What does the future hold for the treatment of Fuchs endothelial dystrophy; will ‘keratoplasty’ still be a valid procedure?

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a well recognized corneal disorder characterized by the presence of collagenous warts extending from Descemet membrane (guttae) and endothelial cellular dysfunction due to cell loss and/or degeneration. Because of the characteristic abnormal cell morphology as seen with specular microscopy as well as the limited regenerative capacity in vivo, the endothelial cells were considered to be 'dystrophic'. Hence, FECD is commonly managed by replacement of the endothelium with donor tissue by means of a penetrating or endothelial keratoplasty. The latter procedure has now been refined to the isolated transplantation of a donor Descemet membrane and its endothelium, referred to as Descemet membrane endothelial keratoplasty (DMEK). Unexpectedly, clinical observation made after DMEK seemed to challenge the current concept of the state of the endothelium in FECD; we actually observed an important role for the 'dystrophic' host endothelium in reendothelialization of the denuded DM, and subsequent corneal clearance. In addition, recent studies regarding the pathophysiology of FECD made us realize that the endothelial cells are not 'dystrophic' per se, but in the course of time may have acquired a dysfunction instead. This paper describes the rationale behind this new concept and based on this, discusses the possibilities for future, less invasive treatment modalities for FECD.

A Mathematical Model to Predict Endothelial Cell Density Following Penetrating Keratoplasty With Selective Dropout From Graft Failure

“…This impact of peripheral damage is most prominent in PACE where there is no recipient endothelium to contribute to maintenance of the endothelial population of the graft. However, cell loss is most likely moderated in Fuchs' dystrophy by contribution of the recipient endothelium not affected by the disease, 24 particularly if there is excellent posterior wound apposition between the recipient bed and the donor. The end result observed clinically is profound central endothelial cell loss.…”

“…Given the limited ability for cell division in the donated endothelial population, stabilization in ECD in at least the grafts for Fuchs' dystrophy may be as a result of the contribution of recipient endothelium over the donor bed. 24 Limitations of the previously mentioned analyses on endothelial cell loss are that they do not account for correlated data from repeated measures on the same subject or the selective dropout among subjects with lower ECDs who are more likely to experience graft failure. The latter is particularly important to capture because a model for such cell loss could be biased by the selective loss of eyes with low ECDs.…”

Descemet membrane endothelial transfer

“…The apparent reason for this difference in efficacy may lie in the fact that with bullous keratopathy there may be a significant depletion of host corneal endothelial cells, whereas in Fuchs endothelial dystrophy, the endothelium of the peripheral cornea may be relatively spared. This is especially as Fuchs endothelial dystrophy probably represents a phenotypic continuum with a significant genetic overlap, and in some situations there could be a mosaic of nonaffected and affected cells [18]. Therefore, it appears that both donor and remaining host endothelial cells play a role in the restoration of corneal clarity after DMET.…”

A review of the evidence for in vivo corneal endothelial regeneration

“…In addition to removing the contact inhibition, it is possible that by removing the dysfunctional Descemet membrane and guttae that the physical barriers to cell migration are removed and that the bare corneal stroma is a better substrate for cell migration. 18 Recently, in vitro studies have shown that, when endothelial cells are grown on a patterned scaffold to mimic guttae, the formation of a monolayer is much slower than cells grown on a smoother surface. 85 Similar findings were seen in vivo in 3 patients who underwent descemetorhexis.…”