Surgical Maneuvers

Quarter-DMEK quadruples available tissue to transplant

Visual outcomes are similar to conventional DMEK, with rapid clearance of the central cornea underlying the graft.

Corneal transplantation has continued to improve over time and has reached significant heights in recent times with selective tissue transplantation, namely Descemet’s membrane endothelial keratoplasty. In patients with a cloudy cornea secondary to endothelial decompensation, DMEK offers selective replacement of the recipient Descemet’s membrane and its decompensated endothelium with a donor Descemet’s membrane and healthy endothelial cells. Such an advanced endothelial allotransplantation technique provides a near normal anatomic restoration of the recipient cornea along with markedly improved vision over a relatively short period of postoperative time. Early recovery of vision with DMEK results in satisfied patients who can return to their normal activities faster compared with other corneal transplantation techniques. DMEK and other forms of selective tissue corneal transplantation have continued to raise the bar for restoration of vision in cases of corneal blindness.

DMEK requires donor corneal tissue with healthy endothelial cells. Human corneal endothelial cell density declines over time, from about 3,500 cells/mm2 to 4,000 cells/mm2 at birth to about 2,000 cells/mm2 to 2,500 cells/mm2 in adults. Traditionally with full-thickness penetrating keratoplasty, a relatively large number of donor corneal endothelial cells are transplanted, but clinicians have seen clear corneas with cell counts as low as 500 cells/mm2. With this knowledge, combined with the global demand for donor corneal tissue, there has been a continued search for methods to expand the donor tissue pool. This continued quest has led to techniques such as constructing a biomimetic corneal endothelial graft, culturing of corneal endothelial cells, use of Rho kinase signaling pathway to induce cell proliferation and cytoskeleton modulation favoring cell adhesion.

In this column, Drs. Dockery, Parker, Dhubhghaill and Melles describe their technique of quarter-DMEK in an attempt to provide more recipients with DMEK surgery, especially in global areas with donor endothelial tissue shortage.

Thomas “TJ” John, MD
OSN Surgical Maneuvers Editor

quarter-DMEK
Figure 1. In vitro light microscopy images of the right (a) and left (b) donor cornea procured from the same 74-year-old male donor, and in vivo specular microscopy images (c to f) at 3 months postoperatively of the four recipient eyes that received quarter-DMEK grafts from the right donor cornea (c and d) and the left donor cornea (e and f). Endothelial cell density at this time point was 641 cells/mm2 (case 1), 886 cells/mm2 (case 2), 1,440 cells/mm2 (case 3) and 1,085 cells/mm2 (case 4). Slit lamp images of the four quarter-DMEK eyes before the procedure (g) and 3 months postoperatively (h). The orientation of the quarter-DMEK grafts is outlined by orange arrows in the retroillumination images (i) and the dashed lines in row (h).

Source: Philip Dockery, MPH, Jack S. Parker, MD, PhD, Sorcha Ni Dhubhghaill, MD, PhD, and Gerrit R.J. Melles, MD, PhD

Endothelial keratoplasty revolutionized corneal transplantation by improving visual outcomes and reducing surgical morbidity. Descemet’s membrane endothelial keratoplasty is now widely considered the gold standard, offering a 1:1 ratio of removed to transplanted tissue with consistently better visual outcomes and more patients reaching a best corrected visual acuity of 20/20 (1.0) or better when compared with other endothelial keratoplasty approaches. However, in many areas of the world, the demand for endothelial grafts far surpasses the supply of donor tissue. The aim of quarter-DMEK is to widen the donor pool so that four eyes can be treated with one donor endothelium (Figure 1). These grafts may also, in theory, reduce the risk for allograft rejection by reducing the antigenic load delivered to each patient.

Quarter-DMEK yields similar visual outcomes as conventional DMEK: 100% achieving a BCVA of 20/40 (0.5), 90% achieving 20/25 (0.8) and 50% achieving 20/20 (1.0) by 6 months postoperatively. The central cornea underlying the graft clears rapidly, while the peripheral bare stromal regions slowly improve over several months. Because endothelial cells migrate more freely from the radial cut edges, corneal clearance can be observed sooner along those margins than along the curved graft edge (Figure 2).

Figure 2. Schematic diagram of the endothelial cell migration pattern. The big arrows indicate relatively quick donor and recipient endothelial cell migration along the straight-cut edges while the small arrows represent more indolent cell migration along the rounded edge of the quarter-DMEK graft, possibly due to increased collagen integration in the endothelial extracellular matrix in the far periphery.

Quarter-DMEK grafts experience an initially rapid decrease in endothelial cell density, which may be partly due to widespread cell migration. This decline appears to stabilize after 1 month and subsequently follows the same trajectory as conventional DMEK. For reasons not entirely clear, an increased rate of partial graft detachment may be experienced with quarter-DMEK compared with conventional DMEK (33% vs. 12%), which may be attributed to the curvature mismatch between the paracentral donor cornea and central recipient cornea or simply due to an early learning curve for a new procedure. Refining the surgical technique can improve the rate of graft detachment and overall outcomes. Here are some of our tips for successful quarter-DMEK graft preparation and surgical technique.

Graft preparation

As with conventional DMEK graft preparation, the Descemet-endothelial complex is stripped from the remaining corneoscleral button. However, instead of making a circular trephination, and thus discarding much of the peripheral rim, for quarter-DMEK grafts, two perpendicular bisections are made on the untrephined tissue to form four “pie-shaped” transplantable grafts (Figure 3). After removing the trabecular meshwork and making the radial cuts, each graft spontaneously forms a roll with the endothelium facing out.

Figure 3. Diagram showing graft preparation from (a) a full-diameter corneoscleral button to obtain (b) a single 8.5- to 9.5-mm standard DMEK graft or (c) two semicircular hemi-DMEK grafts and (d) four quarter-DMEK grafts.

Surgical technique

While in many ways similar to a full-sized graft in DMEK, the smaller graft responds more quickly to all attempts to move it, be it by fluid injection or air bubble manipulation, so patience is key. A few trial runs with rejected donor material in an artificial anterior chamber is advised to appreciate the loading and handling. It is highly recommended that the surgeon has significant experience in conventional DMEK and that this is not performed during the initial learning curve. During initial attempts, try selecting simpler cases with a shallower anterior chamber and lightly colored irides to make surgery easier. The descemetorhexis should be smaller, approximately 5 mm to 6 mm in diameter. Despite its small size, the graft will still retain the same rolling properties, and the Moutsouris sign can still be used to confirm orientation. Making sure that the roll is correctly aligned in the injector does half the work for you, as dealing with an upside-down graft can be frustrating. Once unrolled, a tiny air bubble is used to maintain orientation as gentle external tapping is used to center the graft. Once centered, you can complete the air fill to lift the graft as normal.

Conclusions

Although other techniques have been developed to reduce the burden of the demand for endothelial tissue, such as descemetorhexis without endothelial keratoplasty (DWEK) or cultured corneal endothelial cell therapy, quarter-DMEK may be the best option that can be immediately implemented. It reseeds the cornea with normal endothelial cells and has consistently faster visual reconstitution compared with DWEK, and it does not rely on Rho kinase inhibitors. When we compare the approach to cutting-edge cultured cell therapies, we should be mindful that these treatments will not come cheap as the additional regulatory hurdles of proving that the cultured product meets the quality standards will add significantly to the bottom line. While we are still optimizing the technique to make it more user-friendly, we believe that quarter-DMEK is a cheaper and more elegant way to do more with less.

Disclosures: The authors report no relevant financial disclosures.

Corneal transplantation has continued to improve over time and has reached significant heights in recent times with selective tissue transplantation, namely Descemet’s membrane endothelial keratoplasty. In patients with a cloudy cornea secondary to endothelial decompensation, DMEK offers selective replacement of the recipient Descemet’s membrane and its decompensated endothelium with a donor Descemet’s membrane and healthy endothelial cells. Such an advanced endothelial allotransplantation technique provides a near normal anatomic restoration of the recipient cornea along with markedly improved vision over a relatively short period of postoperative time. Early recovery of vision with DMEK results in satisfied patients who can return to their normal activities faster compared with other corneal transplantation techniques. DMEK and other forms of selective tissue corneal transplantation have continued to raise the bar for restoration of vision in cases of corneal blindness.

DMEK requires donor corneal tissue with healthy endothelial cells. Human corneal endothelial cell density declines over time, from about 3,500 cells/mm2 to 4,000 cells/mm2 at birth to about 2,000 cells/mm2 to 2,500 cells/mm2 in adults. Traditionally with full-thickness penetrating keratoplasty, a relatively large number of donor corneal endothelial cells are transplanted, but clinicians have seen clear corneas with cell counts as low as 500 cells/mm2. With this knowledge, combined with the global demand for donor corneal tissue, there has been a continued search for methods to expand the donor tissue pool. This continued quest has led to techniques such as constructing a biomimetic corneal endothelial graft, culturing of corneal endothelial cells, use of Rho kinase signaling pathway to induce cell proliferation and cytoskeleton modulation favoring cell adhesion.

In this column, Drs. Dockery, Parker, Dhubhghaill and Melles describe their technique of quarter-DMEK in an attempt to provide more recipients with DMEK surgery, especially in global areas with donor endothelial tissue shortage.

Thomas “TJ” John, MD
OSN Surgical Maneuvers Editor

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quarter-DMEK
Figure 1. In vitro light microscopy images of the right (a) and left (b) donor cornea procured from the same 74-year-old male donor, and in vivo specular microscopy images (c to f) at 3 months postoperatively of the four recipient eyes that received quarter-DMEK grafts from the right donor cornea (c and d) and the left donor cornea (e and f). Endothelial cell density at this time point was 641 cells/mm2 (case 1), 886 cells/mm2 (case 2), 1,440 cells/mm2 (case 3) and 1,085 cells/mm2 (case 4). Slit lamp images of the four quarter-DMEK eyes before the procedure (g) and 3 months postoperatively (h). The orientation of the quarter-DMEK grafts is outlined by orange arrows in the retroillumination images (i) and the dashed lines in row (h).

Source: Philip Dockery, MPH, Jack S. Parker, MD, PhD, Sorcha Ni Dhubhghaill, MD, PhD, and Gerrit R.J. Melles, MD, PhD

Endothelial keratoplasty revolutionized corneal transplantation by improving visual outcomes and reducing surgical morbidity. Descemet’s membrane endothelial keratoplasty is now widely considered the gold standard, offering a 1:1 ratio of removed to transplanted tissue with consistently better visual outcomes and more patients reaching a best corrected visual acuity of 20/20 (1.0) or better when compared with other endothelial keratoplasty approaches. However, in many areas of the world, the demand for endothelial grafts far surpasses the supply of donor tissue. The aim of quarter-DMEK is to widen the donor pool so that four eyes can be treated with one donor endothelium (Figure 1). These grafts may also, in theory, reduce the risk for allograft rejection by reducing the antigenic load delivered to each patient.

Quarter-DMEK yields similar visual outcomes as conventional DMEK: 100% achieving a BCVA of 20/40 (0.5), 90% achieving 20/25 (0.8) and 50% achieving 20/20 (1.0) by 6 months postoperatively. The central cornea underlying the graft clears rapidly, while the peripheral bare stromal regions slowly improve over several months. Because endothelial cells migrate more freely from the radial cut edges, corneal clearance can be observed sooner along those margins than along the curved graft edge (Figure 2).

Figure 2. Schematic diagram of the endothelial cell migration pattern. The big arrows indicate relatively quick donor and recipient endothelial cell migration along the straight-cut edges while the small arrows represent more indolent cell migration along the rounded edge of the quarter-DMEK graft, possibly due to increased collagen integration in the endothelial extracellular matrix in the far periphery.

Quarter-DMEK grafts experience an initially rapid decrease in endothelial cell density, which may be partly due to widespread cell migration. This decline appears to stabilize after 1 month and subsequently follows the same trajectory as conventional DMEK. For reasons not entirely clear, an increased rate of partial graft detachment may be experienced with quarter-DMEK compared with conventional DMEK (33% vs. 12%), which may be attributed to the curvature mismatch between the paracentral donor cornea and central recipient cornea or simply due to an early learning curve for a new procedure. Refining the surgical technique can improve the rate of graft detachment and overall outcomes. Here are some of our tips for successful quarter-DMEK graft preparation and surgical technique.

PAGE BREAK

Graft preparation

As with conventional DMEK graft preparation, the Descemet-endothelial complex is stripped from the remaining corneoscleral button. However, instead of making a circular trephination, and thus discarding much of the peripheral rim, for quarter-DMEK grafts, two perpendicular bisections are made on the untrephined tissue to form four “pie-shaped” transplantable grafts (Figure 3). After removing the trabecular meshwork and making the radial cuts, each graft spontaneously forms a roll with the endothelium facing out.

Figure 3. Diagram showing graft preparation from (a) a full-diameter corneoscleral button to obtain (b) a single 8.5- to 9.5-mm standard DMEK graft or (c) two semicircular hemi-DMEK grafts and (d) four quarter-DMEK grafts.

Surgical technique

While in many ways similar to a full-sized graft in DMEK, the smaller graft responds more quickly to all attempts to move it, be it by fluid injection or air bubble manipulation, so patience is key. A few trial runs with rejected donor material in an artificial anterior chamber is advised to appreciate the loading and handling. It is highly recommended that the surgeon has significant experience in conventional DMEK and that this is not performed during the initial learning curve. During initial attempts, try selecting simpler cases with a shallower anterior chamber and lightly colored irides to make surgery easier. The descemetorhexis should be smaller, approximately 5 mm to 6 mm in diameter. Despite its small size, the graft will still retain the same rolling properties, and the Moutsouris sign can still be used to confirm orientation. Making sure that the roll is correctly aligned in the injector does half the work for you, as dealing with an upside-down graft can be frustrating. Once unrolled, a tiny air bubble is used to maintain orientation as gentle external tapping is used to center the graft. Once centered, you can complete the air fill to lift the graft as normal.

Conclusions

Although other techniques have been developed to reduce the burden of the demand for endothelial tissue, such as descemetorhexis without endothelial keratoplasty (DWEK) or cultured corneal endothelial cell therapy, quarter-DMEK may be the best option that can be immediately implemented. It reseeds the cornea with normal endothelial cells and has consistently faster visual reconstitution compared with DWEK, and it does not rely on Rho kinase inhibitors. When we compare the approach to cutting-edge cultured cell therapies, we should be mindful that these treatments will not come cheap as the additional regulatory hurdles of proving that the cultured product meets the quality standards will add significantly to the bottom line. While we are still optimizing the technique to make it more user-friendly, we believe that quarter-DMEK is a cheaper and more elegant way to do more with less.

Disclosures: The authors report no relevant financial disclosures.