Descemet Membrane EndothelialKeratoplasty: A Simplified Technique toShorten the Learning Curve and AvoidComplicationsSenior Instructor: Mark A Terry MDCourse: 224Sunday, October 16, 201611:30 AM - 12:30 PMRoom: S403APublished: 8-7-16 9:45 PM

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AAO Annual Meeting 2016

Chicago

Descemet Membrane Endothelial Keratoplasty:

A Simplified Technique to Shorten the Learning Curve

and Avoid Complications

Course #224

October 16, 2016

11:30 AM –12:30 PM

Mark A. Terry, M.D.

Michael D. Straiko, M.D.

Paul M. Phillips, M.D.

Christopher Sales, M.D.

Recommended Reading List

1. Terry MA. Endothelial Keratoplasty: Why aren’t we all doing DMEK? Cornea 2012 (Editorial); 31(5): 469-71

2. Terry MA, Straiko MD, Veldman PV, Talajic JC, VanZyl C, Sales CS, Mayko ZM. A standardized DMEK technique: Reducing complications using pre-stripped tissue, novel glass injector, and sulfer hexafluoride (SF6) gas. Cornea 2015;34(8):845-52

3. Hamzaoglu EC, Straiko MD, Mayko Z, Sales C, Terry MA. DSAEK v DMEK: First 100 eyes of each using a standardized technique at one institution. Ophthalmology, 2015. 122(11): p. 2193-9

4. Veldman, PB, Mayko Z, Sales CS, Stoeger C, Straiko MD, Terry MA. The S-stamp in Descemet Membrane Endothelial Keratoplasty Safely Eliminates Upside-down Graft Implantation. Ophthalmology, 2016. 123(1): p. 161-4.

5. Veldman PB, Dye PK, Holiman JD, Mayko ZM, Sales CS, Straiko MD, Stoeger CG, Terry MA. Stamping an S on DMEK Donor Tissue to Prevent Upside-Down Grafts: Laboratory Validation and Detailed Preparation Technique Description. Cornea, 2015. 34(9): p. 1175-8.

6. Veldman PB, Terry MA, Straiko MD. Evolving indications for Descemet’s stripping automated endothelial keratoplasty. Curr Opin Ophthalmol 2014, 25:306-311

7. Van Zyl C, Terry MA. DMEK: The Grand Prix of corneal transplant surgery. Expert Rev. Ophthalmol. 9(2), 89-98 (2014)

8. Sales CS, Straiko MD, Terry MA. Novel technique for re-bubbling DMEK grafts at the slit lamp using IV extension tubing. Cornea 2016 35(4):582-5

9. Sales CS, Terry MA, Veldman PB, Mayko ZM, Straiko MD. The relationship between tissue unscrolling time and endothelial cell loss. Cornea 2016 35(4):471-6

Descemet Membrane Endothelial Keratoplasty (DMEK): Step by Step Mark A. Terry, M.D.

June 2013 Endothelial Keratoplasty has now evolved to the point where we can attain perfect anatomic replacement of the diseased endothelium and Descemet’s membrane with healthy donor tissue. The procedure of DMEK however requires a different surgical skill set than DSAEK surgery, and the nuances of DMEK surgery can be important for success. This manuscript is created to ease the learning curve of the novice DMEK surgeon, but should not be considered an adequate substitute for a “hands on” DMEK course assisting an experienced DMEK surgeon at the operating microscope nor for the insights gained in the DMEK in-vitro wet lab. Pre-op considerations: We routinely use DMEK for cases of Fuchs dystrophy and Pseudophakic Bullous Keratopathy (PBK) which do not have any other complicating issues. Eyes with anterior chamber IOLs, filtering tubes, trabeculectomy bleb, aphakia or extensive peripheral anterior synechiae are not good candidates for DMEK and are better served with DSAEK. We have also found that eyes that have previously undergone a posterior vitrectomy also are not easy to do with DMEK, due to the difficulty in shallowing the anterior chamber for donor unscrolling. DMEK can be done in eyes with a prior failed PK, but this is slightly more difficult than on a virgin cornea. The majority of cases of failed endothelium, however, can be done with DMEK, either as a single procedure or as a combination of DMEK with phacoemulsification cataract surgery. DMEK Tissue Ordering: One of the initial obstacles to the acceptance of the DMEK procedure was the worry that when the surgeon was preparing the donor by stripping the Descemet’s membrane from the donor tissue that it would tear or rip and the tissue would be destroyed, cancelling the case and still incurring a bill from the eye bank. We are very fortunate that that obstacle has now been removed by the development of “pre-stripped” tissue from the eye bank for use in DMEK. We obtain all of our pre-stripped tissue from the Lions VisionGift (LVG) Eye Bank in Portland, Oregon, a leading eye bank in the Eye Bank Association of America (EBAA). Tissue from a surgeon’s local eye bank can be shipped to LVG in Portland for pre-stripping the day before scheduled DMEK surgery if the surgeons local eye bank does not provide this service. LVG has shipped DMEK tissue as far as Hong Kong and Europe. It is expected that more and more eye banks will offer pre-stripped tissue as DMEK becomes more common. Pre-stripped DMEK tissue is 90% stripped by the skilled eye bank technician, leaving a hinge of attachment of Descemet’s membrane to the peripheral posterior stroma. This allows the donor tissue to remain attached and yet still be shipped in Optisol in the same plastic viewing chamber as standard tissue. The location of the hinge is designated by a cut out “notch” in the scleral rim at that position. Tissue is evaluated by slit lamp after the stripping, and pre and post stripping specular microscopy is done. The diameter of the viable stripped tissue is noted and is usually at least 9.0 mm diameter. The donor age influences the ease in which the donor Descemet can be unscrolled (older donors have thicker Descemet’s membrane and become less tightly scrolled), and so choosing tissue with a donor that is older than 50 years old is usually advisable. Younger donors can of course be used, but there is a higher chance of getting tightly scrolling tissue.

Recently, the eye bank has been able to place a dry ink “S” stamp on the Descemet’s portion of the DMEK pre-stripped donor tissue. Validation studies by the eye bank have demonstrated only a 1% cell loss from this “S” stamp on the tissue. We have found the mark of an “S” invaluable for determining the proper orientation of the donor tissue before securing it with a gas bubble and it has eliminated the adverse event of an upside down DMEK graft. Like all tissue for transplantation, the donor tissue is removed from cold storage box at least 1 to 2 hours prior to surgery to allow warming of the tissue to room temperature and allow the endothelium metabolism to awaken. This serves the purpose of 1: having the chance of some endothelial pump function soon after surgery and 2: to allow the antibiotics in the Optisol to work (they are antibiotics, not antiseptics, and so require metabolic activity to be effective) Pre-operative medications: It is very important that the pupil be as small as possible for the insertion and unscrolling of the DMEK tissue, and therefore I prefer not to use any cycloplegic drops for any DMEK case preoperatively, even when cataract surgery is planned at the same time as the DMEK. Adequate dilation for the cataract portion of the procedure can be accomplished with intraoperative epinephrine in the operating room. If the surgeon must have better dilation for the patient, then a single drop of a very short acting mydriatic (such as Mydriacyle) is recommended, and only if necessary. In addition, we avoid the use of non-steroidal drops (such as Ocufen) to avoid persistent dilation effect. If the eye already has a posterior chamber IOL in place, then use of a single dose of Pilocarpine 1% can be useful to attain a small pupil, although it does make visualization of the stripping of recipient Descemets and the creation of the peripheral iridotomy slightly more difficult. Other preoperative drops such as antibiotics are according to the surgeon’s preference. Anesthesia: DMEK surgery is easiest in the first few cases with the patient under general anesthesia, as the stress and frustration level of the novice DMEK surgeon can be high and it is always better when the patient does not hear the surgeon curse! DMEK surgery can be performed under retrobulbar/peribulbar injection anesthesia quite easily and this is easiest on the patient. It does cause temporary pupillary dilation, which helps with some parts of the case, but can make pupillary constriction slightly more difficult prior to tissue injection. DMEK surgery can be performed under topical anesthesia, but this puts the responsibility on the surgeon to get the case done more quickly and on the patient to be quite cooperative, especially during the unscrolling of the tissue and the injection of the gas to secure the tissue. Topical anesthesia is not recommended until the surgeon reaches a high level of comfort with the procedure. Preparation of the Recipient Cornea: The patient’s head is positioned to make sure that the eye is exactly facing up toward the ceiling. I generally position the body in slight reverse Trendelenburg (feet down) incline to reduce the pressure on the eye. After anesthesia (see above), the eye is prepped and draped in the usual fashion and the lid speculum placed. Care is taken to prevent pressure on the sclera and the globe by the lid speculum, and so I usually place a 4X4 sponge pad beneath the handle of my Lieberman speculum to lift the separated lids away from the globe.

I sit temporally for nearly all my ophthalmic surgery and the description of surgical approach below reflects that orientation. (However, any surgeon seated position is possible and is entirely a surgeon preference) A calipers set at 3.0 mm is used to mark the clear corneal limbus at the 180 degree meridian for the main wound and this is marked with a marking pen in the epithelium. Two additional ink marks are made in the superior and the inferior temporal limbal cornea to mark the paracentesis sites. A stab incision paracentesis with a 1 mm diamond keratome is made at the two sites and the chamber is filled with cohesive viscoelastic (Healon). The central surface of the cornea is marked with an 8.0 mm circle indentation and this is marked with multiple spots of marking pen ink. A reverse Terry-Sinskey hook is used to strip Descemet’s membrane, making sure to score exactly along the template circular mark so a full 8.0 mm area is bared of Descemets. Care is taken to make sure that the stripped area does NOT overlap the posterior entrance wound of the paracentesis or the main wound, so that the subsequent graft does not overlap the entry points. The chamber is filled again with Healon to pressurize the eye and the main wound is created. A guarded diamond knife is set for 300 microns and a vertical 3.0 mm incision is placed at the temporal limbus where previously marked. A 3.0 mm (or smaller) diamond or steel microkeratome is placed through the vertical main incision edge and used to create a beveled entrance wound with about 1.5 mm of length before entry into the anterior chamber. The stripped Descemets is removed. The inferior peripheral iridotomy is then performed: Healon is used to fill the chamber and also some is put beneath the posterior iris inferiorly. Care is also taken to sweep the posterior iris to make sure that there are no posterior synechiae which would impede pupillary constriction or movement. A 30 guage short needle is then bent with a needle driver. The sharp tip is bent anteriorly and the hub is bent to provide a convenient angle of entry. The needle tip is placed through the superior paracentesis site and passed through the pupil, walked along the posterior iris inferiorly, and then pressed upward against the far peripheral iris tissue. At the same time, a straight Sinskey hook is placed through the inferior paracentesis site, into the anterior chamber and anterior to the iris. The hook is then used to scrape down on the location of the needle tip that is tenting up the iris tissue in the inferior periphery. Once the tip of the needle perforates the iris from behind, this creates a hole where the Sinskey hook tip can then be placed and using the needle and the hook, the small iridotomy hole can be stretched wide open. This is liberally done to about a 2 mm hole, as the P.I. will tend to become a slit opening by the next am. I will usually also use intraocular scissors to also cut the peripheral base of the P.I. further, to be absolutely sure that the P.I. remains patent. Prior to removing the Healon, I then check to make sure that my tissue injector device tip will fit snugly into the main 3.0 mm wound. We use a modified Jones Tube (designed by Mike Straiko, MD of Devers Eye Institute) which is FDA approved for human use and is used off-label. This glass tube (part number 80000-DMEK) is made by Gunther Weiss Scientific Glassblowing Co., Inc.in Portland, Oregon and contact information is: 503 644-4056 and info@guntherweiss.com) (price in 2013: $95.00). Most of the time, the incision needs to be opened with an angled blade to 3.2 or 3.5 mm in order for the tip to fit snugly into the anterior chamber. Once the main wound is the proper size, the irrigation/aspiration tip is used to remove ALL of the Healon. This only takes 15 or 30 seconds, as cohesive Healon does NOT coat surfaces and comes out quickly. At this point it is VERY IMPORTANT to make the pupil as small as possible. We inject Miochol (short acting) initially and will also “stroke” the iris surface to bring the pupil down to at least 3 mm in size,

but preferably smaller. If the pupil will not come down after this, then we also will add Miostat (long acting). A small pupil will cause less problems and damage to your donor tissue during the injection and unscrolling process. The IOP of the recipient is left normal or slightly soft using BSS injections and attention is turned to the donor table. Preparation of the Recipient in eyes undergoing concurrent Cataract Surgery with DMEK Cataract surgery can be safely performed at the same time as DMEK with a few minor changes from the above steps. Once again, we do NOT use cycloplegics at any time prior or during the triple procedure surgery, as we want the pupil to be as small as possible for the DMEK portion of the procedure. If the pt has a pupil that cannot be dilated with intraocular epinephrine, then use of a mild short acting mydriatic (mydriacyl) can be used preoperatively. We do not use NSAIDs such as Ocufen to prolong the dilation when also doing DMEK. We make sure that there are NO dilation agents (epinephrine) in the irrigating bottles when doing phaco and DMEK, as this can inadvertantly cause dilation later in the procedure. For phaco at the time of DMEK, we inject “Sugarcaine” (intraocular epinephrine and lidocaine) into the anterior chamber after the paracentesis incisions are made and BEFORE the Healon is injected. This dilation will last at least 20 minutes and ample time for doing the phaco. We use the main wound for the phaco and the insertion of the IOL, before it is enlarged to accept the tip of the insertion device. The P.I. is made after the IOL is inserted into the bag. The Descemet’s is stripped after the phaco and the P.I. are done. Every effort is made to get the pupil as small as possible using Miochol or Miostat and iris stroking. The rest of the recipient preparation is done the same as detailed for standard DMEK. Preparation of the Recipient in eyes that are Phakic and we leave the crystalline lens in place with DMEK In young patients (ie: less than 50 years old) that are phakic and do not have a cataract, DMEK can be safely performed. There are only slight variations: Preoperatively, the phakic eye is given 1% pilocarpine drops (2 sets) I use AIR to fill the chamber after the paracentesis incisions are made and do the stripping of Descemet’s under air. This is more difficult than using Healon, but I have found it difficult to get all the Healon out without iris prolapse and worry of lens damage during the I/A portion of the procedure. The P.I. cannot be made with the 30 guage needle through the pupil without damaging the crystalline lens, so in phakic eyes, I make a vertical paracentesis incision at 6 o’clock far limbus, pick up the anterior iris stromal tissue with a capsularhexis forceps, pull the iris base up through the paracentesis, and cut a small hole with scissors. This creates a small peripheral iridectomy. Care must be taken to insure that there is pigment in the tissue excised so that the P.I. is known to be patent. The remainder of the DMEK operation is exactly as described for DMEK in eyes with an IOL. Preparation of the Donor Tissue:

The operating microscope MUST be used to prepare and load the donor tissue. These steps cannot safely be done using just the naked eye…even by pre-presbyopic surgeons. The donor table should include: -- 7.75 mm donor trephine punch that enables the surgeon to look down the bore of the trephine during the punch process to ensure that the edges of the trephine do not include damaged tissue edges from the pre-stripping. We have used trephines from Katena (Hessburg/Barron trephine) and also from Moria. -- 3.0 cc syringe with a Luer lock tip -- 14 French gastric tubing (and a very heavy drape scissors to cut it) -- Vision Blue (trypan blue) -- tying forceps -- A shallow container filled with BSS (like a petri dish or the cap of a jar) -- Multiple miracell sponges -- 5 cc syringe filled with BSS and with a 27 guage cannula -- the Straiko modified Jones Glass Tube used for loading and injecting the DMEK tissue The donor cornea-scleral tissue cap is picked up from the viewing chamber with forceps and placed endothelial side up onto the donor table. Trypan blue (Vision Blue/ DORC, The Netherlands) is dripped onto the surface of the endo, left in place for 1 minute then gently wicked off (with a miracyl sponge) at the scleral edge of the donor that is directly OPPOSITE the scleral notch placed by the eye bank. This insures that as the vision blue is wicked off, the pre-stripped donor Descemet’s membrane will lie flat along the edges on the underlying posterior stroma. If it does not, re-float the Descemets and wick the fluid again until folds along the edges are gone. The tissue is mounted onto the punch block (endothelial side up) and suction applied to the block to secure the tissue for trephination. The trephine punch is then lowered very slowly onto the block until the trephine edge meets the endothelium. Gentle pressure and even tapping are done to the trephine to cut through the donor Descemets and into the underlying stroma, but care is taken to NOT trephine all the way through the entire cornea. The trephine is then carefully removed. The tying forceps are then used to remove the Descemets that is peripheral to the trephination cut. Great care must be taken not to pull this tissue away too quickly, because even the sharpest trephine will sometimes cut 300 degrees, but not 360 degrees of Descemets tissue! If you find that there is a segment that is not cut through by the trephine, then we have used a diamond knife (or 75 beaver blade) to hand cut the Descemets in the areas that the trephine did not cut. Alternatively, the trephine can be re-mounted and used to cut again, if there are extensive areas not cut originally. Rather than discard it, I use that peripheral Descemets donor tissue to later test my injector. So I place segments of peripheral donor Descemets into a petri dish (or cap) filled with BSS on the donor table. The trephined donor tissue is then covered with BSS. The tying forceps are used to gently pick up the edge of the tissue that is OPPOSITE the scleral notch placed by the eye bank, as this edge is OPPOSITE the hinge of the pre-stripped tissue. Under the BSS, the edge is lifted up until the final hinge area and then lifted out of the BSS, and it immediately scrolls in air. The well of the donor corneal-scleral tissue is then filled with Vision Blue (trypan blue) and the donor Descemets is then gently lowered back into the well. More Vision Blue is placed on top of the tissue so it is submerged in Vision Blue. The tissue is left to stain in place for at least 3 minutes to get a dark stain. (There is no damage to the tissue if it stains for even 3 hours). These methods of handling the donor tissue insures that the tissue transplanted is only touched once along the edge during the entire transplant surgery.

Construction of the insertion device is as follows: The 14 French Gastric Tubing is used as a connecting junction between the glass Jones tube and the 3 cc syringe. You only need 15 mm of it, so there is more than enough! Cut a middle section of tubing for a length of 15 mm or so. Wet the inside with BSS. Connect the tubing into the Luer lock of the 3 cc syringe. Connect the other end over the proximal tip of the modified Jones tube. Make sure both ends are tightly bound. Suction up 2.5 cc of BSS from the petri dish and inject it back. Make sure the junctions are water tight. Testing the Jones Tube prior to use as an injector: Remember the NASA space program in the early days?? Before they sent an astronaut into space, they sent a monkey into space first to make sure all systems work as expected, with no glitches…I like to do the same with my DMEK surgery. I call those peripheral pieces of donor Descemets that we previously saved my “space monkeys”. Take the Jones tube with 2.0 cc of BSS, submerge the tip into that petri dish of BSS with the space monkeys, and placing the tip bevel up, suction a space monkey into the tip of the Jones tube and note how much suction effort it took to bring the space monkey into the tip. You want to suction the space monkey far enough into the tip that it floats into the flared out portion of the tip. Mike Straiko designed the modified Jones tube so that the flared out portion of the tube would create a Bernulli effect, slowing down the tissue as it was aspirated from a constricted high flow area to a larger, low flow area. This protects the tissue from being sucked up all the way into the syringe. After loading the space monkey, shake the tube and syringe in your hand to demonstrate to yourself that the tissue stays loaded and the system is sound. Then put the tip back in the petri dish of BSS and inject the space monkey back into the dish to get a feel for how much syringe pressure it takes and to see that the tissue can easily be injected. Repeat all this with space monkeys until you feel comfortable that your system is foolproof. Loading the Donor Descemets: REMEMBER – THE DONOR SCROLL HAS ENDOTHELIUM ON THE OUTSIDE SURFACE OF THE SCROLL Before loading the actual tissue we are transplanting, we need to dilute the solution that is staining it. Take the BSS syringe and cannula and irrigate the well where the tissue is staining. (ie: the well is the donor cornea-scleral cap sitting in the donor punch) Use a miracell sponge to wick off some of the Vision Blue in the well. TAKE GREAT CARE NOT TO WICK OFF FLUID TOO QUICKLY OR THE TISSUE WILL END UP ON THE SPONGE. Continue irrigating and wicking, slowly diluting the well of fluid until the tissue is easily seen as a dark blue scroll sitting in nearly clear fluid. Fill the well completely with BSS. Take the Jones tube tip and place it bevel up into the well, directly next to the edge of the donor scroll, or even with the tip of the bevel beneath it. Gently aspirate the tissue into the tip of the Jones tube. If you are aspirating and the fluid is coming but not the tissue, fill the well again with BSS to get the tissue to “float” and try aspirating again. Get the tissue into the flared portion of the Jones tube and inspect it to see (if possible) which way it is curling up. Bring the loaded tube and microscope over to the patient. Injection of the donor Descemet’s membrane into the Anterior Chamber: The recipient eye should be normal or low IOP and the pupil should be small prior to inserting the tip of the Jones glass tube into the main wound. If possible, inspect the tissue in the Jones Tube to determine which side of the tube allows the tissue to be face up upon injection. Face up for the tissue is where the tissue scrolls toward you with the double scroll formation best with the scroll edge on either side facing anteriorly, “hugging” you.

Insert the tip of the Jones tube, bevel down, into the main wound so that the tip is over the pupil then rotate the tube if necessary so that the tissue will be injected scroll sides up. Inject slowly with short bursts of fluid if necessary to get the tissue to move. Once the tissue is in the chamber, it is sometimes helpful to give short bursts of fluid to allow the tissue scroll to orient perpendicular to the tip to have a harder time coming back into the tip or out the wound. To remove the injector tip, release fluid from the paracentesis site with a cannula held with your other hand. DO NOT REMOVE THE INJECTOR TIP UNLESS THE ANTERIOR CHAMBER IS NEARLY EVACUATED AND THE EYE IS VERY SOFT. If the chamber is well formed and the IOP is high, then the tissue will follow the tip out of the wound. To remove the tip, place the cannula on the cornea just central to the wound and slowly remove the tip while depressing with the cannula on the anterior corneal surface so that the wound closes as the tip is removed. This will trap the tissue in the anterior chamber. Once the tip is removed, immediately place one interrupted 10-0 nylon suture in the wound to close it. Now the “dance” begins to unroll the tissue and center it for placement. Determining if the tissue is right side up (scrolling up) or upside down (scrolling down): Before anything else is done, it is paramount to know the orientation of the tissue and because the tissue is so thin, it is sometimes hard to tell immediately. Remember, the tissue will always scroll with the endothelium on the OUTSIDE, so if the scrolls are facing anteriorly, then the tissue is correct, if posterior, then the tissue is upside down. After injection into the AC and suturing of the wound, the chamber is shallow or flat. I will usually inject a burst of fluid through the paracentesis and then watch how the tissue reacts to the deepening of the chamber. The tissue can “swirl” around and then settle with a curling of the edges in the deepened chamber. That movement is a dynamic way of watching how the tissue curls, and often that is enough to know if the scrolling is anteriorly (correct) or posteriorly (incorrect). If there is doubt, repeat the irrigation and tissue movement until you are sure. Another useful but more invasive method of determining orientation is to use the Mountsouri sign described by Gerrit Melles. This sign is demonstrated in his excellent published technique paper (ARCH OPHTHALMOL/VOL 129 (NO. 1), JAN 2011)  and also in my accompanying lecture slides. Basically, if the tissue it correctly oriented (scrolls up), then a silver spatula placed into the AC between the two scrolls edges will be silver, but when passed to left or right, the spatula passes below the edge of the scroll and is tinted blue by the overlying scroll edge of tissue. This demonstrates that he tissue is correct. If the tissue is upside down (scroll edges down) then that same silver spatula when passed from left to right will stay silver, because the scrolls are facing downward and do not obstruct or tint the spatula which is above them. Finally, another way to determine the orientation is by using a mounted or hand-held penlight slit beam. This can be passed across the chamber with the lights out and if there are two scroll reflections then the tissue is right side up, if one reflection, then it is upside down. Once you are sure that the tissue is “right side up”, then the tissue is centered and opened with a shallow chamber. Unrolling the tissue and centering it: The Yoeruek Tap Technique The key to unrolling the tissue is to be able to have a very shallow chamber and to use short taps on the surface of the cornea to generate fluid waves that push the scrolls open. The surgeon’s non-dominant hand is used at the same time to put intermittant gentle digital pressure on the sclera (about 4 mm from the limbus), as this can provide changes in chamber depth that will allow an unscrolled edge to “catch” from the shallow chamber and remain unscrolled. The Yoeruek tap technique is well described in his original article published in 2013 in Cornea (Yoeruek, et al: Cornea 2013; 32:370-73). Centering of the tissue is done either before or after unscrolling. Centering is accomplished by having a shallow chamber and then applying short “golf stroke” taps to the limbus near the decentered graft edge to create fluid waves that bump the tissue along the surface of the iris until it is centered. Unlike

DSAEK, sweeping along the surface of the cornea along the entire length of the donor tissue does not help to center it. Another way to move the tissue and also to help unfold an edge is to create short bursts of fluid release from the anterior chamber through the paracentesis site nearest the edge that you want to uncurl. This can be done using a cannula through the paracentesis site and “flicking” the site open while quickly removing the cannula. While removing AC fluid through the main wound can also help center tissue or uncurl edges, great care is taken at this site of fluid removal, as the tissue can expel through an opened main wound quite quickly and easily. A surgical movie is worth a million words and for a superb teaching video on tips for DMEK surgery, I recommend Dr Mike Straiko’s video available on YOUTUBE accessed by: http://www.youtube.com/watch?v=NuC7ZjHGICc Injection of air or gas (20% concentration of SF6) to secure graft in place: Because the DMEK graft tends to have graft edge separation inferiorly at about post-operative day #4 or 5, we feel that the DMEK graft needs a longer time of bubble support than DSAEK tissue. Therefore, we have transitioned to using only SF6 gas for the retained bubble for DMEK surgery. This gas bubble resolves in 6 to 8 days, giving longer lasting support and reducing our re-bubble rate to less than 10% for DMEK surgery. With the graft now fully uncurled and flat on the iris surface in a very shallow chamber, a 3 cc syringe filled with a 20% concentration of SF6 gas is used to put the tissue up against the recipient corneal bed. The 27 guage cannula is placed through the paracentesis, onto the iris surface, and hugging the iris, the tip moved centrally beneath the donor tissue all the way to the central pupil (or even slightly beyond center). Great care is taken not to inject the gas bubble too soon or the tissue will be displaced and folded. Once in the central pupil, the gas is SLOWLY injected, as this allows the edges of the graft to flatten out as they are pushed up by the expanding bubble onto the posterior surface. With the graft now in position the chamber is filled with gas. All the edges of the graft must be completely flat with no folding of the edges anywhere. Any “flat edge” of the circular tissue must be investigated for graft edge folding onto itself. If this is seen, the edge MUST be corrected or postoperatively, there is a greater risk of detachment. Melles has described “bubble bumping” to correct this problem. Basically, the gas bubble is reduced in size to about the diameter of the tissue. The eye is then rotated TOWARD the edge of concern. This moves the bubble proximally away from the edge and the folded edge is now with only fluid around it. A few taps of the surface of the cornea and the edge will unfold. When this is seen to occur, the eye is righted and the bubble now covers the edge, locking it into proper unfolded position. A final check of the graft should show clean round edges, good centration, and no folds. I usually will do a final sweeping with the Cindy Sweeper for 30 seconds over the entire surface of the cornea with a soft eye with the AC filled with gas to insure that there is no gross interface fluid and to also smooth out any visible microfolds in the central or peripheral graft. Final Check and Gas Bubble: When the tissue is in position, with all edges clean and round and no folds, the chamber is filled completely with gas to an elevated IOP for a couple of minutes then the IOP is normalized with gas release through a paracentesis site to a normal IOP. After 5 to 10 minutes, the gas bubble is reduced with

injection of BSS through the paracentesis site so that a gas fill of about 90% is achieved and the inferior peripheral iridotomy is uncovered, or will be uncovered in the seated position. The iris plateau should be flat, the chamber deep, and the IOP normal at the end of the case. If topical or general anesthesia was used for the case, only a Fox shield is placed on the eye and the patient is started on antibiotic and steroid drops every two hours while awake immediately and then seen the next day. If retrobulbar or peribulbar anesthesia is used, then the eye is dressed with a collagen shield soaked in antibiotic and steroid, the lid closed and lightly patched, and the patient keeps the patch on until seen the next day. Post-operative instructions: The patient is instructed to lie supine (“with your nose facing the ceiling”) as much as possible, allowing 20 minutes for bathroom or meal breaks or if their back is hurting. They are allowed to sleep in whatever position is comfortable. We do not take the patch off an hour after surgery to check the IOP, as we trust our inferior P.I. will prevent pupillary block, but we do tell the patient to call us if they have extreme pain or nausea. The usual positioning schedule for the patient with SF6 gas bubble is as follows: --Supine as much as possible for day of surgery and also Post op day 1 --Supine for two hours, up for two hour, supine for two hours, up for two hours, etc while awake for Post op days 2, 3 and 4 --Supine for one hour in the morning and one hour in the evening with hyperextension of the neck or with looking behind them in order to get the remaining bubble to come in contact with the inferior graft for Post op days 5, 6, and 7. Patients are seen on Post op day 1, 6 and 14 and then seen at 1, 3, 6 and 12 months post op. Patient with graft edges that are separating or with more edema of the recipient cornea may be seen more frequently. The Melles group has shown that if there is 30% or less of the graft with interface fluid at the one week postop visit, that 100% of these grafts will be attached and with good function at 6 months post op. (Yeh et al: Ophthalmology 2013; 120:240-45) Therefore, not every graft edge separation needs to be re-bubbled. Medications instructions are begun after the patient is seen in clinic and are as follows: Prednisolone 1%: one drop every two hours while awake for first week, then 4 times a day for 3 months, then 3 times a day for 3 months, then 2 times a day for 3 months, then once a day for three months. We usually try to get the patient off steroids at one year. There is some evidence that DMEK grafts may need much less steroids after 6 months than PK or DSAEK grafts, but controlled studies are pending. Antibiotic drops: 4 times a day for one week then stop Glaucoma drops: If used pre-operatively, used postoperatively. Monitoring of the DMEK graft:

An OCT that can show the entire diameter of the graft is invaluable in assessing the postoperative edge position of the DMEK graft. On the first day post-op the gas bubble is usually covering the pupil and filling 60 or 70% of the chamber and the inferior P.I. is cleared and the vision is H.M. with the gas over the pupil. The edges of the graft should all be attached with no interface fluid and most importantly, the overlying stroma should be clearer than what you usually see with DSAEK. If the recipient stroma is very edematous throughout the grafted area, beware that the tissue is either not functioning well or is upside down (the endothelium is anterior, against the stroma). This type of patient I will see two days later and repeat the OCT. By then, the stoma will either be clearer, showing the graft is now functioning, or the stroma will be diffusely still edematous and the OCT will show an inferior edge which is starting to detach. Look closely at the edge of detachment on the OCT. If the edge of detachment is curling anteriorly, toward the cornea, then the graft is correctly oriented (“correct side up”) and you can watch the graft or add more air or position the patient to have the gas bubble better cover the inferior graft. These corneas will clear over time. If the edge of detachment is curling posteriorly, away from the cornea, toward the anterior chamber, then the graft is “upside down” and no amount of re-bubbling or positioning will help. We will then schedule the patient for either a repeat DMEK or DSAEK the next week. For routine cases of DMEK we get an OCT pre-op, one day, one week, one month and 6 months after surgery. Small edge lifts on OCT that are not visually significant are watched and will always resolve with either peripheral recipient endothelium filling in the gap or the edge re-attaching (usually the former). Edge lifts with greater than 30% of the grafted area exposed are re-bubbled.

Frequently  Asked  Questions  About  DMEK      

1. Do  you  deliberately  strip  the  host  DM  larger  than  the  graft  diameter  or  smaller  as  in  DSAEK?  

I  always  strip  an  8  mm  recipient  and  punch  out  a  7.50  to  7.75  mm  graft.  What  I  find  is  that  the  graft  will  always  punch  out  slightly  larger  than  the  trephine  size  chosen  because  the  tissue  is  like  a  bedsheet  that  is  not  pulled  tight  so  you  cut  out  excess  than  the  trephine  diameter      2.What  is  your  air  fill  protocol  after  you  have  the  graft  positioned?      Once  graft  unfolded  and  centered  on  iris  surface  in  a  VERY  shallow,  nearly  flat  chamber,  I  inject  a  20%  concentration  of  SF6  gas  to  a  complete  air  fill.  I  then  pressurize  the  chamber  with  gas  to  about  30  or  40  mm  Hg,  use  the  Cindy  sweeper  to  sweep  corneal  surface  from  the  center  to  peripheral  edge  of  graft  for  a  minute  to  make  sure  graft  is  smooth  without  wrinkles,  and  it  seems  to  also  get  out  some  microscopic  interface  fluid  by  OCT.  Then  I  leave  filled  with  gas  for  another  5  minutes  before  releasing  some  gas  with  injection  of  BSS,  leaving  a  90%  gas  fill  and  a  normalized  IOP.  We  never  inject  air  anymore.    

2.  PI  or  no  PI?      ALWAYS  need  an  inferior  P.I.  And  ALWAYS  make  sure  it  is  patent.  We  do  the  P.I.  at  the  time  of  surgery  with  the  30  guage  needle  through  the  pupil  technique  that  Mike  Straiko  showed  on  his  YOUTUBE  video    3.  Are  you  still  recommending  20%  SF6  instead  of  air?  If  so,  what  %  fill  do  you  aim  to  leave?    20%  SF6  and  leave  a  90%  fill  so  that  when  pt  sits  up,  the  inferior  P.I.  is  uncovered.    4.  What  is  your  post  op  review  schedule?      I  do  NOT  see  the  pt  until  the  next  morning  or  afternoon  and  leave  the  patch  on  until  then.  They  call  me  if  they  have  severe  pain  (hasn't  happened  with  P.I  and  SF6)  I  then  see  them:  POD  #1,  6,  14,  and  30.    If  the  cornea  is  unduly  swollen  and  I'm  worried  about  the  graft  on  day  1,  then  I  will  see  them  on  POD  3.  The  gas  bubble  is  usually  still  present  enough  to  give  some  support  on  POD  4  through  7  so  during  that  time  I  have  the  pt  give  me  an  hour  in  the  am  and  an  hour  in  the  pm  lying  flat  with  neck  hyperextended  or  looking  behind  them  while  flat  so  the  gas  bubble  will  cover  the  inferior  edge  of  graft  where  a  detachment  is  most  likely  to  start.    5.  If  a  partial  detachment,  do  you  always  rebubble?      Melles  group  had  a  great  article  in  Ophthalmology  this  year  (2013)  that  showed  that  if  30%  or  less  of  the  graft  is  detached  at  1  week  after  surgery,  ALL  the  grafts  with  this  status  were  fully  attached  and  functional  3  months  after  surgery,  so  we  use  that  data  as  a  guide  of  when  to  re-­‐bubble.  If  there  is  an  area  of  detachment  into  the  visual  axis,  I  watch  those  pts  more  closely,  but  only  re-­‐bubble  if  detachment  is  getting  worse.    6.  If  a  total  detachment,  do  you  rebubble  or  replace  the  graft?      If  a  total  detachment,  the  graft  is  clear  and  floating  in  the  AC  and  the  recipient  cornea  is  fully  swollen  and  cloudy.  I  don't  know  of  any  way  to  re-­‐attach  this  invisible  totally  detached  graft,  so  we  always  replace  it.  If  the  pt  is  willing,  then  we  do  another  DMEK,  but  if  the  pt  appears  "tired"  and  disappointed  with  this  "new"  technique  (and  especially  if  they  have  had  a  successful  DSAEK  in  the  other  eye),  then  we  replace  the  DMEK  with  a  DSAEK.

Surgical Instrument List Glass injector 14G tubing 3ml syringe Scissors Punch/ block with syringe attached (7.5-8.0mm) 1 tryphan blue syringe 2 Healon or Provisc 2 tying forceps 1 fine-toothed forceps 1 needle holder 1 Sinskey hook 1 Utrata forceps 1 8mm corneal marker 1 tissue marker 1 10/0 nylon 1 Vannas scissors 2 3ml syringes with cannulas - air & BSS 3 blades - 15 degree, crescent, 3.0mm keratome 1 bottle of BSS Additional syringe & needle to pressurize globe

Resource Links DMEK Tips and Tricks http://www.youtube.com/watch?v=NuC7ZjHGICc This is a video a corneal transplant technique for endothelial dysfunction such as Fuch's corneal dystrophy. The video emphasizes tips and techniques for unfolding and positioning a DMEK graft. It features clips from numerous surgeries. The surgeries are being performed by Dr. Michael Straiko at Devers Eye Institute / Legacy Good Samaritan Hospital. The type of transplant in this video is a DMEK (Descemet's Membrane Endothelial Keratoplasty). In this type of transplant only the dysfunctional inner layers of the cornea are replaced. This technique allows for a safer surgery and a more rapid recovery than conventional transplants. In this video Dr Straiko is using a novel injector system to insert the tissue ad providing some pearls on unfolding a difficult DMEK graft. DMEK Surgery Using a Modified Alcon B Cartridge http://www.youtube.com/watch?v=SmJcZM3M9rk This is a video of a corneal transplant for Fuch's corneal dystrophy. The surgery is being performed by Dr. Michael Straiko at Devers Eye Institute / Legacy Good Samaritan Hospital. The type of transplant in this video is a DMEK (Descemet's Membrane Endothelial Keratoplasty). In this type of transplant only the dysfunctional inner layers of the cornea are replaced. This technique allows for a safer surgery and a more rapid recovery than conventional transplants. This is the latest iteration of endothelial keratoplasty. In this video Dr Straiko is using a novel injector system to insert the tissue ad providing some pearls on unfolding a difficult DMEK graft.

DMEK Corneal Transplant Using a No-Touch “Tap-Technique” http://www.youtube.com/watch?v=nxPtifLyE2E This is a video of a corneal transplant for Fuch's corneal dystrophy. The surgery is being performed by Dr. Michael Straiko at Devers Eye Institute / Legacy Good Samaritan Hospital. The type of transplant in this video is a DMEK (Descemet's Membrane Endothelial Keratoplasty). In this type of transplant only the dysfunctional inner layers of the cornea are replaced. This technique allows for a safer surgery and a more rapid recovery than conventional transplants. This is the latest iteration of endothelial keratoplasty. DMEK Injectors 1 http://www.youtube.com/watch?v=HuJ-DHMwtgE This is a video of a corneal transplant for Fuch's corneal dystrophy. The surgery is being performed by Dr. Michael Straiko at Devers Eye Institute / Legacy Good Samaritan Hospital. The type of transplant in this video is a DMEK (Descemet's Membrane Endothelial Keratoplasty). In this type of transplant only the dysfunctional inner layers of the cornea are replaced. This technique allows for a safer surgery and a more rapid recovery than conventional transplants. Lions VisionGift Prepared DMEK Graft http://www.youtube.com/watch?v=aNcF9ndXmiY Dr. Mike Straiko performs a DMEK transplant utilizing tissue prepared by Lions VisionGift.

Contact Information Devers Eye Institute 1040 NW 22nd Ave., Suite 200 Portland, OR 97210 Zachary Mayko Research and Training Questions ZMayko@deverseye.org Phone: (503) 413-8377 Fax: (503) 413-6937 Mark A. Terry, MD mterry@deverseye.org Phone: (503) 413-6223 Michael D. Straiko, MD mike.straiko@gmail.com phone: (503) 413-8202 Lions VisionGift 2201 SE 11th Avenue Portland, Or 97214-5303 Eligibility Specialist & Distribution Manager Jameson Clover, CEBT jameson@visiongift.org Phone: (503) 808-7012