C orneal transplantation is the most commonly performed tissue transplant procedure in the United States, and among the most successful. To minimize risk and prevent adverse outcomes, strict guidelines and criteria are in place for donor evaluation, tissue recovery, and tissue preparation. They are continuously updated in accordance with the Eye Bank Association of America (EBAA) medical standards. Eye banks are responsible for ensuring seronegative status for a panel of transmissible diseases and for discarding donor tissue for several infectious and systemic diseases that may affect tissue suitability for surgical use. Corneal tissue is closely monitored and regulated, with multiple rounds assessing tissue suitability for transplantation. These criteria are in place to ensure patient safety and reduce adverse events (AEs) or adverse reactions among transplant recipients. ^,,,

The EBAA has closely monitored AE reporting among its member eye banks since 1990, requiring member banks to track and report postoperative data from surgeons. ^, Early reports from 2013 to 2016 identified national and regional trends in AEs, with AE rates ranging from 0.139% to 1.2% in the United States. ^, The most common AEs of corneal transplantation include primary graft failure with endophthalmitis and keratitis as leading infectious sequelae. ^,

Over the last decade, significant advances have been made by the eye bank in surgical techniques and in postoperative management in corneal transplantation. These improvements have optimized donor tissue safety, enhanced tissue preparation efficiency and quality, and increased standardization of quality assurance, thereby reducing complications associated with corneal transplantation. ^, Additionally, advanced processing techniques, such as precut or preloaded grafts for endothelial keratoplasty (EK), minimize the risk of tissue damage or contamination, fueling further adoption of Descemet stripping automated EK (DSAEK) and Descemet membrane EK (DMEK) for the management of diseases that were previously treated with full-thickness corneal transplants. ^, The partial-thickness corneal grafts are associated with lower immunological rejection rates and improved graft survival compared to traditional penetrating keratoplasty. ^,

Despite low rates of AEs and significant strides in eye banking and transplantation techniques over the last decade, the current rates and trends of tissue-related AEs from transplant procedures in the last decade of corneal transplantation in the United States have not been well characterized. ^, Furthermore, the relationship between tissue characteristics and the types and rates of AEs across time, as eye banking practices have changed, remains underexplored.

In light of the rapidly evolving landscape of eye banking and transplantation, characterized by advances in donor screening, tissue preservation, and surgical techniques, a comprehensive, data-driven assessment of AEs is both timely and critical. By systematically quantifying rates of reported complications in corneal transplantation and comparing them across tissue attributes (eg, preservation interval, endothelial cell density), this study aims to identify trends in AEs, factors associated with adverse outcomes, and how these relationships have shifted over time. Such insights have the potential to inform eye banks and clinicians about current trends in AEs, aid in developing and refining processing and storage protocols, and inform clinicians and patients about the evolving safety of tissue-related AEs.

This trend study of a single eye bank investigated the rates of reported AEs at a large regional Midwest eye bank (Eversight, Ann Arbor, MI), which provides corneal tissue to corneal surgeons nationally and internationally. The study received exempt status from the University of Michigan Institutional Review Board (IRBMED, HUM00276726). It adhered to the tenets of the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies. Given the study’s retrospective nature and secondary analysis of tissue characteristics, patient consent was not required for participation.

All donor medical history, tissue biomicroscopy findings, and processing details were stored in the Midwire database (Data Intuitions). Patient outcomes were also monitored, and physicians were provided with forms for reporting AEs. AE reporting was strongly encouraged but not mandatory; Eversight sought postoperative follow-up between 3 and 6 months for all cases, but not all additional inquiries resulted in surgeon correspondence.

When a transplanting surgeon reported an AE, staff members conducted a thorough review of the medical record, a physician interview, and an examination of eye bank records to determine the root cause. The eye bank medical director reviewed the investigation findings to assess the imputability of the donor tissue to the event. Only tissues determined to be at least possibly tissue-related were included in the longitudinal analysis. These investigations included assessment of all information related to the donor, tissue, processing, storage, shipping, or any unusual event. An example of root cause determination for primary graft failure is shown in the Supplemental. Definite events were those with conclusive evidence beyond a reasonable doubt for attributing the AE to the tissue; likely or probable events were those where evidence was clearly in favor of attributing the AE to the tissue, whereas possible events were those where evidence was indeterminate for attributing the AE to the quality or safety of the tissue. This information was subsequently entered into the Midwire software. For the purposes of this study, “adverse events or reactions (AEs)” were defined as any unfavorable medical occurrence associated with the use of transplanted ocular tissue that was reported to the eye bank and was determined to be at least a possible tissue-related cause by root cause determination, to include adverse reactions (ie, endophthalmitis) and serious adverse reactions.

The EBAA defines the criteria for primary graft failure as corneal edema present at the time of keratoplasty that does not clear after 8 weeks, with no known operative or postoperative complications or underlying condition that would better explain the biological dysfunction. EBAA defines early regraft as corneal edema from the time of keratoplasty, which does not clear prior to the time of regraft, with no known operative or postoperative complication that would better explain dysfunction, which is regrafted less than 8 weeks, and which may include cases where there is failure of the graft to attach.

Raw data for this study were systematically obtained from the Midwire eye banking software, using a set of structured SQL queries. This comprehensive dataset encompasses all corneas distributed by Eversight between May 2007 and December 2024. Key data points relevant to the analysis of infectious post-transplant complications were extracted. Following extraction via the SQL queries, the complete dataset was output in a comma-separated values format. This deidentified dataset was then securely stored on dedicated and secure Eversight internal servers. Access to these servers and the stored data was strictly controlled and limited to authorized personnel, ensuring data integrity, confidentiality, and compliance with data security protocols.

Statistical analysis was conducted in R 4.5.2 (R Core Team). Descriptive findings were calculated to assess the rate of events and the means of tissue characteristics. One-way ANOVA and chi-squared tests were used as appropriate to examine differences between groups with and without AEs. Binary logistic regression was performed to assess the year-over-year rate of AEs. Additional regression analyses were performed to assess AEs between three main procedure types (penetrating keratoplasty [PKP], DSAEK, and DMEK) and across common AE types (infectious keratitis, endophthalmitis, and graft failure).

A total of 126,072 donor tissues were distributed for surgical use between May 2007 and December 2024. Of the 125,896 tissues without AEs, 65,040 (51.7%) were used for penetrating keratoplasty (PKP), 36,181 (28.7%) for DSAEK starting in 2007, 17,962 (14.3%) for DMEK starting in 2010, and 6713 (5.3%) for other corneal procedures (eg, shunt coverage, anterior or tectonic grafts, implants).

During the same period, a total of 176 AEs were reported to the EBAA, underwent formal investigation, and were determined to be at least possible tissue-related causes. Root cause analysis determined that 8.5% were definite, 64.2% were probable, and 27.3% were possible tissue-related causes. 37 (21.0%) were international, and 139 (79.0%) were within the United States. The causes included 30 cases of endophthalmitis (considered “adverse reaction”), 34 cases of early regraft, 23 cases of infectious keratitis, 86 cases of primary graft failure, and 3 cases of other causes. This represented a total tissue-related AE rate of 0.14% (95% CI: 0.12%-0.16%) or 1.4 AEs per 1000 tissues. The infection rate was 0.04% (95% CI: 0.031%-0.053%). Of the 176 AEs, 61 (34.7%) were PKP, 79 (44.9%) were DSAEK, 34 (19.3%) were DMEK, 1 (0.57%) was Boston Keratoprosthesis (KPro), and 1 (0.57%) was lamellar keratoplasty (LKP). Of the total 176 AEs, 5 tissue-related AEs (2.8%) resulted in recipient enucleation. Descriptive rim culture findings for tissue-related AEs are shown in the Supplemental . The mean time to report a tissue-related AE was 151.8 days, with a SD of 128.7 days.

No differences were found in tissue-related factors between tissues with AEs and those without, including final endothelial cell counts ( P =.38), death-to-procurement time ( P =.56), or whether ocular cooling was performed ( P =.65). However, there were significant differences in calendar year of the tissue ( P <.001) and the eye bank location ( P =.012). These findings are further described in Table 1 .

TABLE 1

Tissue Characteristics by Adverse Events and Without Adverse Events.

	No Adverse Event	Adverse Event	P Value
	n = 125,896	n = 176
Calendar year			<.001 a
	10.7 (4.8)	9.1 (4.9)
Admit to death, d			.90 a
	6.7 (280.6)	4.0 (5.5)
Death to procurement, h			.56 a
	12.4 (5.2)	12.2 (5.1)
Death to cooling, h			.74 a
	3.1 (12.9)	2.8 (2.9)
Cell count			.38 a
	2669.2 (422.1)	2697.1 (279.2)
Procurement to shipment, d c			.48 a
	4.5 (2.0)	4.6 (1.9)
Eye bank location (anonymized)			.012 b
Primary site	39,769 (31.6%)	53 (30.1%)
1	45,216 (35.9%)	85 (48.3%)
2	16,326 (13%)	13 (7.4%)
3	15,655 (12.4%)	16 (9.1%)
4	6796 (5.4%)	6 (3.4%)
5	2134 (1.7%)	3 (1.7%)
Cooling performed			.65 b
No	9070 (7.2%)	11 (6.2%)
Yes	113,036 (89.8%)	165 (93.8%)
Unknown	3790 (3%)	0 (0%)
Storage solution			.69 b
Optisol GS	96,561 (76.7%)	146 (83%)
Life4C	19,249 (15.3%)	23 (13.1%)
Eusol C	5428 (4.3%)	5 (2.8%)
Kerasave	1000 (0.8%)	1 (0.6%)
Eye jar (KLA/LKP)	297 (0.2%)	1 (0.6%)
Saline	2 (0%)	0 (0%)
Other	3359 (2.7%)	0 (0%)

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