In PK a full-thickness cornea with clear stroma and viable endothelium is transplanted. There are several variations upon the surgical technique, but clinical outcomes are generally comparable [32].

Although successful in many cases, PK has several disadvantages. The surgery causes significant structural changes in the cornea and causes the cornea to be permanently weakened. Thus, even years after surgery, minor blunt trauma may lead to devastating wound dehiscence and globe rupture.

Due to the slow corneal wound healing, sutures have to remain in place for at least 1 year after PK. Although, optical properties tend to stabilize during this period, large refractive changes may occur after suture removal [49, 59, 103]. Thus, visual recovery after PK is slow and typically extends for 1.5–2 years after surgery, since unexpected postoperative ametropia or high astigmatism may require further surgical interventions. In a large registry study of more than 1100 eyes, an average astigmatism of 4.56 dioptres was reported [21]. Various attempts have been made to try to control the postoperative refractive outcome, including suture adjustments or selective removal of single sutures in the postoperative period. However, in most reports, the effect of these approaches is limited and with considerable variation [29, 31, 42, 110]. In addition, suture regularity has been found to have only little influence on the postoperative astigmatism [45].

New technological developments such as femtosecond laser (FS) penetrating keratoplasty allow precise and identical cuts to be made in donor and recipient. FS laser penetrating keratoplasty allows sutures to be removed earlier than after PK. However, FS laser-based approaches were hoped to improve the postoperative refractive outcome, but has so far disappointed. Thus, in several studies, the average astigmatism after FS laser PK is reported to be of the same magnitude or only marginally better than that of conventional surgery [13, 34].

In most cases, the unpredictable refractive outcome after PK can be relieved with glasses or rigid contact lenses; however, additional surgical interventions may be needed including arcuate keratotomy or laser keratorefractive surgery [58, 117]. In some patients, development of cataract may allow postoperative ametropia to be corrected during subsequent cataract surgery.

Immunological rejection is a major complication after penetrating keratoplasty. In most cases the immunological response is raised towards the endothelial cells leading to acute cell loss and imminent graft failure. The patient typically complains of slight ocular irritation or inflammation and reduced visual acuity and clinically presents with endothelial precipitates, sometimes in a Khodadoust line, and overlying stromal oedema [51]. If the condition is treated promptly, the inflammation may be controlled leading to gradual resolution. However, untreated or late-treated endothelial rejection will eventually lead to failure of the graft. An immunological response towards stromal cells is much more rare but should also be aggressively treated, since an untreated stromal rejection may lead to clouding of the graft [75]. The risk of endothelial rejection after PK varies with the pathology that led to corneal transplantation [25]. In keratoconus patients, the risk of endothelial rejection is reported from 5.8 to 6.8 % within the first 5 years [3, 20], whereas in high-risk corneas (Table. 17.1), the risk of rejection may be more than 50 % [2]. In a recent graft registry study, the 10-year graft survival was reported to be 89 % in keratoconus patients, 73 % in patients with endothelial dystrophy, 66 % in corneal scars, 59 % in herpetic scars, 42 % in secondary endothelial failure and 37 % in regrafts [118]. Thus, in patients with one or more risk factors, the indication for PK should be carefully considered, and the expected outcome thoroughly discussed with the patient.

Over the last years, it has been recognized that penetrating keratoplasty is followed by an accelerated loss of endothelial cells that fits a bi-exponential decay [9]. Thus, an initial rapid loss during the first approximately 4 years is followed by a slower but abnormal cell loss. Since endothelial cells are required to maintain corneal hydration and clarity, the accelerated loss of cells eventually leads to graft failure. The underlying pathology that led to keratoplasty, however, influences the rate of late endothelial changes. Thus, one study found that patients with bullous keratopathy or herpetic uveitis had a higher cell loss than patients with keratoconus [61]. In another study, the incidence of endothelial failure 15 years after PK was 8 % in keratoconus patients and 33 % in patients with bullous keratopathy [12], and it was hypothesized that a reservoir of viable endothelial cells in the recipient cornea reduce the overall cell loss, thus explaining the better outcome in patients without underlying endothelial pathology.

As detailed above, two of the major reasons for graft failure after PK are loss of endothelial cells and risk of endothelial rejection [2, 9, 12]. Thus, it makes sense to conserve the endothelial cell layer in patients with isolated stromal conditions such as scars, stromal dystrophies or ectatic disease. Depending on the extent of the stromal changes and the employed equipment, different types of ALK can be performed.

In patients with endothelial failure due to Fuchs dystrophy or secondary bullous keratopathy, endothelial keratoplasty as either DSAEK or DMEK is the obvious surgical approach. The refractive outcome is generally excellent in both procedures, although a minor hypermetropic shift may occur [48]. However, DMEK usually offers better visual acuity than DSAEK, as well as a lower rejection rate, but the surgery is more complicated and with higher risk of perioperative tissue loss and postoperative graft detachment. Thus, local organization and tissue availability may make DSAEK the preferred approach. Furthermore, DMEK is usually not recommended in patients with anterior segment abnormalities, whereas DSAEK may be attempted in these cases.

Both DMEK and DSAEK can be performed as triple procedures with concurrent cataract surgery. However, in patients with limited changes due to endothelial dystrophy, it may be appropriate to do cataract surgery alone and postpone keratoplasty [109].

Before keratoplasty is considered in patients with keratoconus, an attempt to correct the refraction with rigid, gas-permeable contact lenses should have been performed.

Other surgical interventions including implantation of intrastromal corneal ring segments should also have been considered [23]. However, if these approaches are found insufficient to help the patient, keratoplasty may be attempted.

During recent years, there has been a gradual shift in the preferred treatment of keratoconus at some institutions. Where PK used to be the preferred procedure of many surgeons, the use of DALK is gradually becoming more widespread. The main complication of both procedures is an unpredictable refractive outcome; yet, the best-corrected visual acuity is usually good. DALK offers the advantage of eliminating the risk of endothelial rejection; however, graft survival after PK in keratoconus is usually excellent, and a 10-year survival of 89 % has been reported [118]. Two recent studies found similar long-term graft survival after DALK or PK in keratoconus patients, with marginally better visual outcome after PK, but fewer postoperative complications after DALK [65, 122]. In this context, both procedures may still be considered as acceptable approaches when keratoplasty is needed in keratoconus patients.

Keratoplasty for stromal dystrophies other than keratoconus constitute only a fraction of the total number of corneal transplantations. The surgical approach to stromal dystrophies varies according to the location of the stromal changes. In patients with predominantly superficial changes such as early granular dystrophy, treatment with excimer laser photoablation or superficial ALK may be performed. With deeper stromal changes, DALK or PK may be considered. Overall, the outcome of transplantation in stromal dystrophies is good with respect to the risk of rejection episodes. Unfortunately, several dystrophies show a high tendency towards recurrence, which severely may limit the outcome after transplantation, as detailed elsewhere in this book. Thus, knowledge of the tendency towards recurrence of the various dystrophies is of high importance in order to decide whether keratoplasty should be performed.

Scars after infectious keratitis or corneal trauma may vary considerably in their extent. Furthermore, stromal scars tend to diminish over time due to slow corneal remodelling, why keratoplasty eventually may not be needed [67]. Thus, in most cases the surgeon should wait for several months, before surgery is considered. The specific surgical approach may be varied according to the depth of the stromal changes. In very superficial scars, excimer laser photoablation may be attempted or superficial ALK considered. With deeper scarring, DALK or PK may be preferred, but in patients with previous corneal perforation, DALK is unlikely to succeed.

A 10-year graft survival of 66 % has been reported after PK in patients with stromal scars, whereas only 47 % of grafts after traumatic injury were clear after 10 years [118]. In one report of DALK for infectious scars or trauma, a six-month graft survival of 94 % was reported [112]; unfortunately long-term studies are lacking.

It should be noted that stromal scars due to infection or trauma represent a very diverse group due to varying degree of accompanying risk factors. In many patients with stromal scarring, vascularization or glaucoma may be present, which will negatively affect the outcome of subsequent keratoplasty. Thus, in each case, the presence of risk factors should be noted and incorporated into the preoperative assessment.

Stromal scarring secondary to herpetic eye disease may lead to severely compromised visual acuity and photophobia. However, performing a keratoplasty in herpetic eye disease may represent a significant challenge. First, vascularization of the stroma is often present which increases the risk of graft rejection significantly. Furthermore, even if the underlying infection has been quiet for years, the surgical insult and the subsequent steroid treatment may lead to herpetic recurrence [26, 63]. Viral reactivation will also lead to accompanying inflammation within the eye, further increasing the risk of a rejection episode [46, 102]. To reduce the possibility of viral reactivation, prophylactic antiviral medication should be administered for a long time after surgery [10, 33, 111]. Overall, there is considerable risk of graft failure, but with prophylaxis, a 2-year failure rate of 14 % was reported as compared to 56 % in patients with no prophylactic treatment [10]. Since the endothelium may be assumed to be unaffected in most patients, DALK may reduce the risk of a rejection episode and was recently reported to have better postoperative outcome than PK [119], whereas another study reported of a high percentage of postoperative complications including rejection and graft failure [64]. Thus, both PK and DALK may be attempted, but the indication for performing keratoplasty in patients with herpetic eye disease should be carefully considered, and the patient thoroughly informed about the potential outcome of the surgery.