Graft survival and endothelial outcomes in the new era of endothelial keratoplasty

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Abstract

Corneal endothelial cells do not proliferative in vivo sufficiently to enable endothelial regeneration, and thus diseases of the corneal endothelium, which cause poor vision and discomfort, require treatment by transplantation of cadaveric donor corneal endothelial cells. The two major goals of any corneal transplant procedure are to restore vision and to promote longevity of the donor cornea by maintaining a healthy donor endothelial cell density. Over the last decade, the surgical treatment for endothelial disease has rapidly evolved toward endothelial keratoplasty, or selective tissue transplantation, and away from full-thickness penetrating keratoplasty (PK). While endothelial keratoplasty offers distinct advantages over PK in terms of visual outcomes and a smaller incision, the new surgical manipulations of the fragile donor tissue cause significant donor endothelial cell trauma. As a result, donor endothelial cell loss is much higher during the first month after Descemet stripping endothelial keratoplasty (DSEK) compared to after PK, and the primary (or more appropriately, iatrogenic) graft failure rate of 5% remains unacceptably high. Nevertheless, the rate of endothelial cell loss rapidly decreases beyond 6 months after DSEK, and thus endothelial cell loss at 5 years after DSEK appears to be lower than that at 5 years after PK. In the absence of primary (iatrogenic) graft failure, graft survival through 5 years after DSEK is similar to that after PK. Given the promising longer-term endothelial outcomes of DSEK, the quest for optimizing the visual outcomes has spurred interest in Descemet membrane endothelial keratoplasty (DMEK). While early results after DMEK suggest better visual outcomes than after DSEK, the technique needs to be simplified, and longer-term outcomes must show an advantage over DSEK with respect to vision, endothelial cell loss, and graft survival. DMEK also has a high rate of primary (iatrogenic) graft failure, and additional donor tissue wastage occurs when preparation of DMEK grafts is unsuccessful. This review discusses endothelial keratoplasty techniques and the associated endothelial outcomes.

Highlights

► Endothelial keratoplasty (EK) has rapidly evolved for treating endothelial disease. ► Surgical manipulation of donor EK tissue causes high early endothelial cell loss. ► Endothelial cell loss declines beyond 6 months after EK. ► The rate of primary or iatrogenic graft failure after EK averages 5%.

Introduction

The corneal endothelium is a delicate monolayer of neural crest-derived cells that maintains corneal deturgescence and transparency. The endothelial cells do not proliferate to any significant extent in vivo, and therefore diseases of the corneal endothelium frequently result in morbidity by causing poor vision and discomfort. Our understanding of corneal endothelial cell biology has been dramatically advanced by Nancy Joyce, PhD, and her laboratory, not least with their efforts to determine how to stimulate proliferation of the senescent endothelial cells.

Despite the advances in the basic science mechanisms pertaining to endothelial cell biology and disease, the current treatment of endothelial disease remains surgical. In 2010, 42,000 corneal transplants were performed in the United States, and over half of these were for endothelial disease (EBAA, 2010). For decades, penetrating (full-thickness) keratoplasty (PK) was the only procedure for endothelial replacement. PK was first reported by Eduard Zirm in 1906 (Zirm, 1989), and subsequently refined by Ramon Castroviejo (Castroviejo, 1931, Castroviejo, 1932a, Castroviejo, 1932b). Since the late 1990s, the surgical treatment of endothelial disease has rapidly evolved, with the current treatment of choice being endothelial keratoplasty (EK); in 2010, 19,000 EK procedures were performed in the United States (EBAA, 2010). EK is an intraocular procedure in which posterior host corneal layers are replaced by posterior donor corneal layers to restore endothelial function. The advent of EK has heralded new techniques, new challenges, new complications, and new uncertainties for long-term outcomes.

This review discusses endothelial keratoplasty techniques and how they pertain to the integrity of the corneal endothelium. Outcomes with respect to endothelial cell loss and graft survival will be discussed primarily.

Section snippets

Keratoplasty for endothelial disease

Knowledge of the surgical techniques for EK is important for understanding the factors that cause endothelial cell loss. The EK era has generated new questions about the resilience of the corneal endothelium to surgical trauma and the resulting long-term effects on graft survival.

Endothelial outcomes of keratoplasty

The success of corneal transplantation has traditionally been assessed by graft survival, which is the time to graft failure (Coster and Williams, 2005). Endothelial cell loss has also been frequently reported, although cell loss might not always indicate overall loss of endothelial function (Lass et al., 2010). Visual outcomes were difficult to assess in the era of PK, but are gaining more importance as EK predominates (Patel, 2011). Keratoplasty outcomes should be interpreted with caution,

Visual outcomes

The initial experience and results of DSEK have provided optimism for long-term graft survival and for the potential of restoring normal vision. The major advantages of EK over PK for vision are better uncorrected visual acuity and a predictable postoperative refractive error (Chen et al., 2008, Patel et al., 2009a, Price and Price, 2005). Although PK can provide a similar rate of visual recovery as DSEK (Patel et al., 2009a), visual recovery is considered to be quicker, and quality of vision

Future prospects for treating endothelial disease

Future treatments for endothelial disease would ideally avoid the need for surgery, and might include pharmacologic agents to stimulate endothelial cell proliferation (Joyce and Harris, 2010, Okumura et al., 2011, Okumura et al., 2009) or function (Hatou et al., 2010), or therapies to slow or halt disease progression. Until such novel therapies become available, keratoplasty will remain the mainstay of treatment, and efforts should continue to improve keratoplasty techniques and outcomes. Most

Role of the funding source

The funding sources had no involvement in the study design, collection, analysis and interpretation of data, in the writing of the report or in the decision to submit for publication.

Financial disclosure

None.

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    Dr. Patel is supported by: National Institutes of Health (EY 19339), Bethesda, MD; Research to Prevent Blindness (unrestricted departmental grant, and as Olga Keith Wiess Scholar), New York, NY; and Mayo Foundation, Rochester, MN.

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