedure, the tissue will be prepared by either Lions VisionGift or Sightlife. Each 
participant will undergo surgery only once and will take approximately 1-2 hours. This study 
requires 6 visits to the clinic over a period of 2 years, there may be additional post-operative visits 
(above what the study requires) following this surgical procedure. 
4.2.1 
DSAEK 
For DSAEK, 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.    
4.2.2 
DMEK 
For DMEK, 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. 
4.3 Examinations During Follow-up Visits 
There will be 4 follow-up visits for this study – Month 3, 6, 12, and 24; all of these visits would be 
expected in normal post-operative care. During each follow-up appointment, tests will be done on 
the participant’s study eye; these include: BSCVA, intraocular pressure (IOP), corneal thickness 
using a Pachymeter, manifest refraction, slit lamp and slit lamp photography, endothelial imaging, 
Pentacam topography and densitometry, and optical coherence tomography (OCT) testing. Dilated 
retinal exam will be performed at the discretion of the surgeon. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
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4.4 Study Schedule 
 
Table 1: Study Schedule 
 
Visit 1 
Pre-op  
Visit 2 
Surgery 
Visit 3 
Month 3  
Visit 4 
Month 6 
Visit 5 
Month 12 
Visit 6 
Month 24 
Forms 
 
 
 
 
 
 
Consent and 
Authorization form  
X 
 
 
 
 
 
Baseline form  
X 
  
  
  
  
  
NEI-VFQ 
X 
(for 1st eye) 
 
 
 
X 
 
Follow-up form  
  
  
X 
X 
X 
X 
Final form 
  
  
  
  
  
X 
Procedures 
 
 
 
 
 
 
 
DMEK or DSAEK surgery 
  
X 
  
  
  
  
Tests 
 
 
 
 
 
 
IOP 
X 
 
X 
X 
X 
X 
Pachymetry U/S 
X 
 
X 
X 
X 
X 
Pentacam (densiometry & 
topography) 
X 
 
X 
X 
X 
X 
OCT 
 
 
X 
X 
X 
X 
Endothelial imaging  
 
 
X 
X 
X 
X 
Slit Lamp Photography* 
A few patients 
 
 
X  
 
 
BSCVA/ETDRS/MRx 
X 
 
X 
X 
X 
X 
Total visit time 
2 hours 
2 hours 
1 hour 
1 hour 
1 hour 
1 hour 
* Slit lamp photography also taken upon an adverse event 
 
 
 
 
5. STUDY MEDICATIONS 
5.1 Prednisolone, Ofloxacin, and Tropicamide/Phenylephrine 
The following medications will be administered for treatment purposes: Prednisolone, Ofloxacin, 
and Tropicamide/Phenylephrine.  
5.1.1 
Treatment schedule for study medications 
The following drug schedule will be followed by all participants: Prednisolone and Ofloxacin four 
times a day post-operation. Standardized protocol will be to continue Ofloxacin for 1 week, then 
stop.  Prednisolone will be taken four times a day for 4 months, then decreased by 1 drop per 
month until at 1 drop per day.  Participants will stay on 1 drop for at least one year.  Steroid 
treatment can be altered at the discretion of the clinician.  The aforementioned drugs will be used 
for FDA approved indications and will not require an IND. All medications will be protected and 
only appropriate personnel will administer the drugs. Tropicamide/Phenylephrine drops will be 
used at the screening exam and at postoperative visits when required. They would be used for pre- 
and postoperative eye monitoring whether participants are involved in the study or not. These 
drops are not included in the below dosing schedule since they will be utilized on an as needed 
bases.  
 
Table 2: Dosing schedule for Prednisolone and Ofloxacin 
Medication 
Day 1-Day 8 
Day 9-Month 3 
Month 4 
Month 5 
Month 6- 12 
Prednisolone 
4 times/day 
4 times/day 
3 times/day 
2 times/day 
1 time/day 
Ofloxacin 
4 times/day 
 
 
 
 
 

 
 
 
 
 
 
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5.2 Possible Side Effects of Study Medications 
Prednisolone: eye irritation, swelling, pain, or redness; pressure within the eye; cataract growth; 
eye infection 
 
Ofloxacin: eye irritation, swelling, pain, or redness 
 
Tropicamide/Phenylephrine: eye irritation, swelling, pain, or redness; Eye dilation may result in 
temporary blurred vision, light sensitivity, and increased heart rate.  
 
 
6. PROTECTION OF HUMAN SUBJECTS 
6.1 Institutional Review Board Approval 
6.1.1 
Oregon Health & Science University Institutional Review Board (OHSU IRB) 
The OHSU IRB will annually review study protocol for ethical approval. 
6.1.2 
University of California, San Francisco Committee on Human Research (UCSF CHR) 
The UCSF CHR will annually review study protocol for ethical approval. 
6.1.3 
Stanford University Institutional Review Board (Stanford IRB) 
The Stanford IRB will annually review study protocol for ethical approval. 
6.2 Informed Consent 
OHSU and Stanford personnel will obtain full written consent from each patient enrolled. The 
primary surgeon will screen participants and determine their eligibility. He/she will clearly explain 
the process and risks involved and will also ask the patient to sign any necessary consent 
documents. The study participant will have 6 visits total per eye included in the study; visits include 
surgery and will take place over a period of 2 years. The patient has the ability to withdraw at any 
time and will not be forced into anything with which he/she is not comfortable.  Consent 
documents have been uploaded to the IRB application. 
 
6.3 Risks to Study Participants 
Study participants will not have any increased risk or cost for participating in this study. 
Participants in the study have the same risks as those undergoing corneal transplantation in other 
settings. Many of the risks in this study are inherent risks of corneal transplantation; thus, there is 
no known increased risk associated with participation in this study.  
 
As with any surgery, there are risks associated with these surgeries, and both surgeries have 
similar risks. There is a risk of infection or bleeding which could result in vision loss. There may be 
damage to the tissue graft during tissue preparation, and the tissue graft can fail to attach to the 
cornea; thus, there may be a need for repeat air injection. Below, the other risks associated with 
each type of surgery are listed: 
 
• 
DSAEK: There may be slightly decreased vision after surgery compared to DMEK, although 
this is unknown. The healing process may also be slower. Some think there is an increased 
risk of rejection compared to DMEK, although this is also unknown.  
 

 
 
 
 
 
 
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• 
DMEK: There may be increased risk of tissue loss, repeat air injection, detachment of the 
tissue graft to the cornea compared with DSAEK. There may be higher costs associated with 
this surgery, although these additional costs will be covered by insurance.  
 
Blindness due to infection may occur in extremely rare cases. There may also be differences in rates 
of difficulty with donor preparation, increased intra-operative times, graft rejection and graft 
survival, and donor attachment in DMEK versus DSAEK. Even if there is a total detachment during 
DMEK, we will continue to move forward with secondary treatment. These risks will be addressed 
by OHSU by making sure all protocols are being followed thoroughly and by following up with 
participants after surgery.  
 
There are no known risks directly related to the Endoserter and jones tube. There may be some 
discomfort during follow-up testing (BSCVA, IOP, slit lamp, Pachymeter, Pentacam, endothelial 
imaging and OCT testing and photo imaging inside the eye), but this will be kept to a minimum. The 
participant will be asked to tell the doctor if any of this testing feels painful. 
 
Anesthesiology will be determined as per the participants needs.   They will generally be awake 
with medications given to help them relax and feel comfortable.  This is called monitored 
anesthesia care. Other participants may require general anesthesia care.  While this is generally 
safe, there are small increased risks to the heart and lungs which will be discussed with the 
anesthesiologist.   Both types of anesthesia are routinely used for DMEK and DSAEK surgeries, 
although generally monitored anesthesia care is the typical route. 
6.4 Privacy, Confidentiality, and Data Security 
All data will be stored and transferred using a secure server with de-identified information. 
 
We will take steps to keep the participant’s personal information confidential. Health information 
will be kept secure and separate from information which identifies participants.  Upon enrollment, 
participants will be assigned a code that will be used instead of their name, medical record number 
or other personally identifying information. Electronic files for data analysis will contain only the 
participant code. The code will be stored at OHSU/Stanford on a secure server and will only be 
accessed by study personnel – the PI, study coordinator, or other member of the study team). 
Access to study-related patient information will be limited only to members of the study team. 
 
Only a small number of researchers related to this study will have direct access to the participant’s 
medical information. Paper files will be stored in locked filing cabinets in restricted access offices at 
OHSU. Access to data/specimens is restricted to study personnel. 
 
Information may be released to others outside of OHSU/Stanford who are involved in coordinating 
or overseeing research, but information which identifies the participant will be kept secure. To 
ensure the success of this study, OHSU and Stanford have partnered with University of California, 
San Francisco (UCSF)’s   F.I. Proctor Foundation, which is a center that specializes in ophthalmology 
research. The coordinating center at UCSF will have access to de-identified information using a code 
number. UCSF’s role is to support OHSU and Stanford on the data analysis portion of this study and 
assisting with the development of consent and study-related materials. UCSF has received IRB 
approval to take part in this study (IRB number: 14-13728). 
6.5 Exclusion of Vulnerable Populations 
The following populations will not be enrolled in this study: children (18 years and under), 
pregnant women, decisionally impaired adults, and prisoners. 

 
 
 
 
 
 
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6.6 Compensation to Participants 
There is no additional cost or compensation for the study participant. There will be no 
compensation for research-related injury.  
 
 
7. DATA COLLECTION AND MANAGEMENT 
7.1 Data Collection and Entry 
All data will be collected using hardcopy patient forms at OHSU and Stanford during baseline and 
follow-up visits. De-identified data will be uploaded to a Dropbox account in order to share the data 
with the UCSF study coordinator. De-identified data will be input into a database using double data 
entry at UCSF.  
7.2 Data Consistency, Validity, and Monitoring 
Data monitoring reports will be prepared using STATA and Excel. If the forms are not filled out 
completely, the UCSF study coordinator will contact the person responsible for completing the form 
to provide the missing data, or clarify any inconsistent data. The OHSU and Stanford study 
coordinators are the only people who are authorized to add missing data or make any changes to 
the study forms.  All changes should be made with a red ink pen, and then signed and dated. 
7.3 Data Storage and Security 
De-identified data will then be input into a database using double data entry at UCSF. Data will be 
stored at UCSF for about 10 years. 
 
8. STATISTICAL ANALYSIS 
Please see the Statistical Analysis Plan (SAP) for details on the statistical analysis.  
 
 
 

 
 
 
 
 
 
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9. REFERENCES 
1. Price FW, Jr., Price MO. Evolution of endothelial keratoplasty. Cornea. Nov 2013;32 Suppl 
1:S28-32. 
2. 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. Jun 
2008;27(5):514-520. 
3. 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. Oct 2009;23(10):1990-1998. 
4. Price MO, Giebel AW, Fairchild KM, Price FW, Jr. Descemet's membrane endothelial 
keratoplasty: prospective multicenter study of visual and refractive outcomes and 
endothelial survival. Ophthalmology. Dec 2009;116(12):2361-2368. 
5. Guerra FP, Anshu A, Price MO, Price FW. Endothelial keratoplasty: fellow eyes comparison 
of Descemet stripping automated endothelial keratoplasty and Descemet membrane 
endothelial keratoplasty. Cornea. Dec 2011;30(12):1382-1386. 
6. Anshu A, Price MO, Price FW, Jr. Risk of corneal transplant rejection significantly reduced 
with 
Descemet's 
membrane 
endothelial 
keratoplasty. 
Ophthalmology. 
Mar 
2012;119(3):536-540. 
7. Dapena I, Ham L, Netukova M, van der Wees J, Melles GR. Incidence of early allograft 
rejection 
after 
Descemet 
membrane 
endothelial 
keratoplasty. 
Cornea. 
Dec 
2011;30(12):1341-1345. 
8. Dirisamer M, van Dijk K, Dapena I, et al. Prevention and management of graft detachment in 
descemet 
membrane 
endothelial 
keratoplasty. 
Archives 
of 
ophthalmology. 
Mar 
2012;130(3):280-291. 
9. Kruse FE, Laaser K, Cursiefen C, et al. A stepwise approach to donor preparation and 
insertion increases safety and outcome of Descemet membrane endothelial keratoplasty. 
Cornea. May 2011;30(5):580-587. 
10. Rudolph M, Laaser K, Bachmann BO, Cursiefen C, Epstein D, Kruse FE. Corneal higher-order 
aberrations after Descemet's membrane endothelial keratoplasty. Ophthalmology. Mar 
2012;119(3):528-535. 
11. Neff KD, Biber JM, Holland EJ. Comparison of central corneal graft thickness to visual acuity 
outcomes in endothelial keratoplasty. Cornea. Apr 2011;30(4):388-391. 
12. Hindman HB, Huxlin KR, Pantanelli SM, et al. Post-DSAEK Optical Changes: A 
Comprehensive Prospective Analysis on the Role of Ocular Wavefront Aberrations, Haze, 
and Corneal Thickness. Cornea. Dec 2013;32(12):1567-1577. 
13. 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. Jun 2013;120(6):1186-1194. 
14. Dapena I, Dapena L, Dirisamer M, Ham L, Melles GR. [Visual acuity and endothelial cell 
density following Descemet membrane endothelial keratoplasty (DMEK)]. Archivos de la 
Sociedad Espanola de Oftalmologia. Dec 2011;86(12):395-401. 
15. 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. Dec 2011;118(12):2368-2373. 

 
 
 
 
 
 
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10. APPENDICES 
10.1 Study Forms 
Please see appropriate separate documents for the study forms.  
 
Study forms include:  
• 
Study visit checklist 
• 
Baseline edibility and patient form 
• 
NEI-VFQ 
• 
Follow-up patient form 
• 
Final patient forms 
 
10.2 Protocols 
Please see appropriate separate documents for the study protocols.  
 
Protocols include:  
• 
Best Spectacle-Corrected Visual Acuity Protocol 
• 
Eye Bank Protocol; Donor Eligibility and Assignment 
• 
Pentacam Protocol 
• 
Pachymetry Protocol  
• 
Endothelial Cell Count Protocol 
• 
Slit Lamp Photography Protocol 
• 
Optic Coherence Tomography Protocol