Endothelial Cell-Density Measurements Report Anomaly in Corneal Donor Eyes Cohort

Wuqaas M. Munir, MD

A recent cross-sectional study found a discontinuity in endothelial cell density measurements just below 2500 cells/mm² in a large cohort of corneal donor eyes.

The investigators do not believe the algorithm used in specular microscopy had a particular weakness at 2500 cells/mm², making it likely to be a systematic bias by the observers.

“We postulate that there may be a subtle bias to nudge endothelial cell density above 2500 cells/mm² –whether consciously or subconsciously – to influence cornea surgeon tissue acceptance rate, which may be responsible for the anomaly in the study,” wrote study author Wuqaas M. Munir, MD, Department of Ophthalmology & Visual Sciences, University of Maryland School of Medicine.

Munir and colleagues noted that endothelial cell density has been a key component in determining corneal graft suitability for transplant. They aimed to describe the association of systematic and demographic characteristics of corneal transplant suitability and endothelial cell density.

In doing so, they uncovered an anomaly in the endothelial cell–density measurements suggestive of a systematic bias in the semi automated method used in the measurement. The study then set out to evaluate and confirm the anomaly and determine potential sources of the discrepancy in the large cohort of corneal donor eyes.

Investigators obtained donor information from the CorneaGen eye bank from June 2012 to June 2016. The data set included donor demographics, endothelial cell count, time of death, medical and surgical history, and suitability for transplant.

The deidentified eye bank data set consisted of information on 48,207 donated eyes and following exclusions of those missing endothelial cell density, the data set consisted of 44,479 donated eyes. Data show the mean donor age was 58 years and the mean endothelial cell density was 2717 cells/mm².

Investigators observed a clearly distinguishable discontinuity at 2500 cells/mm² with a plateau at 2000 cells/mm² as well. Moreover, the resultant heat map highlights these areas, with a brightening along the 2500-cells/mm² line and a drop-off below 2000 cells/mm².

They additionally suggest a Bayesian change point analysis confirmed with high probability only a true disconitutinity at 2500 cells/mm².

Investigators noted their belief that without a large cohort of corneal conor eyes, the subtle anomaly may have been imperceptible. However, limitations exist here as well, as data was sourced from only 1 eye bank and may make it difficult to generalize the findings without further investigation.

“Although we show a clear discordance in endothelial cell density in this large cohort, the true source of this anomaly requires further investigation,” Munir concluded.

The brief report, “Characteristics of Semi Automated Endothelial Cell-Density Measurements Among Corneal Donor Eyes,” was published in JAMA Ophthalmology.