The long and short of corneal preservation times

Just how long can corneal tissue be kept and still remain viable for use? Investigators determined that tissue stored for up to 11 days had success rates equal to tissue preserved for a much shorter period, according to Jonathan Lass, MD, Case Western Reserve, University Hospitals Eye Institute, Cleveland.

This study, published in JAMA Ophthalmology, grew out of an earlier donor graft study, with investigators deciding that the issue of cornea preservation would be the next major question with regard to the donor pool.(1)

“There was a major prejudice against using tissue beyond 7 or 8 days even though the intermediate storage solution was approved by the FDA to go out to 14 days,” Dr. Lass said. “Also, we were aware that the eye banks, because of this prejudice, were shipping the tissue out of the country and successfully using it internationally,” Dr. Lass said. Surgeons in the U.S. were reluctant to use tissue that had been preserved longer, based mainly on what they had been taught. “They learned to do this in their fellowships, but there was no solid evidence for doing this,” he said. Included in the study were 1,330 eyes, with about an equal distribution between both groups, Dr. Lass noted, adding that they chose DSAEK as the procedure with which to test preservation time because this is currently the most common keratoplasty technique in use. In this masked study, the only thing surgeons knew about the donor was the thickness of the corneal tissue after lamellar dissection. “They needed that information for doing the procedure,” Dr. Lass said. When a cornea was found to be eligible, this was then assigned to a patient, with half of the individuals receiving corneas that had been preserved for 7 days or less and the other half preserved for 8–14 days. In addition, the groups were subdivided into 0–4 days, 5–7 days, 8–11 days, and 12–14 days.

At the 3-year mark, results were promising. However, they were unable to prove non-inferiority as a whole of the tissue preserved for a longer time. To prove this, the confidence interval needed to be 4% or lower, but this was at 5.4%, Dr. Lass reported. However, the overall success rate was high in both groups at around 95% for the tissue preserved for the short time period and 92% for that in the longer preservation group. However, when the subgroup analysis was considered, it became clear that the failures in the longer preservation group were mainly coming from the oldest 12- to 14-day tissue. “In the paper we came out saying that there was no difference up to 11 days, and even at 12 to 14 days, the success rate was at 89%, so it’s still good,” Dr. Lass said. Clinically speaking, this means that there is no difference up to 11 days, but if logistically you need to use tissue that has been preserved for 12–14 days, that’s still good. For eye banks, this means more time to research the donors. “It’s going to give them 3–4 more days to evaluate the tissue and distribute it both domestically and internationally, and there will now be hard evidence that this is OK,” Dr. Lass said. Investigators also determined that most of the failures were coming in the first 60 days after surgery. “Primary donor failure was defined as everything went fine at the time of surgery, but postop the cornea never cleared,” he said, adding that in this initial time period there were 22 failures in the group preserved for longer and 11 in the shorter group. Investigators think that while this tissue may still appear good when considered with the normal process of donor evaluation, it doesn’t withstand the stress of the longest preservation time and fails early on. “There’s a subset, which we can’t detect with our current methods for donor evaluation, that could not withstand that stress,” Dr. Lass said. A separate analysis of cell loss led by Dr. Lass likewise boded well for tissue preserved for longer periods.2 At the 3-year mark, investigators found that this was comparable in the 0- to 7-day preservation group and the 8- to 14-day one. “But again, we found that the longest group had more cell loss of clear grafts in 3 years than the shorter group did,” Dr. Lass said, adding that there was 37% cell loss compared to baseline for the shorter group versus a 40% loss in the longer group. Once again, when a subgroup analysis was done, it was determined that most of the cell loss was coming in that longest preservation group, particularly at day 14. “Again, this supported the findings that it was fine to go out 11 to 12 days,” he said. “It suggests that the preservation time had an effect on the ones that are surviving at 3 years.” This means that it may be necessary to follow these eyes a little longer in order to determine if there are going to be any more late failures in the ones that were preserved for 13 or 14 days. Dr. Lass hopes that practitioners come away from this with a new confidence in using donor corneas that have been preserved for up to 11 days. “There’s no difference,” he said. The hope is to change people’s minds and increase the average preservation time in the U.S. from 7–8 days and move it more toward 10–11 days. “This is going to help eye banks now and in the future as the demand for corneas is going to increase with an aging population,” Dr. Lass said.

1. Rosenwasser GO, et al. Effect of cornea preservation time on success of Descemet stripping automated endothelial keratoplasty: a randomized clinical trial. JAMA Ophthalmology. 2017;135:1401–1409. 2. Lass JH, et al. Corneal endothelial cell loss 3 years after successful Descemet stripping automated endothelial keratoplasty in the Cornea Preservation Time Study: a randomized clinical trial. JAMA Ophthalmology. 2017;135:1394–1400. Editors’ note: Dr. Lass has no financial interests related to his comments. Contact information Lass: Jonathan.Lass@UHhospital.org

Source: https://www.eyeworld.org/