DMEK, DSO, and Gold Standards

Feb 2, 2024 | Research Articles

An article1 recently appearing in the journal Cornea, entitled “Descemet Stripping Only for Fuchs Endothelial Corneal Dystrophy: Will It Become the Gold Standard?” poses an important question regarding the contemporary and emerging treatment of Fuchs Endothelial Corneal Dystrophy (FECD). When applied to medical research and treatment, the term “gold standard” implies that a form of therapy has been rigorously studied and tested, and when put into medical practice, over time and with sufficient experience, becomes accepted as the best available approach to treating a specific disease2. There is no implication that such an approach is a panacea, but rather, in the context of overall risk-benefit analysis, it has become accepted as the best current alternative against which others need to be measured. In contemporary practice, the gold standard in the definitive treatment for FECD has involved continuously refined techniques of transplantation of donor corneal tissue. It remains to be seen whether Descemet Stripping Only (DSO) will successfully challenge this standard.

Although uncommon enough in the general population (estimated prevalence of 4-7%3-5) that most lay people and even many non-ophthalmologist physicians are unaware of the disease, FECD is among the most common forms of corneal dystrophy6. Until the very recent development of DSO, definitive treatment for FECD has, for decades, involved various types of transplantation of donor corneal tissue. In fact, “Corneal transplantation or keratoplasty is the most commonly performed and also the most successful allogenic transplant worldwide,”7 and FECD has become the most frequent indication for corneal tissue transplantation in the United States.6,8

The treatment of FECD has a long and fascinating evolution. First described by Austrian ophthalmologist Ernst Fuchs in 1910, FECD is known as a progressive disorder of the posterior cornea which often features a prolonged period of minimal or no symptoms, wherein the diagnosis is made serendipitously during examination. Once more noticeable symptoms begin, however, the course can accelerate more rapidly and, if untreated, can lead to corneal degeneration and visual loss.5,7

From the time of its discovery over a century ago, it became apparent that medical treatments for FECD, although potentially able to ameliorate early symptoms, were unsuccessful in forestalling disease progression. This remains the case today, and “definitive treatment requires surgery.”5 For over a century, the surgical approach to FECD involved transplantation of an entire, intact donor cornea, a process called “Penetrating Keratoplasty (PK).”9 Although effective in restoring visual acuity in certain cases and comprising the only alternative for decades, PK was fraught with many potential complications. These included infection, suture-line complications leading to wound dehiscence (rupturing of the wound), very lengthy time to visual recovery with variable acuity, severe astigmatism, and a high risk of transplant rejection.10

The past twenty-five years have witnessed an astounding evolution in corneal tissue transplant techniques, prompted by the recognition that minimization of the many complications of PK might be achieved by focusing attention on the microscopic layers of corneal tissue where the disease process occurs. In the case of FECD, this includes corneal endothelial cells and the layer of tissue on which they reside, Descemet Membrane, on the back surface of the cornea. With the exception of very advanced cases of FECD, the remainder of the cornea is generally healthy. Thus, techniques involving transplant of multiple layers or full-thickness cornea (PK) expose patients to many more complications without significant benefit.7,11

Thus was born a remarkably rapid progression of efforts to isolate and transplant ever-thinner layers of corneal tissue including the endothelial layer, collectively called “endothelial keratoplasty (EK).” Such pioneering corneal surgeons as Melles, Terry, Price, Gorovoy and others spearheaded these efforts in the first decade of the current century, developing increasingly refined procedures with acronyms such as PLK, DLEK, DSEK, and DSAEK, each involving thinner layers of tissue. Associated surgical techniques required high levels of precision, experience and proficiency, along with parallel advances in eye bank donor tissue acquisition, preservation, and presentation to the surgeon.7,11,12 Each advance yielded progressively improved results in terms of visual acuity, postoperative time required to attain best visual acuity, and reduced complications.

The most recent technical iteration in this progression, Descemet Membrane Endothelial Keratoplasty (DMEK) was introduced by Melles in 2006.11 It involves transplanting only the diseased tissue in FECD, the endothelial cells and the membrane on which they reside, using a donor graft only 10 microns thick and devoid of any deeper corneal tissue (stroma). It is the inclusion of stroma which augments the risk of immunologic rejection. Because it involves manipulation of microscopically thin tissue, DMEK is an intricate procedure, requiring considerable practice and experience on the part of the corneal surgeon to achieve the best outcome. Given its steep learning curve,13 DMEK took time to become widely embraced but, in recent years, with sufficient experience, outcomes have improved and complications greatly diminished.14 In the years since its introduction, DMEK has seen an annual increase in frequency of use compared to older forms of EK,7,11 and is now regarded as the technique offering the best and fastest improvement in visual acuity and the lowest incidence of graft rejection,12 especially with ongoing use of topical steroid eye drops.15,16 For these reasons, many surgeons consider DMEK to be the current gold standard in the treatment of FECD.

Still, all of these techniques require the use of donor tissue which, under the best of circumstances, carries some degree of risk. DSO is the first technique which avoids the need for donor grafts and, if proven successful in terms of benefit vs risk, and given a sufficient track record over time, has the potential to replace DMEK as the standard of care in FECD. However, as mentioned at the outset, this will require rigorous study to generate a statistically valid volume of data for analysis as well as copious experience among surgeons and patients.

The observation that some FECD patients experienced clearing of vision after removal of a small central portion of Descemet membrane along with its attached, diseased endothelial cells, but without transplant, was a serendipitous finding that led to hope for the possibility of spontaneous healing due to the migration of potentially healthy endothelial cells from the periphery of the cornea to the denuded center.1,6 This prompted the consideration of intentional stripping of a small (4 mm) portion of the central corneal endothelium/Descemet membrane in an effort to repopulate the area with endothelial cells from the periphery (DSO)

A comparatively new procedure, in many ways DSO can be considered a work in progress, with an estimate, per Dr. Mark Gorovoy, of the total procedures performed worldwide numbering only in the hundreds.17 Although some expert corneal surgeons have achieved striking success, rates generally reported in the literature vary considerably.18 This may be due in part to the fact that the subset of corneal surgeons who have extensive experience with the technique remains relatively small in comparison to those adept at the various forms of thin-layer partial corneal transplant such as DSAEK and DMEK.17

Avoiding the use of donor tissue removes a number of potential complications, including graft rejection and those occasionally related to ocular steroid use (e.g., cataracts, increased intraocular pressure). However, DSO also presents a number of limitations and possible disadvantages.19 Patients must be chosen carefully, and those with an inadequate volume of healthy peripheral endothelial cells are much less likely to experience a good outcome.18 Even in those patients considered good candidates for DSO, the time required for migration of healthy endothelial cells to the denuded central area varies considerably, and visual recovery is typically slower than that associated with DMEK, which some patients find distressing.6,17 There is accumulating evidence that the use of a class of medication called “rho-associated kinase (ROCK) inhibitors” can accelerate the migration of peripheral endothelium. However only one, netarsudil (Rhopressa), is approved by the FDA (for the treatment of glaucoma), and it is felt to be less effective in DSO than ripasudil (Glantec) which, at present, is only available in, and must be obtained privately from, Japan.1,7

Finally, more time is needed to evaluate the long-term success of DSO in large series of patients. A number of DSO patients have had good results for several years, however there is at least one case report of a patient who redeveloped symptoms and signs of FECD six years after DSO,20 presumably due to the genetic and biochemical predisposition of one’s own endothelial cells in FECD to degenerate, in contrast to cells from donors without FECD.

In summary, DSO represents the latest development in the evolving continuum of surgical treatment of FECD and has great promise. Just as transplant techniques have become highly refined, we may see the day when, for properly selected patients with FECD, treatment that does not involve transplantation of donor tissue will become the new “gold standard” of care. It does not appear that we are there yet.

References

  1. Colby K: Descemet Stripping Only for Fuchs Endothelial Corneal Dystrophy: Will It Become the Gold Standard? Cornea 2022; 41:269–71
  2. Jones DS, Podolsky SH: The history and fate of the gold standard. The Lancet 2015; 385:1502–3
  3. Singh RB, Parmar UPS, Kahale F, Jeng BH, Jhanji V: Prevalence and Economic Burden of Fuchs Endothelial Corneal Dystrophy in the Medicare Population in the United States. Cornea 2023 doi:10.1097/ICO.0000000000003416
  4. Aiello F, Gallo Afflitto G, Ceccarelli F, Cesareo M, Nucci C: Global Prevalence of Fuchs Endothelial Corneal Dystrophy (FECD) in Adult Population: A Systematic Review and Meta-Analysis. Journal of Ophthalmology Edited by Figus M. 2022; 2022:1–7
  5. Eghrari AO, Gottsch JD: Fuchs’ corneal dystrophy. Expert Review of Ophthalmology 2010; 5:147–59
  6. Blitzer AL, Colby KA: Update on the Surgical Management of Fuchs Endothelial Corneal Dystrophy. Ophthalmol Ther 2020; 9:757–65
  7. Singh R, Gupta N, Vanathi M, Tandon R: Corneal transplantation in the modern era. Indian J Med Res 2019; 150:7
  8. Park CY, Lee JK, Gore PK, Lim C-Y, Chuck RS: Keratoplasty in the United States. Ophthalmology 2015; 122:2432–42
  9. Maghsoudlou P, Sood G, Akhondi H: Cornea Transplantation, StatPearls. Treasure Island (FL), StatPearls Publishing, 2023 at <http://www.ncbi.nlm.nih.gov/books/NBK539690/>
  10. Moffatt SL, Cartwright VA, Stumpf TH: Centennial review of corneal transplantation. Clinical Exper Ophthalmology 2005; 33:642–57
  11. Price MO, Gupta P, Lass J, Price FW: EK (DLEK, DSEK, DMEK): New Frontier in Cornea Surgery. Annual Review of Vision Science 2017; 3:69–90
  12. Moshirfar M, Thomson AC, Ronquillo Y: Corneal Endothelial Transplantation, StatPearls. Treasure Island (FL), StatPearls Publishing, 2024 at <http://www.ncbi.nlm.nih.gov/books/NBK562265/>
  13. Debellemanière G, Guilbert E, Courtin R, Panthier C, Sabatier P, Gatinel D, Saad A: Impact of Surgical Learning Curve in Descemet Membrane Endothelial Keratoplasty on Visual Acuity Gain. Cornea 2017; 36:1
  14. Marques RE, Guerra PS, Sousa DC, Gonçalves AI, Quintas AM, Rodrigues W: DMEK versus DSAEK for Fuchs’ endothelial dystrophy: A meta-analysis. European Journal of Ophthalmology 2019; 29:15–22
  15. Gurnani B, Kaur K: Penetrating Keratoplasty, StatPearls. Treasure Island (FL), StatPearls Publishing, 2023 at <http://www.ncbi.nlm.nih.gov/books/NBK592388/>
  16. Hos D, Tuac O, Schaub F, Stanzel TP, Schrittenlocher S, Hellmich M, Bachmann BO, Cursiefen C: Incidence and Clinical Course of Immune Reactions after Descemet Membrane Endothelial Keratoplasty. Ophthalmology 2017; 124:512–8
  17. Manzone Carr P: Personal communication
  18. Garcerant D, Hirnschall N, Toalster N, Zhu M, Wen L, Moloney G: Descemet’s stripping without endothelial keratoplasty. Current Opinion in Ophthalmology 2019; 30:275–85
  19. Kuriakose RK, Patel R: A New Frontier: Descemet’s Stripping Only/Without Endothelial Keratoplasty (DSO)/(DWEK) 2023 at <https://eyesoneyecare.com/resources/descemets-stripping-only-without-endothelial-keratoplasty-dso-dwek/>
  20. Kaufman AR, Bal S, Boakye J, Jurkunas UV: Recurrence of Guttae and Endothelial Dysfunction After Successful Descemet Stripping Only in Fuchs Dystrophy. Cornea 2023; 42:1037–40
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