Donor, Recipient, and Operative Factors Associated with Increased Endothelial Cell Loss in the Cornea Preservation Time Study

the Cornea Preservation Time Study Group

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm 2 ), lower screening ECD (-234 [-331 to -137] per 500 cells/mm 2 ), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm 2 ), and operative complications (-324 [-516 to -133] in cells/mm 2 ). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalJAMA ophthalmology
Volume137
Issue number2
DOIs
StatePublished - Feb 1 2019

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Time and Motion Studies
Cornea
Descemet Stripping Endothelial Keratoplasty
Corneal Edema
Endothelial Cells
Tissue Donors
Cell Count
Fuchs' Endothelial Dystrophy
Eye Banks
Transplants
Graft Survival
Causality
Reading
Cohort Studies
Randomized Controlled Trials
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Donor, Recipient, and Operative Factors Associated with Increased Endothelial Cell Loss in the Cornea Preservation Time Study. / the Cornea Preservation Time Study Group.

In: JAMA ophthalmology, Vol. 137, No. 2, 01.02.2019, p. 185-193.

Research output: Contribution to journalArticle

@article{eaa07b6960dd4ff08a4ea69e395e533b,
title = "Donor, Recipient, and Operative Factors Associated with Increased Endothelial Cell Loss in the Cornea Preservation Time Study",
abstract = "Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0{\%}]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4{\%}]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6{\%}]). Of these, 801 eyes (60.2{\%}) belonged to women and 1207 (90.8{\%}) to white individuals. A total of 749 participants (913 eyes; 164 [21.9{\%}] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99{\%} CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm 2 ), lower screening ECD (-234 [-331 to -137] per 500 cells/mm 2 ), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm 2 ), and operative complications (-324 [-516 to -133] in cells/mm 2 ). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47{\%} (99{\%} CI, 42{\%}-52{\%}) for participants receiving tissue from donors with diabetes vs 43{\%} (99{\%} CI, 39{\%}-48{\%}) without diabetes; it was 53{\%} (99{\%} CI, 44{\%}-62{\%}) for participants diagnosed with PACE vs 44{\%} (99{\%} CI, 39{\%}-49{\%}) for those diagnosed with Fuchs dystrophy, and 55{\%} (99{\%} CI, 48{\%}-63{\%}) in participants who experienced operative complications vs 44{\%} (99{\%} CI, 39{\%}-48{\%}) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.",
author = "{the Cornea Preservation Time Study Group} and Lass, {Jonathan H.} and Benetz, {Beth Ann} and Patel, {Sanjay V.} and Szczotka-Flynn, {Loretta B.} and Robert O'Brien and Ayala, {Allison R.} and Maguire, {Maureen G.} and Daoud, {Yassine J.} and Greiner, {Mark A.} and Hannush, {Sadeer B.} and Lee, {W. Barry} and Mauger, {Thomas F.} and Menegay, {Harry J.} and Mifflin, {Mark D.} and Raizman, {Michael B.} and Jennifer Rose-Nussbaumer and Schultze, {Robert L.} and Schmidt, {Gregory A.} and Alan Sugar and Terry, {Mark A.} and Verdier, {David D.} and Roy Beck and Robin Gal and Maryann Redford and Aldave, {Anthony J.} and Dunn, {Steven P.} and McCall, {Ty L.} and Lisa Navarro and Sudeep Pramanik and Rosenwasser, {George O.} and Verdier, {David T.} and Ross, {Kevin W.} and Patricia Dahl and Drury, {Donna C.} and Farazdaghi, {Sameera M.} and Hoover, {Caroline K.} and Penta, {Jeffery G.} and Soper, {Mark C.} and Stoeger, {Chris G.} and Williams, {Doyce V.} and Musch, {David C.} and William Bourne and Colby, {Kathryn A.} and Marian Fisher and Fishman, {Rabbi Samuel} and Gregg Berdy and John Bokosky and Christopher Croasdale and Thomas Gillette and Yoo, {Sonia H}",
year = "2019",
month = "2",
day = "1",
doi = "10.1001/jamaophthalmol.2018.5669",
language = "English (US)",
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pages = "185--193",
journal = "JAMA Ophthalmology",
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TY - JOUR

T1 - Donor, Recipient, and Operative Factors Associated with Increased Endothelial Cell Loss in the Cornea Preservation Time Study

AU - the Cornea Preservation Time Study Group

AU - Lass, Jonathan H.

AU - Benetz, Beth Ann

AU - Patel, Sanjay V.

AU - Szczotka-Flynn, Loretta B.

AU - O'Brien, Robert

AU - Ayala, Allison R.

AU - Maguire, Maureen G.

AU - Daoud, Yassine J.

AU - Greiner, Mark A.

AU - Hannush, Sadeer B.

AU - Lee, W. Barry

AU - Mauger, Thomas F.

AU - Menegay, Harry J.

AU - Mifflin, Mark D.

AU - Raizman, Michael B.

AU - Rose-Nussbaumer, Jennifer

AU - Schultze, Robert L.

AU - Schmidt, Gregory A.

AU - Sugar, Alan

AU - Terry, Mark A.

AU - Verdier, David D.

AU - Beck, Roy

AU - Gal, Robin

AU - Redford, Maryann

AU - Aldave, Anthony J.

AU - Dunn, Steven P.

AU - McCall, Ty L.

AU - Navarro, Lisa

AU - Pramanik, Sudeep

AU - Rosenwasser, George O.

AU - Verdier, David T.

AU - Ross, Kevin W.

AU - Dahl, Patricia

AU - Drury, Donna C.

AU - Farazdaghi, Sameera M.

AU - Hoover, Caroline K.

AU - Penta, Jeffery G.

AU - Soper, Mark C.

AU - Stoeger, Chris G.

AU - Williams, Doyce V.

AU - Musch, David C.

AU - Bourne, William

AU - Colby, Kathryn A.

AU - Fisher, Marian

AU - Fishman, Rabbi Samuel

AU - Berdy, Gregg

AU - Bokosky, John

AU - Croasdale, Christopher

AU - Gillette, Thomas

AU - Yoo, Sonia H

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm 2 ), lower screening ECD (-234 [-331 to -137] per 500 cells/mm 2 ), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm 2 ), and operative complications (-324 [-516 to -133] in cells/mm 2 ). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

AB - Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm 2 ), lower screening ECD (-234 [-331 to -137] per 500 cells/mm 2 ), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm 2 ), and operative complications (-324 [-516 to -133] in cells/mm 2 ). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.

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U2 - 10.1001/jamaophthalmol.2018.5669

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JO - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

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