Surgeons require tissue that they can successfully manipulate and transplant into recipients. Empirically, older donors provide DMEK tissue that scrolls less tightly, which can make unfurling it easier for the surgeon [1, 12]. Thickening of DM with age [2] likely imparts this desirable property.

Donors over 50 are routinely assigned to DMEK at our organization, but surgeons drive this age cutoff, and it could be lower. Many new or adopting DMEK surgeons will specifically request a lower donor age limit of 65 to decrease the chance of having to unfurl a tight scroll. To date, we do not know the lower age limit for safely and reliably peeling DMEK grafts, and our hope is that donors even younger than 50 may become acceptable for DMEK as new approaches to the procedure continue to develop.

The upper age limit for donor criteria is driven by surgeon preferences as there is limited published data available related to donor age and long-term DMEK outcomes. Mannis et al., in the landmark Cornea Donor Study (CDS), reported small but significant differences in graft failure rates for donors aged 72–75 versus younger donors. In donors aged 52–71, 74 % of corneas remained clear at 10 years. Whereas 62 % of 72–75 year old donors were clear at 10 years. These differences in graft failure rates were not apparent until after 6 years postoperatively in penetrating keratoplasty recipients [13]. As DMEK recipient outcomes are tracked for the long term, it will be important to ascertain whether older donor tissues have similar rates of graft failure to what was observed in the Cornea Donor Study.

Older donors, while easier to unfurl, are often accompanied by lower endothelial cell densities and represent a potential compromise. Our eye bank currently has a lower limit of 2000 cells/mm² for the endothelial cell density to be deemed suitable for EK. In practice, however, many surgeons request higher endothelial cell densities than the minimum allowed by our standard. This is a permissible practice thanks to the current donor population in the USA, but increased donor age coupled with demands for high endothelial cell densities may stress the donor pool as interest in DMEK grows.

At Lions VisionGift, we have not seen any evidence to suggest that older donors will perform inferiorly to younger donors in the long term. At our institute, the upper donor age limit is routinely set at 75. There are reports from other centers of using much older donors, especially in Europe, as reported by Schlötzer-Schrehardt et al., where the upper age of a series of 350 grafts was 95 [16]. Minimizing surgical manipulation may supplant any small long-term benefits seen in the CDS from younger donors.

Not all EDMs behave the same. Some EDMs peel readily and almost easily, whereas others are so brittle that they break into pieces with minimal force. What causes these differences? Schlötzer-Schrehardt et al. postulate that it is the ultrastructure of the membrane itself that “complicates or prevents proper DM stripping, irrespective of any surgical experience and skills.” Evidence of “peg-like interlockings between DM and stroma” from electron microscopy of failed tissue preparations supports this theory [16].

Whatever the cause may be, there are corneas that eye banks should ideally exclude from the DMEK donor pool to avoid peeling EDMs that are at high risk of preparation failure. While we cannot unequivocally identify these corneas for exclusion from the donor pool, collaborative research efforts have revealed important risk factors to consider.

In a landmark eye banking study by the University of Iowa and Iowa Lions Eye Bank, Greiner et al. recently published data showing that corneas with a history of diabetes mellitus are more difficult to peel and more likely to result in preparation failure. Compared to nondiabetic (1.9 %) donors, diabetic (15.3 %) donors had a startlingly higher frequency of preparation failure [8], suggesting that avoiding such donors could increase the likelihood of preparation success. Vianna et al. performed a comprehensive analysis of a large number of DMEK tissue preparations from Lions VisionGift and confirmed Greiner et al.’s findings [21]. This work also found correlates between preparation failure and the duration of diabetes, obesity, hypercholesterolemia, and hypertension.

As DMEK grows in popularity, it may be too limiting to exclude all diabetic donors from the donor pool. In light of the high prevalence of diabetes mellitus and its wide spectrum of severity in the population, we have developed a novel tool for risk-stratifying diabetic donors by the severity of their disease, as described in Table 6.1. We retrospectively applied this rating to 125 consecutive donors (only the first eye peeled was included in the analysis) and found that donors with a rating of 3 or lower on our scale were less likely to fail than those rated 4 or 5. Use of this scale has been successfully employed at Lions VisionGift since December of 2014 to help us better utilize our tissue pool.

Another important selection criterion to consider is the lens status of the donor (i.e., pseudophakic vs. phakic), especially in light of the older age demographic of DMEK donors. Recovering corneas from pseudophakic eyes is a routine practice of our eye bank, but in the setting of DMEK, the corneal incisions from cataract surgery limit the graft size by requiring the technician to peel the EDM central to scars.

We have developed a guide to aid tissue evaluation so that grafts that cannot yield an adequate graft size are excluded from the DMEK donor pool, and those that yield a marginal graft size can be avoided, when possible. This guide is illustrated in Fig. 6.3. The guide is used in conjunction with our chosen preparation technique that leaves a peripheral hinge of attached DM. This peripheral DM “hinge” keeps the graft anatomically oriented for post-preparation evaluation, transportation to the operating room, and surgical trephination. The guide is still instructive if other methods or preparation are employed but would require modification.

Laser refractive surgery such as LASIK and PRK are an exclusion for PK and ALKP [5]; however these tissues are acceptable for EK [15] so long as the endothelium is in acceptable condition. Radial keratotomy (RK) must be evaluated on a case-by-case basis due to the depth of scars associated with the procedure, but it is generally acceptable. Deep, adherent scars that raise the risk of tearing the EDM and full-thickness scars should be avoided.

Corneas with EDMs that are difficult to peel usually come in mated pairs. This observation reflects our own experience and has been corroborated by others [7, 18].

It is important to “listen to the tissue.” If the first cornea of a mated pair proves difficult to peel or even tears and fails, it is important to understand why. When the failure is determined to be due to properties inherent in the tissue and not a processor error, do not peel the mate with the hopeful wish that the second tissue will be different. It is better to reallocate these corneas into the donor pools for penetrating keratoplasty and DSAEK, where they are unlikely to present any impediments to tissue preparation.

Figure 6.4 illustrates our screening process, which excludes most corneas that have been recovered with the intent for transplant from the DMEK donor pool. On average, the DMEK donor pool is only 40 % of the total pool, which is a stark reality.

Reliably narrowing the donor pool down to a cohort suitable for DMEK requires a significant number of man-hours. The paired nature of DMEK failures also requires a degree of flexibility and cooperation among the staff that is unique to a DMEK program. When a tissue preparation fails, for example, it triggers a domino effect of responses across our departments to prevent a second failure and to assure that the surgeon still receives a graft as promised.

A team approach to tissue selection, preparation, and distribution is indispensable to preventing tissue loss in a DMEK program. Every department in our organization plays a critical role in implementing the donor and tissue parameters that we employ to meet surgeons’ requests and to increase the likelihood of successful tissue processing. Table 6.2 summarizes these parameters.