Historically, the principle indication for undertaking corneal transplantation for endothelial diseases in Singapore (with a predominance of Chinese (73 %) followed by Malay (12 %) and Indian patients (11 %)) over a 15-year period (1991–2006) was pseudophakic bullous keratopathy (PBK) (23 %) with only 7.1 % accounted for by Fuchs’ endothelial dystrophy (FED) and 12.4 % regrafting procedures [19, 63]. More recent data from the Singapore Corneal Transplant Study has indicated that the rate of PBK is proportionally even higher, up to 34 % [60].

In other countries outside of Asia, a similar high proportion of grafts were historically undertaken for PBK (25 %) in Australia with 7 % for dystrophies and 18 % regrafts [71]. These figures were mirrored from a German data from the same period with 9.5 % of grafts being undertaken for FED, 33 % for PBK and 22 % regrafts between 1996 and 2000 in Berlin [15]. Twenty-six to twenty-eight percent of keratoplasties in the Wills Eye Hospital between 1989 and 2005 were also undertaken for PBK, and 10.8–15.77 % were for FED and 17.8–22 % were regrafts [32]. A large, single centre US data also showed that PBK previously accounted for more corneal transplantation (PK) than FED (32.1 % vs. 23 %, respectively) in the Midwestern United States between 1982 and 1996 [27]. The Swedish registry revealed FED as an indication for PK in 15 % and PBK in 22 % [23]. In the United Kingdom (UK), by contrast, between 1990 and 1999 in a single, large centre study, revealed a smaller proportion of patients who underwent corneal transplantation for PBK (7.6 %), 9.3 % for FED but a remarkably higher percentage were regrafts (40.3 %) [1]. Interestingly of the high proportion of regrafts, 58.3 % were for endothelial failure or rejection. For the following decade (1999–2009), in the UK as a whole the proportion of grafts undertaken for FED continued to increase from 17.3 to 22.3 %, while the number of grafts for PBK remained stable at 14 %, while the proportion of regrafts increased from 11.9 to 16 % during the same period [35]. Similarly, the US data highlights a shift in the indication for the transplantation from PBK to FED during the last decade (as high as 80% for FED in some centres) [22, 24, 52], which is discussed further in this chapter and elsewhere (See Chap. 6).

There are other unique challenges in Asia including viral causes of endothelial failure such as cytomegalovirus (CMV) endotheliitis [20, 41]. Not only is an infectious aetiology unusual as a primary cause of endothelial failure but also presents challenges in differentiating episodes of reactivation from conventional rejection and indeed rejection as a result of reactivation of CMV.

Endothelial dysfunction has been managed historically by undertaking PK. The 5-year graft survival rates in Singapore with this procedure up to 2006 were 58.6, 50.1 and 18.3 % for FED, PBK and regrafts, respectively [63]. This represented an overall (including all indications for transplant) 5-year graft survival of 63.7 %, lower than the commensurate Australian registry data at 72 % and UK at 82 % [55, 71]. It is important to note that the success of transplantation internationally for PBK is lower, and this is reflected in the higher proportion of these cases in Asia.

The time period that these data pertain to also overlap with a paradigm shift in how corneal transplant was approached for endothelial disease. The details of the evolution from full thickness to selective endothelial transplantation are covered extensively in Chapters 6. Briefly however, the potential for undertaking a partial-thickness graft offered greater mechanical stability, a reduction in postoperative astigmatism, a theoretical reduction in antigen load and therefore a reduction in graft rejection and a faster postoperative recovery. The challenge represented by EK was on safe and reliable insertion of the graft material without a large incision. If one considers the analogy of a mechanical puzzle, the issue is akin to how one might go about the seemingly impossible task of successfully placing a model ship into a glass bottle, but without damaging it. This conundrum of course is exaggerated in the context of (i) smaller anatomical anterior chambers and (ii) a higher rate of more challenging pathology including PBK in Asia.

At the turn of the millennium, two broad approaches were conceived: the anterior ‘endokeratoplasty’ approach described by Busin and the posterior approach described by Melles [16, 45]. The latter gained popularity because it offered the advantage of a closed technique and evolved to become a Descemet stripping endothelial keratoplasty (DSEK), and with the assistance of a microkeratome (or latterly by femtosecond laser), a Descemet stripping automated endothelial keratoplasty (DSAEK). The term DSAEK is almost universally synonymous with endothelial keratoplasty as we understand it. Further iterations including ultrathin DSAEK, pre-Descemet’s endothelial keratoplasty (PDEK) or indeed Descemet’s membrane endothelial keratoplasty (DMEK) have facilitated progressively thinner grafts, and with them increasing technical challenges in the way surgeons can safely insert the corneal tissue and simultaneously maintain endothelial cell counts (ECCs). A full appraisal of these issues is beyond the scope of this chapter and is discussed elsewhere in this book.

The advent and uptake of DSAEK are reflected in a significant change in global trends in corneal transplantation generally and indeed the indications for transplantation itself. In the USA, the rate of uptake from EK rose exponentially from 3.2 to 49.7 % of all grafts between 2005 and 2014 with a corresponding drop in rates of PK from 94.9 to 41.5 % [49]. A marked shift in the indications for surgery reflected a change in the disease profile as discussed, with PBK and FED accounting for 17.8 and 47.7 %, respectively, of EK surgery by 2014. A similar increase has been observed in large series in the USA, the UK and Australia [24, 25, 33, 35, 49, 60].

These changes have also been reflected in other Asian countries, including India but with a preponderance of EKs being undertaken for bullous keratopathy (47.9 %) compared to Fuchs’ endothelial corneal dystrophy (10.8 %) and regrafting (20.0 %) [47]. The high incidence of BK and the anatomical differences from Western populations already discussed highlight a particular challenge encountered in Singapore when switching from PK. This transition including the problems encountered and the steps to overcome them will be discussed in the rest of this chapter.