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.

Effect of Graft Attachment Status and Intraocular Pressure on Descemet Stripping Automated Endothelial Keratoplasty Outcomes in the Cornea Preservation Time Study.

PURPOSE: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN: Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS: 1090 individuals (1330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N = 675) or 8-14 days (N = 655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and (99% confidence intervals). RESULTS: Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio [OR]: 2.29 [1.30, 4.02]), increased pre-lamellar dissection central corneal thickness (OR: 1.13 [1.01, 1.27] per 25µ increase), and operative complications (OR: 2.97 [1.24, 7.11]). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; P < .001) and 29 (2.4%; P = .04), respectively, of 1226 eyes without GD. 24 (2%) of 1330 study eyes had early acutely elevated postoperative IOP that was associated with a higher risk of graft failure through 3 years (hazard ratio: 3.42 [1.01, 11.53]), but not with a lower mean 3-year ECD (mean difference 61 (-479, 601) cells/mm2, P = .77). History of elevated postoperative IOP beyond 1 month was not significantly associated with 3-year graft success or ECD. CONCLUSIONS: Donor diabetes, increased donor corneal thickness, and intraoperative complications were associated with an increased risk of GD. Early acutely elevated postoperative IOP and GD significantly increased the risk for graft failure following DSAEK.

Effect of Cornea Preservation Time on Success of Descemet Stripping Automated Endothelial Keratoplasty: A Randomized Clinical Trial.

Importance: Demonstrating that success of Descemet stripping automated endothelial keratoplasty is similar across donor cornea preservation times (PTs) could increase the donor pool. Objective: To determine whether the 3-year rate of graft success using corneal donor tissue preserved 8 to 14 days is noninferior to that of donor tissue preserved 7 days or less. Design, Setting, and Participants: A multicenter, double-masked, randomized noninferiority clinical trial was conducted from April 16, 2012, to June 5, 2017, at 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 1090 individuals (1330 study eyes) underwent Descemet stripping automated endothelial keratoplasty (1255 eyes [94.4%] for Fuchs endothelial corneal dystrophy). Interventions: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with a PT of 7 days or less (0-7d PT) or 8 to 14 days (8-14d PT). Main Outcomes and Measures: Graft success at 3 years. Results: Of the 1090 participants (1330 study eyes; 60.2% women and 39.8% men; median age at enrollment, 70 years [range, 42-90 years]), the 3-year cumulative probability of graft success was 95.3% (95% CI, 93.6%-96.9%) in the 0-7d PT group and 92.1% (95% CI, 89.9%-94.2%) in the 8-14d PT group (difference, 3.2%). The upper limit of the 1-sided 95% CI on the difference was 5.4%, exceeding the prespecified noninferiority limit of 4%. The difference was mostly owing to more primary donor failures in the 8-14d PT group, with the conditional probability of failure after the first month being 2.4% in the 0-7d PT group and 3.1% in the 8-14d PT group. In preplanned secondary analyses, longer PT was associated with a lower rate of graft success (unadjusted hazard ratio for graft failure per additional day of PT, 1.10; 95% CI, 1.03-1.18; P = .008 [PT analyzed as days]), with success rates of 96.5% (95% CI, 92.3%-98.4%) for PT of 4 days or less, 94.9% (95% CI, 92.5%-96.6%) for PT of 5 to 7 days, 93.8% (95% CI, 91.0%-95.8%) for PT of 8 to 11 days, and 89.3% (95% CI, 84.4%-92.7%) for PT of 12 to 14 days (P = .01 [PT analyzed as categorical variable]). Conclusions and Relevance: The 3-year success rate in eyes undergoing Descemet stripping automated endothelial keratoplasty was high irrespective of PT. However, the study was unable to conclude that the success rate with donor corneas preserved 8 to 14 days was similar to that of corneas preserved 7 days or less with respect to the prespecified noninferiority limit. Although longer PT was associated with a lower success rate, the difference in rates was small when PT was less than 12 days.

Corneal Endothelial Cell Loss 3 Years After Successful Descemet Stripping Automated Endothelial Keratoplasty in the Cornea Preservation Time Study: A Randomized Clinical Trial.

Importance: Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty. Objective: To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT. Design, Setting, and Participants: A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks. A total of 945 eyes of 769 participants were included in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK, performed primarily for Fuchs endothelial corneal dystrophy (96% of the cohort). The study was conducted from April 16, 2012, to June 5, 2017. Interventions: DSAEK with random assignment of a donor cornea with PT of 0 to 7 days (0-7d PT) or 8 to 14 days (8-14d PT). Main Outcomes and Measures: Endothelial cell density (ECD) at 3 years determined by a central image analysis reading center from clinical specular or confocal central endothelial images. Results: Nine hundred forty-five eyes of 769 participants (median age, 70 years [range, 42-90 years], 60.8% women, 93.0% white) in the Cornea Preservation Time Study that had not experienced graft failure 3 years after DSAEK were included. At the initial eye bank tissue screening, mean (SD) central ECD was 2746 (297) cells/mm2 in the 0-7d PT group (n = 485) and 2723 (284) cells/mm2 in the 8-14d PT group (n = 460). At 3 years, the mean (SD) ECD decreased from baseline by 37% (21%) in the 0-7d PT group and 40% (22%) in the 8-14d PT group to 1722 (626) cells/mm2 and 1642 (631) cells/mm2, respectively (mean difference, 73 cells/mm2; 95% CI, 8-138 cells/mm2; P = .03). When analyzed as a continuous variable (days), longer PT was associated with lower ECD (mean difference by days, 15 cells/mm2; 95% CI, 4-26 cells/mm2; P = .006). Endothelial cell loss (ECL) was comparable from 4 to 13 days' PT (n = 878; 36%-43% when tabulated by day). Available extension study ECD results at 4 years mirrored those at 3 years in the 203 eyes in the 0-7d PT group (mean [SD] ECD, 1620 [673] cells/mm2 and mean [SD] ECL, 41% [23%]) and 209 eyes in the 8-14d PT group (mean [SD] ECD, 1537 [683] cells/mm2 and mean [SD] ECL, 44% [23%]) (mean difference, 112 cells/mm2; 95% CI, 5-219 cells/mm2; P = .04). Conclusions and Relevance: Although ECL 3 years after Descemet stripping automated endothelial keratoplasty is greater with longer PT, the effect of PT on ECL is comparable from 4 to 13 days' PT.

Cornea preservation time study: methods and potential impact on the cornea donor pool in the United States.

PURPOSE: The aim of this study was to describe the aims, methods, donor and recipient cohort characteristics, and potential impact of the Cornea Preservation Time Study (CPTS). METHODS: The CPTS is a randomized clinical trial conducted at 40 clinical sites (70 surgeons) designed to assess the effect of donor cornea preservation time (PT) on graft survival 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK). Eyes undergoing surgery for Fuchs endothelial corneal dystrophy or pseudophakic/aphakic corneal edema were randomized to receive donor corneas stored ≤7 days or 8 to 14 days. Donor and patient characteristics, tissue preparation and surgical parameters, recipient and donor corneal stroma clarity, central corneal thickness, intraocular pressure, complications, and a reading center-determined central endothelial cell density were collected. Surveys were conducted to evaluate pre-CPTS PT practices. RESULTS: The 1330 CPTS donors were: 49% >60 years old, 27% diabetic, had a median eye bank-determined screening endothelial cell density of 2688 cells/mm, and 74% eye bank prepared for DSAEK. A total of 1090 recipients (1330 eyes including 240 bilateral cases) had: median age of 70 years, were 60% female, 90% white, 18% diabetic, 52% phakic, and 94% had Fuchs endothelial corneal dystrophy. Before the CPTS, 19 eye banks provided PT data on 20,852 corneas domestically placed for DSAEK in 2010 to 2011; 96% were preserved ≤7 days. Of 305 American Academy of Ophthalmology members responding to a pre-CPTS survey, 233 (76%) set their maximum PT preference at 8 days or less. CONCLUSIONS: The CPTS will increase understanding of factors related to DSAEK success and, if noninferiority of longer PT is shown, will have great potential to extend the available pool of endothelial keratoplasty donors.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01537393.

Impact of surgeon acceptance parameters on cost and availability of corneal donor tissue for transplantation.

OBJECTIVE: To examine the effects of more restrictive donor corneal parameters on the cost and availability of transplantable tissue. METHODS: Corneal tissue data from the Midwest Eye-Banks were collected from 2008 through 2011. Endothelial cell density (ECD) and donor age were arbitrarily restricted in a statistical model based on donor tissue availability. A hypothetical baseline corneal donor tissue fee of $3000 was used for the model. RESULTS: Overall, 19,990 tissues were recovered from 10,668 donors and met Food and Drug Administration and Eye Bank Association of America donor eligibility criteria and current age and ECD criteria for surgical use for corneal transplantation. The mean corneal ECD of screened corneas was 2694 ± 338 cells per square millimeter (range, 2000-4694 cells/mm2). The average age of the recovered donor corneas eligible for surgery was 55.6 ± 14.4 years. Donors aged 51 to 75 years contributed 70.5% of the surgical tissue. In this model, a minimum ECD restriction of 2300, 2500, or 2800 cells per square millimeter would reduce the corneal tissue availability to 87.7%, 70.6%, or 36.5% of current levels, respectively. If donor age were restricted to ≤ 70, ≤ 65, or ≤ 60 years, the percentage of corneal tissue available would decrease to 89.5%, 74.3%, or 57.5% of current levels, respectively. CONCLUSIONS: Tissue criteria restrictions would affect corneal surgeons and eye banks. Restrictions on donor age and ECD would decrease the availability of surgically suitable tissue and increase the costs of cornea transplant tissue.

Infectious disease risk factors of corneal graft donors.

OBJECTIVE: To determine how donor health status affects the risk of infection after corneal transplant. METHODS: An adverse reaction surveillance registry was used to conduct a matched case-control study among transplanted donor corneas from January 1, 1994, to December 31, 2003. Cases comprised 162 reports of endophthalmitis after penetrating keratoplasty including 121 with microbial recovery, of which 59 had concordant donor and recipient microbial isolates. Two controls were matched to each case by surgery date. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals according to the premortem status of decedent donors. RESULTS: Postkeratoplasty endophthalmitis was associated with recent hospitalization (odds ratio, 2.84; 95% confidence interval, 1.61-4.98) and fatal cancer (odds ratio, 2.46; 95% confidence interval, 1.53-3.97) among donors. Endophthalmitis appeared more likely with tissues transplanted longer than 5 days after donation (odds ratio, 1.55; 95% confidence interval, 1.02-2.35). The prevalence of concordant microbial isolates from donors and recipients was greater among fungal endophthalmitis than among bacterial endophthalmitis (P < .001). CONCLUSIONS: Corneal grafts with eye tissue obtained from donors dying in the hospital or with cancer may have an increased risk of postsurgical endophthalmitis, possibly due to donor-to-host microbial transmission. Together with donor screening and processing, improvements in microbiological control may reduce infection associated with corneal transplant.

Evaluation of an emergency department-based enrollment program for uninsured children.

STUDY OBJECTIVE: We evaluate the effectiveness of an emergency department (ED)-based outreach program in increasing the enrollment of uninsured children. METHODS: The study involved placing a full-time worker trained to enroll uninsured children into Medicaid or the State Children's Health Insurance Program in an inner-city academic children's hospital ED. Analysis was carried out for outpatient ED visits by insurance status, average revenue per patient from uninsured and insured children, proportion of patients enrolled in Medicaid and State Children's Health Insurance Program through this program, estimated incremental revenue from new enrollees, and program-specific incremental costs. A cost-benefit analysis and breakeven analysis was conducted to determine the impact of this intervention on ED revenues. RESULTS: Five thousand ninety-four uninsured children were treated during the 10 consecutive months assessed, and 4,667 were treated during program hours. One thousand eight hundred and three applications were filed, giving a program penetration rate of 39%. Eighty-four percent of applications filed were resolved (67% of these were Medicaid). Average revenue from each outpatient ED visit for Medicaid was US135.68 dollars, other insurance was US210.43 dollars, and uninsured was US15.03 dollars. Estimated incremental revenue for each uninsured patient converted to Medicaid was US120.65 dollars. Total annualized incremental revenue was US224,474 dollars, and the net incremental revenue, after accounting for program costs, was US157,414 dollars per year. CONCLUSION: A program enrolling uninsured children at an inner-city pediatric ED into government insurance was effective and generated revenue that paid for program costs.