Cost-Benefit and Cost-Utility Analysis of Amphotericin B Supplementation of Corneal Storage Media With Endothelial Keratoplasty-Prepared Tissue.

PURPOSE: To determine the cost-effectiveness of amphotericin B supplementation, we analyzed both current costs to treat postendothelial keratoplasty (EK) fungal infections and potential costs associated with amphotericin B supplementation. METHODS: We collected 19 US cases of post-EK fungal eye infections from the published literature and assessed the associated costs from the literature. A survey of surgeons was also conducted with questions regarding their experiences in managing these infections. RESULTS: We estimated that the costs to diagnose, manage, and treat post-EK fungal keratitis and post-EK fungal endophthalmitis are USD $21,113 and $34,850, respectively. The largest portion of the costs can be attributed to the need for additional surgical management, which is required in 79% of the cases. We estimated the total cost of amphotericin B supplementation to be $44.39 per graft with use of conventional amphotericin B and conservative assumptions regarding supplementation processes. Cost-effectiveness analysis demonstrated that amphotericin B supplementation is cost-effective at $100,000 per quality-adjusted life-year level only if amphotericin B supplementation can prevent more than 69.62% of post-EK fungal infections, assuming the incidence of post-EK fungal infection remains at the level it was between 2012 and 2017. CONCLUSIONS: We found that amphotericin B supplementation can be cost-effective under conservative assumptions if it is moderately effective in preventing post-EK fungal infections.

Safety of Long-Term Storage and Shipping of Prestripped, Prestained, and Preloaded Descemet Membrane Endothelial Keratoplasty Tissue.

PURPOSE: The purpose of this study was to determine the safety of long-term storage and shipping of prestripped, prestained, and preloaded Descemet membrane endothelial keratoplasty (pDMEK) grafts. METHODS: A total of 33 cadaveric corneas were prestripped, prestained, and preloaded using modified Jones tube injectors as pDMEK. The corneas were masked to groups that were prepared <9 hours (control), 48 hours, and 72 hours before unloading and analysis. The 48- and 72-hour tissues were shipped by airfreight on each day before arrival to simulate domestic and international shipping. The corneas were then stained using Calcein AM vital dye (Molecular Probes, Eugene, OR) and imaged using an inverted confocal microscope. Primary outcome measures were endothelial cell loss (ECL, %) and sustainability of staining. MetaMorph software (Molecular Devices, Downingtown, PA) was used to quantify ECL, and staining was evaluated subjectively using all-or-none rating. RESULTS: There was no difference in the mean ECL for the control, 48-hour, and 72-hour groups, which were 25.1% ± 8.8%, 26.4% ± 17.5%, and 19.2% ± 11.5%, respectively (P = 0.45; Kruskal-Wallis test). In all tissues of each group, no loss of staining was identified at each time point of analysis. CONCLUSIONS: ECL in pDMEK tissue prepared 48 and 72 hours in advance and shipped using standard methods is similar to that in pDMEK tissue prepared on the same day. These findings support the safety of domestic and international shipping of pDMEK grafts.

Comparison of Donor Cornea Endothelial Cell Density Determined by Eye Banks and by a Central Reading Center in the Cornea Preservation Time Study.

PURPOSE: To evaluate agreement between eye banks (EBs) and a reading center on endothelial cell density (ECD) determinations in the Cornea Preservation Time Study. METHODS: The Cornea Image Analysis Reading Center (CIARC) performed variable frame image analysis on EB-obtained-preoperative central endothelial images (after lamellar dissection for Descemet stripping automated endothelial keratoplasty by the EBs or before shipping, if surgeon prepared) to determine ECD. The EBs performed their usual method of ECD determination. The CIARC and EBs also provided ECD determinations from screening central endothelial images taken by the EBs during donor evaluation. Two independent masked CIARC readers determined ECD with measurements averaged. RESULTS: The mean preoperative ECD was 15 cells/mm greater by the EBs than by CIARC (N = 1286, P < 0.001) with 95% limits of agreement of (-644, 675 cells/mm). The limits of agreement in preoperative ECD were wider in the After-Lamellar-Dissection Group (-687, 683 cells/mm) than in the Before Shipping Group [(-505, 633 cells/mm); P = 0.03]. The EBs-determined preoperative ECD was within 10% of the CIARC-determined ECD for 886 (69%) image sets, with 236 (18%) higher by >10% and 164 (13%) lower by >10%. Excellent agreement appeared between the EBs and CIARC when 100-300 cells could be analyzed in contrast to <100 cells (SD = 308 cells/mm vs. SD = 603 cells/mm; P < 0.001). CONCLUSIONS: The mean ECD by the EBs and CIARC were similar, but there was considerable variability between determinations for individual corneas. Agreement improved between the 2 measurements when more than 100 cells were able to be analyzed.

Perceptions of Adult Women on Losing Their Mothers at an Early Age: Implications for Nursing Care During Childbirth.

PURPOSE: To explore the lived experience of women over the age of 21 who lost their mothers before the age of 18. METHODS: Using qualitative methodology, motherless child-adult women were gathered through emails, word of mouth, and snowballing techniques. Interviews were conducted at the convenience of the women. The women coparticipated with identification of emerging themes using thematic analysis. RESULTS: Eight women who lost their mothers before the age of 18 participated. Eight themes emerged: (1) Understanding: For wounded hearts only; (2) Coming apart: Finding my mother's daughter and self-worth; (3) Unconditional love: Grieving for and identifying with my champion; (4) Finding help: Filling the empty place with God; (5) Pitying the motherless child: Making it worse; (6) Filling in: Others as mother; (7) The ebb and flow: Grieving; and (8) Becoming mother: Taking on the Role. CLINICAL IMPLICATIONS: The nurse has the opportunity to improve care for women who lost their mothers before the age of 18 years. During pregnancy, childbirth, and childrearing, the woman may feel sad and anxious without the guidance of her mother. Special ways of caring may be instituted to provide her comfort such as allowing and encouraging her to bring a special item of her mother's to procedures and events so that she may feel connected with her, allowing someone to stand in for her mother, perhaps assisting in finding of another motherless child adult to be with her as needed, and the voicing of understanding of her loss while remaining nonjudgmental about her emotions during these times.

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.

Clostridium perfringens endophthalmitis after penetrating keratoplasty with contaminated corneal allografts: a case series.

PURPOSE: To report the postoperative clinical course of 3 patients who underwent corneal transplantation with corneal allografts contaminated with Clostridium perfringens and to evaluate the risk factors for anaerobic contamination in 2 donors. METHODS: Patient records and adverse reaction reports from a single eye bank related to cases of posttransplant C. perfringens endophthalmitis were reviewed. Records regarding the mated corneas, donor autopsy reports, and other pertinent data were also reviewed. RESULTS: Three adverse reactions associated with transplantation of corneal allografts contaminated with C. perfringens were reported. Two cases were from mated corneas. Both patients developed fulminant endophthalmitis after undergoing uncomplicated penetrating keratoplasty and required subsequent enucleation. Another isolated case (with no adverse reaction in the mate cornea) developed hypopyon postoperatively that resolved with intravitreal and topical antibiotics. Possible risk factors for anaerobic tissue contamination in the donors included illicit drug use in the first donor and exposure to sewage at the time of death in the second donor. CONCLUSIONS: Clostridial endophthalmitis is an aggressive rapidly progressive infection with potentially poor visual outcomes that can be transmitted from infected corneal allografts. Further investigation is needed to clarify the role of anaerobic donor rim cultures and the donor risk factors associated with recovering corneal allograft tissue contaminated with C. perfringens.

Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study.

OBJECTIVE: To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP). DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). METHODS: Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). MAIN OUTCOME MEASURES: Endothelial cell density at 10 years. RESULTS: Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm(2) at 10 years and only 24 (14%) had an ECD of >1000 cells/mm(2). CONCLUSIONS: Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study.

PURPOSE: The Specular Microscopy Ancillary Study was designed to examine donor corneal endothelial specular image quality, compare the central endothelial cell density determined by eye banks with the endothelial cell density determined by a central specular microscopy reading center, and evaluate donor factors that may have an impact on specular image quality and endothelial cell density accuracy. DESIGN: Nonrandomized comparative trial. PARTICIPANTS: Endothelial specular images of donor corneas assigned in the Cornea Donor Study. METHODS: Certified readers assessed donor image quality (analyzable from fair to excellent vs. unanalyzable) and determined the central endothelial cell density. Independent adjudication was performed if there was a difference in the quality of grading or if the endothelial cell density varied by > or =5.0% between readers. Average reading center-determined endothelial cell density was compared with the endothelial cell density determined by each eye bank. MAIN OUTCOME MEASURES: Evaluation of image quality and accuracy of endothelial cell density. RESULTS: Of 688 donor endothelial images submitted by 23 eye banks, 663 (96%) were analyzable (excellent, 40 [6%]; good, 302 [44%]; fair, 321 [47%]), and 25 (4%) were unanalyzable by reading center standards. In situ retrieval and greater epithelial exposure correlated with a higher image quality grading. The eye bank-determined endothelial cell density of 434 of the 663 (65%) analyzable images were within 10% of the endothelial cell density determined by the reading center, whereas 185 (28%) were more than 10% higher and 44 (7%) were more than 10% lower. Greater variation in endothelial cell density between the eye banks and the reading center was observed with shorter time of death to preservation, presence of an epithelial defect, folds in Descemet's membrane, lower image quality, and the use of fixed-frame or center method endothelial cell density analysis. CONCLUSIONS: Overall, donor endothelial specular image quality and accuracy of endothelial cell density determination were good. However, the data suggest that factors that may affect image quality and contribute to variation in interpretation of the endothelial cell density should be addressed, because the donor endothelial cell density is an important parameter for assessing long-term corneal graft survival.