Effect of Cornea Preservation Time on Success of Descemet Stripping Automated Endothelial Keratoplasty: a Randomized Clinical Trial

Supplementary Online Content

Rosenwasser GO, Szczotka-Flynn LB, Ayala AR, et al; Cornea Preservation Time Study Group. Effect of cornea preservation time on success of Descemet stripping automated endothelial keratoplasty: a randomized clinical trial. JAMA Ophthalmol. Published online November 10, 2017. doi:10.1001/jamaophthalmol.2017.4989

eFigure 1. Graft Success Rate Over Time by 2 Preservation Time Groups Including Follow-up Beyond 3 Years eFigure 2. Visual Representation of the Primary Noninferiority Analysis eAppendix 1. Cornea Preservation Time Study Group: Clinical Sites eAppendix 2. Institutional Review Boards eTable 1. CPTS Graft Failure Definitions eTable 2. CPTS Donor Characteristics eTable 3. Surgical Data eTable 4. Postoperative Donor Positioning Complications and Procedures eTable 5. Serious Abnormalities eTable 6. Abnormalities on Cornea Exam / AC Exam eTable 7. Study Eye Procedures eTable 8. Potential Interactions with Preservation Time Groups eReferences

This supplementary material has been provided by the authors to give readers additional information about their work.

eFigure 1. Graft Success Rate Over Time by 2 Preservation Time Groups Including Follow-up Beyond 3 Yearsa

Days Since Surgery 0 1M 6M 12M 24M 36M 48M Preservation Time: 0-7 Days # at risk at beginning of interval 674 656 642 625 602 499 223 # graft failure during interval 16 1 4 3 5 1 1 # censored during interval 2 13 13 20 98 275 222 Preservation Time: 8-14 Days # at risk at beginning of interval 655 621 607 593 548 474 221 # graft failure during interval 32 2 3 6 5 2 0 # censored during interval 2 12 11 39 69 251 221 a For purposes of analyses, all failure or censoring events within 4 year visit window were mapped to month 48. There was not enough month 60 data available to evaluate beyond the month 48 time point. CI = Confidence Interval

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eFigure 2. Visual Representation of the Primary Noninferiority Analysisa

a The difference in 3 year graft success rates (0-7d PT group versus 8-14d PT group) is represented by the circle, with the one-sided 95% confidence interval of this difference represented by the whisker. The pre-specified non-inferiority limit of 4% is represented by the vertical line. The end of the whisker exceeds the non-inferiority limit. Thus, the study cannot conclude that the success rate for donor corneas with PT of 8-14 days is similar (non-inferior) to the success rate for donor corneas with a shorter PT.

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eAppendix 1. Cornea Preservation Time Study Group

Clinical Sites Listed in order of number of patients enrolled in the CPTS are the clinical sites with site name, city, state, number of eyes enrolled (in parentheses), name of the principal investigator, and other investigators ordered alphabetically. The names of the coordinators ordered alphabetically are also included.

Central Pennsylvania Eye Institute, Hershey, PA (220). Investigators: George Rosenwasser, MD (PI), J.E.B. Fugate, OD. Coordinators: Alicia Burrows, Miriam Rosenwasser. Verdier Eye Center, Grand Rapids, MI (107). Investigators: David Verdier, MD (PI), Mary Pat Chelsky, OD, Lyndsay Tomkins, OD. Coordinators: Samantha Ciganick, Paula Johnson, Devon Keeler, Brent Spoelstra, Pamela Van Duyn. Cornea Associates of Texas, Dallas, TX (66). Investigators: Tyrone McCall, MD (PI), Walter Beebe, MD, Charles Bowman, MD, Aaleya Koreishi, MD. Coordinators: Paige Grona, Jennifer Hargrove, Maria Mendez. University of Michigan/Kellogg Eye Center, Ann Arbor, MI (62). Investigators: Alan Sugar, MD (PI), Shahzad Mian, MD. Coordinators: Munira Hussain, Sonal Trivedi. Michigan Cornea Consultants, Southfield, MI (59). Investigators: Steven Dunn, MD (PI), Christopher Chow, MD, David Heidemann, MD. Coordinators: Elizabeth Brazier, Elly Garden, Tina MacLeod. Mid-Atlantic Cornea Consultants, Baltimore, MD (58). Investigator: Sudeep Pramanik, MD (PI). Coordinators: Jessica Byer, Jennifer Freter, Hillary Herman. Northeast Ohio Eye Surgeons, Kent, OH (52). Investigators: Marc Jones, MD (PI), Katie Greiner, OD, Elizabeth Muckley, OD. Coordinator: John Valentine. Devers Eye Institute, Portland, Oregon (50). Investigators: Mark Terry, MD (PI), Mike Straiko, MD. Coordinators: David Davis-Boozer, Mark Greiner, Zachary Mayko, Kelsey Oakes. Dean Medical Center, Madison, WI (41). Investigator: Christopher Croasdale, MD (PI), Coordinators: Lynn Dombrowicki, Michelle Kole, Gayle Walheim-Brown. Eye Associates Northwest, Seattle, WA (40). Investigator: Thomas Gillette, MD (PI). Coordinators: Jennifer Caillier, Michelle Corrigan, David Diaz, Christine Morchin. Mercy-St. John’s Clinic, Springfield, Missouri (39). Investigators: Shachar Tauber, MD (PI), Alison Hood-Kirar, OD. Coordinator: Crystal Trythall. Focal Point Vision, San Antonio, TX (38). Investigators: Kenneth Maverick, MD (PI), James Lehmann, MD. Coordinators: Ashley Grizzard, Lisa Navarro. University of Kentucky Department of Ophthalmology, Lexington, KY (34). Investigators: Woodford Van Meter, MD (PI), Douglas Katz, MD. Coordinators: Judy Beck, Lakisha Jeffries, Toni Scoggins, Jane Webb. Minnesota Eye Consultants, Bloomington, MN (33). Investigators: David Hardten, MD (PI), Marlane Brown, OD, Ahmad Fahmy, OD, Mona Fahmy, OD, Benjamin Fogal, OD, Scott Hauswirth, OD, Richard Lindstrom, MD, Sherman Reeves, MD. Coordinators: Alex Belsaas, Lindsey Fallenstein, Sara Mork, Amanda Stehly, Joshua Tisdell.

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Ophthalmic Partners of PA, P.C., Bala Cynwyd, PA (32). Investigators: Irving Raber, MD (PI), Brandon Ayres, MD. Coordinators: Samantha Campbell, Gordon Drever, Cathy Petrocella, Irene Spanelis. Cincinnati Eye Institute, Cincinnati, OH, (31). Investigator: Michael Nordlund MD, PhD (PI). Coordinators: Jen Bradford, Tracy Cruz. University of Illinois Chicago Eye and Ear Infirmary, Chicago, IL (31). Investigators: Elmer Tu, MD (PI), Ali Djalilian, MD, Maria Soledad Cortina, MD. Coordinator: Marie Dolores Byrne. Northshore University Health System, Glenview, IL (26). Investigators: Marian Macsai, MD (PI), Joshua Herz, MD. Coordinators: Vicenta Martinez, Mira Shiloach. Medical Eye Center, Medford, OR (25). Investigator: Matthew Oliva, MD (PI). Coordinators: Heather Smith, Toni Wild. The Wilmer Eye Institute/Johns Hopkins, Baltimore, MD (25). Investigators: Yassine Daoud, MD (PI), Oliver Schein, MD, Walter Stark, MD. Coordinators: Holly Brown, Kaitlyn Hodges, Mary LoValvo, Regina Morgan, Kimberly Pratzer, Stacey Seabrook, Nadia Wong. Mayo Clinic, Rochester, MN (23). Investigators: Sanjay Patel, MD (PI), Keith Baratz, MD. Coordinators: JaMario Ayers, Melissa Franzen, Rebecca Nielsen, Heidi Rubin, Diane Vogen. University of Utah, Moran Eye Center, Salt Lake City, UT (23). Investigator: Mark Mifflin, MD (PI). Coordinators: Katie Farnsworth, Deborah Harrison. Sadeer Hannush PC, Langhorne, PA (22). Investigator: Sadeer Hannush, MD (PI). Coordinators: Brian Sperling, Lisa Sperling. The Ohio State University Wexner Medical Center- Havener Eye Institute, Columbus, OH (19). Investigators: Thomas Mauger, MD (PI), Andrew Hendershot, MD, Rebecca Kuennen, MD. Coordinators: Dana Doneski, Deniz Eren, Meredith Hiltbrand Andrea Inman Jonda Leser, Sara Oravec, Christoper Petec, Demarcus Williams. Keck Medical Center of USC-Ophthalmology, Los Angeles, CA, (18). Investigators: Jonathan Song (PI), Neda Shamie, MD, J. Martin Heur, MD. Coordinators: Grace Chon, John Gil-Flamer, Yoon Hee Kim, Margaret Padilla, Amelia Weldon. Ophthalmic Consultants of Boston, Boston, MA (16). Investigators: Michael Raizman, MD (PI), Nicoletta Fynn-Thompson, MD, Peter Rapoza, MD. Coordinators: Harrison Bannett, Emily Beem, Joanne Berry, Tina Callina, Amanda Campbell, Allison Coombs, Samantha Hulbert, Jennifer Moro Brent Richardson, Kimberly Santos, Angell Shi. Bascom Palmer Eye Institute, Miami, FL (15). Investigators: Sonia Yoo, MD (PI), Michael Banitt, MD, Kendall Donaldson, MD, Carol Karp, MD, Coordinators: Maria Esquiabro, Ailen Gutierrez, Janika San Roman, Martha Tello, Ruth Vanderbrook, Patrick Waren. Stein Eye Institute, University of California, Los Angeles, CA (14). Investigators: Anthony Aldave, MD (PI), Sophie Deng, MD. Coordinators: Marianne Bernardo, Zach Fenoglio, Serina Gonzales, Ellen Haupt, Mathew Margolis, Elaine Ngo. Eye Care of San Diego, San Diego, CA (13). Investigator: John Bokosky, MD (PI). Coordinators: Jennifer Manke, Tracee McCoy, Mallory Moreno, Natasha Ozerskiy, Deborah Rodriguez.

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New York Eye and Ear Infirmary, New York, NY (13). Investigators: John Seedor, MD (PI), David Ritterband, MD, Elaine Wu, MD. Coordinator: Alice Hong, Kristen Fry Yvonne Lyons, Katy Tai. Eye Consultants of Maryland, Owings Mills, MD (12). Investigators: Verinder Nirankari, MD (PI), Jennifer Nottage, MD. Coordinator: William Bolt. Corneal Associates, PC, Wills Eye Institute, Philadelphia, PA (11). Investigators: Kristin Hammersmith, MD (PI), Parveen Nagra, MD, Christopher Rapuano, MD. Coordinator: Megan DiLeo, William Garvey, Michael Lindsay, Sara Rapuano. Cornea Consultants of Albany, Slingerlands, NY (11). Investigators: Robert Schultze, MD (PI), Robert Eden, MD. Coordinators: Katherine Cavanaugh, Joelle Rifenburgh, Kamil San, Alice Titova. University Hospitals Cleveland Medical Center, Cleveland, OH (9). Investigators: Pankaj Gupta, MD (PI), Kristina Thomas, MD. Coordinators: Lisa Ferguson, Sangeetha Raghupathy, Jessica Tag, Kalisha Washington. Woolfson Eye Institute, Atlanta, GA (9). Investigator: R. Doyle Stulting, MD, PhD (PI), Coordinators: Jane Bryant, Deborah DiChiara, Aubrey Kirchner, Jodi Miller, Jesand Sylve. Eye Consultants of Atlanta, Atlanta, GA (8). Investigator: W. Barry Lee, MD (PI). Coordinators: Kimberly Harber, Teresa Long. University of Iowa Hospitals and Clinics, Iowa City, IA (8). Investigators: Kenneth Goins, MD (PI), Mark Greiner, MD, Anna Kitzmann, MD, Michael Wagoner, MD, PhD. Coordinators: Tammy Burdick, Constance Mullinnix. Ophthalmology Associates, St. Louis, MT (7). Investigators: Gregg Berdy, MD (PI), Robert Brusatti, OD, Ranjan Malhotra, MD. Coordinators: Debi Gravemann, Jill Montgomery, Diane Sanders, Amy Young. Center for Sight, Sarasota, Florida, (7). Investigators: William Lahners, MD (PI), James Lenhart, OD, Kyle Schaub, MD. Coordinators: Karen Hagin, Jamie Leeper, Tina Maler, Ginger Moritz, Gisela Santiago, Dawn Satterlee, Alyssa Willard. University of California - San Francisco, San Francisco, CA (3). Investigators: Jennifer Rose-Nussbaumer, MD (PI), Bennie Jeng, MD. Coordinators: Ariana Austin, Puja Cuddapah, Dionna Fry, Alexandra Neiman, Cissy Yang.

Eye Banks Listed in order of number of eyes enrolled in the CPTS are the eye banks with name, city, state, number of eyes in parentheses, and names of the principal investigators.

Eversight Michigan (formerly Midwest Eye-Banks Michigan), Ann Arbor, MI (226). Kristen McCoy Gift of Life Donor Program Eye Bank, Hershey, PA (220). Nai Liang KeraLink International (formerly Tissue Banks International), Baltimore, MD (132). Sameera Farazdaghi Eversight Illinois (formerly Midwest Eye-Banks Illinois), Chicago, IL (88). Kristen McCoy Sightlife, Seattle, WA (68). Caroline K. Hoover. University of Texas Southwestern, Dallas, TX (66). Donna Drury

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Lions Eye Bank of Delaware Valley, Philadelphia, PA (65). Gregory Dorn Eversight Ohio (formerly Cleveland Eye Bank), Cleveland, OH (61). Kristen McCoy Minnesota Lions Eye Bank, St. Paul, MN (56). Veronique Grimes Lions VisionGift, Portland, OR (51). Chris G. Stoeger Saving Sight, Kansas City, MO (47). Deborah Van Klinken Lions Eye Bank of Wisconsin, Madison, WI (41). Mikelanne Schipper (now with Lions Eye Institute for Transplant & Research) Iowa Lions Eye Bank, Coralville, IA (34). Gregory Schmidt Lions Eye Bank of Lexington, Lexington, KY (34). Patrick Haley Cincinnati Eye Bank, Cincinnati, OH (31). Tina Mays Utah Lions Eye Bank, Salt Lake City, UT (23). Wade McEntire Georgia Eye Bank, Atlanta, GA (17). Eric Meinecke Florida Lions Eye Bank, Miami, FL (14). Elizabeth Fout-Caraza. San Diego Eye Bank, San Diego, CA (13). Jeffrey G. Penta Eye Bank for Sight Restoration, New York, NY (13). Patricia Dahl Miracles in Sight (formerly North Carolina Eye Bank), Winston-Salem, NC (12). Michael Tramber Lions Eye Bank at Albany, Albany, NY (11). Victoria Adler Lions Eye Institute for Transplant & Research, Tampa, FL (7). Patrick Gore (now with Saving Sight), Wilfred Caraballo

Study Chair’s Office, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH. Jonathan H. Lass, MD (Study Chair), Helen Novotney, April Scorzino.

Coordinating Center, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH. Loretta B. Szczotka-Flynn, OD, PhD (Director), Michelle Corrigan, Neda Farooqi, Lisa Ferguson, Lori Karpinecz, Michael Payne, Leslie Richards, Tatiana Riedel, Jessica Tag, Kalisha Washington.

Cornea Image Analysis Reading Center, Case Western Reserve University and University Hospitals Eye Institute, Cleveland, OH. Jonathan H. Lass, MD (Medical Director), Beth Ann Benetz, MA (Technical Director), Glenn Barton, Andrew Bear, Le’Rashaun Jones, Lori Karpinecz, Michele Kit, Mark Madere, Harry Menegay, PhD, Tanisha Rankins-Coker, Garth Wadleigh.

Data Management and Analysis Center, Jaeb Center for Health Research, Tampa, FL. Roy W. Beck, MD, PhD (Executive Director), Allison R. Ayala, MS (DMAC Director), Kenneth Arcieri, Darrell S. Austin, Daphne M. Auza, Mitchell Dupre, Amber Evans, Robin L. Gal, MSPH, Craig Kollman, PhD, Nadine E. Labell, Wendi Liang, MSPH, Alandra S, Powe MSPH.

Operations Committee. Jonathan H. Lass, MD (Chair), Allison R. Ayala, MS, Roy W. Beck, MD, PhD, Beth Ann Benetz, MA, Robin L. Gal, MSPH, Maryann Redford, DDS, MPH, Loretta B. Szczotka-Flynn, OD, PhD

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Executive Committee. Jonathan H. Lass, MD (Chair), Anthony J. Aldave MD, Allison R. Ayala, MS, Roy W. Beck, MD, PhD, Beth Ann Benetz, MA, Michelle M. Corrigan, Steven P. Dunn, MD, Robin L. Gal, MSPH, Ty L. McCall MD, Lisa Navarro, Sudeep Pramanik, MD, Maryann Redford, DDS, MPH, Kevin W. Ross, MS, MPH, George O. Rosenwasser, MD, Loretta B. Szczotka-Flynn, OD, PhD, Mark A. Terry MD, David T. Verdier, MD

Eye Bank Advisory Committee: Kevin W. Ross, MS MPH (Chair), Patricia Dahl, Donna C. Drury, Sameera M. Farazdaghi, Caroline K. Hoover, Jeffery G. Penta, Mark C. Soper, Chris G. Stoeger, Doyce V. Williams

Data and Safety Monitoring Committee David C. Musch, PhD, MPH (DSMC Chair), William Bourne, MD, Kathryn A. Colby, MD, PhD, Marian Fisher, PhD, Rabbi Samuel Fishman, Maryann Redford, DDS, MPH

National Institutes of Health: National Eye Institute, Bethesda, MD. Maryann Redford, DDS, MPH, Steven Oversby, PsyD

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eAppendix 2. Institutional Review Boards

Dean Institutional Review Board Icahn Mount Sinai School of Medicine Institutional Review Board / New York Eye and Ear Infirmary of Mount Sinai Institutional Review Board Johns Hopkins Institutional Review Board Legacy Institutional Review Board Mayo Clinic Institutional Review Board Mercy Institutional Review Board North Shore University Health System Institutional Review Board The Ohio State University Biomedical Institutional Review Board University Hospitals Cleveland Medical Center Institutional Review Board University of California Los Angeles Institutional Review Board University of California San Francisco Institutional Review Board University of Illinois at Chicago Institutional Review Board University of Iowa Institutional Review Board University of Kentucky Institutional Review Board University of Miami Institutional Review Board University of Michigan Medical School Institutional Review Board University of Southern California Health Sciences Campus Institutional Review Board University of Utah Institutional Review Board Wills Eye Hospital Institutional Review Board

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eTable 1. CPTS Graft Failure Definitions CPTS Graft Failure Classification 1. Early: cloudy or equivocal recipient stroma on the first postoperative day that does not clear or requires a regraft within 8 weeks and is associated with intra- and/or perioperative complication 2. Primary Donor: cloudy or equivocal recipient cornea on the first postoperative day that does not clear or requires a regraft within 8 weeks in the absence of surgical complications a 3. Graft rejection: clouded recipient central stroma following an allograft reaction that was initially clear 4. Non-rejection: graft that initially had a clear central recipient stroma and becomes cloudy due to causes other than an immune event (e.g. surface failure, infection, glaucoma/hypotony, endothelial decompensation, interface irregularity/opacity, stromal scarring, blunt or penetrating trauma, or other causes) 5. Refractive/visual: graft that requires regrafting due to inadequate vision while the recipient central stroma is clear a Differs from EBAA Guidance Document for Investigating and Reporting Adverse Reactions1,2 which defines primary graft failure (in the CPTS designated as primary donor failure) as corneal edema from time of keratoplasty that does not clear after 8 weeks with no known operative or postoperative complications or underlying recipient conditions that would explain the biologic dysfunction. Definitions of Recipient Stroma Clarity Post DSAEK:  Clear: clear and compact stroma with sharp iris details over central 4 mm of donor graft  Equivocal: questionable stromal haze with possible thickening and iris details less distinct over central 4 mm of donor graft  Cloudy: definite stromal haze with definite thickening and indistinct iris details over central 4 mm of donor graft

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eTable 2. CPTS Donor Characteristicsa

Preservation Time Group 0-7 Days Group 8-14 Days Group

N=675 N=655 Donor Age (years) <=30 28 (4) 39 (6) 31-50 119 (18) 95 (15) 51-60 188 (28) 169 (26) 61-70 247 (37) 242 (37) 71-75 93 (14) 110 (17) Median (IQR) 60 (51, 67) 61 (53, 68) Gender: Women- n (%) 254 (38) 232 (35) Race/Ethnicity - n (%) White 575 (85) 575 (88) African-American 41 (6) 33 (5) Hispanic or Latino 39 (6) 38 (6) Asian 7 (1) 4 (<1) American Indian/Alaskan Native 2 (<1) 1 (<1) More than one race 1 (<1) 0 (0) Native Hawaiian/Other Pacific Islander 3 (<1) 0 (0) Unknown/Not Reported 7 (1) 4 (<1) History of diabetes: Yes- n (%) 175 (26) 182 (28) Cause of death- n (%) Cancer 125 (19) 125 (19) Cardiovascular Disease 266 (39) 231 (35) Cerebrovascular accident 69 (10) 84 (13) Drug Overdose 11 (2) 15 (2) Motor vehicle accident 29 (4) 30 (5) Organ Failure 19 (3) 22 (3) Pulmonary Embolism 29 (4) 19 (3) Respiratory Disease 50 (7) 48 (7) Other Trauma 28 (4) 28 (4) Other 49 (7) 53 (8) How time of death determined- n (%) Last known alive 37 (5) 33 (5) Pronounced 606 (90) 586 (89) Cross-clamp 31 (5) 36 (5) Established by core temperature 1 (<1) 0 (0) Method of retrieval- n (%) In situ 669 (99) 655 (100) Whole globe 6 (<1) 0 (0) Refrigerated / On ice: Yes- n (%) 609 (90) 576 (88) Storage solution- n (%) Life 4°C 27 (4) 24 (4) Optisol GS 648 (96) 631 (96) Folds severity: - n (%) None 154 (23) 132 (20) Mild 434 (64) 436 (67) Moderate 87 (13) 87 (13) Pleomorphism / Polymegethism- n (%) None 502 (74) 490 (75) Mild 171 (25) 162 (25) Moderate 2 (<1) 3 (<1) Screening endothelial cell density b –– cells/mm2 Mean (SD) 2751 (307) 2720 (287)

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[Min, Max] [2300, 4386] [2304,3663] Lamellar dissection performed by- n (%) Eye Bank 494 (73) 493 (75) Surgeon 181 (27) 162 (25) Pre-operative endothelial cell density c - For subset of corneas that were eye bank prepared (image obtained just after lamellar dissection) Mean (SD) 2754 (426) 2784 (405) [Min, Max] [846, 4995] [970, 4790] Pre-operative endothelial cell densityc - For subset of corneas that were surgeon prepared (image obtained just prior to shipping) Mean (SD) 2737 (315) 2718 (344) [Min, Max] [2057, 3577] [1660, 3759] Death to preservation time – hours Median (IQR) 10 (7, 14) 10 (7, 14) [Min, Max] [0, 20] [0, 22] a 18 donor corneas were ineligible: 1 case in which preservation to surgery time = 15 days; 1 case of death to PT >20 hours; 1 case of death to refrigeration time > 10 hours; 5 cases of moderate polymegethism/pleomorphic; 10 cases had their lamellar dissection of the donor by a non-EBAA-accredited eye bank. b Eye bank determined c Reading center graded

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eTable 3. Surgical Data Preservation Time Group 8-14 Days

0-7 Days N=675 N=655 Surgical Procedures Performed in Addition to EK –n (%) Cataract extraction 337 (50%) 345 (53%) IOL removal 0 1 (<1%) PC IOL placement with capsular fixation 336 (50%) 344 (53%) Sutured PC IOL 0 1 (<1%) Anterior vitrectomy 9 (1%) 8 (1%) Synechiolysis 4 (<1%) 1 (<1%) Lamellar keratectomy with removal of epithelium only 38 (6%) 32 (5%) Lamellar keratectomy with removal of epithelium and anterior 0 2 (<1%) stroma Iridoplasty/Pupilloplasty 11 (2%) 4 (<1%) Iridectomy/Iridotomy 41 (6%) 40 (6%) Limbal relaxing incision 5 (<1%) 4 (<1%) Other (write-ins) 31 (5%) 30 (5%) Intraoperative Complications –n (%) Vitreous loss (unplanned) 5 (<1%) 4 (<1%) Posterior capsule rupture 3 (<1%) 3 (<1%) Suprachoroidal hemorrhage 0 0 Significant blood in anterior chamber 2 (<1%) 0 Flipped “upside down” donor tissue 4 (<1%) 2 (<1%) Difficult unfolding and positioning without use of positioning hook 7 (1%) 0 Difficult unfolding and positioning with use of positioning hook 10 (1%) 6 (<1%) Difficult air fill and retention in positioning 4 (<1%) 5 (<1%) Reinsertion of donor after extrusion 5 (<1%) 0 Other (write-ins) 13 (2%) 24 (4%) Cataract removal difficulty/complication questions 4 (<1%) 3 (<1%) Donor insertion 3 (<1%) 5 (<1%) Difficult air fill and retention after extrusion 1 (<1%) 0 Donor quality 1 (<1%) 7 (1%) Donor preparation—eye bank 0 1 (<1%) Donor preparation—Surgeon 1 (<1%) 0 Retained air in posterior chamber 2 (<1%) 3 (<1%) Other- Severe pain 0 3 (<1%) Superior sclerotomy leaking and corneal patch graft required 0 1 (<1%) Abbreviations: IOL: Intraocular lens; PC: Posterior chamber

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eTable 4. Postoperative Donor Positioning Complications and Proceduresa Preservation Time Group Post- hoc 0-7 Days 8-14 Days P Value N=675 N=655 b Postoperative Donor Positioning Outcome .01 At least 1 occurrence of dislocation total detachment) - n ( 33 (5%) [4] 53 (8%) [6] (%) [# of these with multiple D] At least 1 occurrence of graft repositioning (with no occurrence of dislocation) - n (%) [# of these with multiple 4 (0.6%) [0] 12 (2%) [1] GR] At least 1 occurrence of interface fluid (with no occurrence of dislocation or graft repositioning) - n (%) [# of these with 74 (11%) [39] 78 (12%) [37] multiple IF] No occurrence of any of the above - n (%) 564 (84%) 512 (78%) At Least 1 Air Injection c- n (%) [# of these with multiple .003 54 (8%) [8] 85 (13%) [13] AI] Abbreviation: D = Dislocation (total detachment); GR = Graft Repositioning; IF = Interface Fluid; AI = Air Injection a percentages do not add to 100% due to rounding b Fisher exact test was used in the evaluation of the PT effect on donor positioning outcomes c 1 eye with total air-fluid exchange was counted as air injection

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eTable 5. Serious Abnormalities Preservation Time Group N (%) of eyes where event occurred at least once at any time after 0-7 Days 8-14 Days surgery N=675 N=655 Serious Abnormalities Noted on Ocular Exam Endophthalmitis 1 (<1%)a 0 Suprachoroidal hemorrhage 2 (<1%) 0 Retinal detachment 1 (<1%) 0 Blunt trauma 5 (<1%) 0 Penetrating trauma 0 0 a Escherichia coli endophthalmitis case was considered related to DSAEK, occurring 4 days after surgery

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eTable 6. Abnormalities on Cornea Exam / AC Exam Preservation Time Group N (%) of eyes where event occurred at least once at any time 0-7 Days 8-14 Days after surgery N=675 N=655 Abnormalities Noted on Cornea Exam Fungal, bacterial, or parasitic corneal infectiona 4 (<1%) 3 (<1%) Superficial punctate keratitis 56 (8%) 57 (9%) Herpes simplex keratitis 4 (<1%) 1(<1%) Wound leak 0 0 Iris synechiae to wound 2 (<1%) 4 (1%) Epithelial edema 306 (45%) 334 (51%) Stromal edema 483 (72%) 474 (72%) Stromal corneal vessels present b 4 (<1%) 3 (<1%) Corneal scar (subepithelial, stromal, or interface haze) b 281 (42%) 271 (41%) Epithelial status (% defect) >50% b 33 (5%) 43 (7%) Cloudy central recipient stroma b 221 (33%) 259 (40%) Cloudy central donor stroma b 158 (23%) 215 (33%) Abnormalities Noted on Anterior Chamber Exam– Excessive (>= 2+ cells/flare) intraocular inflammation 8 (1%) 7 (1%) Flat anterior chamber 3 (<1%) 3 (<1%) Hyphema 1 (<1%) 2 (<1%) Vitreous in AC 3 (<1%) 5 (<1%) IOP >25mmHg b 128 (19%) 118 (18%) Corneal Thickness > 750 microns b 253 (37%) 270 (41%) Definite Signs of Graft Rejection b 23 (3%) 30 (5%) a 2 cases in the 8-14d PT group were considered related to DSAEK (Candida albicans infection occurring at 13 days and Candida glabrata infection occurring at 43 days after surgery); all other cases were not considered related to DSAEK (occurring 150-1284 days after surgery) b Events pre-defined in Statistical Analysis Plan to assess potential safety concerns.

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eTable 7. Study Eye Proceduresa Preservation Time Group 0-7 Days 8-14 Days Number of study eye procedures reported at any time after surgery N=675 N=655 Air release due to pupillary block and high IOP b 9 9 Air injection b 50 73 Anterior chamber tap 0 1 Anti-VEGF intravitreal injection 45 52 Blepharoplasty 2 4 Conjunctival resection for conjunctivochalasis 0 1 Corneal graft repositioning b 11 27 Corneal suture removal 2 3 Diode laser (open angle glaucoma) 1 0 Focal/grid laser (non-center involved DME) 1 1 Glaucoma filter (with tube) 3 4 Glaucoma filter (without tube) 3 0 Head positioning 1 1 IOL removal 0 1 IOL replacement 2 2 IOL reposition 2 0 Intravitreal injection - antibiotics 1 0 Iridectomy 1 0 Iridoplasty 1 0 Iris prolapse repair 1 0 Lamellar keratectomy with removal of epithelium and anterior stroma b 1 1 Lamellar keratectomy with removal of epithelium only b 10 6 Laser retinopexy 1 2 Laser trabeculoplasty 1 5 Laser iridotomy 1 0 Laser lysis of posterior synechia 1 0 Lid lesion excision 2 3 Paracentesis 0 4 Posterior sclerotomy 1 0 Ptosis repair 1 2 Punctal plugs 1 6 Pupilloplasty 0 1 Retinal detachment repair-surgical 1 0 Subtenons kenalog injection for uveitis 0 3 Total air-fluid exchange b, c 1 0 Vitrectomy 7 6 Vitreous tap 1 0 YAG capsulotomy 77 65 YAG vitreolysis 0 2 a Above table tabulated as total number of procedures performed, (the same eye can be counted multiple times). b Mandatory reporting of these procedures was required, all other procedures were voluntarily reported c Total air-fluid exchange and corneal graft repositioning are counted as air injections in eTable 4. Abbreviations: VEGF: Vascular endothelial growth factor; DME: Diabetic macular edema; IOL: Intraocular lens; YAG: Yttrium aluminum garnet

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eTable 8. Potential Interactions with Preservation Time Groups Preservation Time Group P Value 0-7 Days 8-14 Days interaction term with

3 year Graft Success 3 year Graft Success Preservation N N Rate (95% CI) Rate (95% CI) Time Groupsa Recipient Age

(years) 42 to <65 177 94.1% (89.2%, 96.8%) 191 91.9% (86.6%, 95.2%) .76 66 to <75 304 95.1% (91.9%, 97.1%) 256 92.9% (88.9%, 95.4%) 76 to <91 194 96.8% (92.9%, 98.5%) 208 91.5% (86.7%, 94.7%) Corneal Diagnosis FECD 631 95.9% (94.0%, 97.2%) 624 92.6% (90.2%, 94.5%) .64 PACE (without 44 85.2% (67.0%, 93.8%) 29 83.8% (61.7%, 93.7%) FECD) Donor Age (years) 12 to 50 147 97.8% (93.4%, 99.3%) 134 92.9% (86.7%, 96.2%) .69 51 to 65 305 93.7% (90.2%, 96.0%) 277 93.3% (89.6%, 95.8%) 66 to 75 223 95.8% (92.2%, 97.8%) 244 90.4% (85.7%, 93.6%) Donor Diabetes

History .80 Yes 175 92.4% (87.3%, 95.5%) 182 88.2% (82.5%, 92.2%) No 500 96.3% (94.2%, 97.7%) 473 93.7% (90.9%, 95.6%) aThe p-values were calculated by including first-order interaction terms into the final multi-variate model. Recipient age and donor age were analyzed as continuous variables. Donor age and donor diabetes history were not pre-specified in the Statistical Analysis Plan. Abbreviations: FECD: Fuchs’ endothelial corneal dystrophy; PACE: Pseudophakic/aphakic corneal edema

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eReferences

1. Eye Bank Association of America. Medical Standards. June 2015. http://www.corneas.org/repository/docs/SurgeonDocs/EBAA-Medical-Standards- with-Appendices-June-2015.pdf. Accessed August 2, 2017. 2. Eye Bank Association of America. Online Adverse Reactions Reporting Systems (OARRS). Washington, D.C. 2017.

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