Ординатура / Офтальмология / Английские материалы / Corneal Endothelial Transplant (DSAEK, DMEK & DLEK)_John_2010

Introduction

Before the 1930s, lamellar keratoplasty was the favored transplantation procedure for corneal opacification (See also Chapter 14, History of Lamellar and Penetrating Keratoplasty). Magitot in 1913, successfully performed lamellar autografts for small, central corneal scars and in 1916 treated recurrent pterygia with lamellar transplan-tation.1-3 After the 1930s, penetrating keratoplasty (PK) has become the gold standard to manage surgical corneal disorders. Despite the advantages of lamellar procedures, such as less risks of intraocular complications and allograft rejection, PK increased in popularity while lamellar keratoplasty steadily declined.1-3 The main drawbacks of a lamellar procedure may be that the procedures are surgically demanding and carry the risk of interface haze development reducing the best corrected visual acuity. However, in the 1960s, Malbran described the “peelingoff” technique, in which the recipient cornea of patients with keratoconus was removed by applying traction to the partially dissected cornea overlying the cone.4-6 Other authors describe a surgical technique for lamellar keratoplasty that consists of a partial trephination of the anterior corneal stroma, and a single plane dissection of the recipient stroma. The depth of resection is judged by the corneal structure and the location of the Descemet’s membrane, which is recognized by its “glossy” appearance. It is often demanding to meticulously dissect the recipient stroma, especially when variable corneal thicknesses are present in the diseased stroma, which increases the likelihood of corneal perforation. In other words, by performing a PK, one is usually able to skip the challenges of a lamellar dissection.7

In 1972, Barraquer was the first to describe the use of the microkeratome in lamellar keratoplasty8 (See also Chapter 14, History of Lamellar and Penetrating Keratoplasty) Previous to the introduction of the microkeratome, lamellar keratoplasty was a tedious and time-consuming manual process used for reconstructive or tectonic surgery, rather than for optical purposes. The approach then consisted in performing an intralamellar dissection of the anterior corneal stroma creating a cap using a piriform spatula. The flap was lifted, and the posterior recipient stroma was trephined out. The tissue was replaced with a donor posterior lamellar button and the overlying flap was then sutured into place. With the application of the microkeratome technique there was an increase in the speed of the operation, but not necessarily in the final quality of vision. Barraquer also outlined the conditions to achieve good visual results with lamellar keratoplasty: (1) achieve the deepest possible interface to reduce scarring, (2) create a posterior layer of uniform

thickness, (3) perform smooth surface sectioning of both the graft and bed, (4) make the graft tissue of appropriate thickness, (5) obtain the highest quality donor material, (6) ensure good coaptation of the edges and uniform traction of the sutures, and (7) make sure there is perfect cleanliness of the interface.8 These conditions have served as a directive for the evolution of lamellar grafting techniques over the subsequent 30 years.

Penetrating Keratoplasty

The total number of cases of corneal transplants with reported recipient diagnoses in the United States in the year 2000 was 31,532, which represents 67% of the corneas distributed by the 80 US eye banks. The most common recipient diagnosis among these cases was pseudophakic bullous keratopathy accounting for 19.6% of the cases.9 Other major indications for PK include Fuchs’ dystrophy, keratoconus, aphakic bullous keratopathy, and regraft. Corneal endothelial failure due to dystrophies or trauma ultimately accounts for most of the cases requiring corneal transplantation. Up to 53% of the US grand total of corneal transplants comprises some form of endothelial cell dysfunction.10

PK is a safe and effective method for restoring corneal transparency and obtaining improved visual acuity in posterior corneal disorders, but it can be complicated by high and/or irregular astigmatism,11-13 insufficient wound healing,14,15 prolonged recovery time, and tissue rejection.16,17 Wound dehiscence after PK may also occur from days to decades after transplantation. Although some patients retain clear grafts and excellent vision following wound dehiscence repair, others suffer significant visual loss, most of whom have associated ocular complications. Mechanisms of injury producing wound dehiscence tend to be mild to moderate blunt trauma (i.e., poked with finger, hit with an object, or punched in the eye), which would be unlikely to rupture a globe in an intact cornea.14,15

Graft failure after PK can be defined as an irreversible loss of graft clarity due to endothelial cell failure.18 Repeated corneal graft rejection reactions may lead to graft failure. Previous studies have highlighted risk factors for graft rejection reactions after PK.19,20 The Collaborative Corneal Transplantation Studies Research Group identified a recipient age less than 40 years, a history of corneal graft, a combined surgery, a graft diameter more than 8.0 mm, and recipient corneal neovascularization as significant risk factors for rejection reactions.19 Rates of graft rejection reaction depend on the series and range from 3.5 to 65%, according to the extent of the recipient corneal neovascularization.20

Corneal transplantation is characterized by an overall high first year graft survival rate that reaches 90%, of cases with only local immunosuppression.16 Some long-term studies reflect that a graft survival in low risk conditions (keratoconus, corneal dystrophies) remains over 90% after 10 years of follow-up. However, the 10-year success rate in high risk recipients (with a history of anterior segment inflammation, corneal neovascularization, etc.) is much lower, achieving less than 35%.16,17

There are other studies in which cases were not divided inlowandhighriskconditions.Thesestudiesreportedthat the graft survival rate at 5-year follow-up for Fuchs’ dystrophy was 85%, pseudophakic bullous keratopathy 84%, and re-grafts 55% with an overall graft survival of 66%.15

Primary graft failure is a gradual corneal decompensation, unresponsive to corticosteroids, and with no history of a rejection episode. It is the most common cause of late graft failure, causing more than 90% of failures beyond 5 years post-keratoplasty.21 Endothelial cell loss rate is a good indicator of the PK outcome. Endothelial cells are indispensable to retain clear grafts and excellent vision after corneal transplantation. An overall endothelial cell loss of approximately 33% has been reported 1 year after PK,22 and the cell density has been found to continue to decrease at an accelerated rate up to 20 years after surgery.23,24 This finding suggests that after the initial surgical trauma, donor endothelial cell survival is compromised in the host ocular environment.25

Another factor that affects quality of vision after PK is surgery-related astigmatism. Many patients with successful corneal grafts have poor vision postoperatively associated with disabling astigmatism. A full spectacle correction of the postoperative refractive error is often poorly tolerated because of anisometropia. Contact lenses are effective in restoring good vision and binocularity in some but not all patients.26 Studies report that early postoperative astigmatism levels vary between 3.0 and 7.0 diopters and are rarely less than the baseline preoperative astigmatism in patients without keratoconus.11-13 Other long-term study suggests that the best corrected visual acuity at 5 years is 6/18 in 53% of cases while the mean keratometric astigmatism is 3.4 diopters.15

Posterior Lamellar Keratoplasty

Newer techniques of lamellar corneal surgery aim at selective replacement of the diseased endothelium in posterior corneal disorders such as Fuchs’ dystrophy, pseudophakic bullous keratopathy and aphakic bullous keratopathy. These diseases have been the subject of study in the last few years.27-30

Currently, there are two main approaches for corneal endothelium and posterior stromal transplantation in

Posterior Lamellar Keratoplasty. In 1998, Busin and coworkers, inspired by previous work of Barraquer, accessed the posterior stroma by creating an anterior flap with the use of a microkeratome.29 They named this lamellar flap approach as endokeratoplasty (EKP). The other approach is through a sclerocorneal pocket incision that was first described by Melles and co-workers in 199831 (See also Chapter 14, History of Lamellar and Penetrating Keratoploasty).

Microkeratome-assisted Posterior Lamellar Keratoplasty

Lamellar corneal surgery has become more popular in the last decade with the development of the laser-assisted in situ keratomileusis (LASIK) and microkeratome instrumentation, now capable ofachieving an excellent cut quality.32 The smoothness of the cut surface may lead to a better surgicalt outcome with a clearer interface, which is essential to obtain a good optical result.33 In parallel, posterior lamellar keratoplasty is re-emerging as an alternative to PK in patients with endothelial cell dysfunction.

Busin et al reported the use of EKP in seven patients with aphakic bullous keratopathy (n = 2), pseudophakic bullous keratopathy (n = 4), and Fuchs’ endothelial corneal dystrophy (n = 1). To perform the procedure they placed a microkeratome on the cornea. The suction ring and its 160 μm base plate was used to create a central, hinged flap of approximately 9.5 mm in diameter and 160 μm in thickness. The flap was lifted and the central posterior recipient bed excised using a 6.5 mm trephine and corneal scissors.

On the donor side, the corneoscleral rims are prepared using two modalities. The first is simple trephination throughtheendothelialsideofacorneoscleralrimbymeans of a 7.0 mm hand-held trephine. The entire thickness of the donor cornea is transplanted to the recipient. A cellulose sponge is used to gently apply 70° alcohol for few seconds tothebuttonsurface.Afterwashingoutthealcohol,extreme care is taken to completely remove the donor epithelium from the button surface by means of a blunt spatula. The cardinal sutures are placed, and the flap is replaced and properly aligned. The flap is then sutured in position using arunning8-biteantitorque10-0nylonsuture.Inthesecond approach the donor corneoscleral rim is placed in an artificial anterior chamber, the chamber is filled with methylcellulose-basedviscoelasticmaterial,andananterior corneal disk is created with a 160 μm thick plate of the microkeratome.Thecorneoscleralrimistheninvertedona Kaufmantrephineblockanda7.0-mmbuttonisobtainedby

trephinationfromtheendothelialside.Theobtainedpartial thickness donor button is placed in the recipient bed, and suturedintopositionusingfourcardinal10-0nylonsutures. A running 8-bite antitorque 8-0 polyglactin suture is then placed around the circumference of the graft.29

Busin and co-workers concluded that EKP appeared to have the potential to restore sight to eyes with endothelial decompensation and to significantly reduce the time it takes to achieve useful vision. With the use of this technique all patients can be refracted as early as 1 month after surgery, a time when this is usually not possible for PK patients. Although the number of patients included in the study was small and follow-up was short, the technique appeared to hold great promise.

Scleral-pocket Incision Approach

The posterior lamellar keratoplasty technique described by Melles et al31 begins by filling the anterior chamber of the donor eye with air through a paracentesis. A 4.0 mm peripheral corneal incision is made, and with a custommade spatula,34 a stromal pocket is dissected across the cornea at 60% stromal depth, using the air-to-endothelial interface as a reference plane for dissection depth.35-37 A plastic strip is inserted into the pocket, and a corneoscleral rim is gently excised from the globe. The rim is mounted endothelial side up onto a punch block, and with a 7.0 or 7.5 mm punch trephine a full-thickness corneal button is excised. The button is placed endothelial side down onto a custom-made, spoon-shaped glide covered with a viscoelastic substance. The anterior lamella and the plastic strip at the lamellar interface are removed, so that a posterior lamellar disk is in situ on the glide.31

In the recipient eye, the anterior chamber is also completely filled with air through a paracentesis. The superior conjunctiva is opened, and a 9.0-mm partial thickness scleral incision is made. With the spatula, a stromal pocket is dissected across the cornea at 80 % stromal depth, using the air-to-endothelium interface as a reference plane for dissection depth. A custom-made, 7.0 or 7.5 mm diameter flat trephine is inserted into the pocket to excise a posterior lamellar disk. After perforation, remaining posterior corneal tissue is cut with custom-made microscissors, and the excised, recipient posterior disk is removed from the eye with fine forceps. The spoon-shaped glide carrying the posterior donor disk is introduced into the recipient stromal pocket, and the ‘same-size’ disk is slid into the recipient posterior opening. The scleral incision is closed with 10-0 monofilament nylon sutures.31

Terry and Ousley slightly modified this 9.0 mm incision stromal pocket technique and renamed it as deep lamellar

endothelial keratoplasty (DLEK).28 Melles and associates further described a modified technique (small-incision DLEK) in a clinical report in which a 5.0 mm scleral tunnel incision is performed in the recipient eye and a stromal pocket is dissected across the cornea, just above Descemet’s membrane, at a visually controlled depth. Then, trypan blue 0.06% is diluted 1:6 with balanced salt solution and injected into the stromal pocket to stain the stromal interface. An 8.5 mm punch trephine is used to make an indentation in the corneal surface epithelium to outline the size of the posterior lamellar disk that is to be excised. Custom-made curved microscissors are used to excise an 8.5-mm diameter recipient posterior lamellar disk. In a whole donor globe a corneal pocket is dissected at 80% stromal depth. Then the corneal disk is excised from the globe, and an 8.5-mm diameter posterior lamellar disk is trephined (endothelium to epithelium). After covering the donor endothelial surface with a viscoelastic material, the posterior lamellar disk is folded with the endothelium at the internal side, using a custom made inserter. After removing all air from the eye, the donor posterior disk is positioned into the recipient anterior chamber. After unfolding the posterior lamellar disk, it is positioned in the recipient posterior opening without suture fixation. The anterior chamber is then completely filled with air, and 5 minutes later all air is exchanged by balanced salt solution. No sutures are used to close the scleral incision.27

A midterm endothelial cell density was evaluated after posterior lamellar keratoplasty. Fourteen consecutive eyes with at least 3 years of follow-up were measured to determine the rate and the pattern of cell loss after this new approach for corneal surgery.38 The comparison was made using two different surgical approaches: in the disks that were implanted into the recipient eye by using a spoonshaped glide covered with viscoelastic or by folding the donor for implantation through a small tunnel incision. In the first group of patients, the endothelial cell counts averaged 2,062 cells/mm2 (27.6% cell loss) at 1 year postoperatively. Except for two, all eyes had an endothelial cell density of 2,000 cells/mm2 or more.38 A similar result was found by Terry and associates, who performed this procedure with some minor modifications in eight patients.39,40 These findings suggest that these techniques may cause considerable endothelial cell loss, but still within acceptable ranges. In addition, the first group showed a rapid decline of the cell density of endothelial cell density measurements in the following years to 1,126 cells/mm2 at 3 years (cumulative cell loss, 61%). However, this rate of cell loss appears to be similar to that after penetrating keratoplasty (53% SD 19).23,39 In the second group of patients, in which the donor tissue was implanted

after being folded, the average endothelial cell counts was 1,215 cells/mm2 at 1 year postoperatively.22 Authors finally conclude that donor endothelial cell density after posterior lamellar keratoplasty may be similar to that after conventional full-thickness penetrating keratoplasty.38

Last Advances in Posterior Lamellar Keratoplasty

Compared to full-thickness keratoplasty performed for corneal endothelial cell disorders, the 5 mm incision for posterior lamellar keratoplasty may represent an advantage because of: (1) a fast visual recovery with a relatively stable refractive error, (2) no sutures are used and the surgeryinduced astigmatism may be minimized, (3) suture-related complications are eliminated, and the risk of wound dehiscence is reduced. (4) suture removal is not required to monitor the astigmatism, and less frequent follow-up visits may be possible.27 However, this approach is laborious requiring a highly skilled surgeon and the endothelial cells may be damaged during the insertion of the donor tissue through the scleral tunnel.38

The creation of a flap by means of a microkeratome to perform a posterior lamellar keratoplasty (PLK) is easier and faster than the manually dissected slerocorneal approach, and the risk of damaging the endothelial cells may be lower. However, in the corneal flap technique, a minimal number of sutures are required to secure the corneal flap and the transplanted corneal disk, which still may be a disadvantage. Use of corneal sutures has been associated to several drawbacks following corneal surgery. A 5-year retrospective study of 361 grafts between 1993 and 1994 reported erosions over the nylon sutures in 10.8% of cases, infiltrates at suture entrance site in 9.4% and infectious keratitis in 3.3%.41 Similarly, the use of sutures in microkeratome-assisted PLK may induce some astigmatism, although significantly lower and for a shorter period than in classic PK.42

Behrens et al and Li et al previously reported 2 different techniques of PLK using an artificial anterior chamber and microkeratome.42,43 In thefirst report, they used 8 interrupted 10-0 nylon sutures in the stromal bed to secure the graft.42 In the second study, they used a running graft suture to secure the graft.43 The mean astigmatism in the first group was 3.3 D,42 and 1.47 D in the group in which running graft suture was used.43 During the execution of these two experiments, they observed that the transplanted corneal disk tended to remain attached to the flap stroma without sutures, when the pressure was within physiologic limits and the flap was secured (Behrens, unpublished data). The stromal surface tension at the donor-recipient interface

A

B

Figure 34-1: Miyake view (posterior approach) of the cornea with lens and uvea removed. A. White arrows show the line that demarcates the anterior flap edge. Blue arrows show the edge of the transplanted posterior stromal disk, smaller than the flap size. B. Stress exerted to the flap/disk adhesion by partially lifting the flap (blue arrow) with forceps (asterisk). Note that the donor disk maintains its location and adhesion to the anterior stromal interface without sliding.

together with a physiologic intraocular pressure, contribute to keep the disk in place without sliding. With the additional pump of endothelial cells, these adherent forces may be stronger. We have performed the sutureless approach of the donor disk in a Miyake approach to demonstrate the adherence of the donor disk to the flap (Figure 34-1).44 We therefore started performing microkeratome-assisted posterior lamellar keratoplasty in patients in year 2002, without using sutures to the grafted corneal disk, and only to the corneal flap. Transplant slippage after the surgery was not observed in these cases, and patients showed significant improvement in best corrected visual acuity after surgery, similar to what has been reported previously in the literature (Behrens, unpublished data).

Modified Microkeratome-assisted Posterior Lamellar Keratectomy (MMAPLK)

Piroushmaneshet al44basedonthesepreviousobservations developed a novel approach to solve the problem of flap suture-inducedastigmatismaftermicrokeratome-assisted posteriorlamellarkeratoplasty.A300µm-thickpartialflap keratectomywasperformedin8humandonorcorneoscleral rims using an artificial anterior chamber and a manual microkeratome. Differing from previously published techniques, this approach attempts to obtain a wide flap hingetoprovidemorestabilitytothewholecorneabyreducing the total corneal opening.39,42,45 After lifting the flap in the recipient cornea, a 6.25 mm trephinationwas performed to remove a disk of posterior stroma, Descemet’smembrane, andendothelium.Thedonordiskwasobtainedinasimilar fashion from a corneoscleral rim using an artificial anterior chamberwiththesametrephinationsize,andpositionedin a sutureless fashion in the recipient stromal bed. Only the flaps were secured either with a novel chondroitin-sulfate- aldehyde–based adhesive or standard nylon 10-0 sutures. The mean astigmatic change after surgery was 1.13 (SD 0.55)D for the adhesive group vs. 3.08 (SD 0.84) D for the suture group (p=0.008), and the mean resisted bursting pressure in both groups was close to 100 mmHg, without significant difference between groups.44

The use of tissue adhesive without any corneal sutures in this approach simplified the surgical technique, considerably decreased surgical time, and produced less corneal astigmatism. The major concerns of this technique are the stability of the graft because of the reduced support of the sutureless disk in the posterior stroma and the wide anterior opening with the flap. In the first case, the donor disk tends to be more stable compared to other similar approaches [especially that observed in the Descemet’s stripping endothelial keratoplasty (DSEK)], because in this approach we have a recipient bed with perpendicular cuts to the stromal lamellae. This wound configuration may induce a stronger healing than a simple apposition of collagen fibers, which may result in a disk more stable over time. Actual wound healing activity can be observed in perpendicular cuts at histology over time contrasted to the weak adhesion “LASIK style” of the donor disk in the DSEK technique. In the second case, the wider opening is certainly of concern. However, from the experience we have gathered from the two-step LASIK procedure in PK, there might be a stronger and faster wound healing response in these patients, possibly because of the particular wound configuration. During the two-step LASIK after PK, a corneal flap covering the trephination is performed in the first step, and the laser treatment is performed in the second step after stabilization of the surface corneal topography (at least

a month apart). It is common to observe significant adhesion of the flap in the area where the donor-recipient interface is located at the time of the flap lift, only after a few weeks. We believe that a similar event may occur in the microkeratomeassisted posterior lamellar keratoplasty, adding more strength to the wound and therefore, to the whole cornea.

Modified Microkeratome-assisted Posterior Lamellar Keratoplasty Surgical Technique

The modified microkeratome-assisted posterior lamellar keratoplasty (MMAPLK) is essentially similar to previously described techniques by Barraquer and others.8,29,42,43 In an attempt to reproduce a more stable postoperative cornea and reducethedependenceonsutures,awiderflaphingeiscreated in the recipient cornea as a result of a partial flap cut up to the pupillary margin (Figure 34-2). Since the flap hinge will obstruct some of the available stromal area for trephination, a dissection with a blunt spatula underneath the hinge is required to expose the stromal bed (Figure 34-3). After the spaceiscreated,ahandtrephinesmallerthantheflapdiameter

Figure 34-2: In the recipient cornea, a partial flap of 300 microns is created with a large hinge (arrows) that is just past the pupil but close to the pupillary margin.

Figure 34-3: The area underneath the hinge is dissected with a blunt spatula (arrow) in order to have sufficient space for the trephination of the posterior stroma and diseased endothelium.

Figure 34-4: A trephine is centered according to the flap margin (black arrow) to allow for some space for the flap to be secured with the adhesive. The hinge area is slightly pushed away with the hand trephine (white arrow) to cut the area that was previously undermined with the spatula.

Figure 34-5: The diseased posterior stroma is cut with scissors in the area underneath the flap hinge.

is placed on the stromal bed and a trephination is performed to discard the posterior stroma and diseased endothelial layer (Figures 34-4 and 34-5). A similar disk is obtained from a corneoscleral rim using an artificial anterior chamber, and placed in the recipient bed (Figure 34-6). The flap is then repositioned and a two component adhesive is applied to the flap edge to seal the corneal wound (Figure 34-7). We have observed in the lab that the adhesive tends to efficiently close the wound with comparable sealing capacity to standard sutures. Moreover, the advantage of a complete seal of the wound (flap) and less postoperative astigmatism may be factors of improvement over suture closure. We observed no donor button dislocations in any of the corneas we tested with this approach.

Corneal Adhesive

Sutures are the gold standard for corneal incisions and wound repair because of the efficiency and strength of the

Figure 34-6: The donor button of the same size consisting of posterior stroma and healthy endothelium is placed in the recipient bed.

Figure 34-7: The flap is repositioned prior confirmation that the bubbles in the interface are removed. Air in the anterior chamber should be left in place, as it helps promoting adherence of the disk (arrows) to the flap. Corneal adhesive (blue) should be applied to the flap edges.

closure. However, sutures may not be the ideal method for wound closure, especially in the cornea. Many corneal surgeons recognize that sutures can be a source of potential problems. Suturing is usually labor intensive and may lead to infection,46 induced astigmatism,47 erosion,48 foreign body sensation, and corneal vascularization,49 among others. In addition, suture removal is required when a nonreabsorbable material is used, which increases the number of patient visits, extends the follow-up period and results in higher costs and inconveniences to the patient.

Alternative methods to the conventional closure methods have been investigated for decades.50-54 Particularly in the past few years, we have been testing two novel adhesives for corneal surgery, and both of these compounds are

biodegradable, which represents an excellent alternative for patient comfort. One of these adhesives is based on chondroitin sulfate, and the other compound is based on collagen, both natural constituents of the cornea.55,56

The chondroitin sulfate aldehyde adhesive was originally developed as an adhesive for cartilage. In initial trials in corneal wounds, it was demonstrated that its adhesive capacity was comparable to nylon 10-0 sutures for clear corneal cataract wounds and for MMAPLK.56 It requires two components to be activated and provide collagen crosslinking. The collagen-based adhesive requires activation by a laser in the 1.45 µm wavelength to induce crosslinking. It showed similar adhesive capabilities when compared to nylon 10-0 sutures for similar wounds. We expect that these adhesives will be available soon for corneal clinical applications, which may be a major advancement for these microkeratome-based corneal transplantation techniques.

Conclusions

The various techniques previously described for posterior lamellar keratoplasty are being currently used in clinical applications. One of the major disadvantages of the microkeratome-based approaches is the requirement of suturing for the flap component. However, the use of novel corneal adhesives may improve the results and safety of the procedure, thereby facilitating the adoption of this technique that appears easier to perform. Further in vivo studies are underway to evaluate the biocompatibility of these adhesives and the feasibility of these techniques in the near future.

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