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Corneal Endothelial Cell Loss 3 Years After Successful Descemet Stripping Automated Endothelial Keratoplasty in the Cornea Preservation Time StudyA Randomized Clinical Trial

Educational Objective
To determine whether endothelial cell loss 3 years after successful Descemet stripping automated endothelial keratoplasty is related to preservation time.
1 Credit CME
Key Points

Question  What is the relationship between cornea preservation time and endothelial cell loss 3 years after successful Descemet stripping automated endothelial keratoplasty?

Findings  In a randomized clinical trial evaluating 945 eyes with graft success, endothelial cell loss was 37% with preservation time 0 to 7 days and 40% with preservation time 8 to 14 days, with mean endothelial cell density of 1722 and 1642 cells/mm2, respectively, at 3 years.

Meaning  Although endothelial cell loss 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer preservation time, the effect of preservation time on endothelial cell loss is comparable from 4 to 13 days of preservation time.

Abstract

Importance  Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty.

Objective  To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT.

Design, Setting, and Participants  A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 945 eyes of 769 participants were included in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK, performed primarily for Fuchs endothelial corneal dystrophy (96% of the cohort). The study was conducted from April 16, 2012, to June 5, 2017.

Interventions  DSAEK with random assignment of a donor cornea with PT of 0 to 7 days (0-7d PT) or 8 to 14 days (8-14d PT).

Main Outcomes and Measures  Endothelial cell density (ECD) at 3 years determined by a central image analysis reading center from clinical specular or confocal central endothelial images.

Results  Nine hundred forty-five eyes of 769 participants (median age, 70 years [range, 42-90 years], 60.8% women, 93.0% white) in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK were included. At the initial eye bank tissue screening, mean (SD) central ECD was 2746 (297) cells/mm2 in the 0-7d PT group (n = 485) and 2723 (284) cells/mm2 in the 8-14d PT group (n = 460). At 3 years, the mean (SD) ECD decreased from baseline by 37% (21%) in the 0-7d PT group and 40% (22%) in the 8-14d PT group to 1722 (626) cells/mm2 and 1642 (631) cells/mm2, respectively (mean difference, 73 cells/mm2; 95% CI, 8-138 cells/mm2; P = .03). When analyzed as a continuous variable (days), longer PT was associated with lower ECD (mean difference by days, 15 cells/mm2; 95% CI, 4-26 cells/mm2; P = .006). Endothelial cell loss (ECL) was comparable from 4 to 13 days’ PT (n = 878; 36%-43% when tabulated by day). Available extension study ECD results at 4 years mirrored those at 3 years in the 203 eyes in the 0-7d PT group (mean [SD] ECD, 1620 [673] cells/mm2 and mean [SD] ECL, 41% [23%]) and 209 eyes in the 8-14d PT group (mean [SD] ECD, 1537 [683] cells/mm2 and mean [SD] ECL, 44% [23%]) (mean difference, 112 cells/mm2; 95% CI, 5-219 cells/mm2; P = .04).

Conclusions and Relevance  Although ECL 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer PT, the effect of PT on ECL is comparable from 4 to 13 days’ PT.

Trial Registration  clinicaltrials.gov Identifier: NCT01537393

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Article Information

Accepted for Publication: September 27, 2017.

Corresponding Author: Jonathan H. Lass, MD, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106 (jonathan.lass@uhhospitals.org).

Published Online: November 10, 2017. doi:10.1001/jamaophthalmol.2017.4970

Author Contributions: Drs Lass and Ayala had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Lass, Benetz, Verdier, Szczotka-Flynn, Ayala, McCall, Ross, Kollman, Gal, Beck.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Ayala, Liang, Kollman.

Obtained funding: Lass, Ayala, Ross, Gal.

Administrative, technical, or material support: All authors.

Study supervision: Lass, Benetz, Szczotka-Flynn, Ayala, Gal, Beck.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Terry receives royalties from Bausch & Lomb for endothelial keratoplasty surgical instruments and educational grants. No other disclosures were reported.

Funding/Support: The study was supported by cooperative agreements EY20797 and EY20798 with the National Eye Institute, National Institutes of Health, Department of Health and Human Services.

Role of the Funder/Sponsor: The National Eye Institute, National Institutes of Health, Department of Health and Human Services (EY20797 and EY20798) had roles in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication The following sponsors had no role the design, conduct, management, analysis, interpretation or publication of the study data, but provided additional support for ancillary work pertaining to this study: Eye Bank Association of America, The Cornea Society, Vision Share, Inc, Alabama Eye Bank, Cleveland Eye Bank Foundation, Eversight, Eye Bank for Sight Restoration, Iowa Lions Eye Bank, Lions Eye Bank of Albany, San Diego Eye Bank, and SightLife.

Group Members: The Cornea Preservation Time Study Group members are as follows: Operations Committee: Jonathan Lass, MD; Allison Ayala, MS; Beth Ann Benetz, MA; Loretta Szczotka-Flynn, OD, PhD; Roy Beck, MD, PhD; Robin Gal, MSPH; Craig Kollman, PhD; Wendi Liang, MSPH; Maryann Redford, DDS, MPH. Clinical Site Principal Investigators: Anthony Aldave, MD; Gregg Berdy, MD; John Bokosky, MD; Christopher Croasdale, MD; Yassine Daoud, MD; Steven Dunn, MD; Thomas Gillette, MD; Kenneth Goins, MD; Pankaj Gupta, MD; Kristen Hammersmith, MD; Sadeer Hannush, MD; David Hardten, MD; Bennie Jeng, MD; Marc Jones, MD; William Lahners, MD; W. Barry Lee, MD; Marian Macsai, MD; Thomas Mauger, MD; Kenneth Maverick, MD; Tyrone McCall, MD; Woodford Van Meter, MD; Shahzad Mian, MD; Mark Mifflin, MD; Verinder Nirankari, MD; Michael Nordlund, MD, PhD; Matthew Oliva, MD; Sanjay Patel, MD; Sudeep Pramanik, MD; Irving Raber, MD; Michael Raizman, MD; Jennifer Rose-Nussbaumer, MD; George Rosenwasser, MD; Robert Schultze, MD; John Seedor, MD; Neda Shamie, MD; Jonathan Song, MD; Walter Stark, MD; R. Doyle Stulting, MD, PhD; Alan Sugar, MD; Shachar Tauber, MD; Mark Terry, MD; Kristina Thomas, MD; Elmer Tu, MD; David Verdier, MD; Sonia Yoo, MD. Coordinator: Lisa Navarro. Eye Bank Principal Investigators: Victoria Adler, RN, BSN, CPTC, CEBT; Wilfred Caraballo; Patricia Dahl, BS; Gregory Dorn, CEBT; Donna Drury, BS, MBA; Sameera Farazdaghi, BS, MPH; Elizabeth Fout-Caraza, MHSA; Patrick Gore, RN, CEBT; Veronique Grimes, COMT, CEBT; Caroline Hoover, CEBT; Debora Van Klinken, CEBT; Nai Liang, CEBT; Tina Mays, CEBT; Kristen McCoy, BS; Wade McEntire, MPH; Eric Meinecke, BA; Jeffrey Penta, AS, BS, MBA; Kevin Ross, MS, MPH; Mikelanne Schipper; Gregory Schmidt, BS, CEBT; Chris Stoeger, CEBT, MBA; Michael Tramber, MBA, BS, CEBT, CTBS.

Meeting Presentation: This paper was presented at the Cornea and Eye Banking Forum, hosted by the Cornea Society and Eye Bank Association of America; New Orleans, Louisiana; November 10, 2017.

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