Artificial DMEK could help tackle endothelial donor tissue shortage

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Ophthalmology Times Europe Journal, Ophthalmology Times Europe September 2021, Volume 17, Issue 07

Newly developed acrylic implant provides option for patients with endothelial dysfunction.

Over 115 years ago, in 1905, Eudard Zirm successfully performed the first corneal transplantation.1 Penetrating keratoplasties remained the gold standard for the treatment of a variety of corneal conditions for much of the 20th century.

More recently, in 1998, Melles and colleagues successfully attached a posterior lamellar graft consisting of stroma, Descemet membrane and endothelium to the posterior surface of the cornea, which initiated a new era in the treatment of corneal diseases primarily affecting the endothelium.2 In 2006, Melles and associates first described the selective transplantation of the endothelium and Descemet membrane (EDM).3

Descemet membrane endothelial keratoplasty (DMEK) involves the surgical removal of the diseased endothelial layer as well as the diseased Descemet’s membrane from the posterior corneal stroma.4 In comparison with traditional full-thickness or penetrating keratoplasty, DMEK allows the patient faster visual recovery, better refractive outcome and superior tectonic integrity.5–7

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At present, endothelial keratoplasties such as DMEK are the gold standard in endothelial dysfunction,8 including Fuchs’ endothelial dystrophy,8 pseudophakic bullous keratopathy,9 graft failure after penetrating or endothelial keratoplasty,9 pseudoexfoliation syndrome keratopathy9 and endothelial decompensation due to congenital glaucoma.10 Known complications such as primary or secondary graft failure, immunological graft rejection and interface keratitis remain a challenge and can have a negative impact on the success of the procedure.8,11,12

Nowadays, donor tissue preparation and insertion into the anterior chamber is routine. However, rupture of the EDM during preparation can lead to graft loss, which can delay surgical intervention and disrupt organisational processes in a clinic.12 Furthermore, prolonged or careless manipulation of the EDM in the anterior chamber can lead to significant endothelial loss with potential primary or (early) secondary graft failure.12

According to a report published by the German Keratopathy Registry, the majority of keratoplasties performed these days are posterior lamellar keratoplasties; only 30% remain penetrating keratoplasties.13 Additionally, because human donor corneas are in constant short supply,10 there is a need for alternative, universally available treatment options.

In 2018, Kinoshita and associates proposed the injection of cultured human corneal endothelial cells supplemented with a rho-associated protein kinase inhibitor into the anterior chamber to increase corneal endothelial cell density.14 A 5-year follow up published in 2020 by Numa and colleagues confirmed the safety and efficacy of this approach, however, it was tested only in a very small number of patients and further long-term data do not yet exist.15

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Another recently introduced technique with no need for donor corneal tissue is Descemet membrane stripping only (DSO) with or without the topical treatment of rho kinase inhibitors. DSO involves removing a small area of central endothelium that has become dysfunctional, without performing an endothelial keratoplasty.16

This method has proven successful in a small number of patients with Fuchs endothelial dystrophy but its long-term efficacy has yet to be evaluated.16 A very limited number of patients are eligible for this method because of the need for healthy peripheral endothelial cells as well as central corneal guttae.

A novel approach involves the implantation of an artificial endothelial layer to the posterior aspect of the cornea.

The artificial implant

The EndoArt (EyeYon Medical) is a flexible, hydrophilic acrylic, dome-shaped permanent implant, 6 mm in diameter and 50 µm thick, specifically designed to replace the diseased corneal Descemet-endothelium layer (Figure 1). Implanting the lamella on the posterior surface of the cornea replaces the diseased endothelium and impedes the transfer of fluids into the central stroma. By covering around 40% of the back corneal surface, blocking the influx of fluids as well as epithelial evaporation leads to a reduction in corneal oedema to restore corneal homeostasis.

This artificial endothelial layer—which has been awarded a breakthrough therapy designation by the United States Food and Drug Administration (FDA), China’s Innovative Device Status and CE certification—could provide a paradigm shift in the treatment of patients with endothelial failure while eliminating the need for human donor tissues.

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The Department of Ophthalmology of the University Eye Clinic in Heidelberg, Germany, was one of the first centres to implant this innovative device, with patients having completed 2 years’ follow-up. The initial long-term evaluations are promising and demonstrate good safety and efficacy results. Currently, the implant is undergoing a first-in-human, multicentre trial across Europe and Asia.

Surgical technique

A 9-mm ring marks the central corneal surface to outline the peripheral extent of the Descemet membrane excision. With two paracentesis incisions at the 10 o’clock and 2 o’clock positions, the implant is folded into the cartridge of an IOL-injector and injected through a 2.2-mm clear cornea incision into the anterior chamber of the eye. The lamella then unfolds itself and is manually positioned onto the posterior corneal surface using an air bubble technique, similar to a DMEK procedure.

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Unlike a human donor lamella, the implant can actually be touched and moved by the surgeon, using a cannula, without compromising its function. The experienced corneal surgeon who is already familiar with the DMEK procedure should be able to place the implant without the need for extra training. Cataract surgeons may require a few extra training sessions.

The Heidelberg experience: case report

A 79-year-old man presented to our clinic after complicated cataract surgery at a private practice. DMEK was not a treatment option because of his wide and non-light reactive pupil and anterior synechiae. The patient was complaining of decreased vision.

On examination, the patient showed significant corneal oedema with corneal bullae and reminiscent lens material in the anterior chamber of the left eye. The patient perceived finger count with the left eye. An epiretinal gliosis was present on both eyes and the patient had received cryotherapy on the left eye due to a retinal tear 10 years earlier.

Figure 2 shows the diseased cornea before and after implantation. After 12 weeks, the cornea was clear with only a slight residual peripheral oedema (Figure 2 B+D). Corneal thickness was stable at 635 µm and visual acuity increased to 20/200 Snellen (Figure 2 D).

Retinal optical coherence tomography imaging revealed a pre-existing macular oedema, which is currently the limiting factor for visual improvement. The patient is being treated with parabulbar injections of steroids and further visual improvement is expected.

Conclusion

In conclusion, this technique shows that an artificial endothelial layer is feasible for treatment of patients with endothelial dysfunction. This shows promise for overcoming the worldwide shortage of donor endothelial tissue. Furthermore, in cases where endothelial keratoplasty may not be possible, this may be a readily available treatment option.

Victor A. Augustin, MD, Maximilian K. Köppe, MD, and Gerd U. Auffarth, MD, FEBO
E: vic.augustin@googlemail.com
The authors are based at the David J. Apple International Laboratory for Ocular Pathology and International Vision Correction Research Centre (IVCRC), Department of Ophthalmology, University of Heidelberg, Germany. Drs Augustin and Köppe declare no conflicts of interest. Prof. Auffarth reports grants, personal fees, non-financial support and consulting fees from Johnson & Johnson and Alcon; grants, personal fees and non-financial support from Carl Zeiss Meditec, Hoya, Kowa, Oculentis/Teleon, Rayner, Santen, Sifi and Ursapharm; grants and personal fees from Biotech, Oculus and EyeYon; and grants from Acufocus, Anew, Contamac, Glaukos, Physiol and Rheacell, outside the submitted work.

References
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13. Flockerzi E, Maier P, Böhringer D, et al. Trends in corneal transplantation from 2001 to 2016 in Germany: A report of the DOG-section cornea and its keratoplasty registry.Am J Ophthalmol. 2018;188:91-98.
14. Kinoshita S, Koizumi N, Ueno M, et al. Injection of cultured cells with a ROCK inhibitor for bullous keratopathy. N Engl J Med. 2018;378:995-1003.
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