Discussion
In contrast to previous histological studies exploring recurrent KCN,17 18 22–25 27 29 30 this study is a masked pathological analysis that compares KCN findings in repeat grafts with those from cases of primary KCN and with those from cases of failed-PK-non-KCN grafts. Breaks and gaps of Bowman’s layer are common findings in corneas with KCN.11–16 In a histological report of KCN, breaks were reported in 92% of corneas.31 Similarly, this study reported breaks in 91% of primary KCN tissues. Moreover, corneas that underwent repeat grafting for KCN were histologically indistinguishable from native corneas with KCN. Breaks and gaps in Bowman’s layer were only occasionally present in the failed-PK-non-KCN group.
Histological evidence of recurrence of KCN after corneal transplant was first described in 1980. They observed gaps in Bowman’s layer during routine histopathologic evaluation.17 Since that report, other cases were described in the literature in both traditional PK18–23 25–28 and lamellar DALK29 procedures. The presence of the pathological reappearance of KCN after a long latency period has also been described.19 20 27 Six patients who had a PK for KCN for at least 10 years underwent a repeat PK, and on unmasked histological analysis, all six corneas had breaks and losses in Bowman’s layer consistent with KCN.30
Based on the literature, recurrence of KCN in a graft is considered to be rare and occurs many years after the transplant. In this study, losses and breaks in Bowman’s layer were seen as early as 4 months postoperatively where the average years of all the grafts in the study were explanted 9 years post-transplant. Interestingly, almost 50% of the grafts in the failed-PK-KCN group in this study had breaks in Bowman’s layer within 5 years of transplantation. This suggests that breaks and gaps in Bowman’s layer occur more rapidly than generally thought in grafts with a history of KCN.
There were two specimens in the failed-PK-KCN group that did not have breaks or losses in Bowman’s layer. One of the specimens was from a DALK transplant that was 3 years post-transplant and was regrafted because of a vision-limiting opacity. The other specimen was also regrafted because of an opacity and the graft was 10 years post-transplant. Breaks and gaps in Bowman’s layer may have been detected if more than three specimens were examined; however, in this study, the histologists were masked and only three specimens were selected for each subject.
In the failed-PK-non-KCN group, three excised grafted tissues also showed breaks and losses in Bowman’s layer. Two of the subjects had a history of PBK and one had Fuchs’ dystrophy. There was no history of KCN in any of the subjects in the failed-PK-non-KCN groups. In the three specimens that demonstrated breaks and gaps in Bowman’s layer, a possible but unlikely explanation is that the donor buttons may have had KCN. In PBK, it has been reported that minor disruptions in Bowman’s layer have been shown as a result of deposition of fibrocellular material.32 In Fuchs’ dystrophy, Bowman’s layer changes with confocal microscopy in eight of 17 eyes has been reproted.33 The disruptions in Bowman’s layer may result from subepithelial fibrosis due to long-standing oedema from both PBK and Fuchs in the three cases in this study. A limitation of this study was that the age of grafted donor tissue was not reported. The effect that donor age had on the presence of breaks in Bowman’s membrane was unable to be determined. Another limitation of this study was that the controls could not be age matched because KCN presented at a younger age than the Fuchs’ dystrophy and PBK cases included in this study. However, it has been reported that keratometric changes after PK occur more commonly in eyes with KCN than in eyes with Fuchs’ dystrophy,34 and the incidence of the recurrence has been reported to be 6%–11% in eyes with KCN based on clinical presentation, histopathology and keratometric changes.35 Yoshida et al defined recurrence of KCN as either acute hydrops or visible whole/inferior graft protrusion and thinning observed clinically. Using these criteria, they identified 36% of 18 grafts within 10 years of PK had recurrent KCN.30 Despite the small sample size, 86% of cases in the failed-PK-KCN group demonstrated histological findings indicative of KCN in the graft itself. Nearly half of these cases demonstrated breaks in Bowman’s layer within 5 years of transplantation.
This pathological study only evaluated the central excised tissue, which did not include the graft–host junction. While it has been stated that ectatic changes are a result of thinning of the host tissue near the junction,34–38 our results indicate that histopathological findings of KCN are present within the graft itself and occur sooner after surgery than previously reported. It has been noted that the peripheral host cornea becomes thinner following keratoplasty, and that the interface between the thicker donor tissue and thinner host corneal tissue at the graft host junction could contribute to steepening and protrusion of the corneal graft.38 Another limitation of this study is that pathological examination was performed on the central 7–8 mm of excised tissue, which was the donor tissue; the peripheral host tissue was not excised nor was it examined pathologically. Therefore, the relationship between thinning of the peripheral host tissue and the presence of breaks in Bowman’s membrane of the donor tissue cannot be established from this study. Future research could determine if there is a correlation between pathological evidence of KCN and keratometric findings.
The mechanism that underlies the possible recurrence of KCN is unclear. It was theorised that keratocytes of the donor tissue were replaced by host keratocytes.17 These cells may produce aberrant collagen found in KCN eyes. The global panellists that convened to reach a consensus on the definition, diagnosis and management, including surgical and non-surgical treatments for KCN, did not state that there was a primary pathophysiologic cause of KCN. Instead, they agreed that KCN development included environmental, genetic, biomechanical and biochemical contributions.39 While not common, acute hydrops in grafted patients with recurrent KCN has been reported.26 28 30 40 No specimens in the failed-PK-KCN group had hydrops.
It is important to recognise early signs of recurrence of KCN, or ectasia in a grafted patient. In this study, only one subject was regrafted due to ectasia. Ectasia in a PK can be challenging to correct. Corneal steepening from ectasia may induce a myopic shift and increase irregular astigmatism. Contact lens visual rehabilitation is the least invasive treatment for ectasia; it can help improve the vision of these patients. However, some patients undergo PK as an alternative to contact lens correction or are intolerant to contact lenses. Surgical options include compressive sutures, arcuate keratotomy, wedge resection, toric intraocular lens implantation, lamellar keratoplasty, DALK overlay, microkeratome assisted anterior lamellar keratoplasty and repeat PK.41 Based on the findings of this study, histopathologic signs consistent with recurrence of KCN may be more common and occur earlier than previously thought.