The first step of DMEK surgery is DM graft preparation [9]. One of the most concerning reasons in graft preparation is graft loss, whereas recent studies have reported successful outcomes with partially implanted grafts [11–13]. The most common cause of graft loss is the tears on the graft due to the tight adhesions or increased fragility of the graft [14]. Although the procedure seems to be standardized, the peripheral tears in DM graft remain a potential risk. While small tears may be salvageable, an extra graft must be reserved in case of a large tear [15].
The differences in histochemical properties of the DM graft and the thickness of the graft may cause a change in the resistance at the peeling stage of the preparation step. The systemic diseases and drugs of the donor may also affect the elasticity and resistance of the tissue. The structural stress of the tissue increases due to the differences in adhesions between tissues. There is a narrow transition zone that includes an amorphous extracellular matrix, called interfacial matrix, between the DM and the stroma. Extracellular matrix and adhesive proteins, such as fibronectin, vitronectin, amyloid P, osteonectin/SPARC, fibrillin-1, fibulin-1 ve fibulin-3, keratoepithelin, collagen type VI, and VIII are found immunohistochemically in this zone [16, 17]. DM graft tears during peeling may be a result of these adhesive properties of the interfacial matrix. During DM graft preparation, adhesions between posterior stroma and DM may resolve spontaneously or result in DM tears if the tractional forces exceed the tensile adhesive strength [18]. The structural and biochemical differences between donors may cause the different adhesive forces between posterior stroma and DM [17].
Failure in DM graft preparation has been reported between 4.2–6.7% [8, 19–21]. The most commonly used technique in graft preparation is the SCUBA technique, in which the success rate has been reported over 95% [20, 22]. In this study, only the SCUBA technique is used to prepare the DM grafts. To eliminate the intersurgeon differences, the DM grafts were prepared by only one experienced surgeon. The first 200 cases of the surgeon were not included in the study to exclude the learning curve of the surgeon. As we know that with younger donors, the adhesive forces and the possibility of tears are higher, donors younger than 40 years old were also not included [23]. No age or gender-related factor was found to affect the failure rate of graft preparation in this study.
As far as we know, no investigation between blood type and DM tears was made. In this study, the highest rate of DM tears was found in donors with a blood type of A Rh+, but no statistically significant difference was found. This finding may be due to the higher rates of A Rh + blood type in our population.
Previous studies have shown that diabetes, hyperlipidemia, obesity, and chronic renal failure in the donors cause failure in preparation of the DM graft [19, 24]. It has been suggested that in diabetes, the tight adhesions between posterior stroma and DM may be the cause of DM tears [24]. In our study, no statistically significant difference was found in the rate of diabetes between groups. All the DM grafts from diabetic donors, whether intact or with tears were used in the surgery and no complications occurred. Moreover, no significant effect of the use of insulin and oral antidiabetic in donors was found on DM tears. In a study by Tien-en Tan et al., it has been shown 4.7% of failure in DM graft preparation and no effect of diabetes on DM tears. Thus, it is thought that not only metabolic diseases, such as diabetes but multiple structural differences may be related to the occurrence of DM tears while graft preparation [25].
It has been reported that systemic diseases, cause of death, and age of the donor may have a role in the failure of DM graft preparation [19, 26]. Among systemic diseases of donors, only the rate of breast cancer was found to be significantly higher in group 1. Increased inflammatory response, vascular endothelial dysfunction, increased vascular endothelial growth factor response, and increased oxidative stress are parts of the pathophysiological process of breast cancer [27, 28]. Thus, the increased oxidative stress may be the cause of the dysfunction of the DM-endothelium complex of the graft and leads to the failure of DM graft preparation.
When systemic drugs that were used more than 1 year were analyzed, only sevelamer use was found to be more common in group 1. Sevelamer is indicated in the control of hyperphosphatemia in patients on hemodialysis or periton dialysis. It is unclear, whether the use of sevelamer itself or the indication, hyperphosphatemia, is responsible for this finding.
While no statistically significant differences were found in anemia or liver function tests between groups, renal function tests (BUN, creatinine) were found to be more common in group 1. The level of urea in the aqueous humor has been shown to increase with increased urea levels in the serum [29]. The design of this study is not suitable to understand the effects of increased blood urea and creatinine levels on DM/endothelium complex so further studies are needed to reveal the pathophysiology.
The limitations of our study are its retrospective nature and the lack of a control group that includes naive donors without any systemic disease or use of any drug. However, it is almost impossible to find enough healthy donors in relatively old age within the criteria of donor bank to form a control group.
In conclusion, most of the death in elderly occurs with individuals with systemic diseases. On the other hand, the need for donor corneas for the patients in transplant lists is exponentially increasing. Therefore, to provide this shortage it would be effective to use all the available donors for transplant. Although diabetic donors have been reported to be inappropriate candidates for the preparation of DM grafts for DMEK, most of the corneas of the donors with several systemic diseases including diabetes can be used in DMEK surgery with the right technique in DM graft preparation.