Tissue Loss During Eye Bank Processing.

This comparative effectiveness research study assesses the rate of tissue loss in ultrathin descemet stripping automated endothelial keratoplasty grafts vs descemet membrane endothelial keratoplasty grafts during eye bank processing.

Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1): outcome masked, placebo-controlled trial comparing two types of corneal transplant surgeries and effect of rho kinase inhibitors on endothelial cell loss protocol.

BACKGROUND: It remains uncertain which endothelial keratoplasty (EK) technique yields the best outcomes while maintaining safety, particularly in eyes with coexisting ocular conditions. Moreover, the impact of endothelial cell loss (ECL) on long-term graft survival requires further investigation. Adjuvant ripasudil, a rho kinase inhibitor, may address the challenge of ECL in corneal transplantation. This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial 1 (DETECT 1), a multicentre, outcome-masked, randomised, placebo-controlled, four-arm clinical trial. METHODS: A total of 160 eligible patients with endothelial dysfunction will be enrolled from five participating sites in the USA. The patients will be randomly assigned in a 2×2 factorial design to one of the following treatment groups: group 1-ultrathin Descemet stripping endothelial keratoplasty (UT-DSAEK) plus topical ripasudil 0.4%; group 2-UT-DSAEK plus topical placebo; group 3-Descemet membrane endothelial keratoplasty (DMEK) plus topical ripasudil 0.4% and group 4-DMEK plus topical placebo. Primary outcomes include the best spectacle-corrected visual acuity at 12 months and ECL at 12 months. Secondary outcomes include visual acuity at different time points, vision-related quality of life, endothelial cell morphology and cost-effectiveness. RESULTS: The study outcomes will be analysed using mixed effects linear regression models, taking into account the treatment arms and relevant covariates. Adverse events, including rebubble procedures, graft failure and graft rejection, will be documented and analysed using appropriate statistical methods. CONCLUSION: DETECT I aims to provide evidence on the comparative effectiveness of UT-DSAEK and DMEK, as well as the potential benefits of adjuvant topical ripasudil in reducing ECL. The results of this trial will contribute to optimising corneal transplantation techniques and improving long-term graft survival, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee (DSMC) has been empaneled by the NEI.All study protocols will be subject to review and approval by WCG IRB as the single IRB of record.This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request.

Comparison of Donor Corneal Endothelial Cell Density Determined by Eye Banks and by a Central Image Analysis Reading Center Using the Same Image Analysis Method.

PURPOSE: The purpose of this study was to evaluate agreement between eye banks (EBs) and an image analysis reading center on endothelial cell density (ECD) determinations using the same image analysis method. METHODS: The Cornea Image Analysis Reading Center (CIARC) determined ECD with a single experienced analyst on EB-obtained central endothelial images from donors intended for keratoplasty from 2 eye banks, Eversight and Lions VisionGift, using the Konan center analysis method. The EBs performed ECD determination on their respective sets of images using the same analysis method with experienced eye bank technicians. RESULTS: The mean age of the 200 donors was 54 years (range 30-75 years). Seventy (35%) of the 200 patients were women, and 57 (29%) were diabetic. The mean ECD was 10 cells/mm2 greater by the EBs than by CIARC (P = 0.39), with 95% limits of agreement of [-304 to 323 cells/mm2]. The mean difference was not substantially changed when the difference between EBs and CIARC ECD was adjusted for sex, donor age, donor diabetes, CV, HEX, number of cells analyzed, and EBs as a random effect (estimated mean difference of 20 cells/mm2 after adjustment in a linear mixed model; P = 0.73). The EB-determined preoperative ECD was within 10% of the CIARC-determined ECD for 178 (89%) image sets, with 15 (8%) higher by >10% and 7 (3%) lower by >10%. CONCLUSIONS: Well-trained eye bank technicians achieve comparable results for ECD determination with an experienced image analyst from an image analysis reading center when the same image analysis method is used.

Predictors of Vision-Related Quality of Life After Endothelial Keratoplasty in the Descemet Endothelial Thickness Comparison Trials.

PURPOSE: To determine which baseline characteristics are associated with vision-related quality of life (QOL) after endothelial keratoplasty. METHODS: A patient- and outcome-masked randomized clinical trial. Consecutive patients presenting with isolated endothelial disease requiring endothelial keratoplasty at Oregon Health Sciences University and Stanford University. Study eyes randomized to one of the 2 types of endothelial keratoplasty were given the national eye institute vision function questionnaire 25 at baseline and 12 months. In this prespecified secondary outcome, we assessed the role of recipient and donor characteristics as predictors of the 12-month national eye institute vision function questionnaire 25 change score. RESULTS: The mean vision function questionnaire (VFQ) score was 74 (SD 14) at baseline and increased to 82 (SD 12) at 3 months and 87 (SD 10) at 12 months. We were unable to find a difference in vision-related QOL in study participants who underwent Descemet membrane endothelial keratoplasty compared with ultrathin Descemet stripping endothelial keratoplasty [coef -0.98, 95% confidence interval (CI) -9.27 to 7.31; P = 0.82]. In multivariable analysis, patients who underwent endothelial keratoplasty in 2 eyes had approximately 8 points higher VFQ at 12 months after the second eye than those who had only one eye enrolled (95% CI 0.10-15.72; P = 0.047). Posterior densitometry produced an approximately 1-point increase each in the VFQ change score for each 1 grayscale unit increase at baseline (95% CI 0.26-1.81; P = 0.009). Although the sample size was small, a diagnosis of pseudophakic bullous keratopathy had approximately 19-points more improvement on average compared with Fuchs (95% CI 7.68-30.00; P = 0.001). CONCLUSIONS: Bilateral endothelial keratoplasty resulted in higher vision-related QOL compared with unilateral. Baseline densitometry, objective measure of corneal haze that predicts vision-related QOL, may play a role in monitoring disease progression.

Eccentrically Punched Descemet Membrane Endothelial Keratoplasty Grafts Expand the Descemet Membrane Endothelial Keratoplasty Donor Pool: One Eye Bank's Reappraisal of the Central Clear Zone Convention.

PURPOSE: To ascertain whether offsetting the Descemet membrane endothelial keratoplasty (DMEK) punch can expand the donor pool in conjunction with prepunched and preloaded services by recapturing the corneas otherwise excluded by the conventional central clear zone criteria. METHODS: In this retrospective review of corneas recovered and processed for DMEK by a single eye bank between March 2017 and October 2018, corneas failing to meet the conventional central clear zone requirement during initial evaluation (defined as an area in the central cornea where an 7.5- to 8.0-mm diameter graft can be obtained free of previous surgical scars, Descemet tears, or confined areas of endothelial defects) were further evaluated for offset punching. Corneas with a central endothelial cell density of at least 2000 cells/mm at the initial screening (average of 3 specular images assessed with the center dot method) that had a clear zone of 7.5- to 8.0-mm diameter where a graft could be obtained were designated as eligible for offset punching for either prepunched or preloaded DMEK. RESULTS: A total of 2607 corneas were found to be suitable for DMEK using the conventional central clear zone criteria. An additional 62 corneas were deemed DMEK suitable by offsetting the punch, yielding a 2.4% increase in the availability of DMEK suitable corneas. CONCLUSIONS: Offsetting the DMEK punch can recapture corneas otherwise excluded from the DMEK donor pool because of a failure to meet the conventional central clear zone criteria, and by our estimation may help eye banks meet the growing demand for DMEK tissue while maximizing the transplant potential of every cornea.

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.

Novel Use of Telemedicine for Corneal Tissue Evaluation in Eye Banking: Establishing a Standardized Approach for the Remote Evaluation of Donor Corneas for Transplantation.

PURPOSE: To determine the feasibility of using telemedicine consultations in the evaluation of recovered donor corneas for transplant suitability. METHODS: This study aims to establish and test the minimum imaging requirements for telemedical consultations of corneal tissue by remote eye bank medical directors. Digital images from the slit lamp, optical coherence tomography, and/or specular microscope were assembled into telemedical consults and emailed to 4 eye bank medical directors (M.A.T., J.W., C.S.S., N.K.R.). Feedback on the minimum image requirements for each corneal finding was collected. After establishing a standardized imaging and presentation protocol, test cases were presented to the medical directors to examine the validity of these remote consults. To establish a benchmark for the study's parameters, one medical director (J.W.) examined each case in person after his initial remote review. Examiners were masked to each other's responses. RESULTS: Minimum image requirements for determination of corneal findings were defined and were specific to each anatomic layer of the cornea (epithelial, stromal, or endothelial). Using a defined set of digital images for a set of common corneal findings, the rate of agreement between remote evaluators, eye bank staff, and the in-person evaluator was 100% (11 of 11 examples). For ambiguous test cases, remote evaluators agreed on 80% of the cases (4 of 5). CONCLUSIONS: Results from this pilot study suggest that telemedical review of corneal tissue using high-quality digital images may be adequate for accurate identification of specific corneal findings commonly encountered by eye banks.

Descemet Endothelial Thickness Comparison Trial: A Randomized Trial Comparing Ultrathin Descemet Stripping Automated Endothelial Keratoplasty with Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction. DESIGN: Patient and outcome-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK. METHODS: Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery. MAIN OUTCOME MEASURES: The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry. RESULTS: A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon Health & Science University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5-0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8-1.0 lines better; P < 0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2-0.7 lines better; P < 0.001). Average endothelial cell counts were 1963 cells/mm2 in DMEK and 2113 cells/mm2 in UT-DSAEK at 6 months (P = 0.17) and 1855 cells/mm2 in DMEK and 2070 cells/mm2 in UT-DSAEK at 12 months (P = 0.051). Intraoperative and postoperative complication rates were similar between groups. CONCLUSIONS: Descemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.

Reduction of Donor Cornea Exposure to Repeat Warming Cycles and Evaluation Times After Implementation of a Rapid Warming Protocol.

PURPOSE: To compare tissue evaluation times and specular image quality before and after the implementation of rapid tissue warming at a single eye bank. METHODS: This retrospective study compares the evaluation of 494 donor corneas. All corneas were stored in Optisol-GS. Group 1 contained 247 corneas evaluated immediately before implementation of a tissue incubator and tissue warming protocol. Group 2 contained 247 corneas evaluated immediately after implementation. Total evaluation times (including specular microscopy, optical coherence tomography for corneal thickness measurements, and 2 slit-lamp examinations) were calculated and compared. Representative specular images of donor corneas were rated and compared using a previously described scale by 2 masked readers. RESULTS: Donor tissue characteristics were not significantly different between both groups (age, P = 0.87; sex, P = 0.93; endothelial cell densities, P = 0.47; and death-to-preservation times, P = 0.18). The mean total evaluation time for group 2 corneas was ∼3 hours, with 97% (201/208) of evaluations completed on the same day. In contrast, only 73% (164/225) of corneas from group 1 were completely evaluated in 1 day, and the mean evaluation time for those corneas was ∼4.25 hours (P < 0.01). Specular images of corneas from group 2 were rated 1 grade higher, on average, than those from group 1 (n = 247 in each group, P < 0.01). Furthermore, 71% of specular images from group 2 were categorized as "good" or "excellent" quality, whereas only 30% of corneas from group 1 received those ratings. CONCLUSIONS: Rapid tissue warming cuts down on tissue evaluation time and reduces the time donor corneas are out of cold storage. Better specular images were obtained after implementation of the rapid warming protocol.

Rapid Warming of Donor Corneas Is Safe and Improves Specular Image Quality.

PURPOSE: To determine whether warming donor corneas to near-physiological temperatures can safely shorten warming times while providing high-quality specular images during tissue evaluation. METHODS: Mated corneas were warmed at room temperature (RT) or at 35°C for 4 hours upon removal from cold storage. Specular images and endothelial cell densities were acquired and rated every hour. Additional mated corneas were subjected to 2 rounds of 4-hour incubation at either RT or 35°C. Endothelial cell loss (ECL) was quantified 14 days after the initial incubation using Calcein-acetoxymethyl (Calcein-AM) and FIJI trainable segmentation. Cultures inoculated with common ocular pathogens were subjected to 2 warming cycles at RT for 4 hours or 35°C for 2 hours. Colony counts were taken over the course of 2 weeks after inoculation. RESULTS: Specular image quality ratings were consistently higher for corneas warmed at 35°C compared with those at RT. Image quality ratings for corneas warmed at 35°C for 1.5 hours were higher than corneas warmed at RT for 4 hours (P = 0.04). No differences in ECL were observed between the 2 warming conditions (RT = 13.1% ± 7.6% ECL, 35°C = 13.9% ± 6% ECL, P = 0.75). There was no difference in colony counts for pathogens tested between the 2 warming conditions. CONCLUSIONS: Warming donor corneas to near-physiological temperatures for a short time can increase specular image quality while reducing the time tissues are unrefrigerated at eye banks. This method allows for more efficient specular imaging without inducing additional ECL or increasing pathogen growth.

Comparison of in situ excision and whole-globe recovery of corneal tissue in a large, single eye bank series.

PURPOSE: To compare the quality of corneal tissue after 2 different procurement techniques, whole-globe enucleation and in situ excision. DESIGN: Cross-sectional study. METHODS: Data in the interval 2005 to 2008 were collected from the Lions Eye Bank of Oregon. A total of 3618 eyes underwent whole-globe enucleation (enucleation group) and 2048 eyes were subject to in situ excision (in situ group). Endothelial cell density (ECD) and death-to-preservation time (D-to-P) were analyzed. Grading scores ranging from 0 (excellent) to 4 (unacceptable for transplantation) were used to evaluate the epithelium, stroma, Descemet fold, and overall endothelium. The incidences of ECD less than 2000 cells/mm(2) (ECD <2000), primary graft failure (PGF), and postoperative infection were investigated. RESULTS: ECD was 2726 +/- 419 cells/mm(2) in the enucleation and 2645 +/- 395 cells/mm(2) in the in situ group (P < .001). D-to-P was 9.81 +/- 3.56 hours and 8.90 +/- 3.65 hours, respectively (P < .001). The mean grade of the stroma was 1.44 +/- 0.51 in the enucleation group and 1.50 +/- 0.56 in the in situ group (P = .001). The mean grades of overall endothelium were 1.51 +/- 0.72 and 1.58 +/- 0.69, respectively (P < .001). The incidence of ECD <2000 was 2.38% in the enucleation group and 2.39% in the in situ group (P > .999), PGF rates were 0.72% and 0.68% (P > .999), and postoperative infection levels were 0.14% and 0.39% (P = .080). CONCLUSION: Although there were minor differences in parameters related to the endothelium, in situ excision seemed equivalent to whole-globe enucleation when various parameters were evaluated.