In the post-operative period of some cases of Descemet-endothelial keratoplasty (DEK or DMEK) we observed dehydration and recovery of corneal transparency even when the endothelial graft was completely detached¹. From this, we developed a new surgical concept, which was presented at the NIIOS Institute in Rotterdam in 2012: the transfer of endothelium from the Descemet’s membrane (DMET)². The DMET represents a step forward from the DEK; it consists on the implantation of a Descemet’s and endothelium roll that is for the most part "floating" freely in the anterior chamber (AC), only adhering to the posterior face of the cornea at the incision.

SURGICAL TECHNIQUE

Briefly, DMET is a simplified version of DEK surgery. As in this one, 3 paracenteses, a 9 mm descemetorhexis with a reverse Sinskey’s hook (D.O.R.C. International, Zuidland, The Netherlands), and a tunneled incision of 3.0 mm in the limbus for graft insertion are performed. The graft should be stained with 0.06% trypan blue solution (VisionBlue^®, D.O.R.C. International), placed in an injector designed specifically for this procedure (Melles’ injector, D.O.R.C. International) and injected into the AC as a double roller.

In contrast to DEK, it is not necessary to perform the maneuvers of unfolding and complete adhesion of the graft to the posterior aspect of the cornea. In any case, some contact with the posterior stroma seems to be necessary for corneal dryness to occur; therefore, the proximal edge of the roll is fixed in the inner lip of the corneal tunnel to ensure a minimum contact area between the graft and the posterior corneal surface. To perform this fixation maneuver, once the graft has been injected, its proximal edge should be kept trapped in the incision but not protruding to the outside of it. It can be performed by delicate movements with the tip of a blunt cannula until the end of the graft is in that position.

The DMET technique represents a tremendous simplification of the DEK. The most difficult surgical steps in the latter – such as the maneuvers of unfolding and adhesion of the graft to the posterior corneal surface – are not necessary, and the need to place an air bubble in the AC is eliminated. This significantly shortens the surgical time and avoids the possibility of postoperative pupillary block.

THE FUNDAMENTALS OF DMET

The universally accepted paradigm for successful endothelial transplant surgery and restoration of transparency has been that the graft must be fully applied to the posterior aspect of the recipient cornea^3,4. However, some clinical observations performed after ELK and DEK^1,5 have shown that even in eyes with partially detached grafts, the cornea has the potential to recover complete transparency (Figure 1). Off-center grafts, partially detached with small or large non-adhered areas, or even in cases with partial detachment in improperly positioned grafts with the descemetic face oriented toward AC, may show some patterns of spontaneous clearance of the uncoated stroma⁶ (Figure 2).

Contribution of endothelial cell migration in corneal clearance after DMET

Previous observations have shown that it is possible to restore corneal clearance and transparency even though there is only a small area of ​​contact between the donor and the recipient. A minimum contact seems to be mandatory, since in those cases in which the detachment is complete, it is not possible to observe any clearing of the corneal stroma. In addition, the presence of a graft is absolutely necessary for stromal deturgescence⁷.

All this has led us to reconsider the dynamic nature of the corneal endothelium and to evaluate the possibility of simplifying DEK surgery, which we later describe as DMET². It has been suggested that the mechanisms of migration and/or endothelial cell proliferation would be those involved in obtaining corneal clearance in these cases of partially adapted grafts^8,9. The migration capacity of human corneal endothelial cells had been previously suggested in cases in which a spontaneous resolution of corneal edema was observed after large detachments of Descemet's membrane after cataract surgery¹⁰ and even in a more striking way, after performing a central descemetorhexis without implanting an endothelial graft^11,12. The migration of donor endothelial cells has also been described both after DEK¹³, and ELK¹⁴ and after PK¹⁵.

The role of recipient and donor endothelia in spontaneous corneal clearance

Despite the endothelialization of the posterior surface of the stroma after DMET, it is unknown whether the cell population of the recipient or the donor is involved in this "spontaneous" corneal clearance. The apparent need for the presence of donor tissue to achieve this clearance suggests an important role for the graft endothelial population. This, however, does not exclude a possible contribution of the residual endothelium of the recipient.

In a series of 12 eyes in which DMET was practiced, in all those (7 cases) in which the underlying pathology was Fuchs' dystrophy, a progressive improvement of the corneal edema was observed, while in the 5 cases in which the cause was an edematous (bullous) keratopathy after aphakia/pseudophakia, no long-term improvement was observed¹⁶. The apparent reason that could justify this difference in behavior could be the absolute lack of peripheral endothelial cell migration/proliferation capacity in cases of iatrogenic edematous keratopathy. In contrast, in those of Fuchs' dystrophy, the surgical elimination of the altered central Descemet’s and the better capacity of proliferative or migratory response towards the central area of ​​a peripheral endothelium in better conditions, would facilitate corneal deturgescence^16,17.

Based on this study and other previous observations, we speculated on the possibility that the insertion of a new endothelial population through the donor tissue in AC induced in some way the cellular migration of the peripheral receptor endothelium. It could be an explanation to the apparent need for the presence of a graft and to the different results obtained in eyes with different indications for DEK. Later, we proposed a possible re-endothelialization pattern in which the endothelial cells – and, consequently, the corneal clearance – would migrate from the periphery to the center (Figure 3). In patients with Fuchs' dystrophy, after the surgical removal of the corpuscles (guttae), which could act as a barrier, and the insertion of an endothelium and Descemet’s graft, the migration of the peripheral endothelial cells, which would cover the posterior corneal surface and return the corneal stroma to its normal state of dryness (Figure 3), would occur.

Contribution of endothelial proliferation to corneal clearance after DMET

Endothelial cell proliferation has been the second mechanism proposed to justify corneal clearance in these cases, although its ability to regenerate in vivo is usually limited. Endothelial defects that occur in the absence of cellularity are usually covered by adjacent cells by elongation and enlargement thereof. In any case, the presence of endothelial cells with a potential similar to the stem cells that would show a continuous centripetal movement has been suggested^18,19.

CONCLUSION

Currently, the most accepted therapeutic option for the surgical treatment of endothelial diseases such as Fuchs' dystrophy or edematous pseudophakic keratopathy is endothelial keratoplasty. The DEK provides an excellent visual recovery in a very fast way. In a certain way, DMET surgery offers a technically simpler alternative and has given us a greater source of knowledge about the processes involved in the healing and endothelial repair phenomena. Although the mechanisms of cell migration and endothelialization are still not sufficiently well defined, DMET may be useful in those complex cases in which, after descemetorhexis, the unfolding of the donor endothelial loop and its apposition in the posterior aspect of the cornea cannot be achieved, without considering the surgery a failure. Converting a DEK surgery to DMET could eventually help in corneal clearance without the need for a re-intervention and a new endothelial graft.