Factors Predictive of Corneal Graft Survival (2024)

Importance The Cornea Donor Study (CDS) showed that donor age is not a factor in survival of most penetrating keratoplasties for endothelial disease. Secondary analyses confirm the importance of surgical indication and presence of glaucoma in outcomes at 10 years.

Objective To assess the relationship between donor and recipient factors and corneal graft survival in the CDS.

Design, Setting, and Participants Multicenter prospective, double-masked, controlled clinical trial conducted at 80 clinical sites. One hundred five surgeons enrolled 1090 participants undergoing corneal transplant for a moderate-risk condition, principally Fuchs dystrophy or pseudophakic or aphakic corneal edema (PACE). Forty-three eye banks provided corneas.

Interventions Corneas from donors younger than 66 years and donors 66 years or older were assigned, masked to donor age. Surgery and postoperative care were performed according to the surgeons’ usual routines. Participants were followed up for as long as 12 years.

Main Outcomes and Measures Graft failure, defined as a regrafting procedure or a cloudy cornea for 3 consecutive months.

Results The 10-year cumulative probability of graft failure was higher in participants with PACE than in those with Fuchs dystrophy (37% vs 20%; hazard ratio [HR], 2.1 [99% CI, 1.4-3.0]; P < .001) and in participants with a history of glaucoma before penetrating keratoplasty, particularly with prior glaucoma surgery (58% with prior glaucoma surgery and use of medications to lower intraocular pressure at the time of surgery vs 22% with no history of glaucoma surgery or medication use; HR, 4.1 [99% CI, 2.2-7.5]; P < .001). We found trends toward increased graft failure in recipients who were 70 years or older compared with those younger than 60 years (29% vs 19%; HR, 1.2 [99% CI, 0.7-2.1]; P = .04) or were African American (HR, 1.5; P = .11) or who had a history of smoking (35% vs 24%; HR, 1.6 [99% CI, 0.9-2.8]; P = .02). Lower endothelial cell density (ECD) and higher corneal thickness (CT) at 6 months (6% vs 41% for ECD ≥2700 vs <1700 cells/mm² [P < .001]; 14% vs 36% for CT <500 vs ≥600 μm [P = .001]), 1 year (4% vs 39% for ECD ≥2700 vs <1700 cells/mm² [P < .001]; 18% vs 28% for CT <500 vs ≥600 μm [P = .04]), and 5 years (2% vs 29% for ECD ≥1500 vs <500 cells/mm² [P < .001]; 7% vs 34% for CT <550 vs ≥650 μm [P < .001]) were associated with subsequent graft failure.

Conclusions and Relevance Most penetrating corneal grafts for Fuchs dystrophy or PACE remain clear at 10 years. The risk for failure is greater for graft recipients with PACE and those with a history of glaucoma. Measurements of ECD and CT during the course of postkeratoplasty follow-up are associated with a risk for failure. However, even with very low ECD and high CT at 5 years, most corneas remain clear at 10 years.

The Cornea Donor Study (CDS) was designed primarily to evaluate the effect of donor age on graft survival and endothelial cell loss in penetrating keratoplasty for endothelial disease. At 5 years, no difference in graft survival (86%) was found between participants who received corneas from donors aged 12 to 65 years and from donors aged 66 to 75 years.¹ By 10 to 12 years, a small but nonsignificant difference (77% survival for the younger group and 71% for the older group) could be detected.² However, the evidence suggested that an age effect at the extremes of the donor age range existed, that is, 96% survival for 80 donors aged 12 to 33 years and 62% survival for 130 donors aged 72 to 75 years.

The effects of recipient, donor, and surgical factors other than donor age on graft survival at 5 years have been reported in prior publications.^3-8 The most prominent finding was that eyes with Fuchs dystrophy had a substantially lower failure rate (7%) than eyes with pseudophakic or aphakic corneal edema (PACE) (27%).⁷ Donor endothelial cell density (ECD) had no effect on outcomes, but 6-month postoperative ECD less than 1700 cells/mm² and corneal thickness (CT) greater than 600 µm at 1 year were associated with an increased risk for failure at 5 years.⁸ Most other factors studied had marginal or no effect on outcomes. The extension of the CDS to 10 to 12 years of follow-up provides opportunities to examine the longer-term effects of donor and recipient factors on graft survival and in particular to assess the relationship of ECD and CT at 5 years to the subsequent course of the grafts.

Complete details of the CDS protocol have been reported previously.^1,9,10 The study protocol was approved by the institutional review board at each investigational site (listed at the end of this article). From January 10, 2000, through August 2, 2002, a total of 1090 eligible patients (median age, 72 [interquartile range, 65-76] years) at 80 sites underwent penetrating keratoplasty for Fuchs dystrophy (62%), PACE (34%; 93% for pseudophakic and 7% for aphakic), or another corneal endothelial disorder (4%). Written informed consent was obtained from each participant for the first 5 years of follow-up, and 663 participants who did not undergo regrafting by 5 years renewed consent for follow-up through 2012.

Eligible donor corneas met the standards of the Eye Bank Association of America for human corneal transplantation.¹¹ Additional donor eligibility criteria included age from 10 to 75 years and an eye bank–measured ECD of 2300 to 3300 cells/mm². Median donor age at the time of death was 61 (interquartile range, 52-69) years. Clinical investigators and participants were masked to certain characteristics of the donor tissue, including age and ECD. Donor tissue was assigned without regard to recipient age or other participant characteristics. Preoperative management, penetrating keratoplasty surgical technique, and postoperative care were provided according to each investigator’s directive. In the first 6 months of the study, follow-up visit frequency was left to each investigator’s routine. Then the minimum follow-up schedule included a visit between months 6 and 12 and then annual visits through 2012. Corneal thickness, measured using an ultrasonic pachymeter per the investigator’s usual routine, was optional at postkeratoplasty follow-up visits. Measurements were recorded to the nearest micrometer.

Graft clarity was assessed at each visit. The definition of graft failure, based on the definition used in the Collaborative Corneal Transplantation Studies,^12,13 was a second graft or, in its absence, a cloudy cornea with loss of central graft clarity sufficient to compromise vision for a minimum of 3 consecutive months. Details regarding classification of graft failure have been published.¹

A subset of the CDS participants also consented to participate in the Specular Microscopy Ancillary Study.⁴ Preoperative specular microscopic images of the central donor corneal endothelium were provided by participating eye banks. Postoperative specular microscopic images of the central corneal endothelium of the graft were obtained at the 6-month and annual follow-up visits. The preoperative donor images and postoperative recipient images were evaluated for quality and ECD by a central reading center, the Cornea Image Analysis Reading Center (formerly the Specular Microscopy Reading Center) at University Hospitals Eye Institute, Case Western Reserve University, using a previously described variable frame analysis method.¹⁴

Cumulative probabilities of graft failure (hereinafter referred to as graft failure rates) along with 99% CIs were calculated at 10 years using the Kaplan-Meier method. Proportional hazards regression was used to assess the association of baseline recipient factors with graft failure in univariate and multivariate analyses. Covariates with P < .10 were included in a multivariate model to control for potential confounding factors; however, owing to multiple comparisons, only covariates with P < .01 were considered statistically significant. The proportional hazards assumption was violated for diagnosis and donor age in the final multivariate baseline recipient factors model. The baseline hazard function was stratified by donor age, but hazard ratios (HRs) were modeled for diagnosis so that the values could be displayed. Results were similar for the other recipient factors when the baseline hazard functions were also stratified by corneal diagnosis (eTable 1 in the Supplement). The association of lens status with graft failure was assessed in separate proportional hazard regressions for patients with Fuchs dystrophy and PACE, with adjustment for participant age and smoking status and stratification of the baseline hazard function by donor age. Additional analyses were performed on the subset of patients who had available ECD and/or CT measurements. Multivariate proportional hazards models were fit conditionally on graft survival at 5.5 years, which was the upper limit for the 5-year visit window. Similar models were run at 6 months and 1 year. No significant deviations from the proportional hazards assumptions were detected for follow-up ECD or CT values.

In all multivariate models, missing data were treated as a separate category for discrete covariates, and a missing value indicator was added for continuous covariates. Similar methods were used to assess the association of donor factors with graft failure. All reported P values are 2 sided. Statistical analyses were conducted using commercially available software (SAS, version 9.3; SAS Institute Inc).

Graft failure occurred in 224 of the 1090 participants (21%). In univariate and multivariate analyses, the 10-year graft failure rate was higher in participants with PACE than in those with Fuchs dystrophy (37% vs 20%; P < .001) and in participants with a history of glaucoma (glaucoma surgery before penetrating keratoplasty and/or use of medications to lower intraocular pressure at the time of penetrating keratoplasty), particularly when prior glaucoma surgery had been performed (58% in participants with prior glaucoma surgery and using medications to lower intraocular pressure at the time of surgery vs 22% with no history of glaucoma surgery or medication use; P < .001) (Table 1). We found trends toward increased graft failure in recipients who were older (P = .04) or who had a history of smoking (P = .02) that did not meet our threshold for statistical significance accounting for multiple comparisons (Table 1). African American race was associated with increased graft failure in univariate analysis (P = .002), and this trend was also observed in multivariate analysis but did not reach statistical significance (HR, 1.5; P = .11).

Further exploration showed that the effects of the recipient’s corneal diagnosis and history of glaucoma were primarily limited to the first 5 years after surgery. During the first 5 years, the HR for graft failure for PACE compared with Fuchs dystrophy was 4.3 (99% CI, 2.6-7.1; P < .001), whereas, among grafts still functioning at 5 years, the corresponding HR for subsequent failure was 1.1 (99% CI, 0.6-2.1; P = .65). Results were similar for individuals with a history of glaucoma: during the first 5 years, the HR for participants with a history of glaucoma surgery and use of medication to lower intraocular pressure at the time of penetrating keratoplasty was 7.2 (99% CI, 3.8-13.5; P < .001) compared with patients with no history of glaucoma surgery, and the corresponding HR afterward was 0.5 (99% CI, <0.1 to 7.3; P = .55).

Among participants with Fuchs dystrophy, the 10-year postoperative graft failure rate was similar in eyes with postoperative phakia and pseudophakia (16% vs 20%; P = .34), with almost all of the pseudophakic eyes having posterior chamber intraocular lenses (IOLs) (96% of 501). Among participants with PACE, graft failure by 10 years was more common when an anterior chamber lens was present postoperatively than with a posterior chamber lens (57% vs 30%; multivariate HR, 1.9 [99% CI, 1.1-3.4]; P = .02) (Table 2). This HR did not vary meaningfully during the 10 years of follow-up. Eyes with a preoperative anterior chamber lens that was retained postoperatively (n = 81) had a 59% graft failure rate by 10 years, whereas those with an anterior chamber lens exchanged for a posterior chamber lens (n = 28) had a 23% failure rate (multivariate HR, 0.4 [99% CI, 0.1-1.2]; P = .04) (eTable 2 in the Supplement). Other than lens status, the effect of the baseline recipient factors on graft failure was similar in participants with Fuchs dystrophy and those with PACE (Table 3).

Measurements of ECD and CT at 6 months and 1 and 5 years were strongly associated with an increased probability of subsequent graft failure (Table 4). Among participants with a surviving graft at 5 years, the conditional probability of graft failure by 10 years was 29% among 46 participants with a 5-year ECD of less than 500 cells/mm² compared with 10% for the 210 participants with a 5-year ECD of 500 to 1499 cells/mm² and 2% for the 57 participants with a 5-year ECD of at least 1500 cells/mm² (P < .001) (Table 4 and the Figure, A). With respect to CT, the conditional probability of failure by 10 years was 34% among the 40 participants with a 5-year CT of at least 650 μm compared with 19% among the 97 participants with a 5-year CT of 600 to 649 μm and 8% among the 305 participants with a 5-year CT of less than 600 μm (P < .001) (Table 4 and the Figure, B). The correlation between the 5-year ECD and CT measurements was −0.31 (n = 273) (99% CI, −0.41 to −0.20; P < .001). Graft failure rates combining the 5-year ECD and CT data are shown in eTable 3 in the Supplement. The addition of preoperative diagnosis in the recipient, glaucoma history, and donor age to the model did not appreciably increase the ability to predict the probability of subsequent graft failure (eTable 4 in the Supplement). As at 5 years, no other donor factors, including eye bank variables and ABO matching, and no operative factors correlated with graft failure at 10 years.

Analysis of the CDS data after 10 to 12 years of follow-up largely showed similar associations of baseline recipient factors with graft failure as were seen after 5 years in eyes undergoing penetrating keratoplasty for corneal endothelial disease. Graft failure was again shown to be more likely in participants with PACE than with Fuchs dystrophy and in participants with a history of glaucoma, particularly when prior glaucoma surgery had been performed. In addition, trends suggested higher failure rates in recipients who were 70 years or older or African American or who had a history of smoking. No other donor factors were significantly associated with graft failure by 10 to 12 years other than the previously reported suggestion of an association between the extremes of donor age and graft outcome.² As at 5 years, we found no indication that ABO blood type incompatibility between donor and recipient was important; however, this finding must be viewed in the context that the study eyes were not considered to be at high risk for rejection failure.⁶

During the course of the study, ECD and CT were strongly associated with subsequent graft failure. However, despite these significant associations, neither factor was strongly predictive of graft failure. Even with an ECD of less than 500 cells/mm² at 5 years, the probability of graft survival at 10 years was 71%. Likewise, even when the CT was at least 650 µm at 5 years, the probability of graft survival at 10 years was 66%. Combining ECD and CT data with donor age, preoperative diagnosis in the recipient, and glaucoma history did not improve the prediction of success. These data may be useful for clinicians in counseling patients and to provide reassurance that most grafts will remain clear for a number of years, even when the ECD is less than 500 cells/mm².

By 10 years, recipient diagnosis remained the most important predictor of outcome, with PACE grafts having failed at almost twice the rate of grafts for Fuchs dystrophy. PACE increased the rate of early failures, but grafts in eyes with PACE that survived the first 5 years had a failure rate from 5 to 12 years similar to that for eyes with Fuchs dystrophy. This finding is consistent with the hypothesis that many eyes developing PACE have a pathologic response to IOL presence that persists after keratoplasty.⁷ That is, many eyes with PACE constitute a subset of all pseudophakic eyes: those with poor tolerance of IOLs. Those eyes manifesting this effect of IOLs may drop out of the surviving graft group early, leaving those with PACE not attributable to continued IOL effects after the first 5 years. The lack of effect of lens status in eyes with Fuchs dystrophy and the detrimental effect of anterior chamber vs posterior chamber IOLs in PACE eyes throughout the 10-year follow-up bolster this notion. The postkeratoplasty presence of an anterior chamber IOL was associated with a 1.9-fold increased risk for failure compared with a posterior chamber IOL in PACE eyes. Unlike the overall IOL effect, the detrimental effect of anterior chamber IOLs persisted from 5 to 10 years. This adverse effect of anterior chamber IOLs on graft survival has been noted in the past.^15,16 PACE eyes in which the anterior chamber IOL was replaced with a posterior chamber IOL at keratoplasty had an approximately 60% reduction in the risk for failure, confirming this effect.

Preoperative glaucoma, particularly prior surgical glaucoma treatment in PACE eyes, also was associated with early failures. Insufficient numbers of participants with glaucoma were available to determine whether this association was true for eyes with Fuchs dystrophy, and data were not collected to evaluate the effect of intraocular pressure control after the first postoperative month. Other studies have associated preoperative and postoperative glaucoma with corneal graft failure in eyes with PACE and Fuchs dystrophy.^17,18 Glaucoma surgery, particularly with tube drainage devices, has been strongly associated with graft failure.¹⁹ These failures are likely related to endothelial cell decline, but the mechanism is unknown.

Diabetes mellitus in recipients did not contribute to graft failure, but we found a trend for a higher failure rate among recipients who smoked compared with those who were nonsmokers. Smoking has been associated with the severity of corneal edema in Fuchs dystrophy.²⁰ Association of smoking and other risk factors with Fuchs endothelial corneal dystrophy may be mediated through oxidative endothelial damage.^20,21 In addition, trends toward a higher failure rate in recipients older than 70 years and African American recipients were found. An association between nonwhite race and corneal graft failure has been noted previously.²²

Analysis of the CDS data after 10 to 12 years of follow-up extends our understanding of the association of donor and recipient factors with graft failure in eyes undergoing penetrating keratoplasty for corneal endothelial disease. To our knowledge, the sample size and the duration and completeness of follow-up exceed those of the few other prospective trials of penetrating keratoplasty in the literature. Most grafts after penetrating keratoplasty for Fuchs dystrophy or PACE will remain clear at 10 years. Of the preoperative risk factors studied, the risk for failure is greater for individuals with PACE or with a history of glaucoma. Measurements of ECD and CT during the course of postkeratoplasty follow-up are associated with the risk for failure. However, even with very low ECD and high CT at 5 years, most corneas will remain clear at 10 years. The applicability of the CDS data to endothelial keratoplasty, which has replaced penetrating keratoplasty as the procedure of choice for the corneal endothelial diseases²³ studied in CDS, cannot be predicted. Penetrating keratoplasty may still have advantages in some complex cases requiring IOL exchange or anterior segment reconstruction. The principles examined herein are broadly applicable to endothelial keratoplasty. Trials to further examine donor and eye banking variables for endothelial keratoplasty, such as the ongoing Cornea Preservation Time Study, are warranted.

Submitted for Publication: March 10, 2014; final revision received July 7, 2014; accepted July 9, 2014.

Corresponding Author: Alan Sugar, MD, c/o CDS Coordinating Center, Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (cds@jaeb.org).

Published Online: October 16, 2014. doi:10.1001/jamaophthalmol.2014.3923.

Writing Committee for the Cornea Donor Study Research Group: Alan Sugar, MD; Robin L. Gal, MSPH; Craig Kollman, PhD; Dan Raghinaru, MS; Mariya Dontchev, MPH; Christopher R. Croasdale, MD; Robert S. Feder, MD; Edward J. Holland, MD; Jonathan H. Lass, MD; Jonathan I. Macy, MD; Mark J. Mannis, MD; Patricia W. Smith, MD; Sarkis H. Soukiasian, MD; Roy W. Beck, MD, PhD.

Affiliations of Writing Committee for the Cornea Donor Study Research Group: W. K. Kellogg Eye Center, University of Michigan, Ann Arbor (Sugar); Jaeb Center for Health Research, Tampa, Florida (Gal, Kollman, Raghinaru, Dontchev, Beck); Davis Duehr Dean Clinic, Madison, Wisconsin (Croasdale); Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Feder); Cincinnati Eye Institute and Department of Ophthalmology and Visual Sciences, University of Cincinnati, Cincinnati, Ohio (Holland); University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio (Lass); Macy Eye Center, Los Angeles, California (Macy); Eye Center, University of California, Davis, Sacramento (Mannis); Triangle Eye Physicians, Raleigh, North Carolina (Smith); Department of Ophthalmology, Lahey Clinic, Burlington, Massachusetts (Soukiasian).

Author Contributions: Dr Beck had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Sugar, Gal, Holland, Lass, Mannis, Beck.

Acquisition, analysis, or interpretation of data: Sugar, Kollman, Raghinaru, Dontchev, Croasdale, Feder, Holland, Lass, Macy, Mannis, Smith, Soukiasian.

Drafting of the manuscript: Sugar, Gal, Raghinaru, Lass, Macy.

Critical revision of the manuscript for important intellectual content: Sugar, Gal, Kollman, Dontchev, Croasdale, Feder, Holland, Lass, Mannis, Smith, Soukiasian, Beck.

Statistical analysis: Kollman, Raghinaru, Dontchev.

Obtained funding: Holland, Lass, Beck.

Administrative, technical, or material support: Sugar, Feder, Holland, Lass, Macy.

Study supervision: Gal, Kollman, Mannis.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This study was supported by cooperative agreements EY12728 and EY12358 with the National Eye Institute, National Institutes of Health, US Department of Health and Human Services, and by the Eye Bank Association of America, Bausch & Lomb, Inc, Tissue Banks International, Vision Share, Inc, San Diego Eye Bank, The Cornea Society, Katena Products, Inc, ViroMed Laboratories, Inc, Midwest Eye Bank (Michigan Eye Bank, Illinois Eye Bank, Cleveland Eye Bank, and Lions Eye Bank of New Jersey), Konan Medical Corp, Eye Bank for Sight Restoration, SightLife, Sight Society of Northeastern New York (Lions Eye Bank of Albany), and Lions Eye Bank of Oregon.

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Members of the Cornea Donor Study Research Group: The following investigators and sites participated in the Cornea Donor Study Research Group (number of patients participating): Christopher Y. Chow, MD, Steven P. Dunn, MD, David G. Heidemann, MD, Tina MacLeod, and Theresa Price, Michigan Cornea Consultants, PC, Southfield, Michigan (77); Michael W. Belin, MD, Robert L. Schultze, MD, Cassandra Semeiks, and Charity Sutherland, Cornea Consultants of Albany, Albany, New York (58); Matthew S. Oliva, MD, Walter M. Rotkis, MD, Cindy Huddleston, Richard McDonald, and Joy Taylor, Seattle, Washington (47); David D. Verdier, MD, and Paula Johnson, Verdier Eye Center, PC, Grand Rapids, Michigan (41); Jonathan H. Lass, MD, William J. Reinhart, MD, Annapurna Singh, MD, Joseph M. Thomas, MD, Stefan D. Trocme, MD, Lauren Brown, Kristee Mines, Megin Murray, Marie Norell, Stephanie Shaffer, and Kalisha Washington, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio (33); Stephen M. Hamilton, MD, Gina C. Jayawant, MD, W. Barry Lee, MD, Jacqueline Larson, and Melanie Simner, Eye Consultants of Atlanta, PC, Atlanta, Georgia (30); Robert H. Gross, MD, Edward L. Shaw, MD, and Pamela Blackburn, Cornea Consultants of Arizona, Phoenix, Arizona (28); Steven L. Maskin, MD, Eloise Eggers, Harriet Lutzk, and Sherry Wagner, Cornea and Eye Surface Center, Tampa, Florida (28); Brandon D. Ayres, MD, Parveen K. Nagra, MD, Irving M. Raber, MD, Joy DiCicco, and Irene Spanelis-Diaz, Ophthalmic Subspecialty Consultants, Narberth, Pennsylvania (26); Joel Sugar, MD, Elmer Tu, MD, and Dolores Byrne, University of Illinois at Chicago (25); Mark S. Gorovoy, MD, Deborah Glinos, Robert Lehet, and Bernadette Nolan, Eye Associates of Fort Myers, Ft Myers, Florida (24); Francis J. Manning, MD, and Brenda Shelly, Eye Physicians of Lancaster, Lancaster, Pennsylvania (24); Thomas S. Boland, MD, Stephen E. Pascucci, MD, and Donna Kunz, Northeastern Eye Institute, Scranton, Pennsylvania (23); Qais A. Farjo, MD, Roger F. Meyer, MD, Shahzad I. Mian, MD, H. Kaz Soong, MD, Alan Sugar, MD, Munira Hussain, Jessica Knowlton, Cindy Pope, and Paulina Radenbaugh, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor (21); Paul G. Galentine, MD, Gerald B. Rosen, MD, David N. Ugland, MD, and Mara Schafer, Horizon Eye Care, Charlotte, North Carolina (21); Sadeer B. Hannush, MD, Langhorne, Pennsylvania (21); John E. Bokosky, MD, and Donna Riner, Eye Care of San Diego, San Diego, California (21); James W. Caudill, MD, and Lea Coleman, Charleston Eye Care, PLLC, Charleston, West Virginia (20); Robert S. Feder, MD, and Lori Kaminski, Northwestern University, Chicago, Illinois (20); John C. Affeldt, MD, Christopher L. Blanton, MD, and Monica Cancino, Inland Eye Institute, Colton, California (20); Edward J. Holland, MD, Amy Jost, and Aimee Meyer, Cincinnati Eye Institute, Cincinnati, Ohio (20); R. Wayne Bowman, MD, H. Dwight Cavanagh, MD, PhD, Mohamed-Sameh H. El-Agha, MD, James P. McCulley, MD, and Mike Molai, University of Texas Southwestern Medical Center at Dallas (20) (Dr El-Agha now practices in Cairo, Egypt); Thomas E. Gillette, MD, Isabel Buchan, and Michelle Corrigan, Eye Associates NW, Inc, PS, Seattle, Washington (20); Alan B. Leahey, MD, and Ann Malinowski, Lehigh Valley Eye Center, PC, Allentown, Pennsylvania (19); Christopher R. Croasdale, MD, Stephanie Blaser, Jane DeBaufer, and LuAnne Moudry, Davis Duehr Dean Clinic, Madison, Wisconsin (19); Richard A. Eiferman, MD, Pamela Durham, and Shannon Shields, University of Louisville, Louisville, Kentucky (16); Sarkis H. Soukiasian, MD, Ken Brown, Patti-Ann Morse, and Patricia Sexton, Lahey Clinic, Burlington, Massachusetts (15); Bhairavi K. Dholakia, MD, James B. Randleman, MD, R. Doyle Stulting, MD, PhD, Jayne Brown, Paul Larson, and Donna Loupe, Emory University, Atlanta, Georgia (14); Walter J. Stark, MD, and Kimberly Pratzer, Johns Hopkins University School of Medicine, Baltimore, Maryland (14); Kenneth R. Kenyon, MD, Richard C. Rodman, MD, and Kari Crompton, Eye Health Vision Center, North Dartmouth, Massachusetts (14); Walter E. Beebe, MD, Henry Gelender, MD, and Sidney Heinle, Cornea Associates of Texas, Dallas (13); Steven S. Ching, MD, Ronald D. Plotnik, MD, Jennifer Anstey, Nancy Fedick, Peter MacDowell, Karen Skrine, and Ann Stoutenburg, University of Rochester, Rochester, New York (13); Marc A. Goldberg, MD, and Kathy Owen, The Eye Institute, Tulsa, Oklahoma (13); Karen Sumers, MD, Lisa Spentz, and Amanda Wykle, Atlanta, Georgia (12); Kenneth C. Chern, MD, Nicoletta A. Fynn-Thompson, MD, Ann Z. McColgin, MD, Michael B. Raizman, MD, Patricia Healy, and Jacqueline Pereira, Center for Eye Research and Education, Boston, Massachusetts (12); Steven I. Rosenfeld, MD, and Ellen Salvati, Delray Eye Associates, PA, Delray Beach, Florida (12); Elizabeth A. Davis, MD, David R. Hardten, MD, Richard L. Lindstrom, MD, Janet DeMarchi, Alexander Jordan, Richard Lindstrom, Sara Mork, and Allison Rockvam, Minnesota Eye Consultants, PCA, Minneapolis (12); Mark J. Mannis, MD, Katrina Imson, Michael Saya, Marilyn Sponzo, and Cindy Wallace, University of California, Davis, Sacramento (12); Jerry G. Ford, MD, Eye Associates of Tallahassee, Tallahassee, Florida (12); David M. Meisler, MD, and Laura Holody, The Cleveland Clinic Foundation, Cleveland, Ohio (11); Kendall Dobbins, MD, Francis W. Price Jr, MD, William G. Zeh, MD, and Clorissa Quillin, Price Vision Group, Indianapolis, Indiana (11); Peter J. Berkowitz, MD, and Lori Zubik, Pittsburgh, Pennsylvania (11); Thomas D. Lindquist, MD, PhD, and Linda Sims, Group Health Cooperative, Seattle, Washington (11); Daniel F. Goodman, MD, and Minah Yang, MD, San Francisco, California (10); Abdulfatah M. Ali, MD, Richard F. Beatty, MD, Michaela Kavanagh, Elizabeth Salinas, and Jackie Varela, Colorado Eye Physicians and Surgeons, Denver (9); John E. Sutphin, MD, Ayad A. Farjo, MD, Kenneth M. Goins, MD, and Connie Mullinnix, University of Iowa, Iowa City (9); Terry E. Burris, MD, Desiree Crowell, Susan Johnson, Dawn Kerns, Jenni Powell, and Portia Swenson, Northwest Corneal Services, Portland, Oregon (9); Peter A. Shriver, DO, Dennis Williams, MD, Kelly Perry, and Monica Wells, Southeast Eye Institute, PA, Pinellas Park, Florida (9); Cynthia A. Self, MD, Garth A. Wilbanks, MD, Courtney Chute, and Cheryl Hart, Eastern Maine Eye Associates, PA, Bangor (8); Roy S. Chuck, MD, PhD, Ronald N. Gaster, MD, Michael Bradley, MD, Winston Chamberlain, MD, Andre Cohen, MD, Kouroush Eghbali, Marjan Farid, MD, Sumit Garg, MD, Jeff Grijalva, and Whitney Lomazow, MD, University of California, Irvine (8); David W. Kielty, MD, Southcoast Eye Care, Inc, North Dartmouth, Massachusetts (7); Garvin H. Davis, MD, J. Mike Bourg, Rhonda Nolen, MD, and Teresa Solis, University of Texas Medical Branch at Galveston (6); Woodford S. Van Meter, MD, and Jane Webb, Lexington, Kentucky (6); Patricia W. Smith, MD, Robbin Bradshaw, Tineta Mewborn, and Jorge Sanchez, OD, Raleigh, North Carolina (6); Alan R. Schaeffer, MD, Chasity Owens, and Charlisha Price, Associated Ophthalmic Specialists, Memphis, Tennessee (6); Elisabeth J. Cohen, MD, Peter R. Laibson, MD, Christopher J. Rapuano, MD, and Andrea Gardiner, Corneal Associates, PC, Philadelphia, Pennsylvania (6); Keith H. Baratz, MD, Mayo Clinic College of Medicine, Rochester, Minnesota (6); Barton L. Halpern, MD, Mark A. Pavilack, MD, and Shawn Gallagher, PhD, Eye Doctors of Lancaster, Lancaster, Pennsylvania (5) (Dr Pavilack is now at Tidewater Eye Center, Virginia Beach, Virginia); Gerald B. Rosen, MD, Lansdale, Pennsylvania (5) (now at Horizon Eye Care, Charlotte, North Carolina); Donald J. Doughman, MD, Stephen C. Kaufman, MD, PhD, Sally Cook, and Ann Holleschau, University of Minnesota, Minneapolis (5); Theodore Perl, MD, Soo Mee Pak, MD, and Angelina Fornelos, Corneal Associates of New Jersey, Fairfield (5); John W. Cowden, MD, and Sue Mussatt, University of Missouri, Columbia (4); Elliot M. Perlman, MD, Joanie Cozzo, and Margaret Gallagher-Sylvia, Rhode Island Eye Institute, Providence (4); Lance E. Olson, MD, Erik D. Skoog, MD, and Elaine Dobbs, Spokane Eye Clinic, Spokane, Washington (4); William D. Gruzensky, MD, Pacific Cataract and Laser Institute, Tacoma, Washington (4); Erich B. Groos Jr, MD, and Denise Alexander, Cornea Consultants of Nashville, PLLC, Nashville, Tennessee (3); Mark D. Mifflin, MD, Maureen K. Lundergan, MD, and Deborah Harrison, University of Utah, Salt Lake City (3); Steven T. Berger, MD, and Sandy Hyszczak, Springfield, Massachusetts (3); Kerry D. Solomon, MD, and Carol Bradham, Medical University of South Carolina, Charleston (2); Richard F. Dennis, MD, Jonathan B. Rubenstein, MD, Sarah Levine, Heena Khan, Nisha Sheth, and Denise Voskull-Marre, Rush University Medical Center, Chicago, Illinois (2); Alexandra M. P. Kostick, MD, Atlantic Eye Center, Palm Coast, Florida (2); Samuel H. Santander, MD, MPH, Raleigh, North Carolina (2); Allen S. Roth, MD, The Cleveland Clinic Foundation, Beachwood, Ohio (1); Laura A. Bealer, MD, Eye Physicians and Surgeons, PC, Decatur, Georgia (1); Jonathan I. Macy, MD, Los Angeles, California (1); David G. O’Day, MD, and Linda Maynard, Charleston Cornea & Refractive Surgery, PA, Mount Pleasant, South Carolina (1); Mark A. Terry, MD, Devers Eye Institute, Portland, Oregon (1); Nunzio P. Sossi, MD, PhD, Palm Beach Eye Clinic, West Palm Beach, Florida (1); and Keith A. Walter, MD, and Joan Fish, Wake Forest University School of Medicine, Winston-Salem, North Carolina (1).

Eye Banks: Midwest Eye-Banks (192) (Michigan Eye Bank, Ann Arbor [145]; Illinois Eye Bank, Chicago [47]), Florence M. Johnston (director [D]), Kyle L. Mavin (coordinator [C]), Kristen E. McCoy (C), and Michael B. O’Keefe (C); Tissue Banks International (119) (New England Eye & Tissue Transplant Bank, Boston, Massachusetts [47]; Indiana Lions Eye & Tissue Transplant Bank, Indianapolis [22]; Lions Eye Bank of North Dakota, Inc, Bismarck [19]; Lions Eye Bank of West Central Ohio, Dayton [11]; Medical Eye Bank of Maryland & Washington Eye Bank, Baltimore [4]; Orange County Eye & Tissue Bank, Santa Ana, California [4]; New Mexico Lions Eye Bank, Albuquerque [3]; Doheny Eye and Tissue Transplant Bank, Los Angeles, California [3]; Medical Eye Bank of Florida, Orlando [2]; Northern California Transplant Bank, Oakland [2]; Lions Eye Bank of New Jersey, Springfield [2]), Gerald J. Cole, MBA (D), Diane F. Johnston (C), Mark A. Jones (C), Sameera M. Farazdaghi, MPH (C), and Elizabeth N. Walunas (C); SightLife, Seattle, Washington (86), Monty M. Montoya, MBA (D), Bernie Iliakis (C), Rick D. McDonald (C), Misty L. Ostermiller (C), and Cathy E. Saltwick (C); Central Florida Lions Eye & Tissue Bank, Inc, Tampa (73), Jason K. Woody (D and C); Northeast Pennsylvania Lions Eye Bank, Inc, Allentown (70), Mark H. Weaver (D), Michael J. Christ (C), and Mark B. Gross (C); Minnesota Lions Eye Bank, Minneapolis (61), Carol R. Engel (D), Raylene A. Dale (C), Stephanie K. Hackl (C), Elena J. Henriksen (C), Kathryn J. Kalmoe (C), Jennifer M. Larson (C), Jackie V. Malling (C), and Brian J. Philippy (C); Sight Society of Northeastern New York, Albany (58), Maryann Sharpe-Cassese, RN, MSN (D), and Sue M. Hayes (C); Lions Eye Bank of Delaware Valley, Philadelphia, Pennsylvania (58), Robert E. Lytle (D) and David A. Rechtshaffen (C); Georgia Eye Bank, Inc, Atlanta (57), Bruce Varnum (D), Erin B. Angel (C), Matt D. Durell (C), and Teresa R. Williams (C); Cleveland Eye Bank, Cleveland, Ohio (45), Susan V. Janssen (D), Brian E. Kraus (C), Marcy B. McLain (C), and Jackie A. Rossi (C); Transplant Services Center UT Southwestern, Dallas, Texas (33), Ellen L. Heck, MS, MA (D), and Marilyn S. Hayes (C); Donor Network of Arizona, Pheonix (28), Gregory C. Davis (D), Tara L. Chavez (C), Lori D. Oswald (C), and Noreen B. Ruiz (C); San Diego Eye Bank, San Diego, California (26), Jeffrey G. Penta, MBA (D), Wayne E. Dietz (C), and Jennifer L. Nary (C); Medical Eye Bank of West Virginia, Charleston (21), Kenneth R. Sheriff (D) and Nancy C. Driver (C); Lifeshare of the Carolinas, Charlotte, North Carolina (21), William J. Faircloth (D) and Paul E. Williams (C); The North Carolina Eye Bank, Inc, Winston-Salem (21), Kurt Weber, MA, MBA (D), Jerry W. Barker (C), Donna M. Bridges (C), Lee Chenier (C), and Mark Soper (C); Inland Eye & Tissue Bank, Redlands, California (20), Betsy Allen (D) and Samantha J. Wright (C); University of Louisville Lions Eye Bank, Louisville, Kentucky (16), James R. Martin (D) and Anne J. Watson (C); Sierra Eye & Tissue Donor Services-DCI, Sacramento, California (15), Greg McDonough, MS (D), and Kristel D. Beilby (C); Rochester Eye & Human Parts Bank, Inc, Rochester, Minnesota (13), Linda K. Fraser (D) and Tammi S. Sharpe (C); Center for Organ Recovery and Education, Pittsburgh, Pennsylvania (11), Robert C. Arffa, MD (D), and Michael A. Tramber (C); Lions Eye Bank of Oregon, Portland (10), Barbara L. Crow (D), Matthew M. Fisher (C), and Chris G. Stoeger (C); Rocky Mountain Lions Eye Bank, Aurora, Colorado (9), Edmund Jacobs (D), Michael P. Filbin (C), James I. Mather (C), Christopher M. McGriff (C), and Eric E. Meinecke (C); Iowa Lions Eye Bank, Iowa City (9), Patricia J. Mason (D), Garret D. Locke (C), and Janice F. Reiter (C); Lions Medical Eye Bank of Eastern Virginia, Inc, Norfolk (7), David E. Korroch (D) and Penelope M. Thomas (C); Southeast Texas Lions Eye Bank, Inc, Galveston (6), Wayne A. Lange (D and C) and Rosemary F. Moore (C); Mid-South Eye Bank for Sight Restoration, Memphis, Tennessee (6), Lee J. Williams (D) and Yvette D. Friedhoff (C); Heartland Lions Eye Bank, Columbia, Missouri (4), Ronald J. Walkenbach, PhD (D), Jennifer E. Glover (C), Brenda A. Kafton (C), and Kraig J. Lage (C); South Carolina Lions Eye Bank, Inc, Charleston (3), Brenda S. Horn (D), H. Tommy Bottoms (C), and Ellen R. Kerns (C); and Utah Lions Eye Bank, Salt Lake City (3), Raymond Jessen, MPH (D and C) and William H. Dennis (C).

Coordinating Center: Roy W. Beck, MD, PhD (principal investigator), Robin L. Gal, MSPH (coordinating center director), Mariya Dontchev, MPH, Craig Kollman, PhD, Dan Raghinaru, MS, Alandra Powe, Katrina J. Ruedy, MSPH, Lee Anne Lester, Heidi J. Strayer, PhD, Shelly T. Mares, Amber Evans, Yazandra A. Parrimon, and Michael Gray, Jaeb Center for Health Research, Tampa, Florida.

Cornea Image Analysis Center: Jonathan H. Lass, MD (medical director), Beth Ann Benetz, MA (technical director), Stephanie Burke, Shannon Edwards, Carmella Gentile, Lori Karpinecz, and Mark Madere, University Hospitals Eye Institute, Case Western Reserve University, Cleveland, Ohio.

National Institutes of Health: Maryann Redford, DDS, MPH, and Mary Frances Cotch, PhD, National Eye Institute, Bethesda, Maryland.

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

Steering Committee: Edward J. Holland, MD (study cochairperson, 1999 to present), Mark J. Mannis, MD (study cochairperson, 1999 to present), Mary Frances Cotch, PhD (1999-2001), Steven Dunn, MD (2001-2002), Ellen Heck, MS, MA (1999-2000), Florence Johnston (2000-2001, 2002-2004), Jonathan H. Lass, MD (1999 to present), Thomas Lindquist, MD, PhD (2000-2001), Monty M. Montoya, MBA (2004 to present), Maryann Redford, DDS, MPH (2001 to present), Alan Sugar, MD (2004 to present), Joel Sugar, MD (1999-2000), and Jason Woody (2001-2002).