Risk assessment in deferred and recovered donors.

Serologic testing and Donor Risk Assessment Interview (DRAI) combined have made tissue transplantation a frequent and safe modality for a variety of trauma and disease conditions. Donate Life America reports 30,000 tissue donors providing more than 1,750,000 tissue transplants annually. This study of 188 potential donor cases addresses issues of risk assessment in a medical examiner population in a metropolitan area, where serologic testing of deferred potential donors were compared with the DRAI screening, which determined the suitability or non-suitability for tissue procurement. Such serologic testing of deferred cases is not usually available in evaluating screening processes. This comparison gives insight into the effectiveness of the DRAI screening in deferring potential serology reactive donors. Results show in 65 cases how the DRAI screening eliminates most, but not all of the serologically reactive donors identified post recovery. The result emphasizes the need for the combined process of DRAI screening and testing to assure transplantation safety.

Positive toxicology and reactive serology in tissue donors: a retrospective study over a 3-year period.

Assessment of donor suitability and criteria development for tissue donation evaluation which appropriately addresses the risk factors for disease transmission, especially high risk for Hepatitis B or C, HIV or other transmissible diseases as defined by the Food and Drug Administration, FDA, is a continuing concern for tissue banks. The relationship of drug use, especially IV drugs, has been determined to be associated with an increased possibility of reactive serology (Centers for Disease Control and Prevention (USCDC) in Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Hepatitis C questions and answers for health professionals. https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm ; Centers for Disease Control and Prevention (USCDC) in infectious diseases, opioids and injection drug use, 2018. https://www.cdc.gov/pwid/opioid-use.html ; HIH National Institute on Drug Abuse in Health Consequences of Drug Misuse, 2017. https://www.drugabuse.gov/related-topics/health-consequences-drug-misuse ). Therefore, prior drug use determined by medical social history screening frequently results in deferral of a potential donor even when the route of drug administration has not been determined to be intravenous. Because of the association of drug use in numerous cases, which come under Medical Examiner jurisdiction, a possible rule out of a number of otherwise suitable medical examiner cases could occur. This retrospective review of medical examiner cases, tissue bank referrals and tissue donors in a 3-year period examines the relationship, if any, between reactive serology and positive toxicology results. These results would appear to indicate assessment of donor medical social history screening is effective in reducing recovery of high-risk donors.

Comparison of hepatitis B, core, HBc, and hepatitis B antibody, anti HBs, in a presumed low risk donor population.

Donors screened by medical social history interview negative for high risk behavior or communicable disease history, but subsequently exhibiting reactive serological markers, emphasize importance of duel safe guarding factors for determining donor suitability. This report examines a relationship between two immunoabsorption assay tests, hepatitis B core (HBc) antibody, a required food and drug administration (FDA) test, and hepatitis B antibody (anti HBs), non-required test. Reactive serology results, 129 cases, 3,581 donors (2008-2012) for HBc as the only initially positive serological marker were subjected to anti HBs testing in this history pre-screened donor population. Enzyme linked immunoabsorption assay kits hepatitis B, core and antibody, were used in this study. All samples were initially tested for human immunodeficiency virus, hepatitis B, and hepatitis C, utilizing nucleic acid testing and antigen antibody immunoabsorption assay. Testing was performed by a FDA-registered CLEA-certified reference laboratory. Samples were deceased donor blood samples and a limited number of pre-mortem samples, separated, stored and analyzed according to manufacturer recommendation and FDA regulations. 129 reactive HBc only samples, were subsequently tested for anti HBs. Of these 129, 94 were found to be reactive for anti HBs. This represented 72 % of samples tested for antibody, a higher percentage than anticipated for a medical history negative, low risk population.

Viral HCV RNA reactivity of corneal cells in plasma HCV nucleic acid-positive eye donors.

PURPOSE: Hepatitis C virus (HCV) infection is a worldwide health concern according to the World Health Organization, and a positive serology test for HCV is currently one of the most common reasons for tissue rejection for transplantation. Demonstrating the presence or absence of viral RNA or DNA in corneal cells, a privileged avascular site, verifies the importance of screening and testing protocols, which eliminate individual donor tissue from potential release for transplantation. METHODS: Improved tests such as nucleic acid test (NAT) have added a significant advantage in the arsenal of measures employed to determine donor eligibility. Standard testing for blood using nucleic acid technology was applied to aliquots of corneal cells obtained by scraping pooled epithelial and endothelial cells from individual donor corneas. RESULTS: Results of the current study further confirm and extend the importance of NAT blood tests by the demonstration of a high percentage (77%) of corneal cells that test positive with HCV NAT in conjunction with concomitant serum-positive ocular tissue donor samples. CONCLUSIONS: These data provide important support for Center for Disease Control and Prevention reports that state that 3 of 4 seropositive individuals were also viremic, and reemphasize the importance of routine NAT blood testing in assuring safe tissue transplants.

Nucleic acid testing and tissue safety: an eye bank's five-year review of HIV and hepatitis testing for donor corneas.

PURPOSE: Tissue safety and added testing is a frequent topic of discussion among those who must evaluate donor suitability and assure appropriate testing. Therefore, the purpose of this report was to examine the data of one eye bank (accredited by Eye Bank Association of America) for the presence or absence of reactive serology in 3592 donors over a 5-year period, from 2005 to 2010. METHODS: The number of specific analytes, human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus, that were reactive and the number of multireactive serologies are presented along with reports related to the identification of nucleic acid testing (NAT), NAT-reactive donors in correlation with other antigen or antibody markers. Antigen or antibody markers are enzyme-linked immunosorbent assay immunoassay kit determinations. NATs are used to measure the presence of RNA or DNA virus. RESULTS: The 249 donors with reactive serologies serve to confirm the importance of serologic testing in history-negative potential donors. Furthermore, the findings of 2 HIV NAT-only reactive individuals is significant because it may indicate an early unrecognized exposure and "window period" infectivity not recognized by antibody testing alone. These results support the appropriate inclusion of this added test to guarantee tissue safety. CONCLUSIONS: The finding of 2 potential donors without identified risk factors but with reactive HIV NAT suggests the need for comprehensive serologic testing in conjunction with medical social history screening. Considered together, screening and testing offer the best allograft tissue safety currently available.

Comparative study of descemet stripping automated endothelial keratoplasty donor preparation by Moria CBm microkeratome, horizon microkeratome, and Intralase FS60.

PURPOSE: To evaluate the quality of stromal bed and the safety on endothelium in preparation of donor tissue for Descemet stripping automated endothelial keratoplasty in a masked fashion using 2 mechanical microkeratomes and a femtosecond laser. METHODS: Deep anterior lamellar dissection was performed on 15 donor corneas. Central endothelial cell density was calculated using specular microscopy before and after the dissection. One cornea from each of 5 donor pairs was cut with the Moria ALTK system with the CBm microkeratome using the 300-µm head and the mate cut with the Horizon disposable 300-µm microkeratome. Five additional donor corneas were cut with the Intralase 60-kHz FS laser. The donor corneas were then bisected with half of the cornea used for Live/Dead assay to study central endothelial viability. The other halves were sent for scanning electron microscopy of the stromal bed. Qualitative surface roughness of the scanning electron microscopy images was graded by 2 masked observers, and quantitative surface roughness was assessed using roughness evaluation software. RESULTS: The Horizon group showed a smoother stromal bed compared with the Moria or Intralase groups by 2 masked observers. However, the Moria group had the smoothest quantitative score of all the groups when assessed by roughness evaluation software. There was no statistically significant difference among the 3 groups in the percentage change in the central endothelial cell density or percentage of viable central endothelium by Live/Dead assay after the dissection. CONCLUSIONS: Both mechanical microkeratomes created smoother stromal bed dissections than the femtosecond laser. All systems provided good endothelial cell viability.

Endothelial cell density to predict endothelial graft failure after penetrating keratoplasty.

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).

Donor risk factors for graft failure in the cornea donor study.

PURPOSE: The purpose of this study was to assess the relationship between donor factors and 5-year corneal graft survival in the Cornea Donor Study. METHODS: Donor corneas met criteria established by the Eye Bank Association of America, had an endothelial cell density of 2300 to 3300/mm, and were determined to be of good to excellent quality by the eye banks. Donor corneas were assigned using a random approach and surgeons were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines and subjects were followed for 5 years. Donor and donor cornea factors were evaluated for their association with graft failure, which was defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. RESULTS: Graft failure was not significantly associated with the type of tissue retrieval (enucleation versus in situ), processing factors, timing of use of the cornea, or characteristics of the donor or the donor cornea. Adjusting for donor age did not affect the results. CONCLUSION: Donor and donor cornea characteristics do not impact graft survival rates for corneas comparable in quality to those used in this study.

The effect of donor age on corneal transplantation outcome results of the cornea donor study.

OBJECTIVE: To determine whether graft survival over a 5-year follow-up period using corneal tissue from donors older than 65 is similar to graft survival using corneas from younger donors. DESIGN: Multicenter prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema); 11 subjects with ineligible diagnoses were not included. METHODS: Forty-three participating eye banks provided corneas from donors in the age range of 12 to 75 with endothelial cell densities of 2300 to 3300 cells/mm(2), using a random approach without respect to recipient factors. The 105 participating surgeons at 80 sites were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Subjects were observed for 5 years. MAIN OUTCOME MEASURES: Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque as to compromise vision for a minimum of 3 consecutive months. RESULTS: The 5-year cumulative probability of graft survival was 86% in both the <66.0 donor age group and the >/=66.0 donor age group (difference = 0%, upper limit of 1-sided 95% confidence interval = 4%). In a statistical model with donor age as a continuous variable, there was no significant relationship between donor age and outcome (P = 0.11). Three graft failures were due to primary donor failure, 8 to uncorrectable refractive error, 48 to graft rejection, 46 to endothelial decompensation (23 of which had a prior, resolved episode of probable or definite graft rejection), and 30 to other causes. Distributions of the causes of graft failure did not differ between donor age groups. CONCLUSIONS: Five-year graft survivals for cornea transplants at moderate risk for failure are similar using corneas from donors >/= 66.0 years and donors < 66.0. Surgeons and patients now have evidence that corneas comparable in quality to those used in this study from donors through age 75 are suitable for transplantation.

Donor age and corneal endothelial cell loss 5 years after successful corneal transplantation. Specular microscopy ancillary study results.

OBJECTIVE: To determine whether endothelial cell loss 5 years after successful corneal transplantation is related to the age of the donor. DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: Three hundred forty-seven subjects participating in the Cornea Donor Study who had not experienced graft failure 5 years after corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema). TESTING: Specular microscopic images of donor corneas obtained before surgery and postoperatively at 6 months, 12 months, and then annually through 5 years were submitted to a central reading center to measure endothelial cell density (ECD). MAIN OUTCOME MEASURE: Endothelial cell density at 5 years. RESULTS: At 5 years, there was a substantial decrease in ECD from baseline for all donor ages. Subjects who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 69% in the study eye, resulting in a 5-year median ECD of 824 cells/mm(2) (interquartile range, 613-1342), whereas subjects who received a cornea from a donor 66 to 75 years old experienced a cell loss of 75%, resulting in a median 5-year ECD of 654 cells/mm(2) (interquartile range, 538-986) (P [adjusted for baseline ECD] = 0.04). Statistically, there was a weak negative association between ECD and donor age analyzed as a continuous variable (r [adjusted for baseline ECD] = -0.19; 95% confidence interval, -0.29 to -0.08). CONCLUSIONS: Endothelial cell loss is substantial in the 5 years after corneal transplantation. There is a slight association between cell loss and donor age. This finding emphasizes the importance of longer-term follow-up of this cohort to determine if this relationship affects graft survival.

Risk factors for infectious disease in corneal transplant screening.

PURPOSE: To identify potential medical and behavioral risk factors associated with infectious disease seropositivity in potential corneal donors using an extensive questionnaire completed by the next of kin. METHODS: Retrospective review of medical history and behavioral risk assessment questionnaire and microbiology data for potential corneal donors seropositive for hepatitis B, hepatitis C, human immunodeficiency virus, human T-cell leukemia virus and syphilis as compared to controls. RESULTS: Tobacco use, cigarette smoking, chest pain and heart disease are each associated with corneal donor seropositivity (P < 0.05). Vaccination in the last twelve months is inversely associated with infectious disease (P < 0.05). Statistically significant factors associated with hepatitis C positive donors include: cigarette use, illicit drug use, chest pain, cardiac medications, kidney stones and lung disease (P < 0.05). Factors most often associated with transmission of this disease panel (such as intravenous drug use, sexual contact with prostitutes and history of blood transfusion) are often not identified by the next of kin in the questionnaire. CONCLUSIONS: While there are questionnaire identified risk factors associated with seropositivity in this study, their clinical usefulness is unclear. Many factors crucial to the elimination of potentially infectious donor tissues are not identified in the posthumous history typically completed by next of kin. These questionnaires alone do not provide exclusion criteria for elimination of potentially infectious tissues from the donor pool.