[Data quality of unsupervised endothelial cell counting vs. reading centre analysis in multicentric clinical trials].

PURPOSE: The aim of this study was to assess data quality from unsupervised endothelial cell counting in the multicentric setting.

PATIENTS AND

METHODS

We performed an endothelial cell counting trial with two fictitious trial sites. The trial protocol simply demanded for marking 30 cells for analysis. Analyses were performed with the cell counting tool as built into the Topcon SP-3000P specular microscope. The first centre consequently dotted 30 cells. The other centre continuously dotted more cells until 30 cells were included in the cell counting analysis. Both sites analysed the same 89 eyes of corneal outpatients and heathy volunteers. Both sites used a dedicated Topcon SP-3000P microscope. The image pairs from both sites were eventually printed, scanned and re-evaluated with a programme that evaluated all visible cells ("reading centre"). The agreement between both sites was statistically assessed by means of Pearson's correlation and Bland-Altman analysis. The same statistical assessments were also performed for the image pairs as analysed in the reading centre.

RESULTS

The determined cell densities as reported by both trial sites differed by -65 % to 42 %. Furthermore, we also observed a systematic deviation between both sites. Consequently, the coefficient of determination from Pearson's correlation was only 0.947. However, the agreement was as high as 0.997 when the image pairs were analysed in the reading centre. Here the difference between the cell densities of the image pairs ranged from merely -15 % to 9 % with no systematic deviation.

CONCLUSIONS

Unsupervised endothelial cell counting does not result in sufficiently objective endothelial cell denstiy estimations. Furthermore, the built-in analysis tools can introduce systematic errors. Both drawbacks can be overcome by a reading centre that evaluates all visible cells on the images. For this reason, we recommend the involvement of a reading centre in multicentric clinical trials on the corneal endothelium.