What DSAEK is going on? An alternative to penetrating keratoplasty for endothelial dysfunction

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1 Optometry (2009) 80, What DSAEK is going on? An alternative to penetrating keratoplasty for endothelial dysfunction Kathryn Mau, O.D. State University of New York, State College of Optometry, New York, New York. KEYWORDS Descemet s stripping automated endothelial keratoplasty; Penetrating keratoplasty; Fuchs dystrophy; Pseudophakic bullous keratopathy Abstract BACKGROUND: Traditionally, penetrating keratoplasty (PK) has been the only surgical treatment for patients with Fuchs dystrophy and pseudophakic bullous keratopathy. Over the last several years, an alternative technique has become viable. Descemet s stripping automated endothelial keratoplasty (DSAEK) is a partial transplant that replaces only posterior corneal tissue, leaving the healthy anterior cornea intact. METHODS: A retrospective review of the current literature was conducted. RESULTS: Initially, DSAEK surgeons were plagued by high graft dislocation and failure rates. However, modifications have been made to drastically reduce these numbers. With a predictable refractive error, lower rejection rates, and faster recovery time, DSAEK appears ready to surpass PK as the primary surgical option for endothelial dysfunction. CONCLUSIONS: Corneal endothelial dysfunction is a problem more commonly seen in the middle-age and elderly populations. Until recently, the only option available for these patients was a full-thickness PK. DSAEK is a promising new alternative that preserves the normal healthy cornea, allowing a faster and more stable recovery. This article discusses the indications, procedure, and management of DSAEK and comparisons to PK. Optometry 2009;80: Corneal endothelial disease is most prevalent in middleage to elderly populations and will become an increasing problem over the next few years as the baby boomer generation ages and life expectancy increases. In 2003, the 5 leading indications for penetrating keratoplasty were 1) pseudophakic corneal edema, 2) corneal ectasia, 3) corneal endothelial disease, 4) failed penetrating keratoplasty (PK), and 5) ulcerative keratitis. 1 With late endothelial failure as the leading cause of failed PK, endothelial disease comprises 3 of these top 5 indications for PK. PK is a successful procedure that has been performed for decades; however, it often results in high and irregular astigmatism and a host of ocular surface issues. Descemet s stripping automated endothelial keratoplasty (DSAEK) is a new partial corneal transplant that replaces only the diseased tissue. This leaves the anterior cornea structurally intact, allowing a faster visual recovery and healing time. This new procedure carries its own unique complications, such as a relatively higher rate of graft dislocation. However, the procedure has been modified, and the complication rates have drastically decreased. DSAEK seems to be a promising alternative to PK. Corresponding author: Kathryn Mau, O.D., State University of New York, State College of Optometry, 33 West 42nd St, New York, New York katiemau@gmail.com Background Fuchs endothelial dystrophy is a bilateral, slowly progressive condition that affects the endothelial layer of the /09/$ -see front matter Ó 2009 American Optometric Association. All rights reserved. doi: /j.optm

2 514 Optometry, Vol 80, No 9, September 2009 cornea, becoming clinically evident in the fourth and fifth decades of life but often not symptomatic until the sixth decade. 2 The inheritance pattern is autosomal dominant with incomplete penetrance, with women affected 3 times more often than men. 2 Histopathologically, the corneal endothelium secretes excessive amounts of abnormal collagen onto Descemet s membrane, which accumulates to form protrusions into the anterior chamber known as guttata. 2,3 The endothelium s function as a barrier remains intact despite the guttata; however, its pump function, which is responsible for regulating stromal hydration, is compromised. As the loss of endothelial cells increases, the efficiency of the pump decreases, resulting in corneal fluid retention and gradually increasing stromal edema. The corneal endothelium is nonreplicating, and normal early adult corneas average an endothelial cell count of 3,500 cells/mm 2 and central corneal thickness of 550 mm. 4 In Fuchs dystrophy, as the endothelial cell count drops to 515 cells/mm 2 or less, and corneal thickness reaches 650 mm or greater, epithelial microcystic edema develops. 3,5 In the early symptomatic stages of Fuchs dystrophy, patients often complain of blurry vision and halos that are worse in the morning and gradually improve throughout the day. As the eyes are closed during sleep, there is decreased evaporation of the tear film, leading to reduced osmolality and less fluid drawn out of the cornea, resulting in edema. Normal corneas swell 4% overnight on average. 2 A decreased endothelial cell count will result in difficulty pumping fluid out, creating edema, slower clearing of the cornea, and blurred vision. As Fuchs dystrophy progresses, the blurred vision may eventually persist throughout the day with the gradual decline in endothelial pump efficiency. As epithelial microcystic bullae rupture, patients may also experience pain and foreign body sensations. The resulting irregular epithelial surface leaves the cornea susceptible to infection, potential scarring, and an irregular basement membrane, which can lead to recurrent erosions. When pseudophakic bullous keratopathy (PBK) occurs, corneal edema is the result of the corneal endothelial cell layer failure precipitated by cataract surgery. Liesegang et al. and Bourne et al. both found that with any cataract surgery there is a subsequent endothelial cell loss of up to 2.5% per year. 5 However, most normal corneas are able to withstand this loss without a resultant corneal edema. Increased endothelial cell loss may occur during or after surgery because of increased intraocular pressure, phacoemulsification power, or contact with surgical instruments. PBK is most commonly associated with subclinical Fuchs dystrophy, which becomes clinically evident after the trauma of intraocular surgery. With early-onset PBK, the cornea will fail to clear during the immediate postoperative period, whereas late-onset PBK can occur months to years after surgery. Other risk factors for PBK include high-power phacoemulsification required for dense mature cataracts, pseudoexfoliation syndrome, and anterior chamber intraocular lenses. 2,5 Surgical treatment options Once the patient s lifestyle has become adversely affected by this condition, surgical intervention is necessary. The conventional treatment is a PK, which is a full-thickness transplant of the cornea. Although a PK offers the opportunity of having new healthy corneal tissue, there are many risks and disadvantages to the surgery, and functional visual success is not guaranteed. The penetrating keratoplasty procedure involves full-thickness trephination and replacement of the central 8.0 to 9.0 mm of recipient cornea. It takes approximately 30 to 90 minutes from the time of host trephination until the donor tissue is sutured into place, depending on the procedure and the experience and speed of the surgeon. 6 This means that the intraocular contents are completely exposed through the 8.0- to 9.0-mm trephinated cornea, leaving an open sky. Any additional procedures, such as cataract extraction, intraocular lens exchange or placement, or vitrectomy, will lengthen the surgery time. Because of the open sky nature of PK causing hypotony, there is increased risk of choroidal hemorrhage and effusion during surgery compared with other intraocular surgeries. There is also a long recovery period for PKs (up to a year or more), and the risk of graft rejection is present for the lifetime of the patient. 1 A list of complications from PK can be seen in Table 1. An alternative to PK is lamellar keratoplasty (LK), which is a selective transplantation of only a certain layer of the cornea. Although technically more difficult, lamellar surgery results in a much more stable cornea tectonically and refractively. Anterior lamellar keratoplasty (ALK) has Table 1 Complications of penetrating keratoplasty Intraoperative complications Damage to lens/iris from instruments Irregular trephination of host Poor graft centration onto host bed Excessive bleeding from iris and wound edge Choroidal hemorrhage and effusion Iris incarceration in the wound Damage to donor tissue during handling Immediate postoperative complications Wound leak Flat chamber/iris incarceration in wound Primary donor failure Persistent epithelial defect Endophthalmitis Long-term postoperative complications Glaucoma Microbial keratitis Suture-related problems Wound dehiscence Immunologic graft rejection Late endothelial failure Graft failure Refractive error, astigmatism

3 Kathryn Mau Literature Review 515 been performed successfully for the last 30 years, but only recently has posterior lamellar keratoplasty (PLK) gained popularity. Interest in PLK has grown because of the significant advantages over PK procedures. There are 5 main goals in endothelial keratoplasty: 8,9 1) smooth surface topography without a significant change in astigmatism, 2) highly predictable and stable refractive error, 3) healthy donor endothelium that resolves all edema, 4) a more tectonically stable globe safer from injury and infection, and 5) an optically pure cornea. The first PLK utilized a flap technique, which involved an anterior flap with a hinge similar to that in a laser-assisted in situ keratomileusis (LASIK) procedure. The resulting host posterior corneal bed was then trephinated, a graft was sutured into the defect, and the anterior flap sutured down. Although intended to decrease the chance of graft rejection, this procedure was no more successful refractively or structurally than the original PK. 8 In 1998, Melles introduced his first version of PLK, involving a lamellar dissection to 80% to 90% stromal depth and intrastromal trephination through a 9.0-mm scleral tunnel incision. 8 The donor tissue button, called a lenticule, was hand-cut and included posterior stroma, Descemet s membrane, and endothelium, measuring approximately 150 mm in thickness. The donor tissue is inserted through the large scleral incision, after which air is introduced into the anterior chamber to hold the donor tissue in place against the recipient stroma. Donor recipient tissue adhesion is caused by the hydrophilic attraction between 2 wet tissues sandwiched by air on both sides and also by the molecular interaction between cut stromal fibrils. Terry 8 was the first to perform this in the United States and, to avoid confusion with the original PLK, renamed this procedure deep lamellar endothelial keratoplasty (DLEK). In 2002, Melles made a modification to the DLEK procedure by utilizing a 5.0-mm clear corneal incision. Because of the smaller incision size and 9.0-mm graft size, the donor tissue had to be folded during the insertion process. 8 Descemet s stripping automated endothelial keratoplasty In 2003, Melles made a further modification, eliminating the most difficult aspect of the procedure, the lamellar dissection. 9 He found that Descemet s membrane and the attached endothelium could be easily stripped from the overlying stroma, and thus the technique of Descemet s stripping endothelial keratoplasty (DSEK) was born. The amount of donor tissue used did not change, resulting in a thicker postoperative cornea that did not deter functional or visual results. Gorovoy soon popularized the use of a microkeratome for donor tissue preparation, allowing for more consistent and accurate donor buttons, and the procedure was renamed Descemet s stripping automated endothelial keratoplasty (DSAEK). 10 Contraindications for endothelial keratoplasty include any anterior corneal scarring, opacity, or dystrophy affecting vision. In these cases, a full-thickness penetrating keratoplasty is indicated. Other contraindications include amblyopia, uncontrolled glaucoma, or any retinal or optic nerve disease that would deter final visual results. In these cases, a conjunctival flap or cautery of Bowman s layer is useful in alleviating discomfort from ruptured bullae. DSAEK can be included in the triple procedure for patients with cataracts, replacing PK in suitable patients. This new Triple Procedure would include cataract extraction, intraocular lens implantation, and DSAEK. Procedure overview Today s DSAEK procedure begins with the microkeratome removing 80% to 90% of the donor anterior cornea. (This tissue can later be used for ALK.) After lamellar dissection, the donor cornea is trephinated to 8 to 9 mm. Peribulbar anesthesia is most commonly used, and the recipient epithelium is marked lightly with the trephine to serve as an outline for the area in which Descemet s membrane and endothelium are to be stripped. Either a scleral tunnel incision or a 5-mm clear temporal corneal incision is made, along with paracentesis openings nasally and at 12 o clock. Descemet s membrane is scored along the outlined epithelial reference mark for 360 and is then gently peeled away using a Descemet s stripper or an irrigating and aspirating (I&A) tool. If necessary, trypan blue can be instilled to help differentiate the stripped and unstripped areas. In cases in which a small corneal incision is used, the donor cornea is then prepared for insertion by coating the endothelial side with viscoelastic and folding the tissue into a 60/40 taco with the stromal side out and the endothelium protected internally. The 60/40 taco configuration is used to ensure that the donor lenticule does not unfold upside down in the eye. The lenticule is then inserted into the recipient through the scleral tunnel or clear corneal incision, and either a Sinskey hook, air, or an I&A tool are used to unfold the tissue. Once the lenticule has unfolded and centered, air is injected to almost completely fill the anterior chamber to hold the lenticule in place. The corneal incision is closed with 3 or nylon sutures. The eye is treated with a cycloplegic, antibiotic, and steroid and is patched; the patient is then taken to the recovery room to lie supine for 30 to 60 minutes. The patient is then brought to a slit lamp to ensure lenticule adherence and to monitor intraocular pressure, and the air bubble is reduced to fill 30% to 50% of the anterior chamber. This re-examination can be done at either the slit lamp or in the operating room, depending on the preference of the surgeon. 6 The eye is then repatched, and the patient discharged and instructed to lie face-up as much as possible over the next 24 hours, with only occasional breaks for the restroom and meals. It should be noted that there are variations to the procedure described above because of the novelty and evolving nature of the surgery.

4 516 Optometry, Vol 80, No 9, September 2009 Figure 2 Expected postoperative improvement of BCVA over time in terms of MAR acuity. This corresponds to approximately 20/70 at 1 week, 20/40 at 1 month, 20/30 at 3 months, and 20/25 at 6 months, considering an otherwise healthy eye with good visual potential. Complications Figure 1 A, Appearance of an eye s/p DSAEK on postoperative day 1. Note the air bubble filling approximately 30% of the anterior chamber. Only 3 sutures were necessary to close the 3.5 mm wound. The outline of the lenticule can be seen, which is decentered slightly superiorly. The trace amount of corneal edema inferior to the lenticule indicates that it was decentered intentionally by the surgeon. The clear cornea indicate that the lenticule is attached. B, S/p DSAEK on postoperative day 1, the air bubble has migrated posteriorly behind the iris. Migration of the air bubble posteriorly may induce angle closure. Photo courtesy of Ophthalmic Consultants, P.C. at the New York Eye and Ear Infirmary. Postoperative care On the first postoperative day, the most imperative observation is whether the graft is attached. The air bubble should be filling approximately 30% or less of the anterior chamber (see Figure 1A), without migration into the posterior chamber (see Figure 1B), which can result in pupillary block and subsequent angle closure. Intraocular pressure should be monitored, and visual acuity (VA) should be approximately 20/400, depending on the amount of edema still present. Best-corrected visual acuity (BCVA) should parallel clearing of corneal edema and improve at a rate as seen in Figure 2, reaching maximum visual potential by approximately 2 to 4 months. Medications will include a prophylactic antibiotic 4 times a day for 1 to 2 weeks and prednisolone acetate 1% every 2 hours for the first week, followed by 4 times a day for 1 month and slowly tapered accordingly thereafter. A clear and attached graft can be seen in Figure 3. Almost all of the surgical complications associated with the DSAEK procedure are caused by 1 or more of 3 factors: a smooth donor recipient interface, fragile graft tissue, and the location of the transplant. All transplanted tissue carries the risk of rejection and graft failure. The presence of the air bubble in the early postoperative period and the use of corticosteroids also pose a risk for glaucoma and necessitate intraocular pressure monitoring. In addition to the preceding complications, as with any intraocular procedure, there is always a risk of infection, cystoid macular edema, and retinal detachment. Graft recipient interface Descemet s membrane is secreted by the endothelium and does not have a secure attachment to the overlying stroma. The main attractive force holding Descemet s membrane to the stroma is the negative pressure gradient created by the endothelial pump, which is responsible for regulating stromal hydration. In the DSAEK procedure, Descemet s membrane is scraped or stripped off of the recipient, leaving a relatively smooth posterior stromal surface. The donor tissue has a difficult time adhering to this smooth, slippery surface, often resulting in graft dislocation, the most common complication of DSAEK. Terry 9 and Ousley and Price and Price both had dislocation rates of 50% on their first DSAEK cases. 9,11 It is hypothesized that the molecular interaction between the donor s cut stromal fibrils and the recipient s stripped posterior stroma holds the tissues together for the first few hours until the endothelial pump function kicks in. Once the endothelial pump is working, the negative pressure gradient is established to further promote adherence. 12 Therefore, any damage to the endothelium and its pump mechanism can result in detachment. A few other factors can lead to graft detachment and are listed in Table 2. Retained interface fluid caused by poor donor edge adherence,

5 Kathryn Mau Literature Review 517 Figure 3 Slit lamp photo of an eye 1 month s/p DSAEK. The lenticule is securely attached, with a clear cornea showing no signs of edema. At the time this photograph was taken, this patient had a VA of 20/25. Photo courtesy of Opthalmic Consultants, P.C. at the New York Eye and Ear Infirmary. a geometric mismatch of recipient and donor corneal curvature, or residual recipient stroma or Descemet s membrane may deter tight graft attachment. 13 Eye rubbing may generate mechanical forces to cause dislocation or allow fluid into the interface. Terry 14 advises patients to exercise caution, i.e., no eye rubbing for at least 2 weeks. The length of storage of a donor tissue postmortem may also be a factor, as Rose et al. 15 showed an increase in corneal swelling from 7% to 16% from 24 to 48 hours postmortem, indicating increased endothelial cell death. Graft dislocation is most commonly seen within the first postoperative week and can be visualized at the slit lamp as a clear, dark space between the translucent recipient and donor corneal tissues (see Figure 4A). The overlying stroma will be edematous (see Figure 4B), which may make this visualization difficult. Anterior chamber ocular coherence tomography is a useful diagnostic tool for ensuring graft adherence in an edematous cornea (see Figure 4C). Partial detachments are also a possibility and are often managed by careful monitoring, as they sometimes self-resolve. Total dislocation requires a return to the operating room and reinjection of an air bubble, which in turn means further manipulation of the graft tissue, the potential consequences of which will be discussed later. Table 2 Possible causes of graft dislocation in DSAEK Smooth graft recipient interface Traumatized endothelium with delayed function Retained pockets of interface fluid Geometric mismatch between donor and recipient curvatures Residual strands of stroma or Descemet s membrane in interface Eye rubbing Time of donor tissue postmortem The initial high dislocation rate of 50% has been drastically reduced by modifications to the DSAEK procedure. Terry and Ousley incorporated scoring of the peripheral recipient stromal bed, which would produce a molecular interaction with a hydrophilic effect to help hold the donor tissue in apposition. Peripheral stromal bed scraping reduced Terry and Ousley s dislocation rate from 50% to 4%. 7,8 Price and Price integrated surface stroking into their procedure, which involved using a Lindstrom LASIK Roller or Cindy sweeper to stroke the superficial corneal surface centrally to peripherally. Surface stroking helps to center the tissue and also remove excess interface fluid, which could prevent graft adherence. This decreased Price and Price s dislocation rate from 50% to 13%. Price and Price then incorporated four 1-mm stab incisions at 12, 3, 6, and 9 o clock in the midperiphery through the full thickness of the recipient down to the graft recipient interface. These stab incisions helped to drain additional interface fluid and, combined with surface stroking, decreased the dislocation rate to 6%. 9,11 Another result of the slippery graft recipient interface can be graft decentration. A decentered graft results in an arcuate band of corneal edema in which the host tissue is not posteriorly covered by donor tissue. Corneal surgeons would originally return to the operating room to re-center the graft; however, the latest trend has been to leave the graft decentered (see Figure 5). The edema resolves on its own after a few weeks to months with no effect on final BCVA, and this is preferable over additional graft handling and manipulation. 6,16 Fragile graft tissue The endothelium is a single layer of nonreplicating cells and is approximately 5 mm thick. Descemet s membrane consists of 3 layers and measures 8 to 10 mm thick in adulthood. 2 In DSAEK, the graft lenticule also includes the posterior stroma, making the entire lenticule approximately 150-mm thick. Because of the thin nature of the graft tissue, the lenticule is extremely fragile and vulnerable to insult, which can damage the endothelial pump function. Primary graft failure is failure of the endothelium to function within 2 weeks postoperatively, and late graft failure is a gradual decompensation of the endothelium, which can manifest months to years later. Both are most commonly associated with excessive handling and manipulation of the graft. Price and Price, Gorovoy, and Koenig et al. had primary graft failure rates of 3%, 6%, and 9% to 12%, respectively. 11,12 Endothelial cell loss rates varied from 24% to 34% for the first year and as high as 41% at 2 years postoperatively for both Price and Price 17 and Terry et al. 18 Attempts have been made to modify the DSAEK procedure to reduce the rate of primary graft failure. These modifications are all aimed at more careful and gentle handling of the lenticule. The use of the microkeratome has resulted in thicker donor tissue of approximately 290 mm,

6 518 Optometry, Vol 80, No 9, September 2009 Figure 4 A, Slit lamp photograph of a dislocated lenticule s/p DSAEK seen on postoperative day 1. Note the gap between the anterior cornea and the edematous lenticule, represented as a dark space between the two lamellae. B, Slit lamp photograph of the same patient demonstrating the edematous overlying corneal stroma, the consequence of a dislocated lenticule. Occasionally the cornea may be so edematous that the lamellar gap between the host cornea and the lenticule graft may be difficult to visualize at the slit lamp. C, Anterior chamber OCT of a dislocated graft s/p DSAEK. The edematous lenticule is clearly detached from the overlying stroma. This patient will require a return to the operating room for a second air bubble injection to reattach the graft. which makes the graft more stable and resistant to damage. The graft endothelial cell count of large scleral tunnel versus small clear corneal incisions has been compared for the DLEK procedure by Terry and Ousley. 19 There was an insignificant difference in cell loss for large and small incisions at 6 months of 23% and 25%, respectively; however, at 2 years the cell loss was measured at 27% and 43%, respectively. 19 This difference in endothelial survival indicates that folding the graft for small clear corneal incisions has an adverse effect on its viability. Through in vitro staining, Ide et al. 20 and Mehta et al. 21 showed the extent of damage that forceps and the insertion process have on endothelial cell survival. Specially crafted forceps have gained popularity, only grasping and compressing the leading edge of the lenticule instead of being in apposition the entire length of the shaft. 22 Tissue injectors have also been suggested; however, this does not seem to be a feasible alternative because the tissue must be rolled to be inserted into the injector. 23 Finally, there is the issue of duration of donor tissue storage by the Eye Bank. Rose et al. 15 found that longer storage of cadaver tissue in Optisol solution results in corneal swelling and endothelial cell loss. In cases of irreversible graft failure, a repeat DSAEK is indicated. There is no theoretical limit to how many times a DSAEK can be repeated. If the surgeon feels that DSAEK is no longer the best option for the patient, then a fullthickness PK can be done. It should be mentioned that 3 to 4 DSAEK procedures can be done in the time that it takes a full-thickness PK to fully heal. Graft location Figure 5 Slit lamp photograph of a decentered lenticule, 3 months s/p DSAEK showing a clear cornea. In the early postoperative period, the cornea had an arc of edema inferiorly in the area not covered by the lenticule, however the edema fully resolved. The patient now has a BCVA of 20/30, and does not report any problems with glare or halos. Because of the posterior location of the endothelium on the cornea, blood vessels and immune cells have less access to the donor lenticule in DSAEK compared with PK. Most antigen-presenting cells are located on the superficial cornea,

7 Kathryn Mau Literature Review 519 Figure 6 Anterior chamber OCT of an eye s/p DSAEK demonstrating the concave shape of the lenticule. It is believed that the consistently measured hyperopic shift of approximately diopter is attributed to this concave-shaped addition to the posterior cornea. allowing the donor endothelial graft to survive undetected by the immune system. 24 Antigen-presenting cells are responsible for recognizing tissue as foreign and signaling the immune response, causing graft rejection. Antigens have been found to be expressed on the endothelium; however, the anterior chamber associated immune deviation (ACAID) actively suppresses the delayed-type hypersensitivity response. Furthermore, there is no direct contact between host blood vessels and the transplanted tissue. Direct contact is necessary for recognition and rejection. 24,25 However, graft rejection can occur in DSAEK. In cases of severe epithelial edema and bullae, tissue distress may signal an inflammatory cascade and promote rejection. Also, few antigen-presenting cells are present in the corneal stroma and can also be recruited by inflammatory cells in the anterior chamber such as lymphokines and interleukins. 6 Both Terry and Price reported a 7.5% (15 of 199 eyes) rejection rate at 2 years postoperatively, with an average time to rejection of 11 months and only 1 case progressing to failure. 26 Comparison of penetrating keratoplasty and Descemet s stripping automated endothelial keratoplasty Penetrating keratoplasty has been performed successfully for many decades, and until recently, it was the only option for patients with endothelial dysfunction. It is still the treatment of choice for most corneal surgeons because of the relative ease of the procedure. However, PK carries a number of postoperative complications that can make the process arduous for both the practitioner and patient alike. DSAEK seems to have multiple advantages over PK, especially in terms of the resulting topography, refractive error, globe integrity, and recovery time. Recipient and donor requirements For any patient with concurrent anterior corneal scarring or dystrophies, a PK is indicated because that opacified tissue would not be replaced or removed in DSAEK. Pre-existing corneal neovascularization or ocular surface conditions such as trichiasis, blepharitis, dry eye, exposure keratopathy, or rosacea may have more adverse effects on PK than on DSAEK. Donor requirements are also less stringent for DSAEK, with most corneas deemed suitable as long as the posterior third is clear of pathology. Conditions such as central scarring, pterygia, keratoconus, laser in situ keratomileusis, or photorefractive keratectomy would exclude tissue from being used for PK but not DSAEK. Armour et al. 27 found similar endothelial survival rates after comparing DSAEK using clear donor tissue and DSAEK using donor tissue with anterior segment pathology. Once the lamellar dissection is made in the donor tissue for DSAEK, the anterior half can later be used for ALK, allowing the most efficient use of cadaver tissue. Recovery time Wound healing in PK can take up to several years (and even then is not always complete) because of the nature of the 360 full-thickness perforating wound that has been created. The cornea is structurally weaker, and there is a 5% to 7% risk of spontaneous wound dehiscence over 10 years. 19,28,30 Long-term immunosuppression with topical corticosteroids is necessary to prevent graft rejection but also has an effect of slowing the healing process. In DSAEK, there is only a small corneal incision between 3 and 5 mm, and so the cornea is inherently stronger and also heals much faster. Additionally, a repeat DSAEK can theoretically be done an infinite number of times, with a full-thickness PK available as an alternative. 6 It takes at least 12 months until the PK wound is stable enough for sutures to be removed, and it is not until a few months after suture removal that the refractive condition is stable enough for correction. However, shifts in corneal architecture have been documented to occur even years after suture removal. 8,29 With DSAEK, there is little to no change to corneal topography, and so visual recovery is dependent on the time it takes the corneal edema to subside. Refractively, PK takes up to 12 months to recover, whereas 90% of DSAEK patients recover functional vision within 4 to 6 weeks. 30 Gorovoy and Price 31 published results from their first 25 cases, and 80% reached visual acuity of 20/ 40 within 6 weeks, with 90% reaching 20/40 by 3 months. The follow-up period for DSAEK is much shorter than PK because of the faster wound healing and visual recovery. Because DSAEK s most common complication of graft dislocation occurs in the early postoperative period, more frequent follow-up visits may be necessary during this time. In the long term, the decreased chance of rejection caused by the posterior location of the graft requires a shorter follow-up schedule and less scrutiny. There should be periodic observation for rare cases of late graft rejection and monitoring of the endothelial cell count.

8 520 Optometry, Vol 80, No 9, September 2009 Figure 7 Scheimpflug images and topographies taken from an Oculus Pentacam corneal topography system. A, B, Virgin eye with mild with the rule astigmatism. C, D, S/p PK with irregular astigmatism as high as 20 diopters. E, F, An eye s/p DSAEK showing only mild astigmatism. Postoperative corneal integrity The difference in postoperative corneal integrity between DSAEK and PK is mainly caused by the incision size and the number of sutures required to close the wound. The ocular surface in DSAEK is undisturbed for the most part, excluding any pre-existing irregularities that may have been caused by ruptured bullae. The small incision, fewer sutures, and selective posterior lamellar replacement decrease the risks of infection, neovascularization, rejection, and high irregular astigmatism, with minimal effect on innervation and refractive error. In contrast, the ocular surface after PK is tremendously affected. The entire central 8 to 9 mm of cornea is replaced, requiring at least 12 to 24 interrupted sutures and/or a continuous running suture. Corneal innervation is completely severed, and persistent epithelial defects are known problems in the post-pk eye. According to Price, 18% to 24% of PK graft failures within the first year were caused by ocular surface complications. 32,33 According to all published data on DSAEK results, there is no significant change to refractive astigmatism, and a

9 Kathryn Mau Literature Review 521 Figure 8 Comparison of endothelial cell loss: Average cell loss in the normal eye is 0.6% per year. 17 Average cell loss after any intraocular surgery is 2.5% per year. 5 Average cell loss s/p PK is 17% at 6 months and 34% at 1 year. 28,39 Average cell loss s/p DSAEK is 29.5% at 6 months and 37% at 1 year. 16,17,28 predictable to diopter (D) hyperopic shift usually occurs This shift has been attributed to the concave shape of the graft, which decreases the overall refractive power of the cornea (see Figure 6). Because of the number of sutures needed in PK to hold the full-thickness graft in place, refractive error is very unpredictable. Spherical equivalents average between and D, although it is well known that it is not uncommon to find a final refractive error much higher than this. 1 However, high spherical equivalent refractive errors are not the biggest problem for practitioners. Rather, it is the high amount and irregularity of astigmatism that are difficult to address. Refractive astigmatism averages between 3.0 and 5.6 D, with 25% of patients having more than 4 D of cylinder (see Figure 7). 1,35 After PK, 72% of patients will need spectacle correction, and 15% will require rigid gas permeable (RGP) contact lenses. 37 Aside from inducing astigmatism, sutures also pose their own risk of infection and neovascularization. Loose or broken sutures are the leading cause of graft rejection. 26 Because of their penetrating nature, they form a track that bacteria can follow into the eye and possibly instigate endophthalmitis. Neovascularization loosens the sutures, making the eye even more vulnerable to microorganisms and also increasing the risk of graft recognition by the host immune system to initiate rejection. Because the cornea is much weaker after PK, the sutures must be left in place for 9 to 12 months, whereas after DSAEK they can be removed much earlier, within 1 to 2 months after surgery if necessary. Graft rejection and failure Corneal transplants are highly successful because of the immune privileged status of the cornea. As discussed earlier, DSAEK has a much lower chance of graft rejection due to its posterior location, making it nearly undetectable by the host immune system. On the other hand, PK has a relatively higher incidence of rejection due to the disrupted ocular surface and presence of sutures. According to a retrospective study by Patel et al. there is a 21% risk of immunologic graft rejection at 10 years after PK. 38 While there are no comparative studies over that length of time for DSAEK, the 2-year rate of rejection for DLEK and DSAEK was 7.5% for Terry and Ousley. 26 While the rates of graft rejection seem to be much lower for DSAEK compared with PK, graft failure is a separate issue. Immunologic graft rejection can certainly lead to failure; however, most graft failures are caused by late endothelial failure or an endothelial cell count that has diminished to the point at which it can no longer adequately regulate corneal hydration. This normally occurs when the cell count has dropped below 515 cells per mm. 2,3,5 Because of the fragile nature of the lenticule in DSAEK, there does seem to be a higher rate of endothelial cell loss compared with PK. As seen in Figure 8, there is a higher rate of cell loss for DSAEK compared with PK at 6 months with a 12.5% difference; however, at 1 year, the gap is much closer at 3%. 16,17,28,39 Long-term results have yet to be seen for DSAEK, as the endothelial cell density seems to suffer more after endothelial keratoplasty. However, it should be mentioned that a repeat DSAEK for endothelial failure is an easier proposition than replacing a failed PK and may still be a better option than the full-thickness PK and its associated complications. 6,31 Optical purity While the average BCVA for DSAEK and PK are comparable at around 20/40 to 20/50, more PK patients are able to reach 20/20. 6,9,11,35 It has been noted in the literature that lamellar keratoplasty often results in a reduced BCVA. ALK is usually limited to a BCVA of 20/25 or 20/30 because of interface haze and optical irregularities, 28 and the results are similar for endothelial keratoplasty. Terry and Ousley have documented a one-line loss to macular potential by comparing pre- and postoperative potential acuity meter (PAM) measurements for DLEK. 8,40,41 One hypothesis is that the lamellar interface increases forward light scatter, which may have an effect on contrast. 42 The cornea is no longer optically pure because of disrupted anatomic relationships. Wavefront testing has been unable to detect any significant higher-order aberrations. 9 Another consideration in DSAEK is that a majority of these patients have had chronic corneal edema, which may have resulted in scarring or permanent changes to the stromal fibril configuration, reducing optical purity. Bourne and Baratz analyzed anterior corneal host tissue after endothelial keratoplasty and found increased light scatter independent of interface scatter. 9 In lamellar keratoplasty, the anatomic restoration of the cornea is inaccurate and/or inadequate, which may affect the corneal clarity and the resulting decreased quality of vision. Nevertheless, the patient

10 522 Optometry, Vol 80, No 9, September 2009 population in this situation must also come into consideration. How necessary is 20/20 vision with mandatory RGP wear versus 20/25 or 20/30 with a mild spectacle prescription or even none at all? This shows the importance of patient communication. The doctor and patient must together decide which procedure is better suited for the patient when taking into account age, demands, activity level, and overall health. Future considerations Although endothelial keratoplasty is relatively new, many surgical advancements on the horizon should simplify the procedure. Use of lasers, such as the femtosecond laser, may help in making the lamellar dissection of donor tissue much more consistent and accurate. Refined techniques and instrumentation should improve surgical success. In 2006, Melles et al. 43 introduced yet another modification to the procedure, which is named Descemet s membrane endothelial keratoplasty (DMEK). The same amount of host tissue is removed as in DSAEK; however, the donor graft consists of only Descemet s membrane and the endothelium. The preliminary trials of DMEK have shown mixed results, with the first patient reaching 20/20 within the first week, but 3 of the first 10 have required a subsequent DSAEK procedure a few weeks later because of graft dislocation and failure. 43 While the DMEK cornea has a near-perfect anatomic restoration that may improve the optical quality, the thinner lenticule is much more fragile, prone to wrinkles and endothelial cell damage. Research in stem cell endothelial layer regeneration has been exciting. The corneal endothelium consists of a single layer of cells incapable of replication and proliferation in vivo. New cells cannot be produced, and when an endothelial cell is damaged and drops out, the neighboring cells must enlarge to cover the area, resulting in polymegathism and pleomorphism. In 2003, Joyce 44 demonstrated human endothelial cell proliferation in cell culture, indicating that there may be inhibitory factors in the aqueous humor. One possibility for endothelial restoration may be culturing a patient s own endothelial cells in vitro for later autograft transplantation. Here, the patient s endothelium would be excised, cultured, and then re-implanted days later. Finally, Mimura 45 demonstrated successful xenograft transplantation in rabbits with bullous keratopathy. By inserting human endothelial cell precursors into the anterior chamber and subsequent face-down positioning, the bullous keratopathy was treated effectively. 45 Conclusions Fuchs dystrophy and pseudophakic bullous keratopathy are conditions that typically affect middle-age and elderly populations. Because these subsets of the population will soon increase due to the aging baby boomer population and increased life expectancy, eye care practitioners will begin to see more patients with endothelial dysfunction. Traditionally, penetrating keratoplasty was the only surgical option for these patients, complicated by unpredictable refractive errors with high amounts of irregular astigmatism, slow recovery time, and the lifelong risk of wound dehiscence and graft rejection. DSAEK is a promising new partial transplant that selectively replaces only the diseased posterior tissue, leaving the normal host cornea relatively untouched. The long-term results have yet to be seen, especially in terms of endothelial cell viability; however, repeat DSAEKs are an option and have been performed with no decrease in success rate. 6,31 With an unaltered corneal topography, faster recovery period, more predictable refractive error, and tectonically stable globe, DSAEK is a new viable alternative to penetrating keratoplasty for patients with endothelial dysfunction. References 1. American Academy of Ophthalmology. Clinical approach to Corneal Transplantation. Basic and Clinical Science Course: External Disease and Cornea. LEO 2006: Bergmanson JPG, Sheldon TM, Goosey JD. Fuchs endothelial dystrophy: a fresh look at an aging disease. Ophthal Physiol Opt 1999;19(3): Weisenthal RW, Streeten BW. Posterior membrane dystrophies. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea: fundamentals, diagnosis, and management. Vol 1, ed 2. Philadelphia: Elsevier Mosby, 2005: Nishida T. Cornea: anatomy and physiology. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea: fundamentals, diagnosis, and management. Vol 1, ed 2. Philadelphia: Elsevier Mosby, 2005: Mian S, Sugar A. Surgical trauma: pseudophakic and aphakic corneal edema. In: Krachmer JH, Mannis MJ, Holland EJ, ed. Cornea: fundamentals, diagnosis, and management. Vol 1, ed 2. Philadelphia: Elsevier Mosby, 2005: Ritterband DC. Personal Interview. January 14, Tan DTH, Mehta JS. Future directions in lamellar corneal transplantation. Cornea 2007;26(S1):S Terry MA. Endothelial replacement. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea: surgery of the cornea and conjunctiva. Vol 2, ed 2. Philadelphia: Elsevier Mosby, 2005: Terry MA. Endothelial keratoplasty: history, current state, and future directions. Cornea 2006;25(8): Terry MA. Endothelial keratoplasty: clinical outcomes in the 2 years following deep lamellar endothelial keratoplasty. Trans Am Ophthal Soc 2007;105: Terry MA, Hoar KL, Wall J, et al. Histology of dislocations in endothelial keratoplasty (DSEK and DLEK): A laboratory-based, surgical solution to dislocation in 100 consecutive DSEK cases. Cornea 2006;25: Terry MA, Shamie N, Chen ES, et al. Endothelial keratoplasty: a simplified technique to minimize graft dislocation, iatrogenic graft failure, and pupillary block. Ophthalmology 2008;115(7): Price FW, Price MO. A non-surgical treatment for donor dislocation after Descemet stripping endothelial keratoplasty (DSEK). Cornea 2006;25(8): Terry MA. Endothelial keratoplasty: DLEK & DSEK sutureless corneal transplant surgery techniques. Available at: com/dsaekprocedure.htm. Last accessed October Rose L, Briceno CA, Stark WJ, et al. Assessment of eye bank-prepared posterior lamellar corneal tissue for endothelial keratoplasty. Ophthalmology 2008;115(2): Terry MA, Chen ES, Shamie N, et al. Endothelial cell loss after Descemet s stripping endothelial keratoplasty in a large prospective series. Ophthalmology 2008;115(3):

11 Kathryn Mau Literature Review Price MO, Price FW. Endothelial cell loss after Descemet stripping with endothelial keratoplasty: influencing factors and 2-year trend. Ophthalmology 2008;115(5): Terry MA, Wall JM, Hoar KL, et al. A prospective study of endothelial cell loss during the 2 years after deep lamellar endothelial keratoplasty. Ophthalmology 2007;114: Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty: visual acuity, astigmatism, and endothelial survival in a large prospective series. Ophthalmology 2005;112: Ide T, Yoo SH, Goldman JM, et al. Descemet-stripping automated endothelial keratoplasty: effect of inserting forceps on DSAEK donor tissue viability by using an in vitro delivery model and vital dye assay. Cornea 2007;26: Mehta JS, Por YM, Beuerman RW, et al. Glide insertion technique for donor cornea lenticule during Descemet s stripping automated endothelial Keratoplasty. J Cataract Refract Surg 2007;33: Price MO, Price FW. Descemet s stripping with endothelial keratoplasty: comparative outcomes with microkeratome-dissected and manually dissected donor tissue. Ophthalmology 2006;113: Kuo AN, Harvey TM, Afshari NA. Novel delivery method to reduce endothelial injury in Descemet stripping automated endothelial keratoplasty. Am J Ophthalmol 2008;145(1): Hill JC. The mechanism and management of corneal graft rejection. New York: Kugler Publications BV, Melles GRJ, Remeijer L, Geerards AJM, et al. The future of lamellar keratoplasty. Curr Opin Ophthalmol 1999;10: Allan BDS, Terry MA, Price FW, et al. Corneal transplant rejection rate and severity after endothelial keratoplasty. Cornea 2007;26: Armour RL, Ousley PJ, Wall J, et al. Endothelial keratoplasty using donor tissue not suitable for full-thickness penetrating keratoplasty. Cornea 2007;26: Terry MA. Deep lamellar endothelial Keratoplasty (DLEK): pursuing the ideal goals of endothelial replacement. Eye 2003;17: Ousley PJ, Terry MA. Stability of vision, topography, and endothelial cell density from 1 year to 2 years after deep lamellar endothelial keratoplasty surgery. Ophthalmology 2005;112: Gorovoy MS. Posterior corneal transplants. August Available at: Last accessed July 19, Gorovoy MS, Price FW. New technique transforms corneal transplantation. Cataract and Refractive Surgery Today 2005; Nov/Dec: Thompson RW Jr, Price MO, Bowers PJ, et al. Long-term graft survival after penetrating keratoplasty. Ophthalmology 2003;110: Price MO, Thompson RW Jr, Price FW. Risk factors for various cases of failure in initial corneal grafts. Arch Ophthalmol 2003;121: Covert DJ, Koenig SB. New triple procedure: Descemet s stripping and automated endothelial keratoplasty combined with phacoemulsification and intraocular lens implantation. Ophthalmology 2007;114: Koenig SB, Covert DJ. Early results of small-incision Descemet s stripping and automated endothelial keratoplasty. Ophthalmology 2007;114: Koenig SB, Covert DJ, Dupps WJ, et al. Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK). Cornea 2007;26: Pineros O, Cohen EJ, Rapuano CJ, et al. Long-term results after penetrating keratoplasty for Fuchs endothelial dystrophy. Arch Ophthalmol 1996;114: Patel SV, Hodge DO, Bourne WM. Corneal endothelium and postoperative outcomes 15 years after penetrating keratoplasty. Trans Am Ophthalmol Soc 2004;102: Bohringer D, Reinhard T, Spelsberg H, et al. Influencing factors on chronic endothelial cell loss characterized in a homogenous group of patients. Br J Ophthalmol 2002;86: Terry MA, Ousley PJ. Rapid visual rehabilitation after endothelial transplants with deep lamellar endothelial keratoplsty (DLEK). Cornea 2004;23: Terry MA, Ousley PJ. Small incision deep lamellar endothelial keratoplasty (DLEK): Six months results in the first prospective clinical study. Cornea 2005;24: Patel SV. Keratoplasty for endothelial dysfunction. Ophthalmology 2007;114(4): Melles GRJ, Ong TS, Ververs B, et al. Preliminary clinical results of Descemet membrane endothelial keratoplasty. Am J Ophthalmol 2008; 145(2): Joyce NC. Proliferative capacity of the corneal endothelium. Progress in Retinal and Eye Research 2003;22(3): Mimura T, Yokoo S, Araie M, et al. Treatment of rabbit bullous keratopathy with precursors derived from cultured human corneal endothelium. Invest Ophthalmol Vis Sci 2005;46: