SPECIAL REPORT

Corneal Transplantation:
The Advancement of DMEK

By Thomas John, MD

Endothelial failure with secondary compromise of corneal clarity and decreased vision requires corneal transplantation for visual rehabilitation. Such corneal transplantation has progressively moved from deep lamellar keratoplasty (DLEK), Descemet's stripping automated endothelial keratoplasty (DSAEK), to Descemet's membrane endothelial keratoplasty (DMEK) (Figures 1-3), and in doing so, there has been a significant increase in retention of the majority of the patient's uninvolved cornea and decreasing the amount of tissue that is replaced from 550 microns (Caucasians 543 microns, African Americans 520 microns, Asians 490-510 microns) for penetrating keratoplasty, to an extremely thin donor tissue of about 15 microns comprising of adult, donor Descemet's membrane 8-10 microns, and healthy corneal endothelium of about 5 microns as a single, circular, longitudinally rolledon-itself, donor tissue in DMEK. From a real world perspective, this donor tissue is comparable in thickness to a food wrap or cling wrap (12.5 microns), a thin plastic film typically used to seal food items. This is a 97% reduction in the amount of transplanted corneal donor tissue in DMEK, offering a biomechanically more stable cornea. DMEK is a true selective corneal transplantation (SCT) or endothelial keratoplasty (EK) procedure that restores the corneal anatomy to a near-normal state following surgery. With such advances in corneal transplantation come new challenges in donor tissue preparation, donor tissue delivery into the recipient anterior chamber, no-touch unrolling of the donor disc, and uniform air-assisted attachment of the donor disc to the recipient cornea with proper tissue orientation for optimal visual recovery following DMEK. This giant leap forward in corneal transplantation technique has restored the diseased cornea to an almost normal appearing human cornea following a DMEK procedure with quicker visual recovery and a full-compliment of improved visual quality as compared to a penetrating keratoplasty (PKP).

Figure 1. Slit-lamp photographs showing a clear cornea OS following DLEK 9 years and 6 months after surgery (Left-undilated pupil, Right-dilated pupil).

The corneal layer of importance in DMEK is the endothelium and its basement membrane namely, Descemet's membrane. The corneal endothelium consists of a single layer of highly specialized, mitochondria-rich, flattened, hexagonal, non-replicating, neural crest-derived cells lining the inner corneal surface with a high cell density of about 6000 cells/mm² during the first month after birth,¹ and decreases with age to about 3500/mm² at 5 years of age.² This decrease in cell density has been partially attributed to both the corneal growth and also to a decrease in the number of endothelial cells.¹ The decrease in the mean endothelial cell density from 3400/mm² at age 15 to 2300/mm² at age 85³ can be attributed in part to the natural, progressive, central, endothelial cell loss at an average rate of about 0.6%/year.⁴ The average, adult, endothelial cell density is estimated to be in the range of 2400-3200 cells/mm². While cell loss continues over one's life span, there is no endothelial cell replication in vivo to compensate for such cell loss. The decrease in endothelial cell density is associated with an increase in variability of the cell size called polymegathism, and cell shape variation called polymorphism. Pleomorphism refers to the disruption in the regular, endothelial hexagonal pattern that decreases the overall endothelial mosaic stability of the corneal endothelial layer.

A New Device to Help Corneas Heal Quickly By Thomas John, MD

Ophthalmologists, especially cornea specialists, have accepted amniotic membrane as a new modality for the treatment of nonhealing corneal surface lesions and other indications. With the introduction of Prokera (Bio-Tissue), this therapeutic modality has moved amniotic membrane transplantation from the high-cost operating room to the low-cost, convenient office setting, providing an added advantage for both the patient and the treating physician. Prokera has a rigid, dual PMMA symblepharon ring system with AmnioGraft (cryopreserved human amniotic membrane) sandwiched between dual rings. This treatment avenue provides a ready-to-use, biologic bandage that provides anti-inflammatory, anti-angiogenic effects and promotes sutureless ocular surface healing, which contributes to decreased ocular pain. The tissue orientation allows the stromal (sticky) side to come into direct contact and drape the corneal surface for maximum therapeutic effect in an easy-to-use clinical product. In addition, the PMMA rings provide an added anti-symblepharon effect in an inflamed ocular surface environment. Some of the common clinical indications of Prokera include but are not limited to: a) epithelial defects, erosions, ulcerations; b) chemical and thermal burns; c) following PKP or LKP procedures; d) following excision of lesions from the ocular surface; e) acute Stevens-Johnson syndrome and toxic epidermal necrolysis, and other indications. ProKera is easy to introduce to the ocular surface by asking the patient to look down, and slipping the device into the superior fornix, then tucking it beneath the lower eyelid to partially cover the ring segments. It usually centers itself. ProKera Pearl: It's essential to partially close the lids temporarily by using an adhesive tape. Partial lid closure increases patient comfort, which is paramount in this treatment approach, decreases surface evaporation of tears and prevents possible slippage or extrusion of the device. Following healing of the lesion, ProKera is removed from the ocular surface. It is important to add a prophylactic fluoroquinolone antibiotic (such as besifloxacin 0.6% tid or gatifloxacin 0.5% or moxifloxacin 0.5% qid) along with non-preserved artificial tears as needed. Amniotic membrane helps corneal surface healing and ProKera delivers this technology in the office setting. ProKera is a welcome addition to our surgical armamentarium. Figure. Prokera-assisted, healing of a large, persistent, corneal epithelial defect

Descemet's membrane represents the basement membrane of the endothelial cells and in the adult, it comprises both banded and non-banded basement membrane. The thickness of Descemet's membrane increases from about 3 microns at birth⁵ to about 13 microns by age 70 years. At birth, the collagen in Descemet's membrane has a banded pattern, while the addition of 10 microns over about seven decades consists of non-banded collagen to give a composite of banded and non-banded Descemet's membrane. Endothelial stress secondary to damage or disease process may result in the secretion of a banded basement membrane to form an abnormal, posterior banded layer,⁶ also called posterior collagenous layer.⁷ In such instances, there can be non-banded basement membrane sandwiched between banded-basement membranes.

Figure 2. 82-year-old Caucasian female with a clear cornea following DSAEK with phacoemulsification and a PC IOL as a combined procedure OD, 6 years and 4 months following surgery.

The lateral membranes of the endothelial cells contain a high density of Na+ , K+ -adenosine triphosphatase (ATPase) pump sites, while the basal side has numerous hemidesmosomes that augments the adhesion to Descemet's membrane. Unlike most other bodily cells, the endothelial cell tight junctions leak, and the zonula occludens is incomplete to suit the functions of this unique monolayer of cells, namely, allow bi-directional movement, namely, nutrients and other molecules to move forwards into the corneal stroma, while pumping fluid out of the cornea into the anterior chamber in a reverse direction to keep the cornea clear. The endothelium is responsible for keeping the corneal stroma in a relatively deturgesced state that permits an orderly arrangement of the collagen fibrils, contributing to the corneal transparency and clear vision.

The corneal, endothelial monolayer of cells can be affected by traumatic injury, the aging process, systemic and ocular diseases, intraocular surgery, intraocular solutions used within the anterior chamber, dystrophies such as Fuchs' dystrophy, posterior polymorphous dystrophy, congenital hereditary endothelial dystrophy and contact lens wear. When the endothelial cells decompensate and fail over time this allows direct fluid entry into the corneal stroma and epithelial layers that result in corneal stromal and epithelial edema and bullous keratopathy with decreased vision that often can only be reversed by surgical intervention. In the absence of central stromal and epithelial scars and no disease processes that involve these corneal layers combined with endothelial decompensation, a partial corneal transplantation is clearly preferred over full-thickness, PKP. DLEK was a relatively complex surgical procedure that was not widely embraced by corneal surgeons, and when the procedure was simplified by the introduction of DSAEK, the latter became the procedure of choice for posterior lamellar keratoplasty (PLK). Although DSAEK continues to be the most pouplar PLK procedure with continued decrease in the transplanted, donor stromal thickness, surgeons are beginning to be attracted to DMEK where the stromal layer is eliminated from the donor tissue and only the monolayer of donor endothelium with its Descemet's membrane is transplanted.⁸ This increased interest in DMEK is attributed to faster and better visual outcomes with DMEK as compared to DSAEK⁹ and also the restoration of the corneal anatomy to its near-normal state. Further, the decreased graft rejection with DMEK as compared to DSAEK¹⁰ is another driving force contributing to the elevated interest in DMEK. However, there are several surgical hurdles with DMEK at the present time. These hurdles include the removal of donor Descemet's membrane with its healthy endothelium under fluid without tearing it. Since donor Descemet's membranes differ somewhat in the way they handle while being removed from the donor corneal stroma, this further challenges the surgeon. Once the donor Descemet's membrane is introduced within the recipient anterior chamber, the proper orientation has to be maintained for a functional post-operative graft. Unlike other transplant procedures, the donor tissue is best handled by a no-touch technique for the most part, which further adds to the current day surgical complexities of DMEK. Hence, the major transition from DSAEK to DMEK will occur with the surgical simplification of the procedure to attract the corneal surgeons who are currently comfortable doing DSAEK with good post-operative results coupled with increased patient satisfaction. New instrumentations and simplification of the surgical steps can be important catalysts for this transition from DSAEK to DMEK. Additionally, eye banks providing donor Descemet's membrane-endothelial grafts that are pre-prepared will decrease the surgical hurdles in DMEK.

Figure 3. Same patient as in Figure 2, with a clear cornea following DMEK OS, 1 year and 10 months following surgery.

It is my belief that DMEK clearly shines over DSAEK for patient satisfaction, quality of post-operative vision, maintenance of biomechanical strength of the cornea, restoration of corneal anatomy, and lowest rate of endothelial graft rejection. However, until the introduction of improved surgical instrumentation to simplify DMEK occurs, corneal surgeons will remain in the side-lines.¹¹ DMEK is here to stay, but increased adaptation of this procedure is yet to happen! ■

References

1. Bahn CF, Glassman RM, MacCallum DK, Lillie JH, Meyer RF, Robinson BJ et al. Postnatal development of corneal endothelium. Invest Ophthalmol Vis Sci 1986; 27: 44-51.
2. Nucci P, Brancato R, Mets MB, Shevell SK. Normal endothelial cell density range in childhood. Arch Ophthalmol 1990; 108: 247-248.
3. Yee RW, Matsuda M, Schultz RO, Edelhauser HF. Changes in the normal corneal endothelial cellular pattern as a function of age. Curr Eye Res 1985; 4: 671-678.
4. Bourne WM, Nelson LR, Hodge DO. Central corneal endothelial cell changes over a ten-year period. Invest Ophthalmol Vis Sci 1997;38: 779-782.
5. Johnson DH, Bourne WM, Campbell RJ. The ultrastructure of Descemet's membrane. I. Changes with age in normal corneas. Arch Ophthalmol 1982;100: 1942-1947.
6. Johnson DH, Bourne WM, Campbell RJ. The ultrastructure of Descemet's membrane. II. Aphakic bullous keratopathy. Arch Ophthalmol 1982;100: 1948-1951.
7. Waring III GO. Posterior collagenous layer of the cornea. Ultrastructural classification of abnormal collagenous tissue posterior to Descemet's membrane in 30 cases. Arch Ophthalmol 1982;100: 122-134.
8. Dapena I, Ham L, Droutsas K, van Dijk K, Moutsouris K, Melles GR: Learning Curve in Descemet's Membrane Endothelial Keratoplasty: First Series of 135 Consecutive Cases. Ophthalmology. 2011;118:2147-2154.
9. Guerra FP, Anshu A, Price MO, Giebel AW, Price FW: Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss. Ophthalmology. 2011;118:2368-2373.
10. Anshu A, Price MO, Price FW Jr: Risk of corneal transplant rejection significantly reduced with Descemet's membrane endothelial keratoplasty. Ophthalmology. 2012;119:536-540.
11. John, T (Ed): Endothelial Transplant, DSAEK, DMEK, & DLEK. Jaypee-Highlights Medical Publishers Inc., Pages 1-428, Chapters 1-39, 2010.