Effect of Body Refrigeration Time on Cornea Donor Tissue.

PURPOSE: To determine how early body refrigeration affects corneal donor transplant suitability and endothelial cell density. METHODS: Donor information was obtained from the CorneaGen Eye Bank including demographics, time of death to preservation, and body refrigeration status, for donors between 2012 and 2016. The death to preservation interval was classified into 3 categories: 0 to 10, 10 to 20, and 20+ hours. Two primary logistic method models were fit using a main effects model and an interaction model to determine the association of body refrigeration on unsuitability of transplantation and endothelial cell density. RESULTS: Analysis was from 42,929 donor eyes, with a mean (standard deviation) endothelial cell count of 2743 (415) cells/mm2. Fifty-nine percent of donor eyes were from male donors in the eye bank data set, and the mean death to preservation interval was 11.0 (5.6) hours for all eyes. Unsuitability for transplantation demonstrated a reduced adjusted odds ratio by 22% (OR = 0.78, P = 0.009) when the body was refrigerated during the death to preservation interval versus when the body was not refrigerated. Eyes that were refrigerated, however, exhibited no statistically significant difference in endothelial cell count from eyes that were not refrigerated (P = 0.12). CONCLUSIONS: We demonstrate an appreciable effect of early body refrigeration on transplant suitability in this large cohort of eye bank eyes. There was no beneficial effect of body refrigeration on endothelial cell count.

Prelamellar Dissection Donor Corneal Thickness Is Associated With Descemet Stripping Automated Endothelial Keratoplasty Operative Complications in the Cornea Preservation Time Study.

PURPOSE: To identify donor and recipient factors, including eye bank tissue observations, predictive of operative complications in the Cornea Preservation Time Study. METHODS: One thousand three hundred thirty study eyes undergoing Descemet stripping automated endothelial keratoplasty for Fuchs dystrophy or pseudophakic/aphakic corneal edema were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (N = 675) or 8 to 14 days (N = 655). Donor factors included demographics, prelamellar corneal and postlamellar lenticule dissection thickness, central endothelial cell density, and tissue processing time. Recipient factors included demographics, intraocular pressure, and glaucoma medications or surgery (trabeculectomy, laser trabeculoplasty). Eye bank observations included donor tissue folds, pleomorphism/polymegethism, and endothelial cell abnormalities. Possible tissue-related operative complications were recorded including difficult donor lenticule unfolding and positioning. Multivariable logistic regression with backward selection was used to identify statistically significant (P < 0.01) associations between factors and operative complications. RESULTS: The only factor predictive of operative complications [58 (4.4%) of 1330 surgeries] was prelamellar dissection donor corneal thickness (P = 0.002). For every 50 µm of donor corneal thickness prior to lamellar dissection, operative complication odds increased by 40% (odds ratio [99% confidence interval (CI)]: 1.40 [1.06-1.83]) adjusting for PT and whether the epithelium was on or off. The estimated mean prelamellar dissection donor corneal thickness for PT 0 to 7 days was 537 µm (99% CI: 516 µm-558 µm) compared with 567 µm (99% CI: 546 µm-588 µm) for PT 8 to 14 days (P < 0.001). CONCLUSIONS: Thicker donor tissue (prelamellar dissection) is associated with operative complications and should be considered in tissue selection for Descemet stripping automated endothelial keratoplasty lenticule preparation.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study.

PURPOSE: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

Predictive Value of Corneal Donor Demographics on Endothelial Cell Density.

PURPOSE: Corneal endothelial cell density (ECD) is an important measure for determining suitability for transplantation. Although age has been correlated with ECD, the impact of sex and ethnicity is unclear. METHODS: Corneal donor information from SightLife Eye Bank was collected between 2012 and 2016. Tests of association were adjusted for covariates using linear regression including age, race, and sex. "Unsuitable for transplantation" was a label assigned to specimens with extensive cell dropout, ECD <2000 cells/mm, and poor cell morphology. Repeated-measures analysis was used to account for the within-individual correlation between left and right eyes. RESULTS: A total of 39,679 donor corneas were analyzed, with a mean ECD 2743.5 cells/mm and mean age of 58. Simple linear regression demonstrated an association between ECD and age (P < 0.001). Multiple regression showed no association between sex and ECD. Compared with whites, African American, and Asian ethnicities were predictors of increased ECD (mean +45.7 cells/mm (P < 0.001) and +90.3 cells/mm (P < 0.001), respectively); Hispanic ethnicity was a predictor of decreased ECD [mean -36.9 cells/mm (P = 0.002)]. A total of 233 (0.59%) corneas were unsuitable for transplantation, which was associated with age (P < 0.001) but not sex or ethnicity. CONCLUSIONS: Analysis of a large sample of donor corneas continues to show age but not sex as a predictor of decreased ECD. African American and Asian ethnicities tend to have slightly higher ECD than that of white donors, whereas Hispanic donors have slightly lower ECD; however, ethnicity was not a predictor of suitability for transplantation. Clinical significance of these findings is yet to be determined.

The Effect of Chronic Pulmonary Disease and Mechanical Ventilation on Corneal Donor Endothelial Cell Density and Transplant Suitability.

PURPOSE: To determine how chronic obstructive pulmonary disease (COPD) and mechanical ventilation time affect corneal donor endothelial cell density (ECD) and transplant suitability. DESIGN: Retrospective cohort study. METHODS: Setting: Institutional. STUDY POPULATION: Total of 39 679 cornea donor eyes from SightLife Eye Bank between 2012 and 2016. Demographics, death-to-preservation time, ECD, lens status, medical history, time on mechanical ventilation, and suitability for transplantation were included. MAIN OUTCOME MEASURES: ECD and transplant suitability. RESULTS: Mean ECD was 2733 cells/mm2. Mean age was 59 years. COPD affected 34.2% of donors. Mechanical ventilation was required in 35% of donors. Mean ventilation time was 1.3 days. After controlling for covariates, COPD was not found to be associated with poor transplant suitability (P = .22). Ventilation >7 days was associated with poor transplant suitability (P = .04). Donors with COPD and donors who were mechanically ventilated exhibited lower cell counts (P < .001, P < .01, respectively). Longer ventilation led to reduced endothelial cell density: ventilation time >7 days (-46.5 cells/mm2, P < .001) and >30 days (-101.4 cells/mm2, P = .02). Limitations of the study included the retrospective nature, dataset obtained from a single eye bank, and medical history documentation completed by eye bank technicians. CONCLUSIONS: A high proportion of cornea donors have respiratory disease prior to donation. Ventilation time >7 days affected transplant suitability but the presence of COPD did not. Donors with COPD and donors who were mechanically ventilated had reduced cell counts. Longer ventilation times lead to increased cell loss. The presence of respiratory disease may affect tissue oxygenation and endothelial cell health.

Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.

PURPOSE: To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. METHODS: Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. RESULTS: Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. CONCLUSIONS: Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Association Between Endothelial Cell Density and Transplant Suitability of Corneal Tissue With Type 1 and Type 2 Diabetes.

IMPORTANCE: The rate of types 1 and 2 diabetes in the United States is increasing. The effect of diabetes on corneal donor tissue is unknown. OBJECTIVES: To determine the association between endothelial cell density and suitability for transplantation in cornea donors with type 1 or 2 diabetes and determine the effect of diabetes on technician-induced endothelial damage during cornea donor tissue processing. DESIGN, SETTING, AND PARTICIPANTS: Donor information was obtained from the SightLife Eye Bank for donors from June 1, 2012, to June 30, 2015. The presence of diabetes was determined based on donor medical history. Severe diabetes was classified based on the presence of comorbidities of diabetes. The donor data set contained information on 34 497 donated eyes during the 3-year period, including donor demographics, time from death to refrigeration and preservation of the cornea, endothelial cell count, lens status, medical and surgical history, and suitability for transplantation. MAIN OUTCOMES AND MEASURES: Endothelial cell density, suitability for transplantation based on tissue analysis, and technician-induced endothelial damage. RESULTS: Among 14 532 donors (mean [SD] age, 58.6 [13.4] years; 8516 men and 6016 women), the mean (SD) endothelial cell count was 2732 (437) cells/mm2. Type 1 or 2 diabetes was listed in the medical history for 8552 of 27 948 donor eyes (30.6%); 5242 eyes (18.8%) were from patients with severe diabetes. After adjusting for age, race/ethnicity, sex, lens status, time from death to refrigeration, and time from death to preservation, the presence of diabetes (adjusted odds ratio, 0.79; 95% CI, 0.51-1.22; P = .28) and severe diabetes (adjusted odds ratio, 95% CI, 0.86; 95% CI, 0.54-1.39; P = .54) were not associated with poor transplant suitability based on results of tissue examination. Donors with diabetes (mean [SD] cell count difference, 9.0 [6.7] cells/mm2; 95% CI, -4.1 to 22.2; P = .18) and severe diabetes (mean [SD] cell count difference, 7.7 [8.1] cells/mm2; 95% CI, -8.1 to 23.6; P = .34) did not exhibit lower cell counts. Technician-induced endothelial damage occurred in 59 corneas (0.2%) but was not associated with the presence of diabetes (adjusted odds ratio, 1.23; 95% CI, 0.66-2.32; P = .52). CONCLUSIONS AND RELEVANCE: These data suggest that cornea donors have a high frequency of diabetes. However, this analysis was not able to show that the presence of diabetes was associated with technician-induced endothelial damage, reduced transplant suitability, or reductions in endothelial cell counts. Eye banks may need to collect medical history in a more robust manner. Additional studies may be valuable to determine the effect on long-term transplant outcomes of diabetes in cornea donors.

Assessment of the Accuracy and Cut-Failure Rates of Eye Bank-Cut Corneas for Use in Endothelial Keratoplasty: A Comparison of Outcomes Between 2010 and 2013.

PURPOSE: To evaluate the accuracy of eye bank-prepared precut donor corneas over time by comparing cut-failure rates and corneal thickness measurements in 2010 and 2013. METHODS: A total of 2511 human corneas cut by a technician-operated mechanical microkeratome intended for endothelial keratoplasty were evaluated prospectively at one large eye bank facility in 2010 and in 2013. The endothelium was evaluated by slit lamp, and specular microscopy both before and after cutting was performed. Graft thickness as measured by pachymetry and/or optical coherence tomography was collected to assess the accuracy of the cut tissue. Cut-failure rates were compared between normal donor tissue and tissue with significant preexisting scarring. RESULTS: The combined cut-failure rate in 2010 and 2013 was 2.3% (23/1000) and 1.6% (24/1511), respectively (P = 0.23). The cut-failure rate among normal tissue in 2010 and 2013 was 2.0% (19/927) and 1.4% (19/1400), respectively (P = 0.24). The cut-failure rate among previously scarred tissue in 2010 and 2013 was 5.5% (4/73) and 4.5% (5/111), respectively (P = 0.74). The mean surgeon-requested graft thickness was 144.7 µm (range 100-150, SD 13.6) and 127.2 µm (range 75-150, SD 25.2) in 2010 and 2013, respectively (P < 0.0001). The mean deviation from target graft thickness was 21.3 µm (SD 16.3) and 13.6 µm (SD 12.5) in 2010 and 2013, respectively (P < 0.0001). CONCLUSIONS: From 2010 to 2013, the combined cut-failure rates trended toward improvement, while the accuracy of graft thickness improved. This study suggests that the accuracy and success rates of tissue preparation for endothelial keratoplasty improve with experience and volume.

Preservation of the Corneal Epithelium in Different Corneal Storage Media.

PURPOSE: With increasing time, epithelial defects (EDs) develop in virtually all corneas stored in corneal storage media. Optisol GS and Life 4°C are commonly available intermediate storage media used for corneal storage before keratoplasty. Epithelial preservation capabilities of Life 4°C and Optisol GS are compared in this study. METHODS: Nine pairs of human corneas were harvested, and 1 cornea of each pair was stored in Optisol GS and the other was stored in Life 4°C. The size and frequency of EDs of corneas stored in Optisol GS and Life 4°C were measured over time within the chambers using a backlit approach for 14 to 17 days of storage. RESULTS: At poststorage days 4, 8, and 12, there were no statistical differences in the percent change in the area of the ED between both groups. Of corneas without initial EDs, 6 of 7 (85.7%) stored in Optisol GS and 5 of 8 (62.5%) stored in Life 4°C developed an ED by the end of the assessment period. At the end of the observation period, there was no significant difference in the change in the percent area of the ED between corneas stored in Optisol GS and Life 4°C [4.3% ± 6.6% and 2.1% ± 2.6%, respectively (P = 0.38)]. CONCLUSIONS: Optisol GS and Life 4°C storage media did not significantly differ in their abilities to preserve the corneal epithelium of the donor tissue for up to 17 days. Most corneas stored in both cold-storage media developed EDs within the 14-day observation period.