Purpose-Identify recipient factors which may be related to risk of corneal graft failure Design-Multi-center prospective, double-masked, controlled clinical trial Participants-1090 subjects undergoing corneal transplantation for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema) Methods-Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea including donor age. Surgery and post-operative care were performed according to the surgeons' usual routines and subjects were followed for five years. Baseline factors were evaluated for their association with graft failure.Main Outcome Measures-Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of three consecutive months.

OBJECTIVE -To evaluate the accuracy and precision of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes.RESEARCH DESIGN AND METHODS -In 30 children with type 1 diabetes (mean age 11.2 Ϯ 4.1 years), the Navigator glucose values were compared with reference serum glucose values of blood samples obtained in an inpatient clinical research center and measured in a central laboratory using a hexokinase enzymatic method and in an outpatient setting with a FreeStyle meter. Median absolute difference (AD) and median relative absolute difference (RAD) were computed for sensor-reference and sensor-sensor pairs.RESULTS -The median AD and RAD were 17 mg/dl and 12%, respectively, for 1,811 inpatient sensor-reference pairs and 20 mg/dl and 14%, respectively, for 8,639 outpatient pairs. The median RAD between two simultaneous Navigator measurements (n ϭ 1,971) was 13%. Ninety-one percent of sensors in the inpatient setting and 81% of sensors in the outpatient setting had a median RAD Յ20%.CONCLUSIONS -The Navigator's accuracy does not yet approach the accuracy of currentgeneration home glucose meters, but it is sufficient to believe that the device has the potential to be an important adjunct to treatment of youth with type 1 diabetes. Diabetes Care 30:59 -64, 2007D irect reading, near-continuous, minimally invasive glucose sensors hold great promise for improving the care of patients with diabetes and other abnormalities of glucose metabolism. These sensors can provide both a measure of the current glucose concentration as well as glucose trends, with alarms for high and low thresholds and predicted hypo-and hyperglycemia. With the recent demonstration that good glycemic control reduces mortality and morbidity in acutely ill nondiabetic patients (1,2), glucose sensors could have an even more expanded role outside the realm of diabetes.A major issue in evaluating the utility of a real-time continuous glucose monitor is its accuracy across a wide range of glucose levels. Previously, we reported on the accuracy of the GlucoWatch G2 Biographer (Cygnus, Redwood City, CA) (3) and the continuous glucose monitoring system (CGMS; Medtronic Minimed, Northridge, CA) (4) in children with type 1 diabetes. The purpose of this article is to report on the accuracy of the FreeStyle Navigator CGMS in children.RESEARCH DESIGN AND METHODS -The study was conducted by the Diabetes Research in Children Network (DirecNet) at five clinical centers. A data and safety monitoring board and the institutional review boards at each center approved the study protocol, consent form, and assent form. A parent or guardian and each subject aged Ն7 years gave written consent and assent, respectively.Eligible subjects were between 3 and 18 years old with a clinical diagnosis of type 1 diabetes of Ն1-year duration. Subjects initially used a Navigator that was blinded so that glucose values could not be seen for approximately 1 week at home. During this time, glucose levels were checked with the built-in FreeStyle blood glu...

Writing Committee for the Cornea Donor Study Research Group IMPORTANCE The Cornea Donor Study (CDS) showed that donor age is not a factor in survival of most penetrating keratoplasties for endothelial disease. Secondary analyses confirm the importance of surgical indication and presence of glaucoma in outcomes at 10 years.OBJECTIVE To assess the relationship between donor and recipient factors and corneal graft survival in the CDS. DESIGN, SETTING, AND PARTICIPANTSMulticenter prospective, double-masked, controlled clinical trial conducted at 80 clinical sites. One hundred five surgeons enrolled 1090 participants undergoing corneal transplant for a moderate-risk condition, principally Fuchs dystrophy or pseudophakic or aphakic corneal edema (PACE). Forty-three eye banks provided corneas.INTERVENTIONS Corneas from donors younger than 66 years and donors 66 years or older were assigned, masked to donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Participants were followed up for as long as 12 years.MAIN OUTCOMES AND MEASURES Graft failure, defined as a regrafting procedure or a cloudy cornea for 3 consecutive months. RESULTSThe 10-year cumulative probability of graft failure was higher in participants with PACE than in those with Fuchs dystrophy (37% vs 20%; hazard ratio [HR], 2.1 [99% CI, 1.4-3.0]; P < .001) and in participants with a history of glaucoma before penetrating keratoplasty, particularly with prior glaucoma surgery (58% with prior glaucoma surgery and use of medications to lower intraocular pressure at the time of surgery vs 22% with no history of glaucoma surgery or medication use; HR, 4.1 [99% CI, 2.2-7.5]; P < .001). We found trends toward increased graft failure in recipients who were 70 years or older compared with those younger than 60 years (29% vs 19%; HR, 1.2 [99% CI, 0.7-2.1]; P = .04) or were African American (HR, 1.5; P = .11) or who had a history of smoking (35% vs 24%; HR, 1.6 [99% CI, 0.9-2.8]; P = .02). Lower endothelial cell density (ECD) and higher corneal thickness (CT) at 6 months (6% vs 41% for ECD Ն2700 vs <1700 cells/mm 2 [P < .001]; 14% vs 36% for CT <500 vs Ն600 μm [P = .001]), 1 year (4% vs 39% for ECD Ն2700 vs <1700 cells/mm 2 [P < .001]; 18% vs 28% for CT <500 vs Ն600 μm [P = .04]), and 5 years (2% vs 29% for ECD Ն1500 vs <500 cells/mm 2 [P < .001]; 7% vs 34% for CT <550 vs Ն650 μm [P < .001]) were associated with subsequent graft failure.CONCLUSIONS AND RELEVANCE Most penetrating corneal grafts for Fuchs dystrophy or PACE remain clear at 10 years. The risk for failure is greater for graft recipients with PACE and those with a history of glaucoma. Measurements of ECD and CT during the course of postkeratoplasty follow-up are associated with a risk for failure. However, even with very low ECD and high CT at 5 years, most corneas remain clear at 10 years.

Objective To examine the effect of donor age and other perioperative factors on long term endothelial cell loss after penetrating keratoplasty (PKP) Design Multi-center, prospective, double-masked clinical trial Participants 176 participants from the Cornea Donor Study cohort who had not experienced graft failure 10 or more 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 post-operative care were performed according to the surgeons’ usual routines. Images of the central endothelium were obtained preoperatively and at intervals for ten years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). Main Outcome Measure 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/mm2 (interquartile range, 522-850), 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/mm2 (interquartile range, 483-694) (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 (24%) of the 176 participants had an ECD below 500 cells/mm2 at 10 years and only 24 (14%) had an ECD above 1,000 cells/mm2. Conclusions Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly higher with older donor age. Higher pre-operative ECD and larger donor tissue size are associated with higher ECD at 10 years. Trial Registration NCT00006411

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.Corneal clarity after penetrating keratoplasty can be affected by endothelial cell loss over time. The exact cause of postoperative cell loss is unknown but may be a result of donor or preservation factors, surgical stress, cellular interactions between the donor and recipient, immune reaction, normal or accelerated cellular aging, or glaucoma. The Eye Bank Association of America requires endothelial cell density (ECD) determination via specular microscopy as a standard corneal tissue evaluation method but does not require a minimum cell density for transplant suitability. 1 Clinicians typically prefer donor corneas with a high pre-operative ECD in order to offset posttransplant cell loss under the belief that this will improve the probability of graft survival. Past studies evaluating endothelial cell loss after corneal transplantation have produced conflicting results with regard to the effect of donor age. Some studies suggest that there is no difference in endothelial cell loss comparing older and younger donor tissue, 2-5 whereas other studies suggest that there is a relationship between endothelial cell loss and donor age. 6 -8The Cornea Donor Study (CDS) has evaluated the effect of donor age on 5-year graft survival in eyes undergoing cornea transplantation for a corne...