The general considerations about endothelial transplantation and cataract surgery have been dealt with in another chapter (6.5.1) of this work. The general advantages of endothelial keratoplasty over penetrating (PK) are evident in cases of endothelial pathology that requires cataract surgery – here, in particular, the fact of respecting the integrity of the eyeball – and have given rise to the concept of the "new triple procedure", initially associated with endothelial lamellar keratoplasty (ELK or DSAEK)¹. Fuchs' dystrophy is the condition that most frequently requires endothelial replacement along with cataract surgery. And it is precisely in this area that Descemet-endothelial keratoplasty (DEK or DMEK) has been shown to offer a faster visual rehabilitation², which is why it is postulated as the technique of choice in this situation. In this chapter we present our experience on DEK combined with cataract surgery in patients with Fuchs’ dystrophy, with special interest in the question of whether surgery is preferable in a single session or a deferred one.

STUDY CHARACTERISTICS

We have retrospectively studied an initial group of 92 eyes of 61 patients operated on for DEK, lensectomy and intraocular lens implantation (IOL), with the following inclusion criteria: symptomatic Fuchs' dystrophy, not intervened of keratoplasty or other corneal surgery, cataract or significant crystalline sclerosis, anterior chamber (AC) ≤2.5 mm and minimum follow-up of 12 months. The characteristics of the simultaneous and deferred surgery groups (lensectomy at least 3 months before the DEK) are summarized in Table 1. The only significant difference was the greater age in the deferred group, which is explained by the cataract surgery performed earlier. Cases with low visual potential due to retinal pathology were included in the analysis of graft survival but were excluded from the functional outcome. Two cases of the deferred group had glaucoma prior to transplantation, controlled with drugs.

OBTAINING THE DONOR TISSUE

Techniques for obtaining and evaluating tissue for endothelial keratoplasty have been treated in other chapters of this work (2.3, 2.4 and 7.2). In this series, the tissue had been stored in a cold medium (Optisol^®) for 2-3 days. The admission criteria for DEK (DMEK) were: minimum age of 50 years, minimum cell density of 2400 cells/mm² and absence of guttae or abnormal morphology. The membranes of Descemet-endothelium (DME) were dissected from the corneoscleral segment with a peeling technique, a mean of 7 days (range 6 to 20 days) before surgery, cut with a Barron punch of 8.75 mm and were stored in a TissueC^® culture medium (Alchimia, Padova, Italy) at 31°C until the time of transplantation. The characteristics of the tissue in both groups are summarized in Table 2, without significant differences.

CATARACT SURGERY

Peribulbar anesthesia and sedation were used in all cases. Cataract surgery was performed with standard phacoemulsification techniques, using an upper incision (12 o’clock) of 2.2 mm and with a cohesive viscoelastic (Provisc^®, Alcon, Fort Worth, USA) that was finally removed by careful irrigation-aspiration. In some cases, the femtosecond laser was used to perform a 4.6 mm diameter capsulorhexis. A capsular ring (Morcher Gmbh, Stuttgart, Germany) and a monofocal IOL (Acrysof^® SN60WF, Alcon) were implanted in the capsular bag.

DESCEMET-ENDOTHELIAL KERATOPLASTY SURGERY

The technique of the DEK was the same in the deferred and simultaneous cases. A circular epithelial mark 9 mm in diameter is made and an air bubble is introduced into the AC by a paracentesis. The main incision is made – or extended if the procedure is simultaneous – to 3.2 mm. A 9-mm descemetorhexis is performed with an inverted Sinskey’s hook and the DME is peeled off in that area. The donor tissue is inserted with an injector for phakic IOL (ICL^®, Staar Surgical, Nidau, Switzerland), with the cartridge filled with balanced saline solution (BSS). The proximal end of the graft is protected from contact with the plunger with a plug of said viscoelastic. Once in the AC, the roll is oriented with the endothelial side down by indirect and careful manipulation with air and BSS. The main incision is sealed with a 10-0 nylon cross suture. The graft is extended on the anterior side of the iris with the help of air injected above, which is extracted and again injected underneath, to elevate the graft towards the receptor stroma (Figure 1).

Once the graft is in position, the AC is completely filled with air for 60 minutes, to then exchange air-liquid leaving a bubble of 60% and the eyeball properly pressurized. A topical dexamethasone regimen is followed 4 times a day for one month, followed by fluorometholone in a descending dose for one year. The patients were evaluated at 24 hours, one week and at 1, 3, 6 and 12 months.

RESULTS

Graft success was considered when it was applied – even if air reinjection was required – and the cornea became progressively transparent throughout the first 3 postoperative months. If the detachment was partial and did not affect the center of the cornea, reinjection of air was optional. The percentage of success in the first intervention of DEK in the deferred group was 71.7% (Figure 2) and in the simultaneous 71.2% (Figure 3), without statistically significant differences (p = 0.733).

Corneal tissue expenditure

In the group of deferred surgeries, 81 donor corneas were used: 74 DME discs (60 for the 1^st DEK and 14 for DEK replacement), as well as 7 full-thickness grafts (PK re-transplantation) to resolve the 60 cases; which means a rate of 1.26 donors per transplanted eye. In the simultaneous group, 40 corneas were used: 38 DME discs (32 for the 1^st DEK and 6 for DEK replacement) and 2 full-thickness grafts (PK re-transplantation) to resolve the 32 cases, that is 1.25 donors per transplanted eye.

Endothelial survival

The endothelial cell survival of the successful grafts after 1^st DEK – measured at 6 and 12 months – is summarized in Table 3. There were no significant differences except in the preoperative density – but not in the rates of cell loss. After one year, all these grafts had remained transparent and above 500 cells/mm².

Complications

Respectively in the deferred and the simultaneous group, the complete detachment of the graft (Figure 4) occurred in 14.8% and 21.4% of the cases, partial detachments (Figure 5) in 7.4% and 10.7%, it was necessary to reinject the air bubble in 29.4% and 31.0%, there was acute hypertension due to pupillary block in 3.7% and 3.6%, and acute primary failure – graft fully adhered, but cornea with edema – in 7.4% and 3.6%.

Functional and refractive results

At 6 months of follow-up, 77.8% of the patients had achieved a best-corrected visual acuity (BCVA) ≥0.5 decimal; 44.4% ≥0.8; and 33.3% ≥1.0. The analysis of maximum visual quality was made with the cases of good visual potential and three other cases were excluded: two that needed a secondary graft, and another with a macular hole. With these exclusions, 100% reached ≥0.5; 66.7% ≥0.8 and 50% ≥1.0. At 12 months, the BCVA (mean±standard deviation) was 0.83±0.17 and 0.86±0.15 for the deferred and simultaneous groups respectively (Table 4).

From the refractive point of view, we found, respectively in the deferred and simultaneous group, efficacy indexes of 2.35 and 1.09 at 6 months, safety indexes of 3.01 and 1.50, and predictability of ±1.00 diopter of spherical equivalent of 76.9% and 93.7%.

COMPARISON WITH PUBLISHED DATA

The discussion on previous or simultaneous cataract surgery in the case of ELK (DSAEK) has already been dealt with in another chapter (6.5.1), and in that context there do not seem to be differences, nor would it be necessary to avoid the use of viscoelastic, provided they are cohesive and are withdrawn exhaustively at the end of the procedure¹. As for the DEK (DMEK), publications are more limited. The group of Melles proposed in 2009 to perform both surgeries in a deferred way, since all viscoelastic should be avoided during DEK. In addition, the improvement of vision after operating the cataract allowed to delay the transplant in 10% to 30% of the cases³. They also report a patient who had been operated on first of DEK and 6 months after cataract, in which the graft remained stable and with a cell density of 1019 cells/mm² at 3 months after the second surgery⁴. However, Price's group has shown good results in terms of graft survival and endothelial cell loss in cases of triple-procedure with DEK due to cataract and Fuchs' dystrophy, with the use of cohesive viscoelastic for descemetorhexis⁵. Neither Kruse's group finds a greater endothelial loss, nor a higher rate of complications with the triple procedure in a retrospective study of 61 eyes⁶.

In our study, the anatomical and functional results are satisfactory and correlate with those described by the Melles’ group for the DEK learning curve in pseudophakia⁷, in the subsequent multicenter study8, and in the Price9 group. The percentage of endothelial cell loss was around 59% at 12 months, higher than that of other series that account for between 30% and 50% at one year^10,11. Possibly this can be attributed to the graft insertion system.

In the absence of comparative, prospective and randomized studies to validate this concept, we believe that there are reasons to consider combined cataract/IOL and DEK (DMEK) surgery as the technique of choice in cases of symptomatic Fuchs' dystrophy with cataract or nuclear sclerosis with significant ametropia, especially if the AC is narrow and age >50 years. A faster visual rehabilitation and better adherence of the graft is obtained than in ELK (DSAEK). No morphological or refractive differences are observed between performing the triple procedure sequentially or simultaneously.

The relationship between glaucoma and keratoplasty is oriented in two ways: the influence of a pre-existing glaucoma or its surgery on the result of the transplant and the possibility that the DEK can induce ocular hypertension, de novo glaucoma or exacerbate a pre-existing one. These types of relationships are known and have been the subject of chapters in reference to penetrating keratoplasty (PK) (3.3.3) and endothelial lamellar keratoplasty (ELK/DSAEK) (6.5.2) and in the present chapter we will review them with regard to the Descemet-endothelial keratoplasty (DEK or DMEK).

The deleterious effect of previous glaucoma or its surgery on the survival of a PK or an ELK is known, as well as the relatively frequent appearance of hypertension or glaucoma in the postoperative period. In endothelial keratoplasty (ELK and DEK) there are also specific problems, such as the difficulty to achieve a good adhesion of the graft in the presence of drainage devices or the possibility of acute hypertension associated with the use of air or another intraocular gas.

DESCEMET-ENDOTHELIAL KERATOPLASTY IN EYE WITH PREVIOUS GLAUCOMA SURGERY

The adherence of an endothelial graft (ELK or DEK) to the stroma of the recipient requires good pressurization of the anterior chamber (CA) at the end of the intervention and during the early postoperative period. The difficulty to obtain it – and therefore a greater risk of graft detachment – may be due to hypotonia, in eyes with filtering surgery and especially if there is a drainage tube – there may be passage of air under the conjunctiva –, or by air migration to the posterior chamber (Figure 1) in the aphakic, vitrectomized or eyes with iris defects. In addition, adherence may be hampered by a long-standing corneal edema that causes low stromal imbibition pressure or in a collapsible eyeball by having thin walls such as in the buphthalmos or myopia magna.

As we saw in the case of ELK (DSAEK), the presence of previous glaucoma surgery – with or without drainage tube – is associated with a high rate of early graft dislocation, as well as secondary graft failure (see chapter 6.5.2). In addition, the presence of a drainage tube in the AC may not leave enough space for the maneuvers of deployment and fixation of the graft. These factors also condition the DEK (DMEK), but in the presence of a drainage tube in AC it can be an advantage to use this technique because it is the finest and most flexible graft, and in fact the rate of graft detachment would be lower than in ELK^1,2.

The causes of the worse survival of PK or ELK in the presence of a drainage tube in the AC are not clear: it could be due to mechanical endothelial damage by the tube itself, by the anomalous flow of aqueous humor on the corneal endothelium, or even by a subclinical rejection because the direct communication of the CA with the extraocular medium puts the antigens of the donor corneal endothelium in contact with the recipient's immune system³. The data in relation to DEK are scarce but the same concepts can be applied.

Precautions during surgery

When practicing a DEK in patients with previous glaucoma surgery we should consider a series of special precautions and maneuvers:

• Obtain miosis with pilocarpine, preoperatively or at the end of surgery, to maintain a good separation of the eye chambers, especially in the aphakia.

• Position the main incision so that it does not affect the filtering surgery or present tube.

• A continuous irrigation with air or balanced saline solution – in the AC or in pars plana in vitrectomized eyes – can compensate the difficulty that the hypotonia supposes to realize the descemetorhexis.

• To resolve as far as possible associated anomalies such as iris defects, vitreous remnants in AC or AC lenses (chapter 7.4.1) or other conditions that may be an obstacle to the deployment and fixation of the graft.

• Perform pressurization slowly until obtaining about 25 mmHg, either with air or adding BSS if the eye remains hypotonic with the AC filled with air and after ensuring the tightness of the incisions.

• Keep the complete air bubble in the AC until the postoperative period, since the risk of pupillary block is very low.

• In the postoperative period, at the slightest suspicion of detachment or the presence of stromal edema that is prolonged in excess, perform air reinjection without delay. In this situation, corneal optical coherence tomography is very helpful for its early detection (Figure 2).

In relation to the drainage tubes in the AC, several maneuvers have been proposed:

• Cut the tube with intraocular scissors and use a smaller diameter graft⁴.

• Implant the tube in the posterior chamber – in pseudophakic patients⁵ (Figure 3) – or in the vitreous cavity via pars plana vitrectomy.

• The Melles’ group proposes not to deploy the graft edge closest to it to avoid contact; the patient's head is tilted towards the side of the tube (usually temporal) and a small air bubble is injected from the opposite side, directly below the graft, to be applied between the tube and the receiving stroma⁶.

• If the hypotension persists despite air and BSS reformation maneuvers, we can occlude the lumen of the tube with viscoelastic or even with a suture.

OCULAR HYPERTENSION AND GLAUCOMA AFTER DESCEMET-ENDOTHELIAL KETATOPLASTY

In the postoperative period of a DEK (DMEK), ocular hypertension can occur early or late, either de novo or by exacerbation of a pre-existing glaucoma⁷. Glaucoma can condition the visual result of a DEK as in other keratoplasties, due to the loss of visual field and endothelial cell damage that favors the secondary failure of the graft.

Acute ocular hypertension in the early postoperative period

In the early postoperative period of a DEK, acute hypertension can occur due to pupillary block due to the air that fills the AC (Figure 4), if the peripheral iridotomy is not permeable or occluded by the bubble, due to an excessive size, or an inadequate location or patient position. This occurs more frequently in phakic eyes, 11% to 15%^7,8.

The blockage is resolved by draining the air bubble through one of the paracenteses until the iridotomy or pupil is released, or by dilation with mydriatics. Hypotensive agents are useful as in other types of acute glaucoma (topical 1% apraclonidine, oral or parenteral acetazolamide 250-500 mg, mannitol 20% iv) and place the patient in the supine position for 1-2 hours. In the phakic eye, a lower peripheral iridotomy may not be effective and hypertension responds only to the reduction of the bubble, since it would be due to a previous tilting of the lower part of the iris-lens by the backward push of the air in the superior, which closes the iridotomy against the cornea.

Postoperative hypertension and secondary glaucoma

Risk factors for chronic hypertension and glaucoma following keratoplasty include previous history of glaucoma or chronic edematous (bullous) keratopathy, use of viscoelastic during surgery, hypertensive response to corticosteroids, damage of the drainage mechanism, loss of angular support and angle closure due to peripheral anterior synechiae. In the absence of specific data, these factors should also be considered after a DEK. The risk of hypertension secondary to peripheral anterior synechiae with the DEK graft would be lower than after an ELK (DSAEK)⁸, even if it is off center, although this is avoided with proper centering of the graft.

The frequency of tension peaks in the postoperative period of DEK is between 6.5%⁷ and 8.0%⁸ and reaches 25% in eyes with a previous history of glaucoma⁷. Although within the first 3 months these differences may be due to the different use of corticosteroids, in a prospective and randomized study, Price et al⁹ found that eyes treated with "mild" corticosteroids such as fluorometholone after DEK have a lower risk (6.1 %) of hypertension than those treated with prednisolone acetate 1% (21.9%), without increasing the risk of rejection. Given the low risk of rejection after DEK¹⁰, it is advisable to switch to fluorometholone-type corticosteroids from the first postoperative month.

Both in our experience and in the cases published^1,2, previous vitreous-retinal surgery has not entailed limitations to perform a Descemet-endothelial keratoplasty (DEK or DMEK). Neither a previous DEK has been any limitation, technical or visual, for the vitreous-retina surgeons. In eyes that have developed vitreous-retinal pathology after a DEK, the practice of a pars plana vitrectomy has not affected the viability of the graft.

CLINICAL CASE

A 72-year-old patient presented with Fuchs’ dystrophy and cataracts in both eyes (OU). The best corrected visual acuity (BCVA) of the right eye (RE) was 0.5 and that of the left eye (LE) of 0.3. The Orbscan^® shows an astigmatism against the rule and corneal thickening in OU, while the specular microscope reveals an endothelial alteration that does not allow cell counting (Figure 1).

We proceeded in the LE to a phacoemulsification surgery with intraocular lens implantation (IOL) and later to a DEK (DMEK), with favorable postoperative evolution and a BCVA = 0.6 decimal in the 2^nd postoperative month. At the end of 8 months, he comes by visual loss, with a BCVA = 0.2. In the exploration of the anterior segment a transparent cornea with a well-attached graft is observed. In the fundus, an epiretinal membrane is observed that causes macular thickening, verified by optical coherence tomography (OCT) (Figure 2).

The patient underwent removal of the epiretinal membrane by pars plana vitrectomy, with good postoperative evolution (Figure 3). The cornea remained transparent during the follow-up period (Figure 4) and the BCVA at 18 months was 0.9.