The most crucial step in deep anterior lamellar keratoplasty (DALK) is to obtain a thin sheet of posterior corneal tissue that includes the Descemet’s membrane (DM), the predescemetic layer of Dua (PDL) and, according to the technique, some stromal lamellae. Therefore, the main intraoperative complications of this surgery are related to the creation of said lamina and the preservation of its integrity.

If discontinuity occurs, micro- and macroperforation can be differentiated according to whether or not the anterior chamber (AC) is maintained with air or viscoelastic in its presence. In the first case, it will often be possible to complete the DALK, even requiring repeated reformations of the AC. In the second, it is usually necessary to convert into penetrating keratoplasty (PK), although this will depend on the skills of the surgeon and other factors such as the importance of avoiding PK or obtaining excellent vision (see chapter 5.6.2).

PERFORATION OR TEARING OF THE POSTERIOR LAMINA

The frequency of DM/PDL perforations during DALK ranges from 0% to 39% according to published series, with a cumulative frequency of 1.25% in a review of 41 studies. The need to convert to PK ranges between 0% and 14%, with a cumulative frequency of 2% according to the same review¹.

Perforation can occur in any of the steps of the surgery: during the trepanation, the insertion of the needle or cannula, the injection of air (Figure 1) or viscoelastic or the dissection with spatulas, the puncture of the cavity or big bubble (BB) (video 5.6.1.1), when the stroma is resected, even during graft suturing. In the event of a perforation, we should try as far as possible to complete the lamellar surgery and avoid the conversion to PK. The difficulty of this will depend, in addition to the size of the rupture, on its location, the moment in which it occurs and the amount of residual tissue (if the technique is descemetic or predescemetic). A central microperforation, although it may not progress, may indicate conversion by conditioning the result to a possible localized edema in the visual area². On the other hand, in case of conversion to PK it should be checked that there are no unnoticed remains of the recipient’s DM. Although this may not have consequences, it has been associated in one case with postoperative edema in an overlying sector of the graft³.

General treatment of microperforation

Regardless of when it occurred, perforation increases the likelihood of a pseudo-AC forming postoperatively. This is because the deformation of the graft by the suture causes it to tend to separate from the receiving DM/PDL, allowing the passage of aqueous humor through the perforation. When a microperforation occurs but it is possible to complete the surgery, it is recommended to fill the AC completely with air and keep it there for at least 8 minutes (video 5.6.1.2). Then we will remove half of the air, leaving a bubble of medium size, we reform the AC with balanced saline solution (BSS) and instill cycloplegic to avoid a pupillary block.

Depending on the size and location of the perforation, some authors recommend injecting a bubble of 18% sulfur hexafluoride (SF6) and leaving the patient in the supine position. To avoid pupillary block and Urrets-Zavalía syndrome – something that has been observed when leaving the AC filled with air after DALK⁴ – pharmacological mydriasis is necessary or even performing an iridotomy.

Learning curve

The learning curve of DALK is considered particularly arduous^5,6, due to the complications that are especially concentrated in the first 10 cases with perforations in at least 20%. On the other hand, it does not appear that the experience of the surgeon influences the final results of graft survival and visual acuity. This seems to be related mainly to residual astigmatism and survival depends above all on the pathology prior to transplantation. In patients with good prognosis for PK, long follow-ups are required to find statistical differences with DALK in terms of survival.

Perforation during trepanation

To avoid this complication, the depth of the trepanation should be selected according to the pachymetric map. If this is not reliable – we must know well the behavior of each device in this regard – we can take several shots with an ultrasonic pachymeter at the beginning of the surgical procedure. In case of doubt, it is preferable not to trepan more than 50-60% of the minimum thickness in the diameter of the selected trepanation. Apparently, the trephines with adjustable depth cutting would have less risk of perforation than those of fixed depth. In case this complication occurs, in general it cannot be treated as a microperforation. The options include⁷:

a) Convert to PK, considering in an individualized way the risks associated with it, such as rejection. If these are low, especially at advanced ages, conversion is a good option.

b) Suture the wound and postpone surgery the necessary time for it to heal well, which will represent at least 6 months.

c) Continue with the DALK immediately after suturing the perforation, more often with a manual dissection by layers, although the possibility of creating a BB is not completely excluded. For this purpose, a technique has been described that consists of filling the AC with viscoelastic after suturing the perforation, followed by injection of air for BB in the opposite sector⁸. To avoid the BB reaching the breakage and collapsing, we should not let it grow to the diameter of the trepanation. The cavity is then filled with viscoelastic, using the same air cannula, to expand it as much as possible and continue with the usual technique. As an alternative, you can go directly to a visco-dissection. It is preferable that the sutures in the perforated sector be penetrating to ensure the fastening of the DM.

Perforation when inserting the needle/air cannula (or viscoelastic)

The risk of perforation when introducing the needle into the deep stroma increases as we get closer to the DM, which on the other hand is necessary to have a greater probability of success in the formation of the BB. The perforations in this phase are often microscopic and can be self-sealing.

Faced with this situation, we usually change to a manual dissection layer by layer after stabilizing the AC with air (video 5.6.1.3). For this it is preferable to puncture the AC with a 30G needle, if we did not already have a paracentesis, since it is important to keep the AC formed at all times. In order not to enlarge the microperforation, the globe must be handled with care. The stroma over the perforation will be the last part that we dissect.

Perforation during manual dissection and adhesive techniques

When it occurs during lamellar dissection, BB opening or stromal resection, the rupture may have a variable size. Firstly, we will reform the AC with air and, if this is maintained, it will be possible to continue the dissection with good visibility of the DM. If the air fails to maintain the AC, it can be tested with viscoelastic, although the visualization of the DM will be worse. It is necessary to avoid an excess of viscoelastic that would enlarge the tear. We will continue the dissection as we have said before, leaving the perforated area to the end and reforming the AC as many times as necessary^7,9. Whenever air is left in the AC at the end of the intervention, we should not forget to instill a mydriatic – preferably cycloplegic.

If AC cannot be maintained even though the perforation is small, several techniques have been described to seal it before continuing the dissection. For tissue tears of up to 2 mm, fibrin tissue adhesive (Tissucol)¹⁰ may be useful. If necessary, we can apply a small fragment of the resected stroma as a stopper before carefully reforming the AC, so that the pressure does not enlarge the rupture. The bed should be dry enough for the bio-adhesive to be effective. At that moment we remove the stromal fragment, we apply one drop of the thickest component (fibrinogen) and then another of the more fluid (thrombin). After waiting for 2 minutes, we "level out" the adhesive plug with the surrounding tissue (usually DM/PDL) as far as possible and very carefully, using blunt-tipped Vannas’ scissors. After 4 minutes we can continue with the dissection, with the utmost care and starting as far as possible from the perforation

Some authors have injected the adhesive from the AC, although this seems less practical. A drop of cyanoacrylate applied with an insulin needle has also been used, always with the reformed AC, preferably with air. Sometimes closure has been achieved with a stromal patch. If the perforation is central, these maneuvers can leave a significant opacity.

Perforation during suturing

During the suturing of the graft, perforations can also occur, especially if very deep steps are attempted, something, which is also recommended for good healing and refractive stability of the graft. The perforation in this phase is easily recognized by the sudden outflow of aqueous humor. It is usually microperforations that seal themselves and do not usually need the injection of air in the AC. If, however, the flow of aqueous humor persists, we must replace the suture with a non-penetrating one and put air into the AC as in other cases of perforation.

When passing the sutures after having undergone a perforation in a previous phase, we must take special care in exerting the minimum pressure on the eyeball. Independent sutures are preferable to continuous ones – since they facilitate postoperative management in case of pseudo-AC – and with a slightly lower tension than usual.

COMPLICATIONS WHEN CARRYING OUT THE BUBBLE

In the techniques that seek the formation of the macroscopic cavity between the stroma and the DM/PDL, either with air (BB) or with viscoelastic, difficulties or complications specific to this step may arise.

Absence of bubble formation

Even in the hands of experienced surgeons, it is not always possible to form an adequate BB. In patients with keratoconus, this has been estimated at between 18% and 55% depending on the series⁶. In this situation we have several options:

a) Repeat the maneuver once or several times in different points, while we have enough visualization. This can be partially recovered by injecting BSS into the emphysematous stroma.

b) If the remaining stroma is thick, we can remove another layer before a new attempt, in which the needle will be placed deeper.

c) Pass to a technique of visco-dissection, what some surgeons do at the beginning (see chapter 5.4.4).

d) Move to a manual dissection layer by layer. Although there are multiple effective variants according to the preference of the surgeon, we recommend using a blunt spatula and injecting serum into the stroma to moisturize it and facilitate its visualization.

Formation of atypical bubbles

As is known, in addition to the most common classic form, between the stoma and the lamina with joined DM/PDL (BB type 1), more rarely the airway is between the PDL and the DM (BB type 2) and it extends more peripherally without the whitish ring. The BB type 2 is more fragile and when it is formed we must be much more careful with the following maneuvers (video 5.6.1.4). There may also be a mixed form (BB type 3) in which the air passes first under the PDL and then through one between the latter and the DM (see chapters 5.2 and 5.4.3).

On the other hand, the passage of air between the fetal (with bands in transmission electron microscopy) and postnatal (without bands) layers of DM¹¹ has also been observed. Unlike the BB type 3, in which the BB component type 2 is usually more peripheral than the portion of BB type 1, the intradescemetic bubble is seen within the contour of the BB type 1. If we press it with a cannula it can be moved, taken it to the periphery and punctured – if it persists after opening the BB cavity, at which time it can spontaneously disappear.

Bubble blowout

If the injection of air is continued when the BB type 1 has formed, has grown to find the resistance area and does not increase further, the back sheet may burst with a characteristic sound. When this happens, it is usually cases in which the BB type 1 was limited to a smaller diameter than usual and we insisted with the injection causing a great overpressure in the BB. If the BB does not grow, it is preferable to try the visco-dissection or a manual dissection. When the outbreak occurs, the resulting rupture is usually large.

OTHER COMPLICATIONS

Sometimes the difficulty to dissect DM/PDL in some areas close to a perforation leads to leaving remnants of stroma without dissection. If they are in the periphery, they will have little influence on the final result, including astigmatism. The use of perioperative OCT systems has been described in DALK¹². Although a reduction in complications has not been shown to date, they could help to better control instrument depth and residual bed thickness (Figure 2).

As is the rule in surgery, any imaginable complication can occur. Recently, a case was published in which the donor button was accidentally sutured in the inverted position, with the epithelium towards the deep bed¹³. Fortunately, the surgeon appreciated the error on the 4^th postoperative day, proceeded to replace the graft with a new one and the patient progressed satisfactorily, without an epithelial growth at the interface.

Deep anterior lamellar keratoplasty (DALK) represents today the technique of choice in almost all corneal pathologies that require a transplant but in which the endothelium remains healthy. It provides a very high long-term graft survival (99.3% after 10 years), possibly because when maintaining the recipient's endothelium rejection is not possible. The endothelial loss after a DALK has been estimated at around 10% and is related to the immediate surgical trauma, which subsequently stabilizes in time¹.

Despite its obvious advantages over penetrating keratoplasty (PK) in many indications, DALK presents a greater technical difficulty. In particular, the separation between the stroma and the posterior lamina formed by the Descemet’s membrane (DM) and the predescemetic layer of Dua (PDL) is a critical step. The rupture of the DM/PDL lamina during the intervention forces it to become a PK in a percentage of cases that varies according to the technique used and the surgeon. In this chapter we review the techniques and maneuvers to prevent the rupture of the DM/PDL, as well as the methods to repair it in case it occurs, so that DALK can be continued without having to convert to PK.

PREVENTION OF TEARS OF THE POSTERIOR SHEET (DM/PDL)

BB technique with cannula

The technique most used today for DALK is the so-called "Big Bubble" (BB) described by Anwar and Teichmann in 2002². In it, the DM/PDL is dissected from the deep stroma by injecting air that will form a cavity (the BB) in that plane. The original technique uses a 27 G needle connected to a syringe filled with air, which is inserted into the deep corneal stroma with the bevel parallel to the DM and facing down. When injecting air, BB is obtained in a percentage of cases that is 60-70% but varies according to several factors, among which the depth stands out: the deeper the air is injected, the greater the probability of obtaining the BB. Since the needle should be as close as possible to the DM/PDL to maximize the formation of the BB, it becomes one of the greatest risks of perforating such a sheet.

To avoid the risk of using a sharp instrument such as a needle, the use of a blunt cannula has been proposed and various models and techniques have been designed. We have described a variant called "big bubble with cannula"³, which follows the technique of Anwar with two important changes: after a partial trepanation, a blunt spatula creates a corneal tunnel where the 27 G cannula attached to a 5-cc syringe full of air is then introduced. The cannula has the outlet hole facing down so that the air is directed towards the DM/PDL. The advantage of using a blunt instrument is twofold: it allows to reach a deeper plane – which has obtained a higher percentage of successful BBs^3,4 – while reducing the risk of creating a perforation of the DM/PDL. Our rate of ruptures in keratoconus patients with the Anwar technique (BB with needle) was 6.5% in 266 eyes, while with the cannula it decreased to 2.5% in 241 eyes (p <0.05)⁵.

Opening of the BB technique protected by viscoelastic and flat scalpel

When the anterior layer of the BB is opened with a sharp-edged scalpel, we again run the risk of perforating the DM/PDL (Figure 1). Some modifications to this step can help avoid this risk.

The BB opening technique has been refined by Goshe et al⁶, who propose to cover the stroma overlying the BB with a layer of cohesive viscoelastic material before opening it. Then an incision of 1.0 to 1.5 mm is created, using only the tip of a diamond scalpel with a "lift" movement. This technique has two advantages:

a) When the stroma is incised to enter the BB, the air finds the resistance of the viscoelastic and exits more slowly, thus preventing a sudden collapse that could cause the accidental perforation of the DM/PDL.

b) There may be a certain air-viscoelastic exchange that maintains space in the bubble to facilitate the resection of the stromal lamina.

The modification that we provide to this step has been the use of a flat keratome for tunneling incision of 2.2 mm cataract. After covering the stromal surface with a drop of viscoelastic, I apply the keratome from bottom to top (Figure 2), which further limits the outflow of air contained in the BB. This tunneled cut makes it easier to inject viscoelastic into the BB, to create a safe space between the residual stroma and the DM/PDL that allows a stromal resection with fewer risks (unpublished data, presented at the 2011 AAO meeting).

TREATMENT OF POSTERIOR LAMINA TEARS (DM/PDL)

The perforation or rupture of the DM/PDL lamina is the most frequent complication during DALK surgery, even in expert hands. The perforation rate varies between 4 and 39% in five series published in the literature⁷, while the conversion to PK has been reported between 0% and 60%^8,9. The latter is gradually reduced as the surgeon acquires experience and learns to treat the ruptures of the DM/PDL. In our practice in the last 12 years, all ruptures of the DM/PDL have been repaired successfully⁸. There are not many works in the literature that explain in detail the management of DM/PDL perforations; for this reason, we present some tricks for the management of this complication.

During the execution of the DALK we can find different types of perforations. The microperforation is a small hole that usually appears in the posterior lamina during pre-descemetic DALK while looking for a deeper dissection plane with the spatula. Macroperforation is defined as a breakdown of the DM/PDL that causes the collapse of the anterior chamber (AC). It may present while the residual stroma is removed in the periphery using corneal scissors after having separated the DM/PDL in a descemetic DALK¹⁰.

General rules for the treatment of perforations or ruptures

Faced with a perforation of the DM/PDL, there are a series of common rules for its management⁸:

a) To complete the stromal resection (stromectomy) to create a regular interface between donor and recipient. If the interface is irregular, it will not allow good and rapid adhesion between both tissues and may cause the rupture to remain open.

b) The area where the rupture is should be dissected at the last moment, since the maneuvers for the removal of the tissue can extend it.

c) When the donor has been sutured and only at this time, an air bubble is injected into the AC. It is useful to perform movements of the eyeball so that the bubble in the AC induces the drainage of the fluid at the interface and thus promotes the binding between the DM/PDL of the recipient and the stroma of the donor.

d) The air bubble will remain a few hours in the AC. If we position the patient's head according to the location of the rupture, we will facilitate its application: semi-sitting when the rupture is superior, supine with the neck in hyperextension when it is inferior, etc.

e) A strict monitoring of the patient is recommended every two hours, to evaluate the need to drain the air in case of pupillary block and to prevent the Urrets-Zavalía syndrome.

Some studies show that the breakdown of DM/PDL during DALK and its management are associated with a large loss of endothelial cells compared with a DALK without incident^11,12. However, we believe that an own endothelium, still affected by a significant intraoperative endothelial loss, is preferable to an allograft. The prognosis in relation to the perforations of the DM/PDL is good in all cases. The recovery is faster in case of upper and lateral ruptures, and not so much in the lower area – perhaps due to the difficulty in compliance by the patient of a supine position with the neck in hyperextension –.

Perforation or rupture with descemetic techniques

In the descemetic DALK we will normally find macro-ruptures. In these cases, the DM/PDL behaves coiling on itself, as it happens in the Descemet-endothelial keratoplasty (DMEK), but more prone to do it outward. Here, after completing the resection of the stroma and suturing the graft, we have to unwind the DM/PDL. For this we inject air into the AC trying to extend that layer. This maneuver is limited by the position of the paracentesis, ideally far from the perforation – something that we do not control – because the perforations normally occur after having made the paracentesis. If the rupture is close to this, we must perform another paracentesis in a distant area, before suturing the donor. Making the new paracentesis after the suture is risky, because the peripheral AC will be narrow and we can cause a new rupture or inject the air wrongly in front of the DM/PDL⁸.

Perforation or rupture with predescemetic techniques

Perforations in predescemetic techniques can be easily repaired, following the general rules described above, except when we encounter a disparity of curvature between the donor and recipient. Such inequality can be an insidious enemy and must be handled intelligently.

Disparity of curvature between donor and recipient

The recipient beds, formed by a thin layer of stroma, DM/PDL and endothelium have their own shape. Since its curvature must coincide with that of the donor cornea so that they can adhere, an inequality can cause the opening of the perforation even if it is small. In cases where the bed is significantly flatter or more curved than the donor, perforation of the DM cannot be resolved by air injection alone.

In cases of post-infectious leucoma with significant scars (Figure 3), the inflammation may cause retraction of the stromal tissue and the recipient bed may be very flat. If a perforation occurs – even if it is small – the tension of the recipient bed will keep it away from the donor stroma, preventing its coaptation. During surgery it is not easy to recognize this inequality, but in the postoperative period it will be evident at the slit lamp where we find the double chamber. The recipient bed is clearly visible, tight and distant to the donor, unlike in the case of double chamber in the descemetic techniques where the bed is relaxed. This complication must be repaired surgically, trying to reduce this tension with a subtotal circular incision in the entire thickness of the recipient bed, which respects some mm in a sector of the lower cornea. After suturing the donor button again, an injection of air into the AC through a paracentesis at 6 o’clock will facilitate adhesion of both tissues⁸.

In the case that the recipient bed is extremely curved, as in the cases of keratoglobus, the BB technique would result in a bubble too large for the AC. That is why a predescemetic technique is preferable. When the inequality is due to excess curvature in the receiver, a perforation will cause folds in the recipient bed that may impede the union between DM/PDL and the donor stroma. In view of this complication, we perform a complete 360 ​° circular cut and full thickness of the recipient's bed, after having completed the stromectomy. This tissue disc (endothelium-DM/PDL/etc.) of the recipient is glued to the donor button (previously stripped of its endothelium), with fibrin adhesive (Figure 4). The graft now consists of the donor button of the DALK and the endothelium etc. of the recipient, which then comes sutured in the receiving penetrating window of the receiver. At the end an air bubble is injected into the AC⁸.

Perforation for excessive trepanation

It is a rare complication. It is possible to avoid it with the careful examination of the patient, the pachymetric evaluation and verifying the calibration of the trephine. However, if it is presented it is possible to repair it.

The best procedure is manual lamellar dissection, after suturing the perforated sector. Delamination plane by plane must be done from the periphery towards the center, avoiding the perforated area. Then we suture the graft except in the area of the perforation and the initial suture, where we will finish the stromal dissection and then we can complete the suture of the donor button. We conclude the surgery with an injection of air in the AC and eye movements to eliminate the fluid in the interface⁸.

Postoperative traumatic disinsertion of DM/PDL

The traumatic disinsertion of DM in a quadrant is rare, but a potential complication in the postoperative period. In a series of more than 1,000 DALKs, we have seen only one case. On day 20 of the postoperative period, we found the DM/PDL rolled up on itself by bio microscopy. Apparently, a strong rubbing by the patient caused it over the operated eye. The DM presented a similar appearance to the tissue that is prepared in a DMEK, although in a single quadrant. We solved this case surgically, performing a mechanical extension of the DM/PDL with a spatula and injecting air into the AC (Figure 5).

The inherent advantages of deep anterior lamellar keratoplasty (DALK) such as low endothelial loss, lower risk of rejection, integrity of the eyeball, etc., make its postoperative management less aggressive and shorter than in penetrating keratoplasty (PK). The indications for the surgery and the risk factors of each patient should be taken into consideration for the postoperative care approach^1,2. This section is dedicated to the usual care of the patient after DALK from the moment of surgery until the graft stabilization and visual rehabilitation. The management of complications is addressed in other chapters.

IMMEDIATE POSTOPERATIVE CARE (1-7 DAYS)

The first postoperative review after DALK is performed 24 hours after surgery. In this, the ocular patch is removed, the eye is examined, and the pertinent instructions are given to the patient. Treatment during the first week should focus on preventing infection, controlling inflammation, restoring the corneal epithelium and treating any operative complications.

To prevent wound contamination and treat microbial inoculation during surgery, topical antibiotics should be administered postoperatively. The ideal antibiotic should be broad spectrum, bactericidal and with low toxicity, in addition to maintaining adequate levels in corneal stroma and anterior chamber. The new fourth-generation fluoroquinolones offer a good combination of these characteristics³. The authors currently prefer the use of moxifloxacin 0.5% (Vigamox 5 mg/ml eye drop, Alcon Cusí S.A., El Masnou, Barcelona), 1 drop 4 times a day for 15 days or until the corneal epithelization has been completed.

To control inflammation, the use of topical corticosteroids is required, usually 1% prednisolone acetate (Pred-forte 10 mg/ml ophthalmic suspension, Allergan S.A., Tres Cantos, Madrid). Topical corticosteroids are administered at least 4 times a day, and this dose is usually maintained throughout the first month, although in cases of severe inflammation it can be increased. Cycloplegic eye drops alleviate early postoperative pain due to ciliary spasm and inflammation and avoid pupillary blockage if air has been left in the anterior chamber.

The restoration of the corneal epithelium is favored with the use of topical lubricants, artificial tears without preservatives during the day, which can be reinforced with topical gel or ointment before sleep.

POSTOPERATIVE CARE OF THE WEEKS 2^nd to 12^th

The period between 1 week and 3 months after surgery is, perhaps, the one with the greatest change and the greatest risk for the corneal graft. Management during this interval should be directed towards the prevention of rejection and infection, along with the early manipulation of corneal astigmatism.

The patient after DALK should be examined frequently, especially until the epithelium is completely restored and stable on the graft. Once this is accomplished and in the absence of other complications, patient follow-up can be planned (table 1). In our practice, routine patients are seen at weekly intervals during the first 2 weeks after surgery and then at monthly intervals in the first 3 months. The follow-up is usually every 3 months. High-risk patients are seen more frequently.

Topical antibiotics are usually stopped once the epithelium is intact, usually 2 weeks after surgery. In the absence of complications, topical corticosteroids are gradually reduced during the first 6 months after surgery. Table 2 shows the corticoid reduction schedule followed by the authors. In case of needing a topical corticoid without preservatives (sensitivity to benzalkonium chloride, epithelial toxicity, etc.), dexamethasone phosphate 0.1% can be proposed as an alternative (Dexafree eye drops 1 mg/ml, Laboratorios Thea S.A., Barcelona).

In the postoperative period, attention should be paid to identify any signs of rejection. Epithelial rejection lines begin at the periphery of the graft and migrate toward the center over time. They are observed as greyish elevations in the epithelium. Signs of stromal rejection are characterized by infiltrates that extend from the periphery to the center of the donor cornea. The treatment of epithelial or stromal rejection with topical corticosteroids is usually successful.

The measurement of intraocular pressure (IOP) should be done at each follow-up visit. Electronic applanation tonometry (Tonopen, Reichert Inc., Depew, NY, USA) may be more accurate on irregular surfaces⁴. In case of using a Goldmann applanation tonometer, due to the high corneal astigmatism, it is better to take a measurement, rotate the prism 90 degrees and take a second measurement, and use the average value of both. Approximately 10-20% of patients with chronic topical corticosteroid therapy will develop elevated IOP. This situation can be managed by changing the topical corticosteroid, reducing the dose, adding simultaneous ocular hypotensive therapy or a combination of them.

Between 1 and 3 months after surgery, the management of corneal astigmatism can be initiated, which will allow a faster visual rehabilitation of the patient. Methods to assess initial corneal astigmatism include keratometry, keratoscopy, and corneal topography. Any of these techniques can be used to characterize corneal astigmatism before any suture adjustments. Keratoscopy, either freehand or attached to the biomicroscope, in which a circular image is projected onto the cornea, is a quick way to quantify approximate corneal astigmatism at the slit lamp (Figure 1). In the case of astigmatism, the circle reflected on the cornea is transformed into an ellipse, with the shortest axis indicating the most curved meridian (more tense sutures). Corneal topography is very useful to accurately identify the most curved and flattest meridians, quantify astigmatism and show irregular astigmatism.

The early manipulation of corneal astigmatism depends, to a great extent, on the suture technique used: simple continuous suture, independent stitches or a combination of both. The use of simple continuous suture, combined with an early postoperative adjustment, has provided the best results in our hands.

Once the nature of the astigmatism has been identified and the postoperative adjustment has been decided, the procedure is performed at the slit lamp under topical anesthesia. In the case of independent sutures, those that compress in excess (curved meridian) are cut with the bevel of a needle; one of the edges is grabbed with forceps and the suture is extracted by rotating it in such a way that it follows the same original path through which it was buried. The continuous suture is manipulated by taking it through the epithelium with a suture forceps. The forceps should be placed parallel to the suture to hold each loop. The suture material should be rotated, lacing after lacing, from the areas of the flat meridian to the zones of the curved meridian (Figure 2). If the rotation of the suture does not have the desired effect, it can be combined with the reopening of the surgical wound in the more curved meridian with the help of the end of the suture forceps (between the sutures). When a combination of continuous suture and radial stitches is used, those between the latter that are tight may be removed before adjusting the continuous suture. Freehand keratoscopy allows observing, step by step, the changes induced on the cornea during manipulation of the sutures, both with independent stitches and continuous suture. Suture manipulation should only be performed in patients with corneal astigmatism greater than 3 diopters. The effects of early manipulation of the suture on the final astigmatism after complete removal of the sutures are not clear⁵.

POSTOPERATIVE CARE AFTER 3 MONTHS

Care after 3 months in routine cases focuses on the withdrawal of topical corticosteroids, avoiding iatrogenic problems, managing long-term complications and final visual rehabilitation of the patient.

Most patients may be without topical corticosteroids at 6 months after surgery. Its chronic administration can induce iatrogenia. The increase in IOP is a frequent complication, which must be detected and treated appropriately. Corticosteroids increase the risk of infectious keratitis and crystalline keratopathy, and also of herpetic epithelial keratitis, even without a history of previous herpes. The development of cataracts is not usually a problem in the young phakic patient after DALK, in which topical corticosteroids should be removed soon.

Although some surgeons remove sutures between 6 and 9 months, the authors do not do it completely until 10 months after surgery. Removing the sutures can still produce significant changes in astigmatism. At 3-4 weeks after removal of the sutures, a refraction may be attempted, which in these patients is difficult. Some forms of objective measurement of corneal astigmatism are useful to begin refraction. Javal's keratometry assesses the refractive portion of the graft, and the corneal astigmatism thus measured is useful to initiate definitive refraction. The final optical correction can be in glasses or contact lenses. The latter is indicated when they are already used in the contralateral eye, in cases of high astigmatism and anisometropia, and in cases of irregular astigmatism. When it is not possible to use contact lenses, surgical correction of residual astigmatism, including relaxing incisions and laser corneal refractive surgery (PRK, LASIK), can be considered^6,7. If indicated, cataract surgery with toric intraocular lens is a very effective technique in the correction of regular residual astigmatism after keratoplasty.

The list of possible complications after a deep anterior lamellar keratoplasty (DALK) is extensive and, due to space problems, we will not be able to make an exhaustive review. In this chapter we will review the complications that are characteristic of this technique, obviating those that are common to penetrating keratoplasty (PK).

DOUBLE ANTERIOR CHAMBER

The double anterior chamber (AC) or anterior pseudo chamber consists of the presence of fluid between the donor stroma and the Descemet membrane (DM) – plus the predescemetic layer of Dua (PDL) – of the receptor. It is a complication that is usually observed in the immediate postoperative period. We can distinguish two forms of presentation.

When double AC appears as a result of a microperforation in the DM/PDL of the recipient during surgery, it usually presents as a bag of mobile, loose-walled aqueous humor between the donor tissue and the recipient (Figure 1a). In these cases, although there may be a spontaneous resolution, the injection of a bubble of air or sulfur hexafluoride (SF₆) at non-expandable concentration in the AC, accompanied by supine decubitus, usually achieves complete adherence of both tissues more quickly (Figure 1b).

The second form of presentation occurs in cases without DM perforation during surgery. In these, the DM/PDL of the recipient is usually extended and is almost parallel to the donor stroma, without mobility (Figure 2). It may be due to the presence of remnants of retained viscoelastic material or incongruence of curvatures between recipient and donor. Unlike the previous one, in these cases the injection of air or SF₆ in the AC is not usually effective. In addition, the presence of gas in the AC can induce iatrogenia in the recipient endothelium, especially when the injection is repeated several times due to lack of response. Surgical washing of the space between donor and recipient should be performed only in case that there is a large amount of retained viscoelastic, as it does not usually resolve the situation and may cause the DM of the receiver to break. Given this situation, it is advisable to wait until the complete adherence between donor and recipient tissue occurs spontaneously, probably by reabsorption of the viscoelastic. This may take several weeks, but it always ends up happening.

PUPILLARY BLOCKING AND PARALYTIC MIDRIASIS (URRETS-ZAVALÍA SYNDROME)

Irreversible damage to the iris sphincter resulting in paralytic mydriasis (Urrets-Zavalía syndrome) is one of the complications described after DALK – as after PK –, especially in patients with keratoconus¹ (Figure 3).

Although it is rare, it has been associated with air/gas injection in the AC, probably due to pupillary block. To prevent it, it is preferable not to leave air in AC at the end of the intervention or, if it is done, avoid a large bubble and always instill cycloplegic, especially in phakic patients. We discourage routinely leaving a bubble in AC – something that the novel surgeon tends to do for fear of double AC – except if a perforation has occurred or we suspect it. In such a case, air and supine decubitus do help prevent double AC. In the absence of DM/PDL perforation, experience indicates that the incidence of double AC is very low and when it appears, it usually resolves spontaneously.

INFECTIONS

Postoperative infections after a DALK can be divided into 2 groups. In the first and most specific of the DALK we find those that occur in the donor-recipient interface. They usually appear in the first days or weeks – although cases have been described by mycobacteria and certain fungi diagnosed up to 3 and 4 months after the intervention^2-4. They can be caused by multiple species of bacteria or fungi, although a majority of those described are due to Candida species. They appear as whitish infiltrates in the graft-receptor interface, generally asymptomatic and without important inflammatory signs in the early stages. Therefore, some cases are diagnosed late in routine check-ups.

The treatment of this type of infections is controversial. The conservative attitude includes the use of antibiotic and/or more potent antifungal eye drops and washing of the interface. Although a few cases successfully treated in this way have been published – usually with residual opacity⁴ –, it has often been shown to be ineffective, even replacing the lamellar graft^2,5-7. This is due to the isolation of the lamellar interface where the infection is located and the difficulty in accessing it to the antibiotics and natural defenses of the organism. The maneuvers at the interface, for washing or taking samples, pose a risk of rupture of the DM/PDL, with possible peripheral or intraocular extension of the infection. In most cases a PK will be necessary, so in this serious situation it is preferable to carry it out in the first instance. The PK removes donor and recipient tissue en bloc, completely including the zone of infection when it is performed early^2,3,5-8.

Infections at the graft-receptor interface can occur due to intraoperative contamination or be pre-existing in the grafted tissue. For this reason, the systematic microbiological study of the remaining sclero-corneal ring from the donor is important.

The second group consists of infections that are associated with an epithelial defect, problems related to sutures, the use of topical corticosteroids, contact lenses or palpebral and/or ocular surface problems. These infections can appear at any time during the postoperative period, early or late. Its characteristics and treatment are analogous to when presented after a PK, with the difference of the ease and safety offered by the DALK to perform a graft replacement. Such a replacement can be curative in case of infections that do not respond to medical treatment but are limited to the donor button – and generally originate on its surface. Consequently, before an infection of this type that is suspected resistant – e.g., fungal – early replacement of the graft should be considered to avoid its extension to the tissues of the recipient.

REJECTION

Since a donor corneal button without endothelium is transplanted into the DALK, there is no risk of endothelial rejection. However, epithelial or stromal rejection is possible. Its frequency is related to the postoperative corticosteroid regimen. We have found that the use of corticosteroids at doses lower than the usual PK – in the hope that they are enough – leads to an increase in stromal and epithelial rejections. Therefore, similar doses – only slightly lower – to those of the PK are recommended. As in this one, all DALK patients should be informed of the possibility of rejection and that they should go to the ophthalmologist as soon as possible in case of loss of vision, discomfort, ocular redness or photophobia, since early diagnosis and treatment clearly improve the prognosis.

If present, both epithelial and stromal rejection usually respond well to topical corticosteroids at lower doses than in endothelial rejection. Unlike the latter, they rarely reach irreversible opacity of the cornea, unless fibrovascular invasion of the interface occurs. We can differentiate 3 forms of presentation of rejection in patients with DALK:

Epithelial rejection

It occurs in the first months after surgery, during the period when the donor epithelium has not yet been replaced by the recipient's epithelium. The cellular infiltrate in the epithelium forms a wave that advances along the corneal surface, the so-called epithelial rejection line (Figure 4).

Sub-epithelial infiltrates

Krachmer and Alldredge⁹ first described them in 1978. They look similar to those typical of adenoviral keratoconjunctivitis and represent an early sign of rejection. They can appear alone or associated with epithelial or stromal rejection. They respond very well to topical corticosteroids and do not usually leave residual opacity.

Stromal rejection

Its frequency has been estimated between 1.4% and 12%, and it has been related to the postoperative corticosteroid regimen^10-12. It presents as an infiltrate in the stroma of cellular appearance, generally accompanied by neovascularization (Figure 5). It can be associated with localized stromal edema, a sign that the reaction compromises the endothelium. Lower endothelial counts have been reported in patients with DALK who have suffered episodes of stromal rejection¹². It often starts in an area of ​​loose and/or vascularized sutures. From there, the cellular infiltrate and stromal opacity will progressively spread, although in most cases topical treatment with corticosteroids is sufficient to stop and reverse this process. The intensity and duration of treatment will depend on the severity and extent of the rejection, and only some authors associate systemic corticosteroids¹⁰. The prognosis is generally good, and the corneal transparency is recovered as long as the treatment is not delayed excessively.

Vascularization in peripheral donor-recipient scar is an important risk factor for rejection and if it is not treated in time it can lead to an invasion of the interface that, once produced, has a difficult solution. As a coadjutant and preventive treatment of stromal rejection in patients with DALK, good results have been described with the injection of anti-VEGF (bevacizumab) plus cauterization of the nutritional vessels¹³ (Figure 6). To prevent stromal rejection, other authors recommend removing sutures early and maintaining low doses of corticosteroids in the long term¹⁰.

PROBLEMS RELATED TO THE INTERFACE

In this section we will briefly discuss some aspects related to the graft-receptor interface, which can affect vision in the postoperative period.

Folds at the interface

We can differentiate 2 types of folds in the interface of a DALK. Some are peripheral and circular, do not usually affect vision and generally disappear slowly over time. The others, straight, cross the cornea horizontally or vertically and may limit vision if they affect the central area. These may disappear over time, but they do not always do so. The frequency of folds at the interface varies according to the characteristics of the recipient and has been estimated in around 10% of cases¹². They are observed especially in cases of keratoconus with very marked ectasia, which points as a cause to an excess of DM/PDL that folds due to the smaller area of ​​the posterior face of the graft. Therefore, to minimize the appearance of folds in this type of patients, some authors recommend a diameter of the graft 0.50 mm greater than trepanation in the recipient¹⁴.

Opacities in the interface

In some patients with DALK we can observe areas of opacity or fibrosis in the interface that can affect vision. They are usually caused by an irregularity in the dissection of the donor or recipient stroma, or by remnants of stromal lamellae on the receiving DM/PDL. They tend to diminish over time and the vision slowly improves months or years after surgery. To prevent them, the DM of the donor must be extracted carefully, avoiding tearing or producing irregularities in the stroma. In addition, the dissection in the recipient must be regular, trying to expose the DM/PDL in a clean and complete way.

Epithelial growth at the interface

The epithelial growth at the interface is exceptional in the DALK – unlike in SALK – provided that the donor button and the recipient tissue are in good apposition and levelled at the end of the intervention, and the sutures have the adequate disposition and tension. This complication usually occurs only in cases of dehiscence of the suture or lysis of the graft that make possible the passage of the superficial epithelium towards the interface. When this occurs, the graft should be lifted, and the epithelium cleaned completely on both the stromal side and the recipient bed. This maneuver has to be very careful to avoid tearing of the DM/PDL. To reduce this risk, it will be useful to decrease the tension in said layer by means of a paracentesis of the AC. The new sutures should be made with adequate proximity and tension to avoid recurrence of epithelial growth.

Growth of neovessels at the interface

It is usually observed in sectors with loose or broken sutures, or in the presence of inflammation or infection in the stroma. The virtual space at the interface between the donor stroma and the receiving bed of a DALK facilitates the growth of neovessels in a faster way than can occur in a PK. Such growth in turn increases the risk of stromal rejection. For this reason, it is recommended to treat it without delay by intrastromal or subconjunctival injection of antiangiogenic drugs, whether or not this is associated with cauterization¹³.

Visual limitation due to insufficient dissection

The vision that can be expected after a DALK depends on the type of dissection. The so-called descemetic, in which we expose the DM/PDL completely (Figure 7), provides excellent postoperative vision but has a greater risk of intraoperative perforation. The predescemetic techniques (Figure 8), which leave some lamellae of the recipient stroma ahead of the DM/PDL, have a lower risk of perforation but get lower visions.

Although the predescemetic technique has utility in cases of high risk of rejection or recurrence of the pathology, with it the visual recovery will be slower and limited. This problem can be increased if the posterior stromal portion of the receptor that is left on the bed present opacities or pathology that may recur.

Deep anterior lamellar keratoplasty (DALK) provides clear advantages over penetrating keratoplasty (PK) for the treatment of corneal diseases in which the recipient endothelium remains intact¹. These advantages have already been discussed in other chapters of this book, although the main one is the elimination of the risk of endothelial rejection², the main cause of PK failure. Consequently, the causes of failure of DALK are of a different nature than in PK.

The outcome of a DALK can be affected by intra- or postoperative complications that compromise the transparency of the stroma or the donor-recipient interface, such as the recurrence of corneal dystrophies (Figure 1), the recurrence of a herpetic keratitis (Figure 2) or the eventual development of other infections (Figure 3). The presence of opacities at the interface may be of residual origin due to a preexisting pathology that has not been resected, due to recurrence of a dystrophy at that level (Figure 4) or due to excessive scarring that causes fibrosis or due to neovascular or fibrovascular invasion.

An excess of residual posterior stromal tissue (> 50-60 μm) will also limit visual recovery in cases of predescemetic DALK performed by manual dissection techniques (Figure 5). Although endothelial rejection is not possible, epithelial and stromal types may occur, which, if not treated in time, can cause irreversible opacities.

Finally, secondary procedures for the treatment of residual refractive errors may present with persistent opacity – like haze after PRK –. The ease of replacing a DALK is one of its advantages; to maintain others, such as the integrity of the globe and respect for the recipient endothelium, graft replacement may be the best option in the face of a poor visual outcome or other cause of failure. Some authors consider it the technique of choice even in cases of poor vision due to irregular or high astigmatism in the absence of opacity³. Table 1 shows the main causes of re-transplantation after DALK.

SURGICAL TECHNIQUE

The substitution of the graft by another new one with similar characteristics is the obvious solution for the alterations of the stroma of a DALK, whether residual or acquired. In the presence of excessive residual stroma at the interface, new opacities or materials deposited at that level, it should be evaluated if they can be eliminated maintaining the integrity of the posterior lamina – Descemet's membrane (DM), Dua's pre-descemetic layer (PDL) and the healthy recipient endothelium. The replacement of a DALK does not usually affect endothelial survival and visual recovery does not differ from the primary procedure, so it can be repeated more than once³.

The surgery is relatively simple and in general does not require special maneuvers (pneumo-dissection or otherwise) to separate the DM/PDL. This eliminates one of the most compromised steps of the DALK. The surgical scar of the previous procedure, as well as the adherence between the donor tissue and the recipient bed are the critical points to successfully replace the DALK, especially if it is done years later. In general, the donor tissue can be separated from the recipient quite easily^3,4,5. One aspect that can make this maneuver difficult is the presence of vascularization in the graft or the interface. The replacement procedure can be broken down into a series of steps that we describe below.

Opening of the previous trepanation

The first surgical step and sometimes the most difficult one is to reopen the edges of the old trepanation. This superficial separation can be done manually – after scraping the epithelium, continuing with blunt dissection of the surgical scar⁴ – or we can perform a new trephination of about 250 μm in depth, which must coincide with the previous scar³. Through manual dissection, we ensure that the primary surgical wound is opened, but there is the disadvantage that the edges may be somewhat irregular, which could affect the postoperative corneal curvature and lead to irregular astigmatism^3,6. The new partial thickness trepanation has the advantage of creating more net edges, but there is a risk that it does not coincide exactly with the old one and generate a double scar.

Complete separation of the peripheral graft-recipient scar

Once the superficial opening of the edges of the old trepanation is obtained by either method, the separation in depth of the same is easily done by blunt dissection in the 360° until reaching the original receiving bed, which is distinguished by its smooth appearance³.

Graft separation from the recipient bed

Once the dissection of the vertical scar of the primary DALK has been completed in 360°, the graft can be easily removed by gentle traction, since usually no adhesions are formed between donor and recipient in this plane, which is usually maintained as a virtual space for at least 4 years³ (Figure 6).

Cleaning of the recipient bed

A thorough cleaning of the recipient bed should be carried out to eliminate deposits, neovessels, fibrosis, etc., which may be or have been formed at that level. If there is excessive residual posterior stromal tissue that has conditioned visual recovery, a new pneumo- or visco-dissection can be performed, although we again face the risk of rupture of the DM/PDL complex (Figure 7).

The surgery is completed just like the primary one: trepanation of the new donor graft, to which we remove the endothelium and suture it to the recipient cornea.

ALTERNATIVE TECHNIQUES

After the failure of a DALK, other surgical techniques other than replacement by a graft of the same type can sometimes be considered:

• Anterior keratectomy – especially with laser (PTK) –. It will be useful in very shallow opacities, generally not more than 100 μm deep. For example, in the case of subepithelial recurrences, or in the superficial stroma of certain dystrophies, or subepithelial scars, or in cases of opacity (haze) after PRK.

• Superficial anterior lamellar keratoplasty (SALK). Useful in the same situations as the previous one, when the opacities are less superficial, up to 200 μm deep.

• Endothelial keratoplasty (DSAEK or DMEK). In case of endothelial failure that occurs in a DALK without stromal opacities, such as in herpes that recur with endothelitis, or after an intraoperative rupture of the DM/PDL that cannot be successfully resolved.

• Penetrating keratoplasty. It will be the only option when there is both endothelial failure and stromal opacity, such as after herpetic recurrence with endothelial failure and stromal scarring. It is also recommended for therapeutic purposes in early infections of the interface, typically fungal (see chapter 5.6.4).

In order to decide the indication and to plan the surgery, it is important to specify the depth and extension of the opacities in the graft that are responsible for the visual loss. For this purpose, anterior segment OCT of spectral domain is a valuable aid, as well as confocal microscopy (Figure 8A-D). In this way, it is possible to decide if the most convenient procedure is a new DALK or, in superficial opacities, a SALK or even a PTK can suffice. They also make it possible to determine if the dissection of an excessive residual stroma or other materials in the bed will be necessary (Figure 5). Likewise, it is important to evaluate the recipient's endothelium, whenever possible, to ensure its viability – although it has already been pointed out that DALK re-transplantation does not involve significant endothelial damage.