Corneal transplants are a life-altering procedure for thousands of people worldwide — but unfortunately, there is a chronic shortage of corneal donors. In an area where demand exceeds supply, two new potential therapies show promise as published in the paper, Evolution of Therapies for the Corneal Endothelium: Past, Present and Future Approaches.1
Penetrating keratoplasty (PK) was first introduced by Eduard Zims in 1905 and for much of the 20th century, it was the predominant technique used to restore visual loss from various diseases of the cornea. However, by the early 2000s, research into alternatives to PK reached the point where Descemet’s stripping endothelial keratoplasty (DSEK) — a technique where a pre-cut endothelial graft is inserted into the recipient’s eye via a small corneal or scleral surgical wound and attached to the host cornea with an air or gas bubble — had become the preferred method. This was further expanded by Descemet’s stripping automated endothelial keratoplasty (DSAEK), and Descemet’s membrane endothelial keratoplasty (DMEK).
While these techniques have a proven track record of success, there are a number of issues that pose challenges and prevent the maximum number of patients from receiving the best possible outcomes. The aforementioned problem with cornea donation is a serious issue, which puts a bottleneck on the number of possible transplantations. Graft failure is always a potential threat, as it is for any procedure involving the transplantation of organs, and the procedure is still high risk, requiring a rare level of skill on the part of the surgeon, not to mention costly.
Ever wanted to replace your cells?
Hence the search for alternatives that can provide the same levels of patient outcomes as DSEK, etc., and also overcome their aforementioned limitations. Given that only 1.5% of worldwide demand for corneal transplantations was being fulfilled, the urgency of this search is particularly acute. Not only that, but a third of donor corneal tissues harvested are reported to be unsuitable for transplant surgeries due to low corneal endothelial cell density, or abnormal donor infectious screening results.
One possible replacement is cell-based therapies which usually involve the in vitro cultivation of primary native human corneal endothelial cell cultures (CECs) from cadaveric donor corneas. Thanks to the innate scalability of human CECs, a single donor cornea can yield sufficient CECs for the treatment of multiple patients instead of one donor equalling just one transplant. As you can imagine, this could revolutionize treatment options and a number of different studies have been performed or are currently ongoing to ascertain this theory’s full practical effect.
The latest development in this area is perhaps the most interesting as it examines not just the use of CECs from donor corneas but from alternative sources, including the differentiation of adult cells into CECs phenotype. This could minimize the risks of allogeneic rejection encountered in conventional keratoplasty surgeries as the cells would be taken from the same individual undergoing surgery. This possibility, combined with related fields like genetic editing, will be fascinating to monitor.
Taking Cells from the Host
Another replacement possibility that looks rather appealing is the examination of Rho-associated kinases (ROCK) inhibitors in corneal diseases. ROCK inhibitors have already been shown to have an effect on intraocular pressure reduction and their use could be expanded into a corneal replacement. This is because the inhibition of ROCK signaling in CECs has been shown to promote cell adhesion, inhibit apoptosis and enhance cellular proliferation in cultivated primate and human CECs.
There are two surgical techniques that use regenerative medicine in the treatment of corneal endothelial diseases, namely Descemetorhexis without endothelial keratoplasty (DWEK)/Descemet’s stripping only (DSO), and Descemet’s membrane transplantation (DMT). The latter technique is particularly promising as the risks of immunological rejection and the need for long-term immunosuppressive agents encountered in conventional transplantation are avoided. Also, donor tissues that are not suitable for conventional keratoplasties can be repurposed and used.
- Ong SH, Ang M, Mehta J. Evolution of Therapies for the Corneal Endothelium: Past, Present and Future Approaches. Br. J. Ophthalmol. 2021;105(4): 454–467.