Corneal Endothelial Transplantation

Excerpt

The cornea is a five-layered structure that provides the majority of the total refractive power of the eye (Fig. 1). In the past, penetrating keratoplasty (PK) had been the gold standard surgical treatment of corneal diseases for any layer, including diseases of the endothelium. With the improvement in technology and innovation over the last two decades, endothelial keratoplasty (EK) techniques involving transplantation of corneal components have been deployed to treat these diseases (Table 1). When compared to PK, EK introduces less foreign antigens, has improved visual recovery and outcomes, minimizes astigmatism, has less risk of dehiscence, and results in better globe stability.

History of Endothelial Keratoplasty Techniques

The first endothelial transplant was developed by Dr. Tillett in 1956. The technique required a large incision and used a partial thickness graft created by the trephination of half of the posterior donor cornea. During the 1960s, Dr. Barraquer developed a method of EK using a microkeratome for an anterior approach similar to a laser-assisted in situ keratomileusis (LASIK) flap followed by posterior trephination and suturing of the graft. These techniques were complex, challenging to replicate, and unable to address the issues posed by PK. In 1998, Melles et al. made a significant advancement in the field by dissecting out a posterior stromal pocket using an intrastromal approach and securing the graft with air instead of the typical suturing that produced tension likely to pull the graft out of place. Some refinements of this technique were made by Dr. Terry, who coined the term deep lamellar endothelial keratoplasty (DLEK) (Fig. 2A). However, this procedure was technically challenging and not universally adopted.

Next, in 2004, Melles et al. revolutionized the field with what is now called Descemet stripping endothelial keratoplasty (DSEK), after a few modifications made by Price et al. DSEK utilizes a novel technique, "descemetorhexis," via an internal approach to remove the pathologic host Descemet membrane and endothelium. This procedure creates a smooth surface for graft application and removes the source of disease while sparing posterior stroma (Fig. 2B). The use of a microkeratome to remove anterior stroma of the donor cornea was described by Dr. Gorovoy and is now referred to as Descemet stripping automated endothelial keratoplasty (DSAEK). However, DSAEK is commonly referred to as DSEK as well. DSAEK has shown to have better visual outcomes compared to the original DSEK, and the technique continued to be refined, such as the addition of venting incisions in the cornea after graft application enhances graft adherence.

DSAEK had become widely adopted, and eye bank produced precut tissue has proven to be reliable; thus, replacing the need for preparation by surgeons. A study by Neff et al. found that thinner grafts, specifically those ≤ 131 μm, were associated with improved visual outcomes; although the correlation between graft thickness and clinical outcomes has been disputed. Another iteration using thinner grafts with less stroma, Ultrathin DSAEK (UT-DSAEK) developed by Busin et al. in 2013, was shown to have the same or better outcomes with faster recovery and similar complications as DSEK. Comparing thicknesses, UT-DSAEK grafts are around 100 μm, whereas DSEK and DSAEK grafts are closer to 200 μm. Melles et al., however, continued to innovate with the development of Descemet membrane endothelial keratoplasty (DMEK).

DMEK uses a graft consisting of endothelium and DM without any stroma (Fig. 2C). The graft is around 10-15 μm in thickness and prepared via a descemetorhexis performed on the donor eye. A similar technique, pre-Descemet Endothelial Keratoplasty (PDEK), is prepared using pneumodissection to include the pre-Descemet layer in the graft, which helps with graft handling. Compared to DSAEK, DMEK has better visual outcomes, faster recovery time, and lower immune rejection rate. However, it was not widely adopted due to the increased surgical skill required and higher rates of complications such as graft detachment and the need to rebubble. Although short-lived, DMEK technique with a stromal rim (DMEK-S) was an attempt to hybridize the ease of handling inside the eye from DSEAK and retain visual benefits of DMEK developed by Studeny et al. (Fig. 2D). Refinement of DMEK techniques continued, such as the development of pre- and intraoperative manipulations to better identify DMEK graft orientation, use of gas bubble tamponade that decreases chances of detachment, and eye bank technicians becoming proficient at producing preloaded DMEK grafts.

The femtosecond laser has also been used to assist in EK procedures. Femtosecond laser-assisted DSEK (FS-DSEK) has been used to produce successful DSEK grafts consistently. However, a visual improvement from FS-DSEK appears limited when compared to DSAEK or PK. Femtosecond and excimer laser-assisted EK (FELEK) uses a Femtosecond laser to dissect a thin graft that is smoothened with excimer photoablation. FELEK has shown some success on a small cohort of patients and may provide similar results to DMEK with less of a learning curve. Femtosecond laser-enabled descemetorhexis DMEK (FE-DMEK) or Femtosecond laser-assisted DMEK (F-DMEK) has been used to perform the descemetorhexis for DMEK, resulting in fewer graft detachments and need for rebubbling when compared to manual descemetorhexis.

In settings with a scarcity of donor tissue, some modified or newer techniques may offer a solution. Hemi-DMEK and quarter-DMEK are variations involving grafts with smaller, modified shapes prepared by surgeons, and they appear to have similar visual outcomes, although with lower endothelial cell density. Mini-DMEK is another technique where a graft is shaped and sized to fit a patient's particular endothelial defect. It has been used to treat acute corneal hydrops secondary to keratoconus in a small cohort of patients.

The observation of corneal clearing despite nonattachment of grafts in some cases has led to investigating techniques that do not use transplants, and instead, rely on primary intention healing of the endothelium (Fig. 2E). These techniques have been termed Descemetorhexis without endothelial keratoplasty (DWEK) coined by Kaufman et al. or, increasingly becoming the norm, Descemet stripping only (DSO) proposed by Dr. Gorovoy. ROCK inhibitors have also been used with DSO to salvage failing cases, speed up the recovery, and improve endothelial cell density in patients with Fuchs endothelial dystrophy.

Further comparison studies are warranted, but DSO may provide similar visual outcomes to DMEK after a longer recovery time without the risk of rejection, detachment, or need for immunosuppression. Corneal clearance, despite subtotal detachment of grafts, has also inspired a purposed technique, Descemet membrane endothelial transfer (DMET), involving a focally attached free-floating graft to serve as a source of endothelial cells (Fig. 2F). However, retrospective studies of DMEK cases with subtotal detachment do not always have satisfying results, and it is not entirely clear whether corneal clearance is due to endothelial cell transfer or simply primary intention healing of host endothelium.