Endothelial cell loss

Endothelial cell loss is an important outcome parameter for corneal transplantation procedures as it is used both as a measure of success and for predicting survival of the transplanted tissue. However, interpretations of data on endothelial cell loss following different keratoplasty techniques should consider that there are a number of limitations affecting the accuracy of the determinations, according to Isabel Dapena MD, PhD. Speaking in London at the 5th EuCornea Congress during a symposium on new trends in endothelial transplantation, Dr Dapena reviewed the factors that may be confounding measurements of endothelial cell density (ECD). She concluded that the reported data on ECD changes after descemet membrane endothelial keratoplasty (DMEK) and other endothelial keratoplasty procedures may overestimate the true loss. “Since endothelial cell loss after endothelial keratoplasty has generally been attributed to donor tissue manipulation during surgery, when DMEK became available as a standardised ‘no touch’ technique, we expected to find that it was associated with a lower endothelial cell loss rate than descemet stripping endothelial keratoplasty. “To our surprise, however, we found in our DMEK series that the ECD loss after six months was between 30 and 34 per cent, which is within the range reported for other endothelial keratoplasty techniques. Therefore, we considered there must be factors other than surgical handling that were affecting our measurements and could explain these results,” said Dr Dapena, cornea specialist, Melles Cornea Clinic, Netherlands Institute for Innovative Ocular Surgery, Rotterdam, Netherlands. Measurement techniques Discussing the possible contributors, Dr Dapena noted that there are limitations introduced by the measurement techniques. The baseline measurement determined by eye bank analysis of the donor tissue is generally overestimated by the cell counting techniques that are used. Introducing further sources for error, the postoperative measurement is performed in vivo by a different observer using different methodology and different instrumentation. Another issue to consider is that endothelial cell count determinations focus on the centre of the cornea. However, there may be field  migration of the endothelial cells post-transplantation from the central region towards the periphery, and that shift would result in an overestimation of endothelial cell loss in the centre. Change in hydration of the cornea after transplantation could also lead to overestimation of endothelial cell loss as the result of an increase in host posterior corneal surface area when the cornea de-swells. Dr Dapena explained that the posterior stroma is more easily hydrated than the anterior layers, and as the posterior layers thicken, the posterior surface of the cornea flattens. As the cornea de-swells post-transplantation, the posterior surface steepens, resulting in an increase in arc length from limbus to limbus and in the posterior surface area. Since the transplant is attached to the posterior surface of the cornea, the cells are stretched outside the fixed area of the specular microscope’s measurement window. Therefore, fewer cells are counted using specular microscopy even though their total number is actually unchanged. Dr Dapena and colleagues recently published a paper in which they developed a mathematical model to investigate how corneal deturgescence after DMEK affects posterior corneal surface area and determinations of endothelial cell loss (Quilendrino R et al, Curr Eye Res. 2013;38(2):260-5). The model was created based on data from 25 eyes that underwent DMEK, including measurements of central corneal thickness, ECD, and pachymetry through follow-up to six months. The analyses showed that de-swelling of the cornea resulted in an 8.6 per cent increase in total posterior corneal surface area that could account for about 25 per cent of the observed average 34 per cent decrease in ECD over the first six months following surgery. “According to these findings, the increase in posterior corneal surface area resulting from postoperative de-swelling of the cornea might lead to an eight per cent overestimation of the actual loss of endothelial cells,” Dr Dapena said.