When cataract and corneal endothelial disease co-exist in a patient, we wonder how much each one contributes to visual loss. We can propose a surgical solution for each one separately or do it in combination. The problem is to decide in each case which is the most successful. On the other hand, one of the complications of cataract surgery is endothelial decompensation (Figure 1) which, despite being less frequent with modern phacoemulsification techniques, remains one of the main indications for an endothelial transplant by the high number of cataract surgeries performed.

ENDOTHELIAL LOSS IN CATARACT SURGERY

Risk factors

The estimated endothelial loss in phacoemulsification surgery varies between 8 and 13% according to various publications^1,2. This loss can vary depending on various aspects such as the hardness of the cataract and the experience of the surgeon. Other factors that can increase endothelial damage are prolonged ultrasound time, a short axial length, rupture of the posterior capsule and diabetic patients^3-5. This is especially important when endothelial dystrophy coexists, above all because of its frequency, that of Fuchs (Figure 2). Although a low endothelial count does not predispose to greater loss during surgery, patients with poor endothelial reserve may suffer deterioration and the remaining endothelium not be able to keep the cornea clear. Some studies with penetrating keratoplasty (PK) confirm that cataract surgery can precipitate the need for a corneal transplant in patients with mainly endothelial dystrophies, but also patients with previous inflammatory or traumatic pathology.

Surgical approach

There are some important considerations during cataract surgery of patients with coexisting endothelial disease that should be considered to improve visualization and minimize endothelial loss:

1. Colorants: The use of trypan blue helps to perform the capsulorhexis and lacks endothelial toxicity if applied correctly.

2. Illumination: The stromal edema can produce reflections and dispersion of the coaxial backlight, which would hinder a correct visualization. The use of reflected light, such as with a slit lamp or an endo-light probe for retinal surgery, either outside the eye or through a paracentesis, improves the visualization to perform the capsulorhexis and the extraction of the crystalline nucleus⁷. The use of a Chandelier catheter has also been described as an aid to perform cataract surgery in patients with edematous keratopathy and to facilitate the completion of a complete descemetorhexis^8,9.

3. Viscoelastics: As protectors of the endothelium during cataract surgery. The "shield" technique combining a cohesive viscoelastic with a dispersive one seems to be the one that produces less endothelial loss and achieves less pachymetry in the postoperative period¹⁰.

4. Core extraction technique ("phako-chop" vs. "divide and conquer"): There seems to be no difference in relation to endothelial loss¹¹. In cataracts with hard nuclei the endothelial loss may be greater with a phacoemulsification than with an extracapsular extraction.

5. IOL selection: Lenses of hydrophobic material should always be used in patients with cataract and endothelial disease, because of the possibility that they may require further transplantation. The hydrophilic materials can be opacified in contact with the air we use to fix the endothelial graft¹².

COMBINED CATARACT SURGERY AND ENDOTHELIAL TRANSPLANTATION

It is difficult to predict the progression of corneal decompensation in patients with endothelial disease, so the indications vary from one author to another. In a 2005 paper in patients with Fuchs' dystrophy, the figure of 640 μm thickness was proposed as the limit from which there would be a need for a corneal transplant¹³. This recommendation has been adopted by the American Academy of Ophthalmology.

In our view, the mere measurement of corneal thickness is not enough to decide between a combined surgical approach or only the cataract. What should guide our procedure is the clinical appearance. That is, before a patient with Fuchs’ dystrophy, we must assess whether there are early signs of corneal decompensation, which would be a stage II (table 1). These are marked by a foggy morning vision that takes a few hours to clear up, although the slit lamp still may not show any edema. We can find ourselves in the following situations (table 2):

A) Cornea not decompensated, without cataract: We will only follow up. For this we periodically assess visual acuity and pachymetry. The endothelial study is not very practical in cases with numerous guttae since it is difficult to assess the progression of endothelial loss.

B) Cornea not decompensated and cataract: We will proceed to surgery only of the latter, with all the maximum care regarding endothelial protection (Figure 3). If the fellow eye has already undergone cataract surgery, its result may serve as an orientation.

C) Decompensated cornea, without cataract: Above 50 years of age it has been seen that the risk of developing cataract after ELK (DSAEK) is high^14,15, so we will indicate a combined surgery. There is also a higher risk in diabetic patients. If the patient is less than 50 years old, we will perform only the endothelial transplant (Figure 4).

D) Decompensated cornea and cataract: Combined surgery is indicated in all cases, either in the same session or the transplant deferred for a while (Figure 5).

COMBINED SURGERY: SIMULTANEOUS OR SEQUENTIAL?

If we have decided to intervene both pathologies, the two surgeries can be done in the same session or sequentially, that is, operate the cataract first and days or weeks later the transplant. The second has certain advantages and disadvantages. Among the first is to have a more stable anterior chamber at the time of keratoplasty, less risk of contacts between the graft and the lens, and less need for viscoelastic and therefore risk of interfering with the adhesion of the graft. In any case, if there is a complication during cataract surgery it is preferable not to do a transplant at that time. The disadvantages are, having to go twice in the operating room with their anesthetic risks and the consumption of surgical resources, greater possibility of infection and delayed visual recovery.

Among the supporters of simultaneous surgery, among which we find ourselves, we think that the complications of doing a triple procedure are not significantly greater and depend in large part on the learning curve. Terry in 2009 and other more recent authors find no difference between performing the surgery separately or in a single procedure, in terms of endothelial count and final visual acuity (VA )^16,17. Others agree with these findings but with a higher rate of secondary bubble reformations (re-bubbling) to achieve definitive adhesion of the graft¹⁸. Another important aspect is the time to do the surgery. When the cornea is decompensated after cataract surgery, transplant should not be delayed much longer, as the appearance of fibrosis, scarring and vascularization can make it difficult to perform and compromise the final VA (Figure 6). A term of less than one year is considered as the most advisable to do the operation^19,20.

COMBINED SURGICAL TECHNIQUE

The standard technique of cataract surgery by phacoemulsification combined with ELK (sometimes called phako-DSAEK) can be seen in video 6.5.1.1. We will consider a series of particularities:

Anesthesia

In general, a retrobulbar or peribulbar block is preferable, although it is also possible to perform it under topical and intracameral anesthesia with 1% lidocaine. This has the advantage of not needing to reverse the mydriasis after implanting the intraocular lens (IOL) to perform the transplant²¹.

Visualization

To have a good view of the structures of the anterior segment during surgery, we will have to remove the epithelium in most cases with corneal decompensation. The edematous epithelium comes out easily, simply with the help of a hemostat (video 6.5.1.2). It will also be useful to use trypan blue to perform the capsulorhexis, which can also stain Descemet's membrane, which facilitates descemetorhexis.

Capsulorhexis

When performing a combined surgery, it is advisable to make a capsulotomy smaller than usual, 4-4.5 mm, which completely covers the periphery of the IOL optics, in order to prevent it from dislocating during the maneuvers of the keratoplasty.

Viscoelastics

We recommend using only the cohesive type (Healon^®, etc.) that are easily removed from the anterior chamber at the end of phacoemulsification and the IOL implant. This will compromise graft-receptor adhesion less. You can also do the descemetorhexis before removing the viscoelastic (video 6.5.1.3).

Type of IOL

It is preferable to use a monofocal aspheric IOL since the ELK (DSAEK) induces a certain spherical aberration. Toric IOLs are not recommended, as astigmatism can change, nor multifocal ones because of the possible limitation in contrast sensitivity. Hydrophobic material should be used, since the calcification of the anterior surface has been described with the hydrophilic ones, due to the concentration of solutes in the space under the bubble of air or gas that is used to initially fix the graft (Figure 7)^12,22. In addition to the hydrophilic material, factors such as high intraocular pressure and the need to reinject air have been associated with this complication.

Hyperopic shift

The greater thickness at the edges of the lenticule carved with microkeratome produces an increase in the posterior corneal curvature, which induces a change towards hyperopia of about 1.5 diopters^23,24. This must be considered when calculating the appropriate IOL for a triple procedure with this type of grafts.

Corneal drainage incisions

This type of maneuvers to avoid the residual fluid in the interface and to favor the adhesion of the graft can be more indicated in complex situations, of which the combination with cataract supposes a first degree (video 6.5.1.4).

Phakic IOL explant

In patients with phakic IOL who have developed cataract and corneal decompensation, it is possible to perform "quadruple procedure" with good results, adding the phakic IOL explant to the previous one (Figure 8, video 6.5.1.5)²⁵.

POSTOPERATIVE PERIOD

A therapeutic contact lens is placed until corneal re-epithelialization, which in older patients may be slower and require other aids. Therefore, it is preferable to use products without preservatives whenever possible. In addition to the standard treatment with corticosteroid and antibiotic eye drops, it is advisable to add topical non-steroidal anti-inflammatories to reduce the risk of cystic macular edema, a more frequent complication in the case of combined surgery than when only the transplant is done²⁶. Visual recovery is slower, and it is not uncommon for it to take up to 3-6 months to reach the maximum.

Endothelial transplantation is currently the established surgical technique to treat endothelial alterations, since it provides a faster visual recovery, better visual results and fewer complications than penetrating keratoplasty (PK)¹. Relationships between endothelial lamellar keratoplasty (ELK, DSAEK) and glaucoma, can be considered in two senses:

1. Patients with glaucoma – in medical treatment or already operated for glaucoma – who subsequently require an ELK.

2. Patients undergoing ELK who develop ocular hypertension or glaucoma – whether or not directly related to the transplant – and will require medical or surgical treatment.

GLAUCOMA PRIOR TO ENDOTHELIAL KERATOPLASTY

Performing an ELK in patients operated on for glaucoma, either with filtering blebs (Figure 1) or with drainage devices (DD), presents the difficulty of maintaining air in the anterior chamber (AC) at supraphysiologic pressures, since drainage allows its outflow^2,3. However, once the balance between the pressures of the subconjunctival space and the AC has been reached, the intraocular pressure (IOP) can be increased. In patients with DD, it is not uncommon for the tube to be poorly positioned and close to the endothelium (Figure 2) – a reason that may have contributed to corneal decompensation. All this can hinder the unfolding, centering and adhesion of the graft. On the other hand, these patients may present associated conditions that hinder surgery such as: large peripheral iridectomies, aphakia, narrow AC, peripheral anterior synechiae and vitreous in AC. It is important to identify all these aspects before surgery, and to anticipate solutions.

Surgical technique

When operating ELK patients with previous glaucoma surgery, certain aspects should be taken care of:

-Facilitate the unfolding and centering of the graft. In cases with a drainage tube, it is advisable to implant a disc with a smaller diameter (≤ 8 mm) so that it does not contact the tube, and to check the situation of the tube. If it is very peripheral, close to the iris and away from the endothelium, it is not necessary to act on it. Otherwise, it is necessary to evaluate the possibility of trimming it – so that it does not reach the central 8 mm or contact the endothelium – or move it to a more posterior position, either in front of the iris, in the posterior chamber through the iris root or in the vitreous chamber. If none of the above is feasible, it has been proposed to cut a semicircle with a 3 mm trephine at the periphery of the graft to accommodate the tube⁴.

-Ensure adequate IOP in the initial postoperative period. The most important factor for adhesion of the graft is to maintain a sufficient, relatively high IOP in the initial postoperative period. Although they may favor it, peripheral stromal scraping^5,6 and corneal drainage incisions⁷ play a secondary role. The risk of graft detachment is greater in the case of hypotonia, while the risk of perforation of a filtration bleb is very low⁸. It may be useful to lengthen the times when AC is completely filled with air after graft implantation or supine decubitus in the early postoperative period⁹. In cases with DD it can be difficult to reach a high IOP, so it has been suggested to plug the entrance of the tube with viscoelastic. The injection of SF₆ gas¹⁰, the continuous infusion of air for 10 minutes maintaining the IOP around 30 mmHg¹¹, or the Trendelenburg position in the first 2 hours postoperatively to avoid air filtering through a superior bleb³ have also been proposed. When planning for high pressure and its duration, it is necessary to consider the pre-existing damage, since it may be harmful in patients with advanced glaucoma.

-Solve other associated problems, such as large iridectomies, aphakia, anterior synechiae, AC lenses or vitreous bridles.

Results and complications

ELK in patients previously operated on for glaucoma is a viable option and generally obtains good results, although the technique is somewhat more difficult than in non-operated eyes (Figure 3). However, the data on complications are not homogeneous. In some studies, the frequency of early intraoperative or postoperative complications is not higher than in the cases of ELK (DSAEK) without previous surgeries⁸. In a series of 227 DSAEK in eyes with trabeculectomy or DD, good visual results were obtained without an increase in graft dislocations, rejections or primary failures compared to cases without prior surgery¹². In another series of 462 DSAEK with or without previous glaucoma surgery – both trabeculectomies and DD – early intraoperative and postoperative complications were similar in both groups, but secondary graft failures were more frequent in patients with prior glaucoma surgery (15.9 % versus 3.2%)¹³. Although a higher frequency of graft dislocations could be expected a priori in these patients, the published series are contradictory^14,15: this complication seems more frequent in eyes with DD – where it reaches up to 36.4%¹⁶ – than in cases with trabeculectomy¹⁷.

In patients with Ahmed type DD, the survival of the ELK at 12 months has been similar to that of PK¹⁸. However, DD are a limiting factor in the survival of a penetrating graft, between 42% and 96% at one year according to the series¹⁹. This percentage drops to become null at 5 years²⁰. In principle, an ELK in an eye with a failed PK would have advantages over a penetrating re-graft. However, Pedersen et al²¹ found that, in failed PKs with glaucoma, the risk of graft failure and rejection was greater with ELK than when a new PK was performed. In ELK after PK with endothelial failure, the presence of DD reduces graft survival at 4 years from 96% to 22%²².

Good results have been reported with ELK in some less frequent types of glaucoma such as in buphthalmos²³, in a case of iridocorneal endothelial syndrome previously operated with a Baerveldt valve that presented a retrocorneal membrane²⁴, as well as in congenital glaucoma by ELK without descemetorhexis (non-DSAEK)²⁵. The combined surgery of non-perforating deep sclerectomy (NPDE) and ELK is an option of special interest in patients with glaucoma and endothelial dysfunction, since it can be performed in a single surgical time and has a lower risk than trabeculectomy of graft detachment due to early hypotony²⁶.

GLAUCOMA AFTER ENDOTHELIAL KERATOPLASTY

Several studies indicate that an increase in IOP is frequent after ELK^12,16,27,28. There are several possible mechanisms of persistent hypertension and glaucoma after ELK. If air passes to the posterior chamber during surgery and remains behind the iris when the patient is in the supine position, peripheral anterior synechiae may form. An intermittent pupillary block could also create these, when the patient already has the head raised, by effect of a bubble that comes to cover the pupil. Other mechanisms include the prolonged use of corticosteroids, angle distortion, inflammatory glaucoma and pupillary block¹. Although the corneas operated by ELK (be it DSAEK or DSEK) have a greater total thickness than usual, a good correlation has been observed between Goldmann applanation and dynamic contour tonometry, so that measurements with the former should not be adjusted²⁹.

The frequency of glaucoma after DSEK varies between 0% and 45%¹. In a series of 211 consecutive cases of ELK (DSAEK), IOP >25 mmHg was found in 97 cases (45%). Of these, close to half (53 eyes) were only responders to corticosteroids, 17 had a history of primary glaucoma, another 17 had pseudo-exfoliative glaucoma and 10 had a pseudo-exfoliation without glaucoma. To control the IOP elevation, corticosteroids were reduced in 6 eyes, hypotensive medication was prescribed in 26 and both measures in 46; 16 eyes required surgery and 3 did not require treatment²⁷. In another series of 54 eyes with pseudophakic corneal edema, it was necessary to increase glaucoma treatment in 41.2% of those treated with ELK, and 5.9% required surgery, proportions that were comparable to those of patients operated on by PK in the same series²⁸.

The surgical treatment of glaucoma after ELK is usually performed by trabeculectomy or DD. Boey et al³⁰ showed better results in the reduction of IOP by trabeculectomy in patients operated on for ELK than in patients with PK. We have observed that NPDE is a good option in these patients (Figure 4)³¹.

It is not uncommon to find patients with corneal decompensation associated with vitreous-retinal pathology, or those who have developed it after a vitrectomy. They often have associated problems such as lack of capsular support with aphakia and iris defects. In these cases, an endothelial lamellar keratoplasty (ELK or DSAEK) is preferable to a penetrating keratoplasty (PK) because of the advantages of working with a closed eyeball and avoiding its collapse. However, endothelial transplantation here faces a special difficulty in achieving adequate adhesion of the graft. Its dislocation is more frequent due to the tendency to hypotonia at the end of the intervention, as it also occurs in cases with previous glaucoma surgery¹. On the other hand, because many of these eyes have lost the natural separation between their chambers, the handling of the air or gas bubbles that normally serve to fix the graft becomes complicated. In some situations, a combined procedure of vitreous-retinal surgery with ELK may be considered.

ENDOTHELIAL LAMELLAR KERATOPLASTY IN VITRECTOMIZED EYES

ELK surgery in patients who have undergone pars plana vitrectomy varies, depending on whether or not there is irido-capsular support.

Preserved irido-capsular diaphragm

In patients who retain the iris diaphragm and intact capsular support after vitrectomy, the ELK technique will not vary from the usual one (Figure 1). The main precaution will be to ensure that in the end the eyeball does not remain hypotonic. To obtain the appropriate tone, we recommend the injection of balanced saline solution (BSS) by pars plana with a 30 G needle (Figure 2).

Even when working with a closed eyeball, it is common for scleral collapses to occur during this surgery in vitrectomized eyes despite having an anterior chamber (AC) maintainer in place, so it is very helpful to have an infusion catheter in pars plana (Figure 3, video 6.5.3.1)².

Defects in the irido-capsular diaphragm

Successful completion of an ELK is a major challenge in vitrectomized eyes and in total or partial absence of the irido-capsular diaphragm.

We can consider two scenarios:

A) Partial irido-capsular defect. In the presence of a certain residual irido-capsular diaphragm that allows maintaining an air bubble in the AC without passing into the vitreous chamber, we will proceed in the usual way, assisted by a pars plana infusion². This will be especially useful when the capsular barrier is missing and, above all, if the aphakia is complete, because it allows to keep the eye pressurized and to inject air through it at the end of the surgery, until the adhesion of the graft is achieved.

Implantation of an intraocular lens (IOL), either on capsular remains (Figure 4) or sutured or fixed to the sclera (sulcus) (Figure 5), may facilitate the pressurization of AC with air at the end of surgery. Another possibility is to place cohesive viscoelastic covering the defect of the iris to prevent the passage of air into the vitreous chamber³.

B) Severe or total irido-capsular defect. If, when injecting air, it immediately passes into the vitreous chamber, it will be very difficult to obtain a bubble that stabilizes the graft. Sometimes it is possible to close the defect with a temporary iris suture, which allows the descemetorhexis to be safely performed, the insertion and centering of the graft and the pressurization with air until its adhesion is achieved, and at the end it is removed. If the spontaneous adhesion of the graft is not achieved, we can fix it with sutures. These can be passed through the graft before insertion in the AC and then anchoring them to the recipient cornea⁴, or they can be placed once the button is positioned against the receptor stroma (Figure 6, video 6.5.3.2).

ENDOTHELIAL LAMELLAR KERATOPLASTY COMBINED WITH VITRECTOMY VIA PARS PLANA

When corneal decompensation coexists with a condition that requires vitreous-retinal surgery – retinal detachment –, lens dislocation or IOL to vitreous chamber, etc., simultaneous surgery with ELK or sequential surgery may be considered. The decisive factor in these cases is the visibility through the edematous cornea: if it does not allow vitrectomy – or after removing the epithelium and applying glycerin – it will have to be postponed until a second time after the transplant regains transparency. This leads to greater endothelial loss, although it rarely involves a risk of graft decompensation⁵.

In most cases, removing the corneal epithelium will give enough transparency to address the vitreous-retinal surgery and we can perform the ELK immediately. We will have the advantage of having an infusion route via pars plana, so the AC maintainer will not be needed. The pupil should be contracted with acetylcholine. Once the graft is introduced, we change the infusion of liquid to air, which when passing to AC will keep the disc stuck against the stroma. At the end of the surgery it is important to close the sclerotomies thoroughly. Through the last one we will add BSS to ensure a sufficiently high ocular tone. If the patient is aphakic and uncooperative to maintain the supine position in the postoperative period, we must consider suturing the graft to avoid its dislocation (video 6.5.3.2).

COMPLICATIONS

In vitrectomized eyes, complications of ELK are more frequent, especially graft detachment and dislocation. When this occurs, several maneuvers have been described to resolve it, in addition to air reinjection. Placing the patient in the prone position allows gravity to help reapplication of the graft⁶. In the absence of "vitreous counterpressure", if the action of the air or gas in AC is not sufficient to keep the graft stuck to the stroma, its own weight in that position can be helpful (Figure 7). It has also been proposed in vitrectomized patients and/or without irido-capsular support to fill the AC with viscoelastic to reposition the dislocated graft⁷.

An exclusive complication of the ELK in vitrectomized eyes is the dislocation of the graft to the vitreous chamber. Since it entails a serious threat to visual recovery, it is advisable to resolve it immediately⁸. The graft can be extracted with vitreous-retinal forceps from a temporary scleral incision⁹ or a classic approach can be performed, with three pars plana routes to re-float the graft with the help of liquid perfluorocarbon and complete the ELK in the same surgical act¹⁰.