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

31.Melles GR, Eggink FA, Lander F, Pels E, Rietveld FJ, Beekhuis WH, Binder PS. A surgical technique for posterior lamellar keratoplasty, Cornea 1998;17:618–26.

32.Behrens A, Langenbucher A, Kus MM, Rummelt C, Seitz B. Experimental evaluation of two current-generation automated microkeratomes: The Hansatome and the Supratome. Am J Ophthalmol 2000;129:59-67.

33.Haimovici R, Culbertson WW. Optical lamellar keratoplasty using the Barraquer microkeratome. Refract Corneal Surg 1991;7:42-5.

34.Melles GR, ten Hoope GW, Rietveld FJ, Beekhuis WH, Binder PS. Depth predictability of stromal pockets in the posterior cornea. Cornea 1998;17:174–9.

35.Melles GR, Rietveld FJ, Beekhuis WH, Binder PS. A technique to visualize corneal incision and lamellar dissection depth during surgery. Cornea 1999;18:80–6.

36.Melles GR, Lander F, Rietveld FJ, Remeijer L, Beekhuis WH, Binder PS. A new surgical technique for deep stromal, anterior lamellar keratoplasty. Br J Ophthalmol 1999;83:327–33.

37.Melles GR, Remeijer L, Geehards AJ, Beekhuis WH. The future of lamellar keratoplasty. Curr Opin Ophthalmol 1999;10: 253-9.

38.Van Dooren B, Mulder PG, Nieuwendaal CP, Beekhuis WH, Melles GR. Endothelial cell density after posterior lamellar keratoplasty (Melles technique): 3 years follow-up. Am J Ophthalmol 2004;138:211-7.

39.Terry MA, Ousley J. Replacing the endothelium without corneal surface incisions or sutures. Ophthalmology 2003;110:755-64.

40.Melles GR, A disagreement. Ophthalmology 2004;111:193.

41.Christo C, van Rooij J, Geerards AJ, Remeijer L, Beekhuis WH. Suture-related complications following keratoplasty. A 5-Year retrospective study. Cornea 2001;20:816-9.

42.Behrens A, Ellis K, Li L, Sweet PM, Chuck RS. Endothelial lamellar keratoplasty using an artificial anterior chamber and a microkeratome. Arch Ophthalmol 2003;121:503-8.

43.Li L, Ellis KR, Behrens A, et al. Laboratory model for micro- keratome-assisted posterior lamellar keratoplasty utilizing a

running graft suture and a sutureless hinged flap. Cornea 2002;21:192-5.

44.Pirouzmanesh A, Herretes S, Reyes J, Suwan-apichon O, Chuck RS, Wang DA, Elisseeff JH, Stark WJ, Behrens A. Modified microkeratome-assisted posterior lamellar keratoplasty using a tissue adhesive. Arch Ophthalmol 2006;124:210-4.

45.Azar DT, Jain S, Sambursky R, Strauss L. Microkeratomeassisted posterior keratoplasty. J Cataract Refract Surg 2001; 27:353-6.

46.Heaven CJ, Davison CR, Cockcroft PM. Bacterial contamination of nylon corneal sutures. Eye 1995;9:116-8.

47.Azar DT, Stark WJ, Dodick J, et al. Prospective, randomized vector analysis of astigmatism after three-, one-, and no-suture phacoemulsification. J Cataract Refract Surg 1997;23:1164-73.

48.Dana MR, Goren MB, Gomes JA, Laibson PR, Rapuano CJ, Cohen EJ. Suture erosion after penetrating keratoplasty. Cornea 1995;14:243-8.

49.Nirankari VS, Karesh JW, Richards RD. Complications of exposed monofilament sutures. Am J Ophthalmol 1983;95:515-9.

50.White RA, Kopchok G, Donayre C, et al. Comparison of laser welded and sutured aortomies. Arch Surg 1986;121:1133-5.

51.White JV. Laser tissue repair with the CO2 laser. Proc SPIE 1989;1066:35-40.

52.Oz MC, Bass LS, Popp HW, et al. In vitro comparison of

THC:YAG and argon ion lasers for welding of biliary tissue. Lasers Surg Med 1989;9:248-53.

53. White RA, Kopchok G, Donayre C. Argon laser welded arteriovenous anastomoses. J Vasc Surg 1987;6:447-53.

54. Stanley CM, Boisjoly H. Advances in the use of adhesive in ophthalmology. Curr Opin Ophthalmol 2004;15:305-10.

55. Noguera GE, Lee WS, Castro-Combs J, Chuck RS, Soltz B, Soltz R, Behrens A. A novel laser-activated solder for sealing corneal wounds. Invest Ophthalmol Vis Sci (in press).

56.Reyes JM, Herretes S, Pirouzmanesh A, Wang DA, Elisseeff JH, Jun A, McDonnell PJ, Chuck RS, Behrens A. A modified chondroitin sulfate aldehyde adhesive for sealing corneal incisions. Invest Ophthalmol Vis Sci 2005;46:1247-50.

Introduction

Penetrating Keratoplasty

For over one hundred years, penetrating keratoplasty (PK) has been the standard of care for corneal diseases.1,2 PK is commonly indicated for failed corneal grafts, pseudophakic bullous keratopathy (PBK), phakic keratopathy, Fuchs’ dystrophy, keratoconus, and corneal scars.3 Being the most commonly performed transplant, the procedure offers patients with these diseases improved vision by way of clearer corneas.4 PK is also practical because it is an “open sky” procedure which allows for concurrent intraocular procedures (i.e. cataract extraction and IOL placement, vitrectomy, iridoplasty, etc.) to be carried out. PK involves replacing a full thickness, circular portion of recipient cornea with that of a donor cornea secured into place with 32, 16 or even 8 sutures. The procedure is widely accepted by corneal surgeons, as it requires the use of familiar surgical skills and instrumentation; these qualities afford the procedure technical simplicity with excellent chance of success.

The development of topical corticosteroids, antibiotics, surgical microscopes, improved trephines, viscoelastics and fine suture materials enable this delicate procedure to be routinely performed with the prospect of success.1 Suture technique has also been modified several times to help improve the outcomes of this surgery. One of the major advancements of corneal transplantation lies in the changes in management of donor tissue by eye banks, which are now able to screen and handle donor tissue in such a fashion that recipient wait time has been significantly reduced.

The average maximum Snellen visual acuity after PK is an important measure because it puts into perspective the probability of 20/20 vision. Several studies have indicated that 20/20 best corrected visual acuity (BCVA) is a likely outcome after PK. Claesson et al,5 in their study of 520 grafts at 2 years after PK, showed a strong association between preoperative visual acuity and the likelihood of obtaining postoperative BCVA of 20/40 or better, which is comparable to that found in other studies.6,7

Another important postoperative measure of PK is the corneal power because a crystal-clear graft with excessively steep or flat curvature can yield significant myopia or hyperopia. One study found that on average, the postoperative corneal power ranges from 41.9 to 42.7 diopters (D) and is stable from one month after surgery up to suture removal; after suture removal the graft steepens slightly at 0.61-0.7 D.8 Although these averages are reassuring, it is common to observe that corneal astigmatism after suture removal often fluctuates considerably.9

Similarly, an important measure of endothelial graft function is the endothelial cell count. Ing JJ et al10 showed a decline in endothelial cell count after PK in large scale study, with means of 2467/mm2 at 2 months, 1958/mm2 at 1 year and 960/mm2 at 10 years. This endothelial cell data is comparable to that found in other studies.11-14 These figures serve as the standard for any procedures that may attempt to replace PK.

PK sometimes produces an unpredictably high or irregular astigmatism which can lead to poor postoperative refraction. Early postoperative astigmatism measures range from 3 to 7 D.14-17 Williams et al study on postoperative astigmatism at 2 or more years in 60 patients showed that 38% of cases had > 5 D of astigmatism in the graft.15 Overall, in approximately 10-20% of PK cases, high amounts of astigmatism (>5.0 D) can actually prevent functional success of the clear graft.17 Most patients can be visually rehabilitated with spectacles or contact lenses, however, if these modalities fail, several surgical and suture adjustment/removal options exist that may improve the patients vision.

A number of factors are thought to contribute to the vexing problem of PK induced astigmatism, one of which is suture tension. The tension necessary to achieve a watertight seal of the full-thickness vertical incision of PK produces a gathering of the donor-recipient junction. This suture-induced tissue stretching yields a topographically “unsmooth” corneal surface that has higher and/or more irregular astigmatism than either the donor or recipient corneas had preoperatively. Irregularities of the trephination margins, donor/recipient thickness disparity and irregular suture technique are other important factors for high astigmatism after penetrating keratoplasty.17,18

Interestingly, the full-thickness vertical incision of PK apparently never heals to preoperative levels of strength. This is supported by the fact that many years after a corneal transplant, a seemingly stable cornea can rupture with trivial trauma leading to possible loss of the eye.19 This is likely because blood vessels are necessary to meetthenutritionalneedsofthewoundhealingprocess,but the cornea is avascular and does not adequately supply these needs. Furthermore, slow recovery of vision,13,20 risk of suture related problems,21 and other interface complications,22 are all untoward outcomes that plague corneal surgeons.

The leading causes of corneal transplant failure are allograft rejection and endothelial decompensation.23-27 Since the cornea is usually avascular, the overall cumulative probability of corneal graft rejection at 10 years

is 21%.10 Most of these rejections occur within the first few years after keratoplasty.28 Once a graft rejection is suspected, it can sometimes be blocked by the use of topical corticosteroids, but up to 49% are irreversible.29

Posterior Lamellar Keratoplasty

While PK remains the gold standard for surgical corneal diseases over the past decade, posterior lamellar keratoplasty (PLK) has gained increasing clinical acceptance in the treatment of corneal diseases that involve endothelial dysfunction. This is groundbreaking for corneal surgeons because corneal endothelial dysfunction is the most common indication for PK in developed countries.30-32 PLK selectively targets the corneal endothelium by replacing some contiguous circular portion of recipient endothelium, Descemet’s membrane and posterior stromal tissue with that of donor tissue. In this manner, the functional donor endothelial cells are able to appropriately transport fluid and solutes away from the stroma leading to an optically transparent cornea. PLK offers several advantages over PK.

The concept of PLK was first introduced by Barraquer wherein the posterior corneal tissue was accessed by creating a hinged anterior corneal flap. From this conception, two separate PLK techniques evolved: one which improved upon this hinged-flap approach and another which changed the approach such that the recipient’s anterior chamber is entered from a smaller curvilinear incision. The hinged-flap approach was named microkeratome-assisted PLK (MAPK also called endokeratoplasty and endothelial lamellar keratoplasty) while the small incision approach was designated deep lamellar endothelial keratoplasty (DLEK).

The MAPK approach is technically straightforward, wherein a microkeratome is used to create a hinged corneal flap exposing the underlying posterior stroma which is then trephined and transplanted. Though promising results have been obtained, case series have shown that microkeratome-assisted PLK carries the possibility of flap problems in addition to several of the same problems that plague PK and DLEK.

The DLEK approach was developed by Melles et al33 who proposed a limbal incision approach to manually dissect a pocket in the midstroma and then trephine the posterior stroma. In 2000, Terry et al31,34 slightly modified Melles’ technique re-designing the instrumentation and performed the first DLEK in the United States. Due to the high difficulty level and other concerns, DLEK has been the subject of several investigations and modifications over the past six years.

A dilemma common to both MAPK and DLEK is postoperative mismatch between donor and recipient stromal thickness. Even if there is a perfect preoperative match between the thickness of the donor tissue and that of the recipient’s, a discrepancy may be measured with the passage of time. This discrepancy occurs because the thickness of donor tissue in corneal preservation media is greater than the thickness of normal physiological corneal tissue due to edema. Thus, if tissue deturgescence is not done before the donor disk is prepared, the donor stroma may become thinner than anticipated during the postoperative period when the donor’s endothelial cells begin to function. This thinning of the donor disk may cause same degree of corneal flattening which can potentially lead to poor postoperative refraction.35 Consequently, donor tissuedeturgescence is usually calculated preoperatively to lessen or possibly prevent unanticipated postoperative donor thinning.

Another problem shared by PLK and MAPK is the issue of haze in the horizontal interface between the donor and recipient stroma.36 This distortion is thought to lead to a limited maximum average Snellen visual acuity that can be attained with these procedures. While PK can attain visual acuities of 20/20, there has been a relative dearth of these cases in MAPK and DLEK; the average highest acuity attained in these procedures has been 20/40 to 20/50.37-42 Terry et al. had only 1 patient who could be fully correctable with spectacles to 20/20 vision in this DLEK series of 98 cases.37 What is interesting is that there is not yet a means for measuring this optical distortion of the transplant interface, and thus several investigations are underway.

Clearly, PLK has not yet been fully standardized and will continue to be modified and improved upon. Any procedure that replaces the endothelium ideally should accomplish the following goals:

1.Smooth surface topography without significant change in astigmatism from preoperative to postoperative.

2.A highly predictable and stable corneal power.

3.A healthy donor endothelium that resolves all edema.

4.A tectonically stable globe, safe from injury and infection.

5.An optically pure cornea.

An additional sixth goal is technical ease with a reasonable learning curve such that a wide array of corneal surgeons can successfully carry out the procedure.34 The further the instrumentation and technique of any given procedure strays from those classically used by corneal surgeons, the greater the technical difficulty. With technical difficulty comes increased inaccuracies, which can yield intersurgeon variability in success rates and possibly unhappy patients. These 6 goals will be referred to throughout the remainder of the text.

Microkeratome-assisted PLK (MAPK)

In microkeratome-assisted PLK, the opening incision is a hinged anterior stromal flap made with a microkeratome, similar to the flap made during laser-assisted in situ keratomileusis (LASIK) procedures. This flap approximates 130-480 μm in thickness and 8.5-9.5 mm in diameter. The flap is retracted with a flat spatula and it is used to expose the remaining cornea which is then trephined with a 7.0- 8.0 mm diameter trephine to create a lamellar disk (posterior stroma, Descemet’s membrane and endothelium). This trephine diameter is dependent on the flap diameter and hinge width. This recipient lamellar disk carries with it the dysfunctional endothelial cells and is accordingly removed from the eye. Viscoelastic is then placed in the anterior chamber to stabilize it.

The donor disk is then prepared (as will be described later) with a similar diameter trephine and positioned into place in the recipient’s stromal bed. The donor-recipient interface is self-adhering, but 8-16 interrupted absorbable or non-absorbable nylon sutures are used to secure the donor disk into place.43

In clinical studies, 50% of patients had a BCVA greater than or equal to 20/60 (range: 20/30-20/200) at a maximum of 1 year of follow up.43,44 One study reported a 1 month average spherical equivalent of -1.25 D.43 At twelve months, Ehlers et al44 found that the endothelial cell density was in the range of 1200-2300 cells/mm2. None of these studies had episodes of graft rejection or wound dehiscence.

An important principle of lamellar refractive and LASIK surgeries is that in order to preserve the tectonic integrity of the cornea, a minimum of half or more corneal tissue must remain after the creation of a flap to prevent refractive instability. As this principle is abided by during the MAPK procedure, Behrens et al.32 showed that average intraocular pressures of up to 88 mmHg could be withstood in laboratory eyes when a 200 μm flap is used for the MAPK procedure. This stability renders the eye resistant to any subsequent injuries that may take place during patient’s daily activities.

As microkeratomes have been enhanced, optical properties of corneal flaps have greatly improved. Interface scarring is almost absent after microkeratome dissection in LASIK. When compared with manual dissection, microkeratomes create a smoother donor-recipient interface and more uniform depth than manual dissection. Interestingly, although interface scarring is essentially absent, there is a limit to the maximum best average Snellen visual acuity seen in the small clinical series of MAPK. LASIK has proven that corneal dissection performed by

means of microkeratome produces an optical quality which is compatible with 20/20 vision, thus further investigations are needed to determine why the average maximum visual acuity is limited with MAPK procedure.

In comparing PK to MAPK, it is widely accepted that both procedures accomplish goals 5 and 3 above. Both procedures also accomplishes goal 6 of technical ease with a very reasonable learning curve. However, as was indicated previously, PK falls short in terms of goals 1, 2, and 4. Although MAPK preserves the original central corneal surface, when flap and intrastromal sutures are put into place, some astigmatism is induced. The MAPK astigmatism is not nearly as high or irregular as that of PK because less sutures are used; thus, goal 1 is relatively (compared to PK, but not to DLEK as we will see later) achieved by the MAPK procedure. Similarly, literature data shows that the MAPK procedure achieves goal 2. Short term studies have indicated that MAPK also achieves goal 4, but large scale studies are needed to determine if goal 4 still holds true over a longer period of time.

The MAPK method has less wound complications than PK because the combined anterior flap/posterior trephine wound is inherently stronger than the full thickness/ complete circumferential wound used in PK. Furthermore, the MAPK flap can be lifted for suture removal (with an argon laser to cut intrastromal sutures or a sharp blade after flap elevation), and although speculative, LASIK over the posterior button may correct residual refractive errors.45 In addition, the decreased amount of sutures used during this procedure improves postoperative visual recovery as well as imparts fewer suture-related problems as compared to PK.

Clearly, MAPK specifically has potential benefits, mostly related to its conventionality. It allows for easy automated access to the stromal bed as well as classic trephination and transplantation, making the procedure relatively reproducible.46 This procedure also allows easy access for concurrent intraocular surgeries. Furthermore, with the ease and automation of surgery, MAPK is afforded a shortened surgical time.

Some possible pitfalls are also incurred specifically with MAPK. This procedure produces a shift in postoperative average corneal power and astigmatism, similar to the transfer of stromal flattening to the corneal surface in LASIK. In MAPK there is a donut effect of donor-recipient interface due to sutures, which is transmitted to the surface flap. Surface sutures may also contribute to this astigmatism and high absolute power. As with LASIK, flap complications may also occur; epithelial ingrowth in the flap-graft interface can decrease the BCVA and has been reported in clinical cases of MAPK.47 As with LASIK, it is suspected

that corneal melting and micro/macrostriae are also possible adverse outcomes of MAPK.

Deep Lamellar Endothelial

Keratoplasty (DLEK)

In the DLEK method, a temporal or 12 o’clock curvilinear incision (either 9.0 mm or 5.0 mm) is made into the sclera, 1 mm away from and parallel to the limbus. A specialized spatula is then used to dissect from this incision into the stroma to a corneal depth of about 75-80% so as to create a lamellar pocket. Once the desired depth is reached, a special dissector is used to extend this lamellar plane over the whole cornea.

A specialized 7.0-8.0 mm interlamellar trephine is then inserted into the created plane to begin cutting out a lamellar disk (posterior stroma, Descemet’s membrane and endothelium) from the posterior cornea. Once the trephine slightly enters the anterior chamber it is withdrawn from the lamellar plane and specialized interlamellar scissors are inserted to complete the trephination to a full 360 degrees. This completes the creation of the recipient’s posterior corneal lamellar disk which is removed from the eye through the temporal incision. The resultant recipient bed diameter is then measured with external calipers (7.0- 8.0 mm). Air is then insufflated into the anterior chamber through a 0.5 mm limbal stab wound at the 2 o’clock position. This air functions to create a fluid free working space for careful insertion and manipulation of the donor tissue and to enhance self-adhere of the donor tissue to that of the recipient.

The donor lamellar disk is then prepared (as will be described later) to match the diameter of the recipient bed and viscoelastic is layered on it’s endothelium. The donor disk is then either folded in a taco-like fashion (endothelial side inside) or placed endothelial side down on a specialized transfer spatula (decision depends on the size of the scleral incision), and inserted into the host anterior chamber through the scleral incision. The donor disk is positioned into the recipient’s posterior corneal defect using the transfer spatula. Minor adjustments to further fit the donor into the recipient bed can then be made with a Sinskey hook through the 2 o’clock limbal stab wound. In this method, no sutures are necessary to secure the donor tissue because it is self-adhering. The scleral incision is also selfsealing and sutures may or may not be used to close it.

Several corneal surgeons have performed large volumes of DLEK procedures and sufficient data is available. On average, BCVA is 20/48 at maximum 2 years follow up.48-51 Melles et al reported that all patients operated on

with the initial PLK procedure who did not have concomitant ocular disease have a BCVA of 20/30 or better; several have 20/20 (Netherlands Institute for Innovative Ocular Surgery, unpublished data). Similarly, these same studies also showed that DLEK yields minimal postoperative astigmatism; on average, astigmatism is 1.46 D. One study showed an average postoperative spherical equivalent of -0.369 Dat 1 year.50 Postoperative endothelial cell density averages 1790.5 cells/mm2 at 36 months at a maximum of 3 years.48,51

As with MAPK, there appears to be a limit to the maximum best average Snellen visual acuity with DLEK; this is likely associated with postoperative interface opacities caused by stromal scarring from manual dissection.52 The lack of significant postoperative changes in astigmatism and corneal power is due to lack of disruption of the surface of the cornea in this procedure. This eliminates postoperative need for special corrective contact lenses which is seen with PK.

Tectonic stability of the eye is in part provided by the continuity of the cornea and limbus. The DLEK technique does not disrupt this continuity and consequently appears to leave the cornea stable, though there are no long-term studies to confirm this. In Terry et al34 laboratory study stability of completed transplant was crudely tested by manually shaking and “pounding” on the globe which did not dislocate the donor disk from the recipient bed. This apparent increased stability renders the eye more resistant to any subsequent injuries that may take place during patient’s daily activities.

The lack of sutures to secure the donor into place imparts some risk of graft dislocation with the DLEK procedure. Terry experienced a 6% donor detachment rate in his first 90 DLEK cases (Ophthalmology Times, May 15, 2005). Sano reported 1 donor detachment in his first 3 DLEK cases.49 Price had a 5% detachment rate in his first 101 PLK surgeries.53

In comparing PK to DLEK, it is widely accepted that both procedures accomplish goals 5 and 3 above. PK also accomplishes goal 6 of technical ease with a very reasonable learning curve, but it falls short in terms of goals 1, 2, and 4 (the reasons for this were discussed earlier). In contrast, DLEK leaves the corneal surface untouched and consequently achieves goals 1 and 2. Short-term studies have indicated that this procedure achieves goal 4, but large scale studies are needed to determine if goal 4 still holds true for DLEK over a longer period of time.

Clearly, DLEK specifically has potential benefits, mostly due to its lack of corneal incisions and suture use. There are less suture-related complications as compared with PK

because the sutures are placed on the sclera rather than the cornea. Most outstanding, there is negligible postoperative astigmatism or changes in corneal power because the corneal topography is essentially unchanged. In addition, because DLEK leaves the corneal surface untouched, the recovery time is considerably hastened such that the astigmatic and corneal power advantages are seen immediately after surgery. Moreover, unlike PK and MAPK, no postoperative suture removal visits are necessary which keeps visual fluctuations at a minimal during the healing process.

However, some possible pitfalls are also incurred specifically with DLEK, which largely lie in it’s difficulty level. During the DLEK procedure, manual lamellar dissection, interlamellar trephination and scissor excision are difficult and tedious skills which could potentially traumatize the anterior chamber structures or the lens. Similarly,graftfolding,andtransplantationofdonorcorneal disk supported only by an air bubble are difficult surgical skills. The accuracy (and thus success) of these techniques is strongly dependent on the surgeon’s skills, making the proceduredifficulttoreproducebecausethelearningcurve isquitesteep.Ontheotherhand,Seitzetalhavedemonstrated inalaboratorymodelthefeasibilityofusingthefemtosecond laserforDLEKtocreateboththeopeningincisionaswellas the stromal dissection, which may allow an easier clinical procedure.55 Otherauthorshavealsocorroboratedthiswith further experimental studies.56-58

Donor Tissue Preparation

For both the MAPK and DLEK methods, donor tissue is prepared a few different ways using an artificial anterior chamber (AAC). In one method, the donor corneoscleral button is mounted on the AAC endothelial side down and a lamellar pocket is dissected similar to the DLEK recipient procedure. Then the button is turned epithelial side down and trephined at a diameter that is dependent on the measureddiameteroftherecipientposteriorlamellardisk. Thedonorposteriordiskisthenseparatedfromitsanterior corneal layers and used as indicated in the respective procedures.

In another method, the donor corneoscleral button is mounted onto the artificial anterior chamber endothelial side down and trephined to approximately 75% depth with a 9.0 mm diameter suction recipient trephine. A special blade and dissector are then used to carefully excise the 9.0 mm anterior corneal disk and to extend the trephinate depth peripherally throughout the remainder of the corneal diameter. The donor tissue is then removed from the anterior chamber and placed endothelial side up on a donor

punch block where it is trephined at a diameter that is dependent on the measured diameter of the recipient posterior lamellar disk. The donor posterior disk is then carefully separated from its anterior corneal layers and used as indicated in the respective procedures.

Yet another method involves the use of a microkeratome wherein a flap is made (as in the MAPK method) and a posterior corneal disk is trephined and used as indicated in the respective procedures. Femtosecond laser preparation of donor tissue from the endothelial side has been done in the laboratory and shows promising results.57

The concerns with donor preparation techniques lie in ensuring endothelial cell survival and technical ease. All procedures have shown comparable endothelial cell survival and no particular method is favored over the other in terms of standardization. Note that viscoelastic is used liberally on the endothelium in all donor preparation techniques.

Descemet’s Stripping with Endothelial Keratoplasty (DSEK)

A very revolutionary refinement of the DLEK procedure was realized when Melles et al proposed a means of stripping Descemet’s membrane from the recipient’s stromal bed so as to create a smooth recipient surface. This smooth recipient surface would theoretically decrease the interface haze that was incurred with the DLEK technique so that there would no longer be a limited average Snellen visual acuity.59-61 Price slightly modified Melles’ technique and was the first surgeon in the United States to carry out such a procedure.62

In this procedure, there are two methods available, manual dissection and microkeratome-assisted which has been coined Descemet’s stripping automated endothelial keratoplasty (DSAEK). During manual dissection, the donor is mounted epithelial side up on an AAC and dissected 8090% corneal depth over the whole area of cornea with blades.61 In the DSAEK donor preparation method, a microkeratome is used to dissect to a 300-350 μm stromal plane. In both techniques, the donor tissue is then placed endothelial side up on a donor punch block and trephined at 8.0-9.0 mm diameter. The donor disk is then placed in storage media for later use.

After marking the recipient cornea with a slightly larger trephine than used for donor tissue, the recipient surgery is then performed. Through a 5.0 mm scleral tunnel, modified Price-Sinskey hook is used to score Descemet’s membrane in a circular pattern beneath the area of the epithelial reference mark. Then, a 45 or 90-degree Descemet’s

stripping instrument is used to strip Descemet’s membrane and endothelium from the recipient’s stroma within the scored area. Once fully stripped, Descemet’s membrane and the endothelium were removed from the anterior chamber with a forceps. The donor disk is then folded and transplanted into the recipient stromal bed as was done in the graft folding method of DLEK.

DSEK offers all of the benefits of DLEK in addition to technical ease and less trauma to anterior chamber structures.62 This procedure achieves goals 1 through 6 of the ideal corneal transplant procedure and recovery of useful vision occurs within weeks. Furthermore, in DSEK, there is no problem with donor/host thickness mismatch because Descemet’s membranes with its endothelial cells are not subject to edematous changes and consequently are all approximately the same thickness.

Six months after DSEK, mean manifest cylinder was 1.5 ± 0.94 diopters, basically unchanged from the preoperative value of 1.5 ± 1.0 D. Mean manifest spherical equivalent refraction was 0.15 ± 1.5 D, also statistically comparable to the preoperative value. Preoperative mean BSCVA was 20/100. Statistically significant improvement in BSCVA was noted at the 3-month and 6-month examinations; six months after DSEK, 62% of the eyes refracted to = 20/40 and 76% saw = 20/50.63

A further study in DSEK compared microkeratomedissected and manually dissected donor tissue.64 Mean refractive astigmatism was 1.5 D preoperatively and 6 months postoperatively in both groups. Spherical equivalent refraction did not change in the microkeratome group but increased by 0.66 D in the hand dissection group. There were 7 primary graft failures.

The major drawbacks of DSEK lie in graft dislocation. It was theorized in the DLEK procedure that good adhesion of donor to recipient tissue is dependent on inherent adhesive quality of bare stromal surfaces when pressed together when assisted by intraocular pressure and stromal bed dissection,65 however, in DSEK there is no stromal bed (perpendicular cuts) thus dislocation may occur. The dislocation rate of DSEK has been quoted as high as 50%,63 making it a significant area of investigation for corneal surgeons.

Several successful efforts have been made to improve this high dislocation rate.64 Using techniques to remove fluid from the donor–recipient graft interface ultimately reduced the detachment rate to <1% (1 in the last 140 cases). Another method is to leave the anterior chamber filled with air for 8 minutes in the operating room, after which most of the air was removed; patients were then sent to the recovery room to lie with their face up for 30 to 60 minutes to allow the remaining air to push the donor tissue up against the

recipient cornea. Furthermore, the corneal surface can be massaged with a Lindstrom LASIK roller to help remove fluid from the graft interface to help prevent dislocation.

In the event of a dislocated or malpositioned graft, a repositioning procedure is undertaken. In this procedure, some fluid is drained from the anterior chamber and air is again insufflated into the chamber. The graft is then manipulated back into place through a virgin posterior limbal wound. Postoperatively, the air in the anterior chamber is allowed to further enhance the donor-recipient corneal adherence. In the event of graft failure, the patient’s eye must be reoperated on to implant a new donor graft.

There are also other challenges incurred with the DSEK technique. In some eyes it may be more difficult to position the graft under the support of an air bubble. In addition, since Descemet’s membrane/endothelium is very thin and friable, donor preparation may be a difficult task with the looming risk of perforation especially if a deepcutting microkeratome is used such as a 350 µm head. In some cases, Descemet’s membrane fragments during Descemetorhexis. In efforts to remedy this risk Price et al, compared microkeratome donor preparation to manual dissection.64 His group found that microkeratome dissection significantly reduced the risk of donor tissue perforation, provided faster visual recovery after DSEK, and did not alter the refractive outcome. Furthermore, the incidence of early graft failures was also significantly less with use of microkeratome-dissected tissue (0.5%), compared with use of hand-dissected tissue (5%). Thus, microkeratome-dissection has pretty much replaced the manual dissection technique, though further investigations are still underway to further improve the delicate donor harvesting process.

What Comes Next? Descemet’s

Membrane and Endothelial Cell

Layer Transplantation

From our experience with lamellar corneal surgery (both anterior and posterior) and the results published in the literature, optical performance in both seems to be affected by factors not yet clearly understood. The final BCVA in both approaches appears to be consistently limited despite appropriate graft clarity, good slit-lamp appearance, and optimal postoperative topography. It seems that there are certain optical properties of the cornea that are not quite measurable with conventional methods in these patients, which still restrict their ultimate visual resolution. However, we have hypothesized, based on certain facts

and observations, that the cornea has particularities in its architecture that should not be disregarded.

The BCVA in patients after keratolamellar transplantation is usually 20/40 or 20/30. We hypothesize that this limitation is due to optical distortions originated in the different distribution and orientation of collagen fibers from different corneas when apposed in a transplant. Seitz et al reported a few years ago the necessity of “harmonization” of the donor and recipient corneas in penetrating keratoplasty to minimize the postkeratoplasty corneal astigmatism.66 We believe that this “harmonization” may be even more determinant in cases of lamellar surgery, although perfect orientation of the cornea might still not solve the problems related to specific collagen fiber distribution encountered in corneas from different patients. However, transplantation of endothelial cell layer and Descemet’s membrane alone may warrant these distortions to be avoided.

In the current literature we found clinical data to support our hypothesis. In addition, surgical observations during LASIK surgery may validate our impressions. Trials reporting excellent visual acuity after performing the procedure of “deep lamellar keratoplasty” up to Descemet’s membrane level are available in the literature. In this technique, the whole epithelium, Bowman’s layer and stroma are removed from the recipient cornea, leaving the Descemet’s membrane and endothelium intact.67,68 This fact speaks of the minimal optical distortion induced by Descemet’s membrane and endothelial cell layer alone. On the other hand, it is widely accepted that “free” caps after LASIK surgery may create severe optical problems when not repositioned in the exact original orientation. It seems that, other than the expected astigmatic change induced by different thicknesses in the cap, there is an additional optical distortion created by the change in orientation of the collagen fibers, which affects the BCVA.

Based on the previous observations, we propose that the ideal treatment for endothelial cell dysfunction would be the replacement of this layer alone. Endothelial cell transplantation is technically difficult in present time, since these cells are very labile and would be challenging to seed them uniformly on the posterior part of the cornea using a surgical approach. However, our approach is based on the transference of these cells using a special carrier that could be thin enough to permit the passage of light without distortions. The natural candidate as a carrier in this case is the Descemet’s membrane, and certain properties of the membrane make it possible to obtain an intact detachment of the structure for endothelial cell transplantation. We have previously published a study describing a technique to dissect the Descemet’s membrane while preserving the viability of most endothelial cells.69

Harvesting of the Descemet’s Membrane with Endothelial Cells

To prepare the donor tissue, the corneoscleral button is placed on the metal base of a commercially available artificial anterior chamber (ALTK system, Moria, Antony, France) with the endothelial side up (Figure 35-1). Negative pressure is then applied within the artificial anterior chamber so that the donor corneoscleral button takes on a concave shape (in reference to the endothelium) and the cornea maintains its centration in the chamber due to the suction from central opening (Figure 35-2). It is important

Figure 35-1: The corneoscleral disk is placed upside down on the metal base of the artificial anterior chamber as the first step of the Descemet membrane harvesting.

Figure 35-2: Suction is performed through the opening of the artificial anterior chamber (folds in the stroma are shown with the arrows) to secure the corneoscleral disk in place when the second ring is placed.

to cover the endothelial surface with viscoelastic material to protect the cells during the whole procedure. A hand trephine is used to create a circumferential cut of Descemet’s membrane just inside the Schwalbe’s line and into a small portion of the posterior stroma (Figures 35-3A and B). Positive pressure is then applied to the AAC such that the cornea takes on a convex shape (in reference to the