During the procedure of Descemet-endothelial keratoplasty (DEK or DMEK), complications may occur in the preparation phase of the donor tissue or in that of surgery in the recipient^1,2.

COMPLICATIONS DURING THE PREPARATION OF THE DONOR TISSUE

Dissecting the approximately 15 μm thickness of the complex Descemet’s membrane and endothelium (DME) of the donor cornea with fine forceps is a challenge, even for an experienced surgeon. Currently, high success rates of around 95% are obtained, which improve progressively due to the development of special techniques. Alternatively, the eye bank can prepare the donor tissue, which facilitates the process. The causes why this phase may fail include:

Abnormal adhesions to the posterior stroma

Sometimes there is a pathological adherence that does not allow complete separation of the DME. If it is in the central zone it cannot be excluded and therefore it will not be possible to obtain an entire disk (Figure 1). However, the rest of the tissue can be used if it is large enough, – in fact, some surgeons have proposed that half DME donor can be enough to obtain good long-term corneal transparency in cases of good prognosis, especially dystrophies.

Difficulty in the identification of the cleavage plane

It is one of the key points in the learning curve of the surgeon or the eye bank technician. The realization of a peripheral descemetorhexis, prior to the separation of the DME from the posterior stroma, facilitates the identification of the cleavage plane and allows obtaining a graft without tears in most cases. Occasionally there may be small peripheral notches that do not affect the usefulness of the graft (Figure 2).

Problems during the passage of tissue to the insertion system

The transfer to the system of insertion in the recipient eye (Figure 3) must be done with care, since it is possible to traumatize – or even lose – the donor tissue. It is important that it is well stained to correctly identify its position.

COMPLICATIONS DURING SURGERY IN THE RECEIVER

Problems with the descemetorhexis

It is important that the diameter of the descemetorhexis is approximately 1 mm greater than that of the graft, since it usually detaches in the overlapping areas. Rarely, there are abnormal adhesions of the DME from the receptor to the stroma, which are eliminated by means of gentle maneuvers with a spatula, but there should be no remnants of DME, which make adhesion of the graft difficult and, if central, limit vision

Problems during graft insertion

Since the isolated DME disc is wrapped with the endothelium outward, the insertion system must provide protection. Different injectors have been developed (see chapter 7.2) but in any case, the materials used must have low surface tension in their internal face, to facilitate the sliding of the graft and avoid a possible injury of the endothelial cells. During the insertion, if the tissue is trapped in the incision, it can be introduced with gentle spatula maneuvers on the inner side (not endothelial) (Figure 4), after checking that the tone of the eye is low. If infusion is used, it must be closed until the graft is completely inside, since it could cause its expulsion.

Graft loss

During insertion or deployment maneuvers the graft may be lost, especially if the staining is insufficient or by injection behind the iris, through the pupil or a large iridectomy, or even through a drainage tube. In the aphakia this can lead to it falling into the vitreous chamber (Figure 5).

Difficulties during the deployment of the graft

The deployment of the DME roll is the most difficult step of the DEK procedure (DMEK) and its learning curve. Various techniques have been developed for manipulation by means of jets of balanced saline solution (BSS), air bubbles, percussions or compressions on the cornea, variation of the depth of the anterior chamber, etc. (see chapter 7.2). In any case, visibility should be ensured, if necessary, by repeating the staining, and care should be taken to ensure that the trauma to the endothelium is as minimal as possible.

Inverted graft

An inverted graft will always fail, even if it is initially attached. The inversion may occur during insertion or deployment. It is important to identify the position of the graft at all times and it will be helpful to have previously marked it on its periphery, either with gentian violet on the stromal side of the DME or by means of small notches with a die.

Folds in the graft

When the graft is already applied under the recipient stroma, folds may appear that, if marked, compromise adherence or vision if they affect the central area. They are usually resolved by means of external massage maneuvers with a cannula and varying the size of the bubble with alternating injections of BSS and air.

Graft of excessive or insufficient size

The diameter of the most usual graft is 8 mm. However, in some cases it may be too large – in small corneas or with peripheral anterior synechiae (Fig. 6) – or small – in buphthalmos or megalocorneas –. The white-white distance should always be measured before deciding the diameter of the graft, which is preferable to having to cut it out during surgery.

Graft fixation

At the end of the surgery, some authors leave the chamber filled with high pressure air with the patient in the supine position for an hour, after which they extract part of it. Others, as in our case, prefer another gas that is more persistent than air, at a non-expandable concentration such as sulphur hexafluoride (SF₆) at 20%. This allows more prolonged support for the adhesion of the graft and if it were necessary to modulate it in specific sectors of the same one by means of movements of the head.

After Descemet-endothelial keratoplasty surgery (DEK or DMEK), we can consider three postoperative periods: immediate, early and advanced.

IMMEDIATE POSTOPERATIVE PERIOD

The immediate protocol after surgery varies according to the surgeons (see chapter 7.2), but typically the patient is left in the supine position for one hour, after which he is examined in the slit lamp and, in our case, we perform an optical coherence tomography scan (OCT) of the anterior segment. We confirm that the graft is adhered, the bubble of air or other gas is adequate, the inferior iridotomy is permeable and is not occluded by the bubble, and there is no ocular hypertension. If everything is correct, we put an eye protector and review the patient the next day. If during the surgery there was a tendency of the air/gas to move behind the iris, or we see in the slit lamp that occupies the retropupillary space, we dilate the pupil and if this does not solve it we remove part of the bubble.

EARLY POSTOPERATIVE PERIOD

We instruct the patient to rest in the supine position as long as possible until the bubble is fully resorbed. During the first week it is important to monitor the good adhesion of the graft. This includes a new OCT at 24 hours and after one week¹. In case of detachment, even incipient, it is advisable to reinject a bubble emergently.

There is no single consensus treatment regime after a DEK, although in general it includes a topical corticoid and antibiotic coverage. Our usual protocol, which follows that of several authors², contains moxifloxacin (Vigamox^®, Alcon, Fort Worth, TX, USA), one drop every 8 hours for 10 days, and dexamethasone 0.1% alcohol (Maxidex^® , Alcon, Fort Worth, TX, USA) or prednisolone acetate 1% (PredForte^®, Allergan, Irvine, CA, USA) the first 4 months, 4 times a day during the first month, with a drop of one drop per month during the next 3 months. In phakic patients, or in those responding to corticosteroids with a history of secondary ocular hypertension, we use fluorometholone from the beginning. In the case of postoperative macular edema, a complication with an incidence close to 13%³, we add a topical NSAID, in our case nepafenac 0.1% (Nevanac^®, Alcon, Fort Worth, TX, USA) in a regimen of 1 drop every 12 hours during the first month.

ADVANCED POSTOPERATIVE PERIOD

We review the patients weekly during the first month, monthly the following 3 months and then every 3 months during the first year. At one month we repeat the OCT and we do an endothelial count at one month that we repeat at 3 months and then every 6 months during the following years.

We have traditionally switched to low penetration corticosteroids such as fluorometholone 0.25% or 0.1% (FML Forte^® and FML^® respectively, Allergan, Irvine, CA, USA) one drop per day or every other day, from the 5^th month onwards and indefinitely. Although the risk of early rejection in this type of transplant is low, close to 1%⁴, the possibility of chronic rejection has been suggested, so it is not clear at what point treatment can be suspended and follow-up is essential with endothelial microscopy. On the other hand, the studies that show the similar utility of low penetration corticosteroids to the classic ones in the prevention of rejection after DEK make the tendency to use them in an increasingly early form, often from the first month (see chapter 7.5.4).

Perhaps the most important complication in corneal transplantation, rejection, is the one that least concerns after a Descemet-endothelial keratoplasty (DEK or DMEK) due to its rarity¹; even so it is a possibility to which we dedicate the next chapter. The most frequent postoperative complications after a DEK have to do with the particularities of the technique and the special delicacy of the transplanted tissue.

GRAFT DETACHMENT

The detachment of a DEK graft is one of the most frequent postoperative complications^2,3. It may be due to several causes: inverted or non-viable graft, bad adhesion due to not having achieved the adequate bubble for a sufficient time, hypotony or poor adhesiveness of the stroma due to chronic edema, peripheral overlap of the graft on the recipient's endothelium, etc. Partial detachments are more frequent in the lower zone and for its reapplication it may be necessary to reinject air repeatedly or else a more persistent gas (SF₆) at a non-expandable concentration.

PRIMARY FAILURE OF GRAFT

It is usually defined as a correctly positioned and adherent graft, in which the corneal edema persists beyond a certain period that may be 1 to 3 months. It is important not to confuse it with the cases in which the lenticule has been positioned backwards. However, an implant with non-viable endothelium can also be manifested by a detachment rebellious to reinjections of air or other gas. In addition to problems in the conservation and trauma during tissue dissection and its implantation in the recipient, the primary failure due to subclinical pre-existing endothelial dysfunction in the donor has been reported. In these cases, a second DEK would be indicated with good prognosis.

PERIPHERAL FOLDS

Contraction folds may appear at the periphery of the graft, which in many cases do not affect the transparency of the cornea and do not require additional measures.

ABNORMAL ADHERENCE OF THE GRAFT

In some cases, a lower adherence of the graft has been described with a tent effect. To allow full adhesion, a lower resection of the graft may be necessary with reinjection of gas or cutting it with Nd:YAG laser after reforming with gas.

EARLY EYE HYPERTENSION

A pupillary block may occur if the inferior iridotomy is not permeable, if it has been left occluded by the air bubble, this one has passed behind the iris, or fibrin – or even posterior synechiae – has formed that obstructs the pupil and/or the iridotomy. It is often resolved by mydriatics and postural modification, or by removing part of the air/gas from the anterior chamber, even reopening the iridectomy with laser. Some rare cases require surgical removal of the retro-iris gas, with eventual release of synechiae.

SECONDARY GLAUCOMA

The appearance of glaucoma after a DEK seems much rarer than after other forms of keratoplasty. This may be due to the fineness of the graft that does not interfere with the angle or less inflammation. However, postoperative intraocular pressure should be monitored while corticosteroids are being used.

Descemet-endothelial keratoplasty (DEK or DMEK) has great advantages compared to other techniques such as the smaller incision and the better visual acuity, but the lower incidence of rejection is undoubtedly one of its greatest attractions. Even so, it is a homograft and the immune reaction is possible, so it is convenient to know its clinical, prevention and treatment.

FREQUENCY

The risk of rejection in DEK is markedly low compared to other types of keratoplasty. Although there are no such long-term data as in penetrating keratoplasty (PK), the available ones are much better than in similar PK follow-ups. The frequency of rejection episodes in large series of DEK is around 1%^1,2, although some series reach up to 5%³. These are mainly endothelial dystrophies and poorly developed postoperative edematous keratopathies – especially during the learning curve – which, in themselves, have a good prognosis. However, these data are much better than those found in the same indications with PK (13% to 17% rejection) or with endothelial lamellar keratoplasty (ELK or DSAEK), between 5% and 14%⁴ (see also chapters 6.7.2 and 6.7.3). Thus, it has been possible to affirm that the risk of rejection after DEK is 15 and 20 times lower than after ELK and PK respectively¹ – although this will depend, as can be seen, on which studies we compare –, it seems in any case a much lower risk.

The most obvious origin of this is the reduction of the antigenic load that supposes the absence of epithelium and of the whole stroma in the DEK graft. However, we know that endothelial antigens are the main target of the immune response in keratoplasty. Other factors may be involved, such as a reduced inflammatory response to DEK surgery. As more and more DEK are performed in cases of progressive complexity and other indications, we can compare their results with other techniques and better analyze the causes of this privilege.

CLINICAL SIGNS AND DIAGNOSTIC

No predictive factors for the rejection of DEK are known. It may present with the same signs and symptoms as in the PK or ELK: redness and eye discomfort, inflammation of the anterior chamber, decreased vision, stromal edema and "keratic" precipitates or even Khodadoust’s line, although often only a few of these signs appear.

On the other hand, the most complete follow-up of these patients – as it is a novel technique – indicates that the rejection of DEK may not be an acute but slow immunological process. The serial realization of specular microscopy has made it possible to detect early changes several months before clinical rejection². They present an endothelial cell activation, with disorganization of cell morphology, size, and its distribution, accompanied by an increase in reflectivity and a more pronounced nucleus. This study proposes 5 stages or degrees, and from >2.5 would indicate an incipient process of rejection². Such cellular changes would allow to monitor the need to adjust or prolong corticoid treatment or the frequency of follow-up visits.

TREATMENT AND PREVENTION

When rejection occurs in a DEK, intense treatment with corticosteroids usually controls the clinical symptoms, although irreversible cellular changes may persist, which could perhaps be avoided with earlier detection and treatment². For prevention, two prospective and randomized studies have shown the same efficacy of topical fluorometholone 0.1%⁵ or loteprednol 0.5%⁶, when each was compared with prednisolone acetate 1%, which is the drug more accepted in the prevention of rejection of keratoplasty. No differences were found in these studies in terms of endothelial loss with the different treatments. However, ocular hypertension was more frequent with the use of prednisolone than with fluorometholone (22% versus 6%)⁵ and with loteprednol (25% versus 11%)⁶. These results recommend the use of "soft" topical steroids in the prophylaxis of rejection of DEK, although the ideal duration of treatment is still unknown due to the novelty of the technique^5,6.

As discussed in the case of ELK (chapter 6.7.2), the possibility of a chronic rejection with few symptoms makes especially important the follow-up of the endothelium by means of specular or confocal microscopy. The widespread concept that rejection is rare after a DEK, although founded, should not make us lower our guard.