Descemet’s stripping only provides alternative to grafting in select cases
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Descemet’s stripping endothelial keratoplasty, Descemet’s membrane endothelial keratoplasty and pre-Descemet’s endothelial keratoplasty have changed the cornea transplant game.
There is also a technique of Descemet’s stripping only/descemetorhexis without endothelial keratoplasty, in which the endothelium-Descemet’s membrane complex is removed without any graft replacement. My guests in this column are experts Gregory Moloney, MBBS, FRANZCO, FRCSC, of Canada and Jodhbir S. Mehta, MBBS, PhD, FRCS(Ed), of Singapore.
Amar Agarwal, MS, FRCS, FRCOphth
OSN Complications Consult Editor
It is now almost 70 years since the first description of Descemet’s stripping only (DSO) and approaching 10 years since its modern renaissance began. What was once an operation that was the focus of curiosity and research has settled into the management algorithms for Fuchs’ endothelial corneal dystrophy (FECD).
As corneal surgeons treating FECD, we have become used to replacing one version of a transplant with another, with penetrating grafts giving way to DSEK and then DMEK. DSO has not followed this pattern in that it is clearly an intervention for a select population of FECD. It is a partner of, not a replacement for, DMEK. With some long-term results and better understanding, we are now able to examine the role of DSO in FECD, where it currently is indicated, what we have learned about its limitations and complications, and where it will lead us next as corneal surgeons. It has also given us an opportunity to learn more about corneal endothelial cell biology and behavior.
Terminology
Since its first modern description by Shah and colleagues, several names have been proposed for the operation in which Descemet’s membrane and associated guttae are removed in FECD without graft placement. Descemetorhexis without endothelial keratoplasty (DWEK) was first coined by Kaufmann and colleagues and remains popular. Due to the fact that keratoplasty is not strictly synonymous with grafting, with confusion among nursing staff and colleagues over another “EK” procedure, DSO was proposed as an alternative by Colby and Gorovoy.
DWEK/DSO
For many years, the proliferative/migratory capacity of the endothelium has been the focus of study of several groups. What DSO quickly taught us was that a wide variability existed between patients in their ability to close an endothelial defect through migration or mitosis. This is not unexpected because donor cell culture of corneal endothelial cells exhibits the same behavior. There is significant variation in cellular behavior depending on donor age, sex and concomitant use of oral medication, to name a few.
Source: Gregory Moloney, MBBS, FRANZCO, FRCSC, and Jodhbir S. Mehta, MBBS, PhD, FRCS(Ed)
In early studies, Colby and colleagues coined the terms “fast,” “slow” and “nonresponders” to this operation. It was not clear at that stage whether patient factors, surgical factors or a combination were responsible. In vitro studies have since demonstrated that a younger age, intact basement membrane and addition of Rho kinase (ROCK) inhibitors in older subjects are promoters of endothelial migration. Using ex vivo donor corneas, Soh and colleagues were able to demonstrate that there was significant improvement in cell migration in younger donors compared with older ones. However, the age-related decline in cellular migration could be negated by the addition of a ROCK inhibitor. In the study, using paired matched donor corneas, a 70-year-old individual was able to achieve corneal endothelial cell closure at seven times the speed of a paired control donor without a ROCK inhibitor. In addition, there was a significant difference in the cellular morphology. Cellular morphology showed that cells had undergone endothelial-mesenchymal transformation (EMT) during cellular migration. However, once closure was achieved, cell maturity was achieved, anatomical at first, but subsequent full physiological function took another few weeks.
Surgical factors have emerged as equally important in determining the success of the surgery in terms of both endothelial closure and visual improvement. Surgical experience has taught us that stromal injury in the absence of graft coverage results in a chronic fibrotic healing response that can affect vision. The latter is due to stimulation of the posterior keratocytes, which have undergone EMT and subsequent myofibroblast transformation. A peeling technique that minimizes stromal scarring is therefore strongly emphasized for DSO. Oversizing the descemetorhexis is also associated with higher failure rates; therefore, the size of the stripped area should generally not exceed 4 mm to 5 mm. If well executed, an optical zone is created in the cornea. As it was with radial keratotomy, excimer ablations and other forms of keratoplasty, centration of this zone is important to avoid higher-order aberrations. However, this has to be balanced with removal of the area of the highest density of the corneal guttata.
The main mechanism of corneal clearance is clearly cell migration, as is illustrated by a decline in peripheral cell counts after DSO. The surgery therefore relies on a peripheral host reservoir. It is best reserved for FECD with central guttae. We recently reported medium-term failure in a case with pancorneal guttae, further reducing optimism for success without a healthy periphery. We also have to bear in mind that the migrating cells are not completely healthy corneal endothelial cells because they may have genotypic and cellular changes associated with FECD, which may affect their long-term cellular function.
Rho kinase inhibitors
ROCK inhibitors have been studied as promoters of endothelial healing by the Kyoto group for many years. All current commercially available preparations are designed as ocular hypotensive agents, with the use of promoting endothelial healing remaining off label. In vitro work suggests ROCK inhibitors play a role in assisting migration, preventing apoptosis and possibly also stimulating some mitosis. Clinical experience in medium-sized trials suggests ROCK inhibitors can accelerate endothelial migration. The observation of “relapse edema” upon withdrawal of the drug and restoration of clearance upon restarting is strong evidence of clinical effect. It also shows that full physiological functional recovery takes some time. This has been shown experimentally by Bhogal and colleagues. It is now clear that fast responders may not require the assistance of ROCK inhibitors to achieve corneal clearance, and some patients will still not achieve corneal clearance with the drug. A large multicenter sponsored study is currently underway comparing placebo to twice a day and four times a day dosing after DSO. It is hoped this will add further clarity to optimal dosing and use of ROCK inhibitors after DSO.
Summary
Future studies will aim to examine the role of other agents in promoting cell migration and mitosis after DSO. Trefoil Therapeutics is already conducting a phase 2 clinical trial analyzing the use of recombinant fibroblast growth factor as a stimulant to healing after DSO.
For the corneal community, it has been a fascinating journey that has shed more light on the healing capacity of the endothelium and provided a surgical alternative to grafting in selected cases.
- References:
- Artaechevarria Artieda J, et al. Cornea. 2020;doi:10.1097/ICO.0000000000002270.
- Bhogal M, et al. Invest Ophthalmol Vis Sci. 2017;doi:10.1167/iovs.17-22106.
- Borkar DS, et al. Cornea. 2016;doi:10.1097/ICO.0000000000000915.
- Garcerant D, et al. Curr Opin Ophthalmol. 2019;doi:10.1097/ICU.0000000000000579.
- Joyce NC. Exp Eye Res. 2005;doi:10.1016/j.exer.2005.06.012.
- Joyce NC. Prog Retin Eye Res. 2003;doi:10.1016/s1350-9462(02)00065-4.
- Kaufman AR, et al. Cornea. 2018;doi:10.1097/ICO.0000000000001528.
- Koizumi N, et al. Cornea. 2013;doi:10.1097/ICO.0b013e318285475d.
- Macsai MS, et al. Cornea. 2019;doi:10.1097/ICO.0000000000001883.
- Moloney G, et al. Cornea. 2017;doi:10.1097/ICO.0000000000001209.
- Okumura N, et al. Cornea. 2011;doi:10.1097/ICO.0b013e3182281ee1.
- Okumura N, et al. Invest Ophthalmol Vis Sci. 2013;doi:10.1167/iovs.12-11320.
- Paufique L. Lamellar keratoplasty. In: Rycroft BW, ed. Corneal Grafts. Butterworth and Co. Ltd; 1955:132-133.
- Soh YQ, et al. Am J Ophthalmol 2021;doi:10.1016/j.ajo.2020.07.029.
- Shah RD, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2011.07.032.
- Soh YQ, et al. Invest Ophthalmol Vis Sci. 2016;doi:10.1167/iovs.15-18300.
- For more information:
- Jodhbir S. Mehta, MBBS, PhD, FRCS(Ed), can be reached at Singapore National Eye Centre, 11 Third Hospital Ave., Singapore 168751; email: jodmehta@gmail.com.
- Gregory Moloney, MBBS, FRANZCO, FRCSC, can be reached at 805 W. Broadway, Suite 1603, Vancouver, British Columbia V5Z 1J9, Canada; email: gregorymoloney@yahoo.com.au.
- Edited by Amar Agarwal, MS, FRCS, FRCOphth, director of Dr. Agarwal’s Eye Hospital and Eye Research Centre. Agarwal is the author of several books published by SLACK Books, sister company of Healio publisher Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery and Presbyopia: A Surgical Textbook. He can be reached at 19 Cathedral Road, Chennai 600 086, India; email: aehl19c@gmail.com; website: www.dragarwal.com.
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