In 1998 Melles and colleagues introduced the first successful approach for posterior lamellar keratoplasty (PLK) in humans, in which an unsutured donor posterior corneal disk, consisting of posterior stroma, Descemet membrane, and endothelium, was transplanted into the anterior chamber through a limbal incision [13, 14]. In 2001, this technique was popularized as “deep lamellar endothelial keratoplasty” (DLEK) in the United States by Terry et al. [15]. In the initial PLK/DLEK technique, a posterior lamellar disk was dissected from the recipient cornea through a 9-mm sclerocorneal incision. Then, an equally sized donor disk was introduced into the recipient anterior chamber and placed against the recipient posterior cornea secured only by an air bubble, while the patient had to remain in a supine position [16]. Along with the trend of minimally invasive surgery, in the year 2000, Melles et al. improved the technique in terms of creating a smaller self-sealing 5-mm tunnel incision through which the donor (endothelium, Descemet membrane, and a layer of stroma) was inserted, while being folded like a “taco” and then unfolded inside the recipient anterior chamber [17]. The modification was popularized as “small incision” DLEK [18]. Even though this new technique soon proved to provide clinical outcomes surpassing PK and diminishing many PK-associated complications [19], [20] the technique was still challenging regarding donor and host tissue manual dissection, making it difficult to be adopted by corneal surgeons worldwide.

To simplify the concept of endothelial keratoplasty, in 2002 Melles et al. introduced a technique that facilitated selective removal (“stripping”) of the host diseased corneal Descemet membrane with its endothelium using a reversed Sinskey hook. This step, known as “descemetorhexis,” was followed by the insertion of a “taco-folded” posterior lamellar disk, similar to that used in PLK/DLEK, that is then positioned onto the denuded host posterior stroma [21]. This technique was later popularized as “Descemet stripping endothelial keratoplasty” (DSEK) by Price and colleagues [22, 23].

In order to facilitate donor preparation, Gorovoy and colleagues introduced an automated microkeratome that enabled standardized dissection of a donor posterior lamella from a corneoscleral button mounted on an artificial anterior chamber; to differentiate this technique from manually dissected tissue, this procedure was termed “Descemet stripping automated endothelial keratoplasty” (DSAEK) [24].

Facilitating donor tissue preparation by using a microkeratome enabled also eye banks to provide precut donor tissue which made this refined endothelial keratoplasty technique rapidly accessible to ophthalmic surgeons worldwide.

These reproducible novel endothelial keratoplasty techniques had evident advantages over conventional PK. Besides better functional outcomes with faster visual recovery, many PK-associated complications could be reduced: First, the intraoperative risk for bleeding or infections was considerably lessened due to the “closed” globe compared to the “open globe surgery” in PK. Second, these suture-free techniques eliminated suture-related complications, preserved the anterior corneal surface, and hereby avoided unpredictable postoperative refractive errors. Third, the lack of a large penetrating wound reduced corneal denervation and provided a tectonically stronger globe with reduced risk of angiogenetic ingrowth or traumatic wound dehiscence. Finally, and most strikingly, also the risk of allograft rejection was minimized [25, 26]. These hard facts together with the techniques’ high accessibility played a key role in the remarkable increase of DSEK/DSAEK procedures in the following years and its implementation as the new “gold standard” for the treatment of endothelial pathologies.

But “where there is light, there must also be shadow” and the main “shadows,” thus drawbacks of the DSEK/DSAEK techniques were that donor tissue preparation was costly, and visual acuity could vary and remain suboptimal despite technically successful surgery owing to thickness irregularities of the donor posterior stroma or stromal interface haze causing optical aberrations [27]. The visual limitation due to graft thickness irregularities was addressed by Busin et al. when introducing so-called “ultrathin DSAEK” grafts, which provided better clinical results than standard DSAEK but still required a costly microkeratome for graft preparation [28].

In 1998, Melles and colleagues also introduced the next refinement of endothelial keratoplasty that eliminated the posterior stroma from the donor graft entirely and hereby allowed selective replacement of an autologous Descemet membrane and endothelium [29]. This modified technique was named “Descemet membrane endothelial keratoplasty” (DMEK). After the first DMEK surgeries that were performed in 2006, it soon became evident that the near anatomic restoration of the corneal anatomy provided unprecedented visual outcomes [12,30–32] and an even lower risk of endothelial immune reaction [33, 34]. Another major advantage of DMEK over previous techniques was that, after donor preparation, the anterior corneal lamella could be used for “deep anterior lamellar keratoplasty,” permitting more efficient donor tissue use [35], also known as “split cornea transplantation” [36, 37].

Despite these advances, difficulties in tissue preparation, intracameral graft unfolding, and the high incidence of postoperative graft dehiscences were perceived as the main obstacles in DMEK [38].

Soon, standardization and reproducibility of tissue preparation, provision of precut tissue, and standardization of intracameral graft unfolding aided corneal surgeons to take the first steps in DMEK or make the switch from DSEK/DSAEK to DMEK [39–43].

With increasing experience also graft detachment rates could be reduced significantly as reported by different groups worldwide [44–46].

After a decisive phase of endothelial keratoplasty innovations, posterior lamellar techniques seem to have left PK behind, when regarding the treatment of corneal endothelial disease, as in FECD, for which DMEK and DSEK/DSAEK meanwhile have become first-line choices of surgical treatment. Because of the better clinical outcomes, in particular DMEK may permit surgical intervention already at an early stage of the corneal disease.

In addition, growing experience with DMEK allowed to gain a better understanding of endothelial cell biology and physiology, as well as endothelial cell migration. For example, corneal clearance with good clinical outcomes was also observed in denuded stromal areas that were not covered by Descemet membrane and endothelium [47, 48], as observed in eyes with graft detachment or eyes that received variously shaped and sized DMEK grafts after difficult tissue preparation [49].