Endothelial cell density to predict endothelial graft failure after penetrating keratoplasty

Jonathan H Lass, Alan Sugar, Beth Ann Benetz, Roy W Beck, Mariya Dontchev, Robin L Gal, Craig Kollman, Robert Gross, Ellen Heck, Edward J Holland, Mark J Mannis, Irving Raber, Walter Stark, R Doyle Stulting, Cornea Donor Study Investigator Group, Christopher Y Chow, Steven P Dunn, David G Heidemann, Michael W Belin, Robert L Schultze, Matthew S Oliva, Walter M Rotkis, David D Verdier, Jonathan H Lass, William J Reinhart, Joseph M Thomas, Stephen M Hamilton, Gina C Jayawant, W Barry Lee, Robert H Gross, Edward L Shaw, Steven L Maskin, Parveen K Nagra, Irving Raber, Joel Sugar, Elmer Tu, Mark S Gorovoy, Francis J Manning, Thomas S Boland, Stephen E Pascucci, Qais A Farjo, Roger F Meyer, H Kaz Soong, Alan Sugar, Paul G Galentine, David N Ugland, Sadeer B Hannush, John E Bokosky, James W Caudill, Robert S Feder, John C Affeldt, Christopher L Blanton, Edward J Holland, R Wayne Bowman, H Dwight Cavanagh, Mohamed-Sameh H El-Agha, James P McCulley, Thomas E Gillette, Alan B Leahey, Christopher R Croasdale, Richard A Eiferman, Sarkis H Soukiasian, R Doyle Stulting, Walter Stark, Kenneth R Kenyon, Richard C Rodman, Walter E Beebe, Henry Gelender, Steven S Ching, Ronald D Plotnik, Marc A Goldberg, Karen D Sumers, Nicoletta A Fynn-Thompson, Ann Z McColgin, Michael B Raizman, Steven I Rosenfeld, Elizabeth A Davis, David R Hardten, Richard L Lindstrom, Mark J Mannis, Jerry G Ford, David M Meisler, Kendall Dobbins, Francis W Price Jr, William G Zeh, Peter J Berkowitz, Thomas D Lindquist, Daniel F Goodman, Niraj P Patel, Abdulfatah M Ali, Richard F Beatty, John E Sutphin, Ayad A Farjo, Menneth M Goins, Terry E Burris, Peter A Shriver, Cynthia A Self, Garth A Wilbanks, Roy S Chuck, Ronald N Gaster, David W Kielty, Garvin H Davis, Stefan D Trocme, Woodford S Van Meter, Patricia W Smith, Alan R Schaeffer, Elisabeth J Cohen, Peter R Laibson, Christopher J Rapuano, Keith H Baratz, Barton L Halpern, Mark A Pavilack, Gerald B Rosen, Donald J Doughman, Soo Mee Pak, Theodore Perl, John W Cowden, Elliot M Perlman, Lance E Olson, Erik D Skoog, William D Gruzensky, Erich B Groos Jr, Mark D Mifflin, Maureen K Lundergan, Steven T Berger, Kenneth C Chern, Kerry D Solomon, Richard F Dennis, Jonathan B Rubenstein, Alexandra M P Kostick, Samuel H Santander, Allen S Roth, Laura A Bealer, Jonathan I Macy, David G O'Day, Mark A Terry, Nunzio P Sossi, Keith A Walter, Florence M Johnson, Kyle L Mavin, Kristen E McCoy, Michael B O'Keefe, Gerald J Cole, Diane F Johnston, Mark A Jones, Sameera M Farazdaghi, Elizabeth N Walunas, Monty M Montoya, Bernie Iliakis, Rick D McDonald, Misty L Ostermiller, Cathy E Saltwick, Jason K Woody, Mark H Weaver, Michael J Christ, Mark B Gross, Carol R Engel, Raylene A Dale, Stephanie K Hackl, Elena J Henriksen, Kathryn J Kalmoe, Jennifer M Larson, Jackie V Malling, Brian J Philippy, Maryann Sharpe-Cassese, Sue M Hayes, Robert E Lytle, David A Rechtshaffen, Bruce Varnum, Erin B Angel, Matt D Durell, Teresa R Williams, Susan V Janssen, Brian E Kraus, Marcy B McLain, Jackie A Rossi, Ellen L Heck, Marilyn S Hayes, Gregory C Davis, Tara L Chavez, Lori D Oswald, Noreen B Ruiz, Jeffrey G Penta, Wayne E Dietz, Jennifer L Nary, Kenneth R Sheriff, Nancy C Driver, William J Faircloth, Paul E Williams, Kurt Weber, Jerry W Barker, Donna M Bridges, Lee Chenier, Mark Soper, Betsy Allen, Samantha J Wright, James R Martin, Anne J Watson, Greg McDonough, Kristel D Beilby, Linda K Fraser, Tammi S Sharpe, Robert C Arffa, Michael A Tramber, Barbara L Crow, Matthew M Fisher, Chris G Stoeger, Edmund Jacobs, Michael P Filbin, James I Mather, Christopher M McGriff, Eric E Meinecke, Patricia J Mason, Garret D Locke, Janice F Reiter, David E Korroch, Penelope M Thomas, Wayne A Lange, Rosemary F Moore, Lee J Williams, Yvette D Friedhoff, Ronald J Walkenbach, Jennifer E Glover, Brenda A Kafton, Kraig J Lage, Brenda S Horn, H Tommy Bottoms, Ellen R Kerns, Raymond Jessen, William H Dennis, Roy W Beck, Mariya Dontchev, Robin L Gal, Craig Kollman, Lee Anne Lester, Shelly T Mares, Yazandra A Parrimon, Alandra S Powe, Katrina J Ruedy, Heidi J Strayer, Jean Paul Tanner, Jonathan H Lass, Beth Ann Benetz, Carmella Gentile, Stephanie Burke, Shannon Edwards, Lori Karpinecz, Maryann Redford, Mary Frances Cotch, Marian Fisher, William Bourne, Maryann Redford, Rabbi Samuel Fishman, Gary Foulks, David C Musch, Edward J Holland, Mark J Mannis, Mary Frances Cotch, Steven Dunn, Ellen Heck, Florence Johnston, Jonathan H Lass, Thomas Lindquist, Monty M Montoya, Maryann Redford, Alan Sugar, Joel Sugar, Jason Woody, Mark J Mannis, Edward J Holland, Michael W Belin, Steven Dunn, Robert H Gross, Mark S Gorovoy, Stephen M Hamilton, Ellen Heck, Jonathan H Lass, Thomas Lindquist, Francis J Manning, Steven L Maskin, Monty M Montoya, Irving M Raber, Maryann Redford, Walter M Rotkis, Robert L Schultze, Walter J Stark, Robert Doyle Stulting, Alan Sugar, Joel Sugar, Bradley Tennant, David D Verdier, Jason Woody, Christopher R Croasdale, Mark D Mifflin, Patricia W Smith, Joel Sugar, Jonathan H Lass, Alan Sugar, Beth Ann Benetz, Roy W Beck, Mariya Dontchev, Robin L Gal, Craig Kollman, Robert Gross, Ellen Heck, Edward J Holland, Mark J Mannis, Irving Raber, Walter Stark, R Doyle Stulting, Cornea Donor Study Investigator Group, Christopher Y Chow, Steven P Dunn, David G Heidemann, Michael W Belin, Robert L Schultze, Matthew S Oliva, Walter M Rotkis, David D Verdier, Jonathan H Lass, William J Reinhart, Joseph M Thomas, Stephen M Hamilton, Gina C Jayawant, W Barry Lee, Robert H Gross, Edward L Shaw, Steven L Maskin, Parveen K Nagra, Irving Raber, Joel Sugar, Elmer Tu, Mark S Gorovoy, Francis J Manning, Thomas S Boland, Stephen E Pascucci, Qais A Farjo, Roger F Meyer, H Kaz Soong, Alan Sugar, Paul G Galentine, David N Ugland, Sadeer B Hannush, John E Bokosky, James W Caudill, Robert S Feder, John C Affeldt, Christopher L Blanton, Edward J Holland, R Wayne Bowman, H Dwight Cavanagh, Mohamed-Sameh H El-Agha, James P McCulley, Thomas E Gillette, Alan B Leahey, Christopher R Croasdale, Richard A Eiferman, Sarkis H Soukiasian, R Doyle Stulting, Walter Stark, Kenneth R Kenyon, Richard C Rodman, Walter E Beebe, Henry Gelender, Steven S Ching, Ronald D Plotnik, Marc A Goldberg, Karen D Sumers, Nicoletta A Fynn-Thompson, Ann Z McColgin, Michael B Raizman, Steven I Rosenfeld, Elizabeth A Davis, David R Hardten, Richard L Lindstrom, Mark J Mannis, Jerry G Ford, David M Meisler, Kendall Dobbins, Francis W Price Jr, William G Zeh, Peter J Berkowitz, Thomas D Lindquist, Daniel F Goodman, Niraj P Patel, Abdulfatah M Ali, Richard F Beatty, John E Sutphin, Ayad A Farjo, Menneth M Goins, Terry E Burris, Peter A Shriver, Cynthia A Self, Garth A Wilbanks, Roy S Chuck, Ronald N Gaster, David W Kielty, Garvin H Davis, Stefan D Trocme, Woodford S Van Meter, Patricia W Smith, Alan R Schaeffer, Elisabeth J Cohen, Peter R Laibson, Christopher J Rapuano, Keith H Baratz, Barton L Halpern, Mark A Pavilack, Gerald B Rosen, Donald J Doughman, Soo Mee Pak, Theodore Perl, John W Cowden, Elliot M Perlman, Lance E Olson, Erik D Skoog, William D Gruzensky, Erich B Groos Jr, Mark D Mifflin, Maureen K Lundergan, Steven T Berger, Kenneth C Chern, Kerry D Solomon, Richard F Dennis, Jonathan B Rubenstein, Alexandra M P Kostick, Samuel H Santander, Allen S Roth, Laura A Bealer, Jonathan I Macy, David G O'Day, Mark A Terry, Nunzio P Sossi, Keith A Walter, Florence M Johnson, Kyle L Mavin, Kristen E McCoy, Michael B O'Keefe, Gerald J Cole, Diane F Johnston, Mark A Jones, Sameera M Farazdaghi, Elizabeth N Walunas, Monty M Montoya, Bernie Iliakis, Rick D McDonald, Misty L Ostermiller, Cathy E Saltwick, Jason K Woody, Mark H Weaver, Michael J Christ, Mark B Gross, Carol R Engel, Raylene A Dale, Stephanie K Hackl, Elena J Henriksen, Kathryn J Kalmoe, Jennifer M Larson, Jackie V Malling, Brian J Philippy, Maryann Sharpe-Cassese, Sue M Hayes, Robert E Lytle, David A Rechtshaffen, Bruce Varnum, Erin B Angel, Matt D Durell, Teresa R Williams, Susan V Janssen, Brian E Kraus, Marcy B McLain, Jackie A Rossi, Ellen L Heck, Marilyn S Hayes, Gregory C Davis, Tara L Chavez, Lori D Oswald, Noreen B Ruiz, Jeffrey G Penta, Wayne E Dietz, Jennifer L Nary, Kenneth R Sheriff, Nancy C Driver, William J Faircloth, Paul E Williams, Kurt Weber, Jerry W Barker, Donna M Bridges, Lee Chenier, Mark Soper, Betsy Allen, Samantha J Wright, James R Martin, Anne J Watson, Greg McDonough, Kristel D Beilby, Linda K Fraser, Tammi S Sharpe, Robert C Arffa, Michael A Tramber, Barbara L Crow, Matthew M Fisher, Chris G Stoeger, Edmund Jacobs, Michael P Filbin, James I Mather, Christopher M McGriff, Eric E Meinecke, Patricia J Mason, Garret D Locke, Janice F Reiter, David E Korroch, Penelope M Thomas, Wayne A Lange, Rosemary F Moore, Lee J Williams, Yvette D Friedhoff, Ronald J Walkenbach, Jennifer E Glover, Brenda A Kafton, Kraig J Lage, Brenda S Horn, H Tommy Bottoms, Ellen R Kerns, Raymond Jessen, William H Dennis, Roy W Beck, Mariya Dontchev, Robin L Gal, Craig Kollman, Lee Anne Lester, Shelly T Mares, Yazandra A Parrimon, Alandra S Powe, Katrina J Ruedy, Heidi J Strayer, Jean Paul Tanner, Jonathan H Lass, Beth Ann Benetz, Carmella Gentile, Stephanie Burke, Shannon Edwards, Lori Karpinecz, Maryann Redford, Mary Frances Cotch, Marian Fisher, William Bourne, Maryann Redford, Rabbi Samuel Fishman, Gary Foulks, David C Musch, Edward J Holland, Mark J Mannis, Mary Frances Cotch, Steven Dunn, Ellen Heck, Florence Johnston, Jonathan H Lass, Thomas Lindquist, Monty M Montoya, Maryann Redford, Alan Sugar, Joel Sugar, Jason Woody, Mark J Mannis, Edward J Holland, Michael W Belin, Steven Dunn, Robert H Gross, Mark S Gorovoy, Stephen M Hamilton, Ellen Heck, Jonathan H Lass, Thomas Lindquist, Francis J Manning, Steven L Maskin, Monty M Montoya, Irving M Raber, Maryann Redford, Walter M Rotkis, Robert L Schultze, Walter J Stark, Robert Doyle Stulting, Alan Sugar, Joel Sugar, Bradley Tennant, David D Verdier, Jason Woody, Christopher R Croasdale, Mark D Mifflin, Patricia W Smith, Joel Sugar

Abstract

Objective: To determine whether preoperative and/or postoperative central endothelial cell density (ECD) and its rate of decline postoperatively are predictive of graft failure caused by endothelial decompensation following penetrating keratoplasty to treat a moderate-risk condition, principally, Fuchs dystrophy or pseudophakic corneal edema.

Methods: In a subset of Cornea Donor Study participants, a central reading center determined preoperative and postoperative ECD from available specular images for 17 grafts that failed because of endothelial decompensation and 483 grafts that did not fail.

Results: Preoperative ECD was not predictive of graft failure caused by endothelial decompensation (P = .91). However, the 6-month ECD was predictive of subsequent failure (P < .001). Among those that had not failed within the first 6 months, the 5-year cumulative incidence (+/-95% confidence interval) of failure was 13% (+/-12%) for the 33 participants with a 6-month ECD of less than 1700 cells/mm(2) vs 2% (+/-3%) for the 137 participants with a 6-month ECD of 2500 cells/mm(2) or higher. After 5 years' follow-up, 40 of 277 participants (14%) with a clear graft had an ECD below 500 cells/mm(2).

Conclusions: Preoperative ECD is unrelated to graft failure from endothelial decompensation, whereas there is a strong correlation of ECD at 6 months with graft failure from endothelial decompensation. A graft can remain clear after 5 years even when the ECD is below 500 cells/mm(2).

Trial registration: ClinicalTrials.gov NCT00006411.

Figures

Figure 1
Figure 1
Endothelial cell density (ECD) over time in graft failures from endothelial decompensation (n = 17) and in nonfailures (n = 483). In the box plots, black dots indicate mean values; horizontal lines in the boxes, medians; and the bottom and top of the boxes, the 25th and 75th percentiles. The horizontal lines outside the boxes represent the range of ECD values.
Figure 2
Figure 2
Cumulative incidence of graft failure from endothelial decompensation by endothelial cell density (ECD) at 6 months (n = 269); 231 participants were excluded, 1 for graft failure before 6 months’ follow-up, 5 were censored before or at 6 months’ follow-up, and 225 for missing 6-month ECD values. See the penultimate paragraph in the “Methods” section.

Source: PubMed

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