September 2017

CORNEA

Research highlight
Glaucoma drug restarts endothelial healing in Fuchs’
patients with Descemetorhexis but no graft


by Liz Hillman EyeWorld Staff Writer

Use the EyeWorldAR app to listen to the podcast
“As Seen From Here,” which featured a
discussion between
Dr. Moloney and
Josh Young, MD, about
this recent research.


 

“There are many reasons that we as a corneal community are hoping that this technique can develop to a stage that it becomes a confident, first-line surgical option.”
—Greg Moloney, MD

Rho kinase inhibitor rescues stalled healing in study evaluating technique that encourages a patient’s own endothelial cell migration

Surgical options for Fuchs’ endothelial dystrophy typically include endothelial keratoplasty with a donor graft or a full corneal transplant to replace the patient’s dysfunctional corneal tissues producing clouded vision. However, there is a growing body of research that suggests removing Descemet’s membrane and leaving the patient without a donor graft could be a viable alternative.
Separately, there is also research showing increasing evidence that a drug, currently indicated for glaucoma and ocular hypertension, could aid in corneal endothelium wound healing.
Recent research by Moloney et al. combines these ideas, not only supporting the possibility of a spontaneous corneal clearance post-Descemetorhexis procedure in some patients, but also that a Rho-associated kinase (ROCK) inhibitor might rescue cases where corneal clearance has stalled after Descemet’s stripping alone.1
This research published in the journal Cornea saw spontaneous clearance of the cornea in nine out of 12 patients who had a Descemetorhexis due to visual symptoms resulting from central guttae. The three whose clearance stalled were put on a topical ROCK inhibitor; two of these achieved complete corneal clearance while one went on to endothelial keratoplasty.
“There are many reasons that we as a corneal community are hoping that this technique can develop to a stage that it becomes a confident, first-line surgical option,” said Greg Moloney, MD, staff specialist, cornea and oculoplastics, Sydney Eye Hospital, and clinical senior lecturer, Sydney University, Sydney, Australia. “It is far quicker, less invasive and does not commit the patient to lifelong topical steroid therapy. It does not require donor tissue, so it expands the available pool of donor tissue for other patients. It also ensures availability of tissue is not a barrier to surgery in less developed countries. For the younger Fuchs’ patient, it is far less likely to induce cataract, allowing retention of accommodation for longer.”
Previous research on Descemetorhexis without a graft for Fuchs’ dystrophy began several years ago after reports of spontaneous corneal clearance after graft detachment in a DMEK case.2 Following there have been multiple reports detailing outcomes of Descemetorhexis without a graft, with varied success.3,4 Complications that have been reported include corneal edema and damage to the posterior stroma, which has affected endothelial cell repopulation and led to inflammation.5 Others have stated that Descemetorhexis without endothelial keratoplasty resulted in slow visual recovery and poor postop visual acuity.6
In November 2016, EyeWorld reported on Dr. Moloney’s prior research on Descemetorhexis without a graft in Fuchs’ patients. In this article, Dr. Moloney emphasized the importance of patient selection for the success of this technique. Moloney et al.’s more recent article reports clinical results in an attempt to better define the appropriate patient population for this procedure and also presented a review of the ROCK inhibitor salvage therapy.
All patients in this study had a central Descemetorhexis 4 mm in diameter or less. Measurements were taken monthly until patients experienced corneal clearance, after which point they were reviewed every 6 months. If patients did not show clearance by 2 months, they were observed more frequently and became candidates for EK. Three patients were pulled to receive salvage therapy.
Why some cases cleared spontaneously while others didn’t is “the great unanswered question that is clouding a full rollout of the procedure,” Dr. Moloney said.
“Some of my patients have now enjoyed excellent vision for years after Descemetorhexis, others have required salvage measures to resolve dense edema,” he said. “We presume there is a cellular signal preventing migration in some patients. This may arise from overlying stroma, implicating surgical factors as important in determining results, or it may arise from intrinsic patient factors that we are yet to determine.”
Of those who did not clear spontaneously in the study, one patient received the compounded drug Y-27632 at 10 mM, while the two others received ripasudil hydrochloride hydrate, the latter of which is currently on the market in Japan and has shown accelerated corneal endothelial healing in rabbit models.7 Dr. Moloney said he had personal communication with Shigeru Kinoshita, MD, Kyoto Prefectural University of Medicine, Kyoto, Japan, whose group has pioneered Phase 1 trials with ROCK inhibitors for acceleration of corneal healing.
The patient who received Y-27632 topical therapy showed no measurable improvement after 2 weeks and required endothelial keratoplasty. This patient’s last best corrected visual acuity was 20/25. The other two cases received ripasudil and saw complete clearance within 2 weeks of therapy.
“The ability of ripasudil to salvage failing cases was startling, and suggests that cases previously considered borderline may prove to be candidates for Descemetorhexis. Before this therapy, we firmly believed that a graft would be required in the failing cases, and indeed, theater time and tissue were allocated,” Moloney et al. wrote, adding later, “We now believe that in the case proceeding to endothelial keratoplasty, the use of ripasudil would have avoided this step.”
The study authors speculated that the difference in success between the two ROCK inhibitors could be due to different inhibition factors.
Complications in this study overall included three cases of partial Descemet detachment (two of which were in the non-responder group); rebubbling was not successful in these cases. There were also three patients with endothelial nodule formation, which faded over time but not completely, Moloney et al. wrote.
Future research, Dr. Moloney said, needs to help physicians better identify who will be fast responders to this technique. So far, the criteria has been elusive. He added that larger trials for the safety and efficacy of ROCK inhibitors to speed healing after Descemetorhexis are also needed. “We have further theories we are working on to make the surgery more likely to succeed; these are unproven with work ongoing,” Dr. Moloney said.
Moloney et al. also pointed out that even successful cases in the long term might prove temporary with grafting needed.
For now, Dr. Moloney said new patients with Fuchs’ coming to his practice will be assessed clinically and with confocal microscopy for a view of their whole endothelial mosaic. He said he would recommend the Descemetorhexis technique for patients with dense central guttata, producing visually significant symptoms, with a clear peripheral cornea. There needs to be a healthy endothelial cell count and cell morphology in the peripheral cornea.
“Corneal pachymetry is a useful surrogate of endothelial health in these patients, with thickness >620 of concern,” Dr. Moloney said.
He also said patients must be able to provide informed consent and be informed that there is a 20% failure rate that might require use of rescue measures like topical ripasudil or endothelial keratoplasty.
If a patient has guttata limbus to limbus, peripheral cell counts <1,000/mm2, dense edema, or thick pachymetry, Dr. Moloney said he recommends Descemet’s membrane endothelial keratoplasty (DMEK).
Ultimately, Dr. Moloney thinks Descemetorhexis without a graft has the potential to become a first-line surgical treatment for a subset of Fuchs’ patients, but he added, “we will always need DMEK surgery for situations of low cell counts.”

References

1. Moloney G, et al. Descemetorhexis without grafting for Fuchs’ endothelial dystrophy–supplementation with topical ripasudil. Cornea. 2017;36:642–48.
2. Balachandran C, et al. Spontaneous corneal clearance despite graft detachment in Descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2009;148:227–234.
3. Moloney G, et al. Descemetorhexis for Fuchs’ dystrophy. Can J Ophthalmol. 2015;50:68–72.
4. Galvis V, et al. Descemetorhexis without endothelial graft in Fuchs’ dystrophy. Cornea. 2016;35:e26–8.
5. Arbelaez JG, et al. Long-term follow-up and complications of stripping Descemet membrane without placement of graft in eyes with Fuchs’ endothelial dystrophy. Cornea. 2014;33:1295–9.
6. Koenig SB. Planned Descemetorhexis without endothelial keratoplasty in eyes with Fuchs’ corneal endothelial dystrophy. Cornea. 2015;34:1149–51.
7. Okumara N, et al. Effect of the Rho-associated kinase inhibitor eye drop (ripasudil) on corneal endothelial wound healing. Invest Ophthalmol Vis Sci. 2016;57:1284–92.

Editors’ note: Dr. Moloney has no financial interests related to his comments.

Contact information

Moloney
: gregorymoloney@yahoo.com.au

Glaucoma drug restarts endothelial healing in Fuchs’ patients with Descemetorhexis but no graft Glaucoma drug restarts endothelial healing in Fuchs’ patients with Descemetorhexis but no graft
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