How endothelial keratoplasty has revolutionized current treatment of endothelial disease

KEYWORDS:

• Cornea
• DMEK
• UT-DSAEK
• endothelial dysfunction
• corneal transplantation

The treatment of corneal endothelial failure, as seen in Fuchs endothelial corneal dystrophy and bullous keratopathy, has undergone significant advancements in recent years, thanks to surgical innovations like Descemet Membrane Endothelial Keratoplasty (DMEK), Descemet Stripping Automated Endothelial Keratoplasty (DSAEK), and Ultrathin-Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK). Historically, the treatment of choice for these conditions was penetrating keratoplasty (PK; a full-thickness corneal transplant), however in comparison to lamellar surgery, PK has showed several disadvantages, such as long recovery times, increased risk of complications due to open sky surgery, reduced post-operative globe integrity and relatively high risks of graft rejection and post-operative astigmatism leading to inferior visual quality [1].

Currently, DMEK surgery is the standard of care for the treatment of corneal endothelial disease. It has earned this status over DSAEK and UT-DSAEK due to its superior outcomes in terms of the level of visual acuity achieved, graft survival, reduced risk of complications, and reduced time to visual recovery, enabling patients to return to their normal activities sooner [2–4]. It allows more accurate replication of the natural corneal anatomy as only the Descemet’s membrane (DM) and the endothelial layer are removed and replaced with donor DM and endothelium without any additional stromal tissue, minimizing scattering of light and risk of graft rejection. Endothelial keratoplasty also minimizes surgically induced astigmatism. This contrasts with procedures like PK, which often involve more sutures and have a higher likelihood of causing astigmatism, which can negatively impact visual acuity [5]. Pre-Descemet Endothelial Keratoplasty (PDEK) is an alternative to DMEK which transplants the DM and endothelial complex with pre-Descemet’s layer. This technique has not yet been broadly adopted (only 5 procedures out of 30,812 EK in 2022) [6]; however, it may be useful when using younger donors because tight scrolling is limited in these tissues [7]. It is essential to acknowledge that DMEK surgery comes with a steep learning curve, making it challenging for ophthalmic surgeons to master. This steep learning curve is attributed to graft preparation, handling of thin grafts, air bubble management, and graft positioning. Due to the delicate nature of DMEK grafts and the need for precise techniques, ophthalmic surgeons are required to practice frequently to build the skills required [8]. This means that a substantial amount of time and resources are invested in training and perfecting the procedure [9]. It is worth noting that the steep learning curve of DMEK has led to the development of training programs and courses designed to help ophthalmic surgeons acquire the necessary skills and knowledge. These programs typically include hands-on training and mentorship, which can expedite the learning process, reduce overall surgical complications, and make DMEK more accessible to a greater number of surgical registrars and fellows and, consequently, more patients [10].

Eye bank prepared DMEK grafts can be a helpful alternative to in-house graft preparation by surgeons, especially for facilities and surgeons with limited experience. Eye banks can provide surgeons with high-quality grafts, reduce the surgeon’s learning curve, and increase graft availability [8,9]. While these eye bank prepared grafts come with some additional costs and logistical considerations, these challenges can be effectively managed, making eye bank prepared DMEK grafts a reliable and efficient option for surgeons with patients in need of this advanced corneal transplant procedure.

UT-DSAEK nowadays represents an alternative to DMEK that addresses the steep learning curve associated with DMEK. Preloaded UT-DSAEK offers certain advantages and characteristics that make it a more accessible option for surgeons while still providing significant benefits for patients with corneal endothelial diseases. Some key points on how UT-DSAEK can be a valuable alternative: grafts are easier to handle and prepare than a DMEK graft, lower learning curve, reduced risk of graft dislocation and similar DMEK visual acuity achieved at 1–2 years after surgery [11]. However, it is also important to note that UT-DSAEK strikes a balance between visual outcomes and surgical complexity, making it a viable alternative in conditions where the ocular anatomy is compromised, for example, in conditions such as aniridia, iris coloboma, and aphakia.

Many research groups globally are currently focused on the development of alternatives to the conventional one donor-one recipient transplant for endothelial disease in an attempt to overcome the global donor shortage. Descemetorhexis without endothelial keratoplasty (DWEK), also known as Descemet Stripping only (DSO), has been developed as an alternative to EK that does not require donor tissue. This technique relies on the peripheral endothelial cells migrating centrally and so is not suitable for all patients including those with advanced edema and <1000 cells/mm² at the periphery [12]. Shigeru Kinoshita and colleagues have pioneered the injected cell therapy approach, which has shown some promising results especially in bullous keratopathy patients where the Descemet’s membrane is free of guttae [13]. The cell-free approach taken by the developers of EndoArt also appears to be showing some impressive outcomes in patients who have chronic edema and a high risk of rejection [14]. Others are continuing to pursue creation of a graft that mimics a DMEK/DSEAK with a monolayer of cells expanded greatly in number in the lab, seeded onto a carrier, utilizing materials such as collagen, gelatin, or poly- epsilon-lysine for example [15]. This approach has many advantages including its use of delivery techniques that are familiar to surgeons often using the same devices to deliver the grafts used for DSAEK or DMEK. Another advantage over conventional graft techniques is that numerous grafts can be created from one donor and the mechanical properties of the carrier can be optimized improving handleability, especially when it comes to unfolding in the anterior chamber. It is hard to see how tissue engineered grafts will be able to improve upon the visual outcomes of DMEK, but for some patients in locations where donor shortage is causing lengthy waiting times, it may be a suitable alternative. The major hurdle for cell therapies is that the manufacture of cells in specialized clean room facilities is a costly process and in order for these therapies to be able to compete with current tissue-based treatments, this financial challenge must be resolved.

In conclusion, DMEK is the gold standard procedure to treat patients with corneal endothelial diseases. UT-DSAEK represents a valuable alternative to DMEK, particularly for surgeons who are looking for a corneal transplantation technique that is easier to learn and perform while still offering significant benefits to patients with corneal endothelial diseases. The choice between DMEK and UT-DSAEK should be based on the surgeon’s skill level, patient needs, and the desired balance between surgical complexity and visual outcomes. New therapies on the horizon offer exciting potential alternatives that may not be suitable for all patients but will hopefully add to surgeon’s arsenal in the continued fight against corneal endothelial disease.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.