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

Abstract

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/mm2 greater by the EBs than by CIARC (N = 1286, P < 0.001) with 95% limits of agreement of (−644, 675 cells/mm2). The limits of agreement in preoperative ECD were wider in the After-Lamellar-Dissection Group (−687, 683 cells/mm2) than in the Before Shipping Group [(−505, 633 cells/mm2); 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/mm2 vs. SD = 603 cells/mm2; 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.

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

“…This is evidenced by the estimated difference in mean ECD after adjustment for these factors with a linear mixed model which was clinically indistinguishable from the difference calculated using an unadjusted paired t test. These results are consistent with findings in the SMAS 11 and CPTS, 10 which reported no effect on relative ECD difference when adjusting for donor history of diabetes and polymegethism/pleomorphism. The SMAS and CPTS also found no difference in relative ECD difference after adjusting for cause of donor death and the presence of stromal edema.…”

“…Previously reported data from the CPTS from multiple eye banks and varying training and image analysis techniques found that the mean difference between eye bank–determined and CIARC-determined preoperative ECD was 15 cells/mm 2 . 10 The same study reported that eye bank–determined preoperative ECD was within 10% of the CIARC-determined ECD for 69% of the image sets (886 of the 1286 image sets). 10 A similarly performed study published in 2005, the SMAS, determined that the mean eye bank–determined screening ECD was 100 cells/mm 2 higher than the CIARC, with mismatch increasing as the image quality worsened.…”

“…The SMAS and CPTS also found no difference in relative ECD difference after adjusting for cause of donor death and the presence of stromal edema. 10,11 Although CV and HEX are not typically reported by eye banks to surgeons, and had no clinically meaningful influence on the ECD mean difference in this study, we conducted a comparison of CV-and HEX-determination between the eye banks and the CIARC. Notably, the mean differences in CV and HEX determination between the EBs and reading center were found to be small, 1 and 22%, respectively, but significantly different.…”

“…The major limitations of the multi-eye-bank studies versus reading center-determined comparative ECD studies were varying training of the technicians performing the specular microscopy and image analysis, differing image selection, varying methods of image analysis, and selection bias for cells analyzed. 10,11 To achieve a more accurate and reproducible ECD measurement across all eye banks, the Eye Bank Association of America has recognized the importance of training in best practices for donor specular microscopy and image analysis for ECD determination by conducting regular web trainings and lectures at its annual meetings for new and experienced technicians. In addition, a standardized specular microscopic image capturing technique to maximize image quality has also been described and integrated into the Eye Bank Association of America Procedures Manual.…”

Characteristics of Semiautomated Endothelial Cell–Density Measurements Among Corneal Donor Eyes

“…The Cornea Donor Study (CDS) examined the accuracy of eye bank measurements in their data set and found most eye bank measurements fell within 10% of an established study reading center with image quality contributing to variability . The more recent Cornea Preservation Time Study (CPTS) also compared endothelial cell–density measurements between eye banks and a central reading center, finding measurements to be similar but with high variability between individual measurements …”