Search

Purpose: To determine endothelial cell density (ECD) from real-world donor cornea endothelial cell (EC) images using a self-supervised deep learning segmentation model., Methods: Two eye banks (Eversight, VisionGift) provided 15,138 single, unique EC images from 8169 donors along with their demographics, tissue characteristics, and ECD. This dataset was utilized for self-supervised training and deep learning inference. The Cornea Image Analysis Reading Center (CIARC) provided a second dataset of 174 donor EC images based on image and tissue quality. These images were used to train a supervised deep learning cell border segmentation model. Evaluation between manual and automated determination of ECD was restricted to the 1939 test EC images with at least 100 cells counted by both methods., Results: The ECD measurements from both methods were in excellent agreement with rc of 0.77 (95% confidence interval [CI], 0.75-0.79; P < 0.001) and bias of 123 cells/mm2 (95% CI, 114-131; P < 0.001); 81% of the automated ECD values were within 10% of the manual ECD values. When the analysis was further restricted to the cropped image, the rc was 0.88 (95% CI, 0.87-0.89; P < 0.001), bias was 46 cells/mm2 (95% CI, 39-53; P < 0.001), and 93% of the automated ECD values were within 10% of the manual ECD values., Conclusions: Deep learning analysis provides accurate ECDs of donor images, potentially reducing analysis time and training requirements., Translational Relevance: The approach of this study, a robust methodology for automatically evaluating donor cornea EC images, could expand the quantitative determination of endothelial health beyond ECD.

Importance: A new analytic method can evaluate factors of interest associated with graft failure after Descemet stripping automated endothelial keratoplasty (DSAEK) or more generally in any ophthalmic surgical setting with a time-to-event outcome., Objective: To reanalyze types of intraoperative complications associated with DSAEK graft failure in the Cornea Preservation Time Study using random survival forests., Design, Setting, and Participants: This cohort study, initially conceived in April 2019, used a prediction model to conduct a post hoc secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. The study included 1090 participants, representing 1330 eyes, undergoing DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic or aphakic corneal edema (75 eyes [5.6%]). Enrollment occurred between April 16, 2012, and February 20, 2014, and follow-up ended June 5, 2017. Statistical analysis was performed from July 10, 2019, to May 29, 2020., Intervention: Descemet stripping automated endothelial keratoplasty with random assignment of a donor cornea with preservation time of 7 days or less or 8 to 14 days., Main Outcomes and Measures: Ranked variable importance for intraoperative complications among 50 donor, recipient, and eye bank variables and restricted mean survival time through 47 months (1434 days) after DSAEK were examined. Random survival forests, a nonparametric method (with less restrictive model assumptions) that is far more flexible in its ability to model nonlinear effects and interactions, was used to analyze the data., Results: This study included 1090 participants (663 women [60.8%]; median age, 70 years [range, 42-90 years]), representing 1330 eyes. Random survival forests ranked a DSAEK intraoperative complication as the third most predictive factor of graft failure, after surgeon and eye bank, in the final model with 5 predictors. In the first 47 months after DSAEK, the estimated mean difference in restricted mean survival time for grafts that experienced a DSAEK intraoperative complication vs those that did not was -227 days (99% CI, -352 to -70 days) based on the final RSF model., Conclusions and Relevance: These findings, while post hoc, support the hypothesis that random survival forests allow for an improved analytic approach for identifying factors predictive of graft failure and for obtaining adjusted graft survival estimates. Random survival forests offer the opportunity to guide the development of future population-based cohort ophthalmic surgical studies, establishing definitive factors for procedural success.

Purpose: To determine whether intracameral moxifloxacin 500 μg is noninferior to 250 μg for central endothelial cell loss (ECL) after phacoemulsification., Setting: Aravind Eye Care System., Design: Prospective masked randomized study., Methods: Eyes with bilateral nuclear cataracts, central endothelial cell density (ECD) of more than 2000 cells/mm, and ECD not differing between eyes by more than 200 cells/mm underwent phacoemulsification at least 14 days apart. Intraoperatively, the first eye was randomized to receive either a 500 or 250 μg dose of moxifloxacin intracamerally and received the other dose for the second-eye surgery. Postoperative course was monitored at 1 day, 1 week, 1 month, and 3 months. Preoperative and 30-day and 90-day postoperative central ECD was determined by a reading center for a masked analysis of ECL at 3 months postoperatively., Results: Fifty eyes of 25 patients (aged 48 to 69 years) underwent uneventful surgery and had normal postoperative courses. The point estimate (PE) and 95% CI for the mean difference in % ECL between the 500 μg and 250 μg doses at 3 months postoperatively was 0.8% (-5.8%, 7.4%). Upon identifying and removing 2 outliers, noninferiority was proven with a mean difference of the PE, -2.2% (CI, -6.5%, 2.1%)., Conclusions: Clinical and corneal endothelial cell were comparable in this study population for the 250 μg and 500 μg doses of intracameral moxifloxacin. Both doses were well tolerated clinically, supporting the use of the higher dose for improved antimicrobial coverage for the prevention of postoperative endophthalmitis.

Purpose: To characterize long-term changes in corneal endothelial cells after phacoemulsification with or without supraciliary Micro-Stent (Alcon) implantation in eyes with open-angle glaucoma (OAG) and visually significant cataract., Design: Three-year safety extension of a 2-year randomized clinical trial., Methods: Patients from the multicenter Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS) trial who underwent Micro-Stent implantation plus phacoemulsification (n = 282) or phacoemulsification alone (n = 67) were analyzed post hoc. Specular microscopy was used to assess endothelial cell loss (ECL), including changes from baseline in endothelial cell density (ECD), coefficient of variation, and percentage of hexagonal cells., Results: Preoperative ECDs in the microstent group (2,432.6 cells/mm 2 [95% confidence interval [CI], 2,382.8-2,482.4 cells/mm 2 ]) were similar to those in the control group (2,434.5 cells/mm 2 [95% CI, 2,356.5-2,512.4 cells/mm 2 ]) groups. ECL at months 48 and 60 was greater in the Micro-Stent group than in the control group. At month 60, the mean percent of changes in ECD was -20.4% (95% CI, -23.5% to -17.5%) in the Micro-Stent group and -10.1% (95% CI, -13.9% to -6.3%) in the control group. No statistically significant between-group changes from baseline in cellular morphology were observed. Nine adverse events were possibly related to ECL, including 3 eyes with transient focal corneal edema and 4 eyes that required Micro-Stent trimming due to protrusion., Conclusions: In eyes with OAG, ECL after phacoemulsification is acute and stabilizes after 3 months, whereas ECL after phacoemulsification plus Micro-Stent implantation proceeds for at least 5 years. Clinical findings associated with ECL in these eyes were uncommon (3.3% of implanted eyes), suggesting that ECL is generally a subclinical phenomenon., (Copyright © 2019. Published by Elsevier Inc.)

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.

Purpose: The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration., Methods: RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52., Results: No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96)., Conclusions: Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.

Purpose: To evaluate a single eye bank's measurement of endothelial cell density (ECD) of Descemet membrane endothelial keratoplasty (DMEK) grafts before and after preparation using 2 separate counting methods., Methods: A series of 60 donor tissues were prepared for DMEK surgery. One to 4 specular images of the central endothelium were taken both before and after preparation, and ECDs were evaluated for a total of 345 unique images. Images were then masked and provided to the Cornea Image Analysis Reading Center (CIARC) for independent analysis., Results: Before preparation, average eye bank-determined ECD with the center method was 2678 ± 259 cells/mm and was 2599 ± 280 cells/mm CIARC-determined by the variable frame method (P < 0.001, n = 176). After preparation, eye bank-determined ECD was 2719 ± 265 cells/mm and CIARC-determined ECD was 2615 ± 344 cells/mm (P < 0.001, n = 169). The difference in ECD before and after DMEK preparation was not found to be statistically significant when evaluated using either analysis method (P = 0.19; P = 0.64) before and after preparation, respectively., Conclusions: Although the absolute ECD value may differ by the analysis method statistically, pre- and post-DMEK preparation ECDs did not significantly change by either analysis method. Other methods such as vital staining to assess tissue damage after preparation in conjunction with specular microscopy are suggested.

Purpose: To assess endothelial cell density (ECD) and model 10-year cell loss after Descemet stripping endothelial keratoplasty (DSEK), and to compare with results after penetrating keratoplasty (PK) performed for the same indications in the Cornea Donor Study (CDS)., Design: Retrospective, longitudinal study., Participants: Five hundred ninety DSEK recipients, 21 to 96 years of age, treated for Fuchs' dystrophy (n = 498; 84%), pseudophakic or aphakic corneal edema (n = 89; 15%), or other endothelial dysfunction (n = 3; <1%)., Methods: Review of 1005 consecutive primary DSEK procedures by 6 surgeons identified 752 grafts (75%) in 590 recipients with ECD measurements at 1 or more postoperative examinations between 6 months and 10 years. Four statistical models applied previously to the CDS PK data were considered. The preferred model (Bayesian Markov chain Monte Carlo) accounted for missing data, selective dropout from graft failure, correlations between fellow eyes, and correlations between longitudinal repeated measures., Main Outcome Measures: Central corneal ECD., Results: The median donor corneal ECD (25th-75th percentiles) was 3005 cells/mm(2) (2852-3203 cells/mm(2)) at baseline, 2077 cells/mm(2) (1660-2411 cells/mm(2)) at 6 months, and 926 cells/mm(2) (617-1433 cells/mm(2)), with a range from 408 to 2538 cells/mm(2) at 10 years. After median cell loss of 32% in the perioperative period, ECD declined at a linear rate of approximately 110 cells/mm(2) per year between 6 months and 10 years after DSEK. At 10 years, the median cell loss was 71% (53%-80%) relative to the baseline donor ECD, comparable with the 76% (70%-82%) median cell loss after PK by 68 surgeons in the CDS. The 10-year ECD correlated with the 6-month postoperative ECD (r = 0.56; P < 0.001), but not with the baseline donor ECD (r = -0.04; P = 0.78). Selective dropout from graft failure did not affect the cell loss model significantly., Conclusions: The linear decline in ECD after DSEK was consistent with shorter-term endothelial keratoplasty studies and was distinct from the biexponential cell loss trend characteristic of PK. By 10 years, cell loss was comparable in surviving clear grafts for both DSEK and PK., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study., Design: Multicenter, prospective, double-masked, controlled clinical trial., Participants: One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States., Methods: Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD., Main Outcome Measures: Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD., Results: There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, -10% to 6%; unadjusted P=0.60). Baseline ECD (P=0.71), 10-year ECD (P>0.99), and changes in ECD over 10 years (P=0.86) were similar comparing donor groups with and without diabetes., Conclusions: The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We constructed several mathematical models that predict endothelial cell density (ECD) for patients after penetrating keratoplasty (PK) for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema)., Methods: In a subset (n = 591) of Cornea Donor Study participants, postoperative ECD was determined by a central reading center. Various statistical models were considered to estimate the ECD trend longitudinally over 10 years of follow-up. A biexponential model with and without a logarithm transformation was fit using the Gauss-Newton nonlinear least squares algorithm. To account for correlated data, a log-polynomial model was fit using the restricted maximum likelihood method. A sensitivity analysis for the potential bias due to selective dropout was performed using Bayesian analysis techniques., Results: The three models using a logarithm transformation yield similar trends, whereas the model without the transform predicts higher ECD values. The adjustment for selective dropout turns out to be negligible. However, this is possibly due to the relatively low rate of graft failure in this cohort (19% at 10 years). Fuchs' dystrophy and pseudophakic/aphakic corneal edema (PACE) patients had similar ECD decay curves, with the PACE group having slightly higher cell densities by 10 years., Conclusions: Endothelial cell loss after PK can be modeled via a log-polynomial model, which accounts for the correlated data from repeated measures on the same subject. This model is not significantly affected by the selective dropout due to graft failure. Our findings warrant further study on how this may extend to ECD following endothelial keratoplasty., (© ARVO.)

Importance: Endothelial morphometric measures have potential value in predicting graft failure after penetrating keratoplasty., Objective: To determine whether preoperative and/or postoperative central morphometric measures (endothelial cell density [ECD], coefficient of variation [CV], and percentage of hexagonality [HEX]) and their postoperative changes are predictive of graft failure caused by endothelial decompensation after penetrating keratoplasty to treat a moderate-risk condition, principally Fuchs dystrophy or pseudophakic corneal edema., Design: In a subset of Cornea Donor Study participants with graft failure, a central reading center determined preoperative and postoperative ECD, CV, and HEX from available central endothelial specular images., Setting: Cornea Image Analysis Reading Center of the Specular Microscopy Ancillary Study., Participants: Eighteen patients with graft failure due to endothelial decompensation and 54 individuals matched for most donor and recipient measures at baseline whose grafts did not fail., Main Outcome Measure: Change in ECD, CV, and HEX values., Results: Preoperative ECD was not associated with graft failure (P = .43); however, a lower ECD at 6 months was predictive of subsequent failure (P = .004). Coefficient of variation at 6 months was not associated with graft failure in univariate (P = .91) or multivariate (P = .79) analyses. We found a suggestive trend of higher graft failure with lower HEX values at 6 months (P = .02) but not at the established statistical significance (P < .01). The most recent CV or HEX values, as time-dependent variables, were not associated with graft failure (P = .26 and P = .81, respectively). Endothelial cell density values decreased during follow-up, whereas CV and HEX appear to fluctuate without an apparent trend., Conclusions and Relevance: Endothelial cell density at 6 months after penetrating keratoplasty is predictive of graft failure, whereas CV and HEX appear to fluctuate postoperatively, possibly indicating an unstable endothelial population in clear and failing grafts., Trial Registration: clinicaltrials.gov Identifier: NCT00006411.

Purpose: To assess 3-year outcomes of Descemet's stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Cornea Donor Study (CDS)., Design: Prospective, multicenter, nonrandomized clinical trial., Participants: A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema) compared with 1101 subjects undergoing PKP from the CDS., Methods: The DSAEK procedures were performed by 2 experienced surgeons using the same donor and similar recipient criteria as for the CDS PKP procedures, performed by 68 surgeons. Graft success was assessed by Kaplan-Meier survival analysis. Central endothelial cell density (ECD) was determined from baseline donor and postoperative central endothelial images by the reading center used in the CDS Specular Microscopy Ancillary Study., Main Outcome Measures: Graft clarity and ECD., Results: The donor and recipient demographics were comparable in the DSAEK and PKP groups, except that the proportion of Fuchs' dystrophy cases was higher in the DSAEK cohort. The 3-year survival rate did not differ significantly between DSAEK and PKP procedures performed for either Fuchs' dystrophy (96% for both; P = 0.81) or non-Fuchs' cases (86% vs. 84%, respectively; P = 0.41). Principal causes of graft failure or regraft within 3 years after DSAEK and PKP were immunologic graft rejection (0.6% vs. 3.1%), endothelial decompensation in the absence of documented rejection (1.7% vs 2.1%), unsatisfactory visual or refractive outcome (1.7% vs. 0.5%), and infection (0% vs. 1.1%), respectively. The 3-year predicted probability of a rejection episode was 9% with DSAEK versus 20% with PKP (P = 0.0005). The median 3-year cell loss for DSAEK and PKP was 46% and 51%, respectively (P = 0.33), in Fuchs' dystrophy cases and 59% and 61%, respectively (P = 0.70), in the non-Fuchs' cases. At 3 years, use of a smaller DSAEK insertion incision was associated with significantly higher cell loss (60% vs. 33% for 3.2- and 5.0-mm incisions, respectively; P = 0.0007), but not with a significant difference in graft survival (P = 0.45)., Conclusions: The graft success rate and endothelial cell loss were comparable at 3 years for DSAEK and PKP procedures. A 5-mm DSAEK incision width was associated with significantly less cell loss than a 3.2-mm incision., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess outcomes 1 year after Descemet's stripping automated endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty (PKP) from the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor Study., Design: Multicenter, prospective, nonrandomized clinical trial., Participants: A total of 173 subjects undergoing DSAEK for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema) compared with 410 subjects undergoing PKP from the SMAS who had clear grafts with at least 1 postoperative specular image within a 15-month follow-up period., Methods: The DSAEK procedures were performed by 2 experienced surgeons per their individual techniques, using the same donor and similar recipient criteria as for the PKP procedures in the SMAS performed by 68 surgeons at 45 sites, with donors provided from 31 eye banks. Graft success and complications for the DSAEK group were assessed and compared with the SMAS group. Endothelial cell density (ECD) was determined from baseline donor, 6-month (range, 5-7 months), and 12-month (range, 9-15 months) postoperative central endothelial images by the same reading center used in the SMAS., Main Outcome Measures: Endothelial cell density and graft survival at 1 year., Results: Although the DSAEK recipient group criteria were similar to the PKP group, Fuchs' dystrophy was more prevalent in the DSAEK group (85% vs. 64%) and pseudophakic corneal edema was less prevalent (13% vs. 32%, P<0.001). The regraft rate within 15 months was 2.3% (DSAEK group) and 1.3% (PKP group) (P = 0.50). Percent endothelial cell loss was 34+/-22% versus 11+/-20% (6 months) and 38+/-22% versus 20+/-23% (12 months) in the DSAEK and PKP groups, respectively (both P<0.001). Preoperative diagnosis affected endothelial cell loss over time; in the PKP group, the subjects with pseudophakic/aphakic corneal edema experienced significantly higher 12-month cell loss than the subjects with Fuchs' dystrophy (28% vs. 16%, P = 0.01), whereas in the DSAEK group, the 12-month cell loss was comparable for the 2 diagnoses (41% vs. 37%, P = 0.59)., Conclusions: One year post-transplantation, overall graft success was comparable for DSAEK and PKP procedures and endothelial cell loss was higher with DSAEK., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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).

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.

Purpose: To describe reliable methods for determining central corneal endothelial cell density (ECD) in a multicenter eye bank study., Methods: The Specular Microscopy Reading Center utilized a dual-grading procedure and adjudication process to classify image quality and determine ECD for a subset of donor endothelial images obtained in the Specular Microscopy Ancillary Study, which is part of the Cornea Donor Study. Two certified readers classified images as analyzable (excellent, good, fair) or unanalyzable and determined the ECD using a variable frame technique. An adjudicator also evaluated the images if quality classifications by the two readers differed by one grade, if any reader found the image unanalyzable, and/or if the ECD determination between the two readers was >or= 5%., Results: Image quality categorization by the two readers was identical for 441 (64%) of 688 donor images. The ECD differed by < 5% for 442 (69%) of the 645 analyzable images. The ECD determined by the adjudicator was < 5% different than the ECD determined by at least one reader for 193 (95%) of the 203 remaining images., Conclusions: The dual-grading and adjudication procedures produce reliable, reproducible assessments of image quality and ECD. The importance of two independent readings is evident in that image quality ratings differed between the two readers by one grade in 36% of all images and ECD counts differed by >or=5% for 31% of analyzable images.

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.