Opacities from macular corneal dystrophy recur less commonly than in lattice and granular dystrophies [28]. There is however a considerable variation in the literature.

In a cohort of patients operated on in Saudi Arabia with PKP for macular dystrophy (229 eyes in 141 patients) followed for a mean of 5.9 years, clinical significant recurrence was observed in 5.2 % of the grafts [37] (Fig. 9.4).

In two recent reports, a comparison of PKP and DALK for macular corneal dystrophy was analyzed.

The highest recurrence figures were reported in a retrospective study where PKP was performed in 57 eyes and DALK in 21 eyes. Mean follow-up time was 5.1 years. Seventeen percent of PKP-treated eyes showed recurrences and so did 42.9 % of the DALK eyes. The younger the onset of the disease and the younger at surgery, the higher the risk of recurrences [38].

In a randomized trial [31] (54 patients an 82 eyes), recurrence of disease (follow-up 30.5 months) was 4.8 % in the PKP group and 5.7 % in the DALK group. There was less endothelial damage in the DALK group [39].

In a British material, 16 patients who underwent 41 transplants in 31 eyes were followed between 25 and 408 months from the initial diagnosis. Six eyes of four patients were regrafted after recurrence of the disease. Clinical recurrence was observed in two more eyes. It was furthermore assessed that a larger graft showed less recurrence [40].

In a report from Iran 2009, 62 eyes of 39 patients underwent PKP for macular dystrophy and were followed for a mean of 52 months. Only one eye showed a minor recurrence [41].

The same low recurrence figures have been reported from Iceland where macular dystrophy is the most frequent indication for PKP. Both MCD types I and II exist. In none of the grafted patients has signs of recurrences been documented [42, 43].

In a retrospective case series of 115 individuals from 34 families with Schnyder dystrophy, it was found that the crystal component of the corneal changes was observed only in 54 % of the affected individuals.

PKP had been performed in 54 % of patients when older than 50 years and in 77% when older than 70 years. In 8 of 39 eyes that underwent PKP for Schnyder dystrophy, the disease recurred in the graft. There was no repeat surgery for dystrophy recurrence [44, 45].

In 77 eyes (48 patients) with stromal dystrophies, recurrence was most common in Bowman layer corneal dystrophy, Reis-Bücklers, and followed by granular and lattice dystrophies. Both macular dystrophy and Schnyder dystrophy were infrequent, and within the comparatively short follow-up (2–3 years), none had recurrences [46].

Granular corneal dystrophy type 2 or Avellino dystrophy is caused by a mutation in the T6FB T I. Several reports exist on a reactive recurrence following PTK, LASIK, and LASEK. Early recurrence was noted after PTK and LASEK in a homozygous individual [47–49].

Holland et al. examined 27 family members with the disease. Of these, 3 had been grafted previously and two of those showed granular deposits in the grafts. The earliest changes were 9 year post-op. The granular deposits also precede lattice lines in the natural development of the disease [50].

In one material, between 1990 and 1999, 1096 procedures were performed; 784 patient records were available for evaluation. Regrafting was the most common indication, accounting for 40.9 % of all cases [1].

Between 1989 and 1995, 16 % (271 of 1689) of transplants performed in Wills Eye Hospital were regrafts compared with 9 % (165 of 1860) in the period from 1983 to 1988 (P < 0.01) [51].

Of 243 repeat PKP performed in 210 eyes of 208 patients were included in the study. 5.7 % of the repeats were stromal dystrophies (constituting 4.9 % of the cases to begin with). Follow-up was 43 months. The best graft survival was in eyes with an original diagnosis of keratoconus (93.8 %), and the worst was in eyes with Fuchs’ dystrophy (23.1 %). Overall, 29.6 % of eyes achieved a final visual acuity greater than 20/200, while only 4.8 % were 20/40 or better. The best visual prognosis was in eyes with an original diagnosis of stromal dystrophy and keratoconus [52].

150 repeat grafts at the Wills Eye Hospital in 1985–1995 were reviewed. Fuchs’ dystrophy constituted 21 out of the 150 (14 %). Corneal dystrophies constituted 1.7 % of the original indications [53].

Damage to the corneal endothelium or disease in the endothelium results in stromal edema and subsequently epithelial edema and then bullous keratopathy.

By definition, a corneal dystrophy is inherited. Spontaneous cornea guttata, followed by stromal edema and bullous keratopathy, is common, whereas true hereditary bullous keratopathy, or Fuchs’ dystrophy, is fairly uncommon. In one US study 13.6 % had a documented family history [54]. If the many spontaneous cases are caused by gene defects remains to be shown. The present knowledge on the basics of “Fuchs’” dystrophy has recently been reviewed [55].

In most materials corneal edema is subdivided into two groups, postsurgical pseudophakic or aphakic bullous keratopathy and Fuchs’ dystrophy. The latter group contains both hereditary and nonhereditary corneal edema. “Fuchs’ dystrophy” constitutes a substantial part of the indications for corneal transplantation. The figures range between 0.5 and 23.8 %.

In two German materials and one US material, the indication for Fuchs’ dystrophy increases [9, 10, 17] and diminishes in one over time [5].

Fuchs’ dystrophy including what is known about the complicated heredity when present has been recently reviewed. There are at least two subforms, one with early onset starting around 30 years of age and one form with a late onset manifesting at about 60 years. Further genetic analysis is needed to clarify the varying aspects of disease [56]. It is an open question whether “Fuchs’ dystrophy” recurs in the graft in the form of cornea guttata. New knowledge of the dynamics of the endothelium in the graft and host makes genuine recurrence possible [26]. The indication for regraft is generally corneal decompensation.

In a large material of PKP in 3993 eyes, Fuchs’ dystrophy constituted 25 % of the primary surgeries. Graft survival after 5 years was 97 and 90 % after 10 years compared to keratoconus, 97 to 92 % [57].

Repeat penetrating grafts in Fuchs’ patients constituted about 15 % of all repeat grafts. Fuchs’ constituted 15 % of the indication for the first graft. The average time to the repeat grafts was 6.3 years. 7.7 % of the repeat grafts failed. The two main reasons were endothelial failure in eight out of the 21 failed regrafts and rejection in another eight 8 [53].

Fuchs’ dystrophy constituted 3.9 % of indications in a large English material of 3555 cases. The group Fuchs’ dystrophy constitutes 140 of the 329 corneal dystrophies undergoing PKP in 1971–1990 [33]. Repeat PKP for Fuchs’ dystrophy showed a survival rate of 23.1 % after 43 months which is very low compared with eyes with the original diagnosis of keratoconus, 93.8 % [52].

In the Swedish National Cornea Register, the failure rate of the first operation was 15 % within 2 years, compared to 34 % for the regrafts. There was a higher rate of postoperative complications (suture related, glaucoma, etc.) following the regraft, 58 % compared to 34 % following the first graft [58].

The prevalence of Fuchs varies in different countries. Fuchs is rare in countries like Japan, Saudi Arabia, China, and Singapore. In the United States the prevalence is about 4 % [55].

There are very few reports of corneal grafts performed for posterior polymorphous dystrophy. Two cases underwent PKP because of posterior polymorphous dystrophy at the age of 25 and 33 years, respectively. Six months and 18 months post-op, signs of recurrence, faint haze, or a dull appearance at the level of the endothelium were noted. Both eyes had to be regrafted 7 and 9 years after the first surgery [51]. Waring III in his review from 1978 states that no recurrences had been documented in grafts from posterior polymorphous dystrophy [29] (Fig. 9.5). The largest material described consisted of 120 patients. 13 of those were grafted in altogether 22 eyes. 9 of the grafted eyes opacified during the follow up period [59].

DSEK and DMEK are becoming the major grafting techniques for treating endothelial disease or “Fuchs’ dystrophy.” The shift from PKP has been fairly rapid. Prospective randomized studies comparing the old and the new technique have not been published.

Result from the Australian Corneal Graft Registry published in 2014 with a large number of corneal grafts (13,920) makes it possible to compare 858 DALK, 2287 endokeratoplasties with PKPs. The main outcome measure was graft survival. It was concluded that graft survival was worse in both DALKs and endokeratoplasties compared to PKPs over the same time frame. They also state that an evidence for a learning curve is unconvincing [60].

In 2011, in a Cochrane Review [61], the authors concluded that there was no high-quality evidence that endokeratoplasty was superior to PKP. Further randomized controlled trials of visual and refractive outcome need to be performed. A similar conclusion, although stressing the force of numerous published case series, was drawn 2013 in a German review. The authors conclude that Descemet’s membrane endothelial keratoplasty (DMEK) is advantageous over Descemet stripping endothelial keratoplasty (DSEK) which in turn has better results than PKP [62]. The value of data in larger numbers in national registers was discussed in detail in a recently published editorial. These data also reflect the level of quality of care that is reached in the medical community in general [63]. Of 396 DSEK procedures, 20 failed, 40 % due to primary endothelial failure, 40 % due to progressive endothelial failure, and 20 % due to endothelial rejection. Repeat DSEK was performed on average 13 months after the first operation. The follow-up from repeat surgery was 27 months. The visual acuity outcome was satisfactory [64].

In 44 eyes with macular corneal dystrophy, 18 eyes with lattice dystrophy, and 12 eyes with granular dystrophy, DALK was completed in 69 cases (94.6 %). The mean follow-up period was 43.5 ± 23.9 months. Postoperative best spectacle-corrected visual acuity of 0.5 or better was present in 52 of 69 eyes (75.4 %). Lattice dystrophy recurred in 6 eyes (35.3 %) [36].

In his commentary from 1998, Larkin concludes that oral antiviral prophylaxis for 1 year following PKP for HSK, accompanied by topical steroids, is a reasonable strategy [112].

This is confirmed in subsequent studies [113–117]. Oral antiviral therapy and postoperative steroids, furthermore, help in preventing relapse of neovascularization [118].

Herpes simplex virus keratitis is reported to be more common in patients with atopic disease [119, 120] (Fig. 9.8).

When comparing the outcome of PKP for HSK, it was shown that nonatopics had significantly more epithelial recurrences, although in general the incidences of recurrences were low and high graft survival numbers were reported [119]. Antiviral prophylaxis for HSV recurrences was proven more effective in reducing infections in atopics and less effective in reducing inflammatory episodes in atopics versus nonatopics. A recurrence of herpetic disease following PKP for HSK is likely to originate from the host, either via nerves from the trigeminal ganglion or from latency in the remaining host epithelium [121].